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Recent documents in eScholarship@UMMS
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Evaluation of an institution-wide guideline for hyperglycemic emergencies at a tertiary academic medical center

Sun, 10/25/2015 - 7:55pm

BACKGROUND: No previous studies exist examining implementation of an institution-wide guideline and order set for hyperglycemic emergencies (diabetic ketoacidosis [DKA] and hyperosmolar hyperglycemic state [HHS]).

OBJECTIVE: Evaluate the impact of an institutional guideline and order set for hyperglycemic emergencies.

METHODS: This retrospective descriptive study evaluated patients with a diagnosis of DKA or HHS. Two time periods were evaluated: phase 1 (PRE) assessed practice preguideline implementation, and phase 2 (POST) assessed practice postguideline and order set introduction.

RESULTS: A total of 172 patients (91 PRE and 81 POST) were included in the analysis. There was no difference in the mean hospital length of stay (LOS) in the PRE versus POST groups (5.2 +/- 4 vs 5.9 +/- 8.6 days, P = .49). The mean intensive care unit (ICU) LOS was shorter in the POST group (64.8 +/- 19 vs 37.1 +/- 74.8 hours, P < .01). The POST group had an increase in frequency of assessments for clearance of urinary ketones (18 vs 33.3%, P = .03) and beta-hydroxybutyrate (16 vs 37%, P < .01). Frequency of point-of-care glucose testing (12.5 +/- 4.6 vs 15.1 +/- 4.7, P < .01) and time to anion gap closure (13 +/- 9 vs 9.3 +/- 7.4 hours, P < .01) improved in the POST group. There was no difference in the number of patients experiencing hypoglycemia or hypokalemia between both groups.

CONCLUSIONS: Implementation of an institutional guideline and order set for hyperglycemic emergencies decreased ICU LOS and time to anion gap closure, with no difference in rates of hypoglycemia.

Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients: the Losartan Intervention For Endpoint reduction in hypertension study

Sun, 10/25/2015 - 7:55pm

BACKGROUND: Left ventricular hypertrophy [LVH, high left ventricular mass (LVM)] is traditionally classified as concentric or eccentric based on left ventricular relative wall thickness. We evaluated left ventricular systolic function in a new four-group LVH classification based on left ventricular dilatation [high left ventricular end-diastolic volume (EDV) index and concentricity (LVM/EDV)] in hypertensive patients.

METHODS AND RESULTS: Nine hundred thirty-nine participants in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy had measurable LVM at enrolment. Patients with LVH (LVM/body surface area > /=116 g/m in men and > /=96 g/m in women) were divided into four groups; 'eccentric nondilated' (normal LVM/EDV and EDV), 'eccentric dilated' (increased EDV, normal LVM/EDV), 'concentric nondilated' (increased LVM/EDV with normal EDV), and 'concentric dilated' (increased LVM/EDV and EDV) and compared to patients with normal LVM. At baseline, 12% had eccentric nondilated, 20% eccentric dilated, 29% concentric nondilated, and 14% concentric dilated LVH, with normal LVM in 25%. Compared with the concentric nondilated LVH group, those with concentric dilated LVH had significantly lower pulse pressure/stroke index and ejection fraction; higher LVM index, stroke volume, cardiac output, left ventricular midwall shortening, left atrial volume and isovolumic relaxation time; and more had segmental wall motion abnormalities (all P < 0.05). Similar differences existed between patients with eccentric dilated and those with eccentric nondilated LVH (all P < 0.05). Compared with patients with normal LVM, the eccentric nondilated had higher LV stroke volume, pulse pressure/stroke index, Cornell voltage product and SBP, and lower heart rate and fewer were African-American (all P < 0.05).

CONCLUSION: The new four-group classification of LVH identifies dilated subgroups with reduced left ventricular function among patients currently classified with eccentric or concentric LVH.

Regional implementation of a pediatric cardiology chest pain guideline using SCAMPs methodology

Sun, 10/25/2015 - 7:55pm

BACKGROUND AND OBJECTIVES: Chest pain is a complaint for which children are frequently evaluated. Cardiac causes are rarely found despite expenditure of considerable time and resources. We describe validation throughout New England of a clinical guideline for cost-effective evaluation of pediatric patients first seen by a cardiologist for chest pain using a unique methodology termed the Standardized Clinical Assessment and Management Plans (SCAMPs).

METHODS: A total of 1016 ambulatory patients, ages 7 to 21 years initially seen for chest pain at Boston Children's Hospital (BCH) or the New England Congenital Cardiology Association (NECCA) practices, were evaluated by using a SCAMPs chest pain guideline. Findings were analyzed for diagnostic elements, patterns of care, and compliance with the guideline. Results from the NECCA practices were compared with those of Boston Children's Hospital, a regional core academic center.

RESULTS: Two patients had chest pain due to a cardiac etiology, 1 with pericarditis and 1 with an anomalous coronary artery origin. Testing performed outside of guideline recommendations demonstrated only incidental findings. Patients returning for persistent symptoms did not have cardiac disease. The pattern of care for the NECCA practices and BCH differed minimally.

CONCLUSIONS: By using SCAMPs methodology, we have demonstrated that chest pain in children is rarely caused by heart disease and can be evaluated in the ambulatory setting efficiently and effectively using minimal resources. The methodology can be implemented regionally across a wide range of clinical practice settings and its approach can overcome a number of barriers that often limit clinical practice guideline implementation.

Cross reactivity of serum antibody responses elicited by DNA vaccines expressing HA antigens from H1N1 subtype influenza vaccines in the past 30 years

Sun, 10/25/2015 - 7:55pm

In the past three decades, ten H1 subtype influenza vaccines have been recommended for global seasonal flu vaccination. Some of them were used only for one year before being replaced by another H1 flu vaccine while others may be used for up to seven years. While the selection of a new seasonal flu vaccine was based on the escape of a new emerging virus that was not effectively protected by the existing flu formulation, there is limited information on the magnitude and breadth of cross reactivity among H1 subtype virus circulation over a long period. In the current study, HA-expressing DNA vaccines were constructed to express individual HA antigens from H1 subtype vaccines used in the past 30 y. Rabbits naive to HA antibody responses were immunized with these HA DNA vaccines and the cross reactivity of these sera against HA antigen and related H1 viruses in the same period was studied. Our data indicate that the level of cross reactivity was different for different viral isolates and the key mutations responsible for the cross reactivity may involve only a limited number of residues. Our results provide useful information for the development of improved seasonal vaccines than can achieve broad protection against viruses within the same H1 subtype.

Cyclic-di-GMP and cyclic-di-AMP activate the NLRP3 inflammasome

Sun, 10/25/2015 - 7:55pm

The cyclic dinucleotides 3'-5'diadenylate (c-diAMP) and 3'-5' diguanylate (c-diGMP) are important bacterial second messengers that have recently been shown to stimulate the secretion of type I Interferons (IFN-Is) through the c-diGMP-binding protein MPYS/STING. Here, we show that physiologically relevant levels of cyclic dinucleotides also stimulate a robust secretion of IL-1beta through the NLRP3 inflammasome. Intriