Improving clerkship preparedness: a hospital medicine elective for pre-clerkship students.

BACKGROUND: Medical students often struggle to apply their nascent clinical skills in clerkships. While transitional clerkships can orient students to new roles and logistics, students may benefit from developing clinical skills in inpatient environments earlier in their curriculum to improve readiness for clerkships. INTERVENTION: Our four- to six-session elective provides pre-clerkship students with individualized learning in the inpatient setting with the aim of improving clerkship preparedness. Students work one-on-one with faculty who facilitate individualized learning through mentoring, deliberate practice, and directed feedback. Second-year medical students are placed on an attending-only, traditionally 'non-teaching' service in the hospital medicine division of a Veterans Affairs (VA) hospital for half-day sessions. Most students self-select into the elective following a class-wide advertisement. The elective also accepts students who are referred for remediation of their clinical skills. OUTCOME: In the elective's first two years, 25 students participated and 47 students were waitlisted. We compared participant and waitlisted (non-participant) students' self-efficacy in several clinical and professional domains during their first clerkship. Elective participants reported significantly higher clerkship preparedness compared to non-participants in the areas of physical exam, oral presentation, and formulation of assessments and plans. CONCLUSIONS: Students found the one-on-one feedback and personalized attention from attending physicians to be a particularly useful aspect of the course. This frequently cited benefit points to students' perceived needs and the value they place on individualized feedback. Our innovation harnesses an untapped resource - the hospital medicine 'non-teaching' service - and serves as an attainable option for schools interested in enhancing early clinical skill-building for all students, including those recommended for remediation. ABBREVIATIONS: A&P: Assessment and plan; H&P: History and physical; ILP: Individual learning plan.

The effect of a translating research into practice intervention to promote use of evidence-based fall prevention interventions in hospitalized adults: A prospective pre-post implementation study in the U.S.

BACKGROUND: Falls are a major public health problem internationally. Many hospitals have implemented fall risk assessment tools, but few have implemented interventions to mitigate patient-specific fall risks. Little research has been done to examine the effect of implementing evidence-based fall prevention interventions to mitigate patient-specific fall risk factors in hospitalized adults. OBJECTIVES: To evaluate the impact of implementing, in 3 U.S. hospitals, evidence-based fall prevention interventions targeted to patient-specific fall risk factors (Targeted Risk Factor Fall Prevention Bundle). Fall rates, fall injury rates, types of fall injuries and adoption of the Targeted Risk Factor Fall Prevention Bundle were compared prior to and following implementation. DESIGN: A prospective pre-post implementation cohort design. SETTING: Thirteen adult medical-surgical units from three community hospitals in the Midwest region of the U.S. PARTICIPANTS: Nurses who were employed at least 20hours/week, provided direct patient care, and licensed as an RN (n=157 pre; 140 post); and medical records of patients 21years of age or older, who received care on the study unit for more than 24hours during the designated data collection period (n=390 pre and post). METHODS: A multi-faceted Translating Research Into Practice Intervention was used to implement the Targeted Risk Factor Fall Prevention Bundle composed of evidence-based fall prevention interventions designed to mitigate patient-specific fall risks. Dependent variables (fall rates, fall injury rates, fall injury type, use of Targeted Risk Factor Fall Prevention Bundle) were collected at baseline, and following completion of the 15month implementation phase. Nurse questionnaires included the Stage of Adoption Scale, and the Use of Research Findings in Practice Scale to measure adoption of evidence-based fall prevention practices. A Medical Record Abstract Form was used to abstract data about use of targeted risk-specific fall prevention interventions. Number of falls, and number and types of fall injuries were collected for each study unit for 3months pre- and post-implementation. Data were analyzed using multivariate analysis. RESULTS: Fall rates declined 22% (p=0.09). Types of fall injuries changed from major and moderate to minor injuries. Fall injury rates did not decline. Use of fall prevention interventions improved significantly (p<0.001) for mobility, toileting, cognition, and risk reduction for injury, but did not change for those targeting medications. CONCLUSIONS: Using the Translating Research Into Practice intervention promoted use of many evidence-based fall prevention interventions to mitigate patient-specific fall risk factors in hospitalized adults.

Nurses' Perceptions of Implementing Fall Prevention Interventions to Mitigate Patient-Specific Fall Risk Factors.

Evidence-based (EB) fall prevention interventions to mitigate patient-specific fall risk factors are readily available but not routinely used in practice. Few studies have examined nurses' perceptions about both the use of these EB interventions and implementation strategies designed to promote their adoption. This article reports qualitative findings of nurses' perceptions about use of EB fall prevention interventions to mitigate patient-specific fall risks, and implementation strategies to promote use of these interventions. The findings revealed five major themes: before-study fall prevention practices, use of EB fall prevention interventions tailored to patient-specific fall risk factors, beneficial implementation strategies, overall impact on approach to fall prevention, and challenges These findings are useful to guide nurses' engagement and use of EB fall prevention practices tailored to patient-specific fall risk factors.

Impact of health information technology on detection of potential adverse drug events at the ordering stage.

PURPOSE: The impact of implementing commercially available health care information technologies at hospitals in a large health system on the identification of potential adverse drug events (ADEs) at the medication ordering stage was studied. METHODS: All hospitals in the health system had implemented a clinical decision-support system (CDSS) consisting of a centralized clinical data repository, interfaces for reports, a results reviewer, and a package of ADE alert rules. Additional technology including computerized provider order entry (CPOE), an advanced CDSS, and evidence-based order sets was implemented in nine hospitals. ADE alerts at these hospitals were compared with alerts at nine hospitals without the advanced technology. A linear mixed-effects model was used in determining the mean response profile of six dependent variables over 28 total months for each experimental group. RESULTS: Overall, hospitals with CPOE and an advanced CDSS captured significantly more ADE alerts for pharmacist review; an average of 336 additional potential ADEs per month per hospital were reviewed. Pharmacists identified some 94% of the alerts as false positives. Alerts identified as potentially true positives were reviewed with physicians, and order changes were recommended. The number of true-positive alerts per 1000 admissions increased. CONCLUSION: The implementation of CPOE and advanced CDSS tools significantly increased the number of potential ADE alerts for pharmacist review and the number of true-positive ADE alerts identified per 1000 admissions.

Effects of an adverse-drug-event alert system on cost and quality outcomes in community hospitals.

PURPOSE: The effects of an adverse-drug-event (ADE) alert system on cost and quality outcomes in community hospitals were evaluated. METHODS: This retrospective observational study evaluated the effects of an ADE alert system in seven hospitals in the Trinity Health network. Outcomes for all inpatients admitted to these hospitals after and one year before the deployment of an ADE alert system were evaluated. Inpatients in two network hospitals that lacked any computerized ADE alert system constituted the external control group. Administrative data were gathered for patients from these facilities for the same time frames as for the preimplementation and postimplementation groups. Primary outcomes evaluated included pharmacy department costs, variable drug costs, and mortality rates. Secondary outcomes included total hospitalization costs, length of hospital stay (LOS), rate of readmission, and case-mix index. Mean differences in primary and secondary outcome measures across all four groups were examined using analysis of variance. RESULTS: Significant decreases in mean pharmacy department costs per patient were observed from preimplementation to postimplementation (p < 0.001), while pharmacy department costs increased significantly in the external control group (p = 0.029). Drug costs decreased significantly from baseline (p < 0.001) in the postimplementation group. Drug costs increased significantly in the external control group (p = 0.029). Severity-adjusted mortality rates and LOS decreased significantly in the postimplementation group. Total patient hospitalization costs, both crude and severity adjusted, significantly increased in both groups. CONCLUSION: Implementation of an ADE alert system in seven community hospitals demonstrated significant decreases in pharmacy department costs, variable drug costs, and severity-adjusted mortality rates.

Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator.

Endometriosis affects 10-20% of women of reproductive age and is associated with pelvic pain and infertility, and its pathogenesis is not well understood. We used genomewide transcriptional profiling to characterize endometriosis and found that it exhibits a gene expression signature consistent with an underlying autoimmune mechanism. Endometriosis lesions are characterized by the presence of abundant plasma cells, many of which produce IgM, and macrophages that produce BLyS/BAFF/TNFSF13B, a member of the TNF superfamily implicated in other autoimmune diseases. B lymphocyte stimulator (BLyS) protein was found elevated in the serum of endometriosis patients. These observations suggest a model for the pathology of endometriosis where BLyS-responsive plasma cells interact with retrograde menstrual tissues to give rise to endometriosis lesions.

A thienopyridazinone-based melanin-concentrating hormone receptor 1 antagonist with potent in vivo anorectic properties.

Melanin-concentrating hormone receptor antagonists containing thieno- and a benzopyridazinone cores were designed and tested as potential anorectic agents. These ligands showed high affinity for the receptor, potent functional activity in vitro, and good oral bioavailabilty in rats. The thiophene analogue exhibited low iv clearance, long half-life, and high brain penetration. In obese rats, the thienopyridazinone demonstrated a dose-dependent reduction in feeding and body weight with doses between 1 and 10 mg kg-1.

A jury of our PEERS.

Recognizing the importance of free and honest communication across its network of 44,000 employees, Trinity Health, Novi, Ml, created what it calls the "Potential Error/Event Reporting System" (PEERS) as a tool to gather data from the system's own physicians, nurses, and staff members. PEERS is anonymous, voluntary, nonpunitive, and available to all through the system's intranet. PEERS makes it possible for any person to alert management to a problem--a medication error, patient fall, inappropriate behavior, procedure, or other problem--that puts patients or caregivers at risk. Since the implementation of PEERS, Trinity Health's leaders have found that physicians, nurses, and other staff members are far more willing than formerly to share their experiences for the benefit of the greater good. Ninety percent of Trinity Health facilities, including home-health sites, have adopted PEERS as part of their regular error-reporting data set.

Rational design, synthesis, and structure-activity relationships of aryltriazoles as novel corticotropin-releasing factor-1 receptor antagonists.

Following the discovery of the very high binding affinity of 4-anilinopyrimidines against corticotropin-releasing factor receptor-1 (CRF(1)) (e.g., 1, K(i) = 2 nM), a new series of triazoles bearing different groups has been synthesized and evaluated. The compounds were prepared by cyclizations of N-acyl-S-methylisothioureas with alkylhydrazines or by cyclizations with hydrazine followed by alkylation. While members of this series showed potent binding affinity against CRF(1) receptor, there were important differences between the different regio- (7 and 12) and stereoisomeric aryltriazoles where the R(1) or R(2) side chain in 7 has an asymmetric center. In terms of overall potency, aryltriazole analogues such as 7r bearing an N-(alpha-branched benzyl)-N-propylamino side chain were the most potent, followed by analogues such as 7a, with an N-bis(cyclopropyl)methyl-N-propylamino side chain, and analogues such as 7m, with an N-(alpha-branched aliphatic)-N-propylamino side chain. While the N-propyl group was crucial for high potency, we hypothesized that the terminal methyl mimicked the 5-methyl of pyrazolo[1,5-a]pyrimidines 3 and 4. Correlation of the low-energy conformers of compounds of type 3 and 7 generated by computational analyses was very good. The size and shape of the N-alkyl group dramatically changed the potency of the triazoles, which is in contrast to the SAR seen for bicyclic CRF(1) antagonists. In general, the S-enantiomer was much more potent than the corresponding R-isomer. Furthermore, to a limited extent in the aryltriazole series the substituent on the 5-phenyl ring changed the potency up to 9-fold. (S)-1-Methyl-3-[N-(4-fluorophenylpentyl)-N-propyl]amino-5-(2-methoxy-4-dichlorophenyl)-1H-[1,2,4]triazole [(S)-7r] showed very potent binding affinity (K(i) = 2.7 nM) to CRF(1) receptors with an IC(50) of 49 nM in a cAMP inhibition assay.

Body weight regulation by selective MC4 receptor agonists and antagonists.

There has been great interest in melanocortin (MC) receptors as targets for the design of novel therapeutics to treat disorders of body weight, such as obesity and cachexia. Both genetic and pharmacological evidence points toward central MC4 receptors as the principal target. Using highly selective peptide tools for the MC4 receptor, which have become available recently, we have provided pharmacological confirmation that central MC4 receptors are the prime mediators of the anorexic and orexigenic effects reported for melanocortin agonists and antagonists, respectively. The current progress with receptor-selective small molecule agonist and antagonist drugs should enable the therapeutic potential of MC4 receptor activation and inhibition to be assessed in the clinic in the near future.

Molecular determinants of melanocortin 4 receptor ligand binding and MC4/MC3 receptor selectivity.

The molecular basis of ligand recognition by the melanocortin 4 receptor (MC4R) has not been fully defined. In this study, we investigated the molecular determinants of MC4R ligand binding, employing a large array of ligands, using three approaches. First, molecular modeling of the receptor was used to identify Phe284, in transmembrane (TM) 7, as a potential site of ligand interaction. Mutation of Phe284 to alanine reduced binding affinity and potency of peptides containing L-Phe by up to 71-fold but did not appreciably affect binding of linear peptides containing D-Phe, consistent with a hydrophobic interaction between the Phe7 of alpha-melanocyte-stimulating hormone and Phe284. Second, we examined the effect of a naturally occurring mutation in TM3 (I137T) that is linked to obesity. This mutation decreased affinity and potency of cyclic, rigid peptides but not more flexible peptides, consistent with an indirect effect of the mutation on the tertiary structure of the receptor. Third, we examined the residues that support ligand selectivity for the MC4R over the MC3R. Mutation of Ile125 (TM3) of the MC4R to the equivalent residue of the MC3R (phenylalanine) selectively decreased affinity and potency of MC4R-selective ligands. This effect was mirrored by the reciprocal MC3R mutation F157I. The magnitude of this effect indicates that this locus is not of major importance. However, it is considered that an isoleucine/phenylalanine mutation may affect the orientation of Asp122, which has been identified as a major determinant of ligand binding affinity. Thus, this study provides further characterization of the MC4R binding pocket.

Multiple sclerosis: deeper understanding of its pathogenesis reveals new targets for therapy.

Recent technological breakthroughs allowing for large-scale analysis of gene transcripts and large-scale monitoring of the immune response with protein chips are revealing new participants in the pathogenesis of multiple sclerosis. Some of these participants may be useful targets for therapy.

Immunological characterization and therapeutic activity of an altered-peptide ligand, NBI-6024, based on the immunodominant type 1 diabetes autoantigen insulin B-chain (9-23) peptide.

The nonobese diabetic (NOD) mouse is a good model for human type 1 diabetes, which is characterized by autoreactive T-cell-mediated destruction of insulin-producing islet beta-cells of the pancreas. The 9-23 amino acid region of the insulin B-chain [B((9-23))] is an immunodominant T-cell target antigen in the NOD mouse that plays a critical role in the disease process. By testing a series of B((9-23)) peptide analogs with single or double alanine substitutions, we identified a set of altered peptide ligands (APLs) capable of inhibiting B((9-23))-induced proliferative responses of NOD pathogenic T-cell clones. These APLs were unable to induce proliferation of these clones. However, vaccinations with the APLs induced strong cellular responses, as measured by in vitro lymphocyte proliferation and Th2 cytokine production (i.e., interleukin [IL]-4 and IL-10, but not gamma-interferon [IFN-gamma]). These responses were cross-reactive with the native antigen, B((9-23)), suggesting that the APL-induced Th2 responses may provide protection by controlling endogenous B((9-23))-specific Th1 (i.e., IFN-gamma-producing) pathogenic responses. One of these APLs that contained alanine substitutions at residues 16 and 19 (16Y-->A, 19C-->A; NBI-6024) was further characterized for its therapeutic activity because it consistently induced T-cell responses (e.g., T-cell lines and clones) that were of the Th2 type and that were cross-reactive with B((9-23)). Subcutaneous injections of NBI-6024 to NOD mice administered either before or after the onset of disease substantially delayed the onset and reduced the incidence of diabetes. This study is the first to report therapeutic activity of an APL derived from an islet beta-cell-specific antigen in type 1 diabetes.

Identification of differentially expressed genes induced by transient ischemic stroke.

We have used a rat model of focal cerebral ischemia to investigate changes in gene expression that occur during stroke. To monitor these changes, we employed representational difference analysis-polymerase chain reaction (PCR). A total of 128 unique gene fragments were isolated, and we selected 13 of these for quantitative reverse transcriptase-PCR analysis. Of these 13 genes, we found seven that were differentially expressed. Four of these genes have not previously been implicated in stroke, and include neuronal activity regulated pentraxin (Narp), cysteine rich protein 61 (Cyr61), Bcl-2 binding protein BIS (Bcl-2-interacting death suppressor), and lectin-like ox-LDL receptor (LOX-1). We demonstrated differential expression of each gene by quantitative PCR analysis, and in the case of LOX-1, we further confirmed differential expression by in situ hybridization. LOX-1 expression is induced greater than ten fold at the core lesion site, and is essentially localized to the ipsilateral half of the brain. LOX-1 appears to be expressed in a non-neuronal cell type, and it does not appear to be expressed in vascular endothelial cells within the brain. This suggests that LOX-1 may serve a novel function in the brain.

Regulation of murine macrophage proinflammatory and anti-inflammatory cytokines by ligands for peroxisome proliferator-activated receptor-gamma: counter-regulatory activity by IFN-gamma.

The prostaglandin, 15-deoxy Delta(12,14)-prostaglandin J2 (15d-PGJ2)(1), and thiazolidinediones are ligands for the nuclear receptor, peroxisome proliferator-activated receptor (PPAR)-gamma, which mediates anti-inflammatory activity by suppressing murine macrophage (Mphi) production of the inflammatory mediator, nitric oxide (NO). Here, we elucidated this anti-inflammatory activity further by investigating whether PPAR-gamma ligands regulated a panel of proinflammatory and anti-inflammatory cytokines produced by primary inflammatory murine Mphi (thioglycollate-elicited peritoneal exudate Mphi; PEM). Thiazolidinediones and 15d-PGJ2 suppressed lipopolysaccharide (LPS)-induced PEM production of NO and IL-12(p40) to a greater extent than IL-6 and TNF-alpha production. Whereas 15d-PGJ2 showed the greatest extent of suppression of proinflammatory mediator production, the thiazolidinedione, BRL49653, was the most potent compound studied. Surprisingly, treatment with the Mphi-activation cytokine, IFN-gamma, prevented PPAR-gamma ligands from suppressing the proinflammatory cytokines completely and reduced their suppression of NO production substantially, demonstrating that activation conditions affect PPAR-gamma-mediated, anti-inflammatory activity. Western analysis demonstrated that the antagonistic activity of IFN-gamma did not involve modulation of PPAR-gamma expression but showed that IFN-gamma interfered with PPAR-gamma ligand regulation of p42/p44 MAP kinase activation and the cytosolic disappearance of NF-kappaB upon LPS stimulation. Finally, we showed that PPAR-gamma ligands did not substantially modulate production of the anti-inflammatory cytokine, IL-10, and that antibody-mediated neutralization of IL-10 did not prevent the ligands from suppressing proinflammatory mediator production. In contrast to studies with noninflammatory human monocytes and Mphi, our results demonstrate that primary murine inflammatory Mphi are extremely sensitive to the anti-inflammatory activity of PPAR-gamma ligands. These results suggest that drugs such as thiazolidinediones may be most effective in suppressing Mphi activity early (i.e., in the absence of lymphocyte-derived IFN-gamma) in the inflammatory process.

Minding your Ps and Qs. Are you measuring up?

It seems that new sets of hospital quality of care and patient safety measures are created monthly. Some of the Joint Commission on the Accreditation of Healthcare Organizations measures are similar but different from the Peer Review Organization Sixth Scope of Work disease-specific measurement set, which varies from the Leapfrog measures, which are not the same as the proposed measures of the Michigan Health and Safety Coalition. These are but a few of the dozens of measurement sets.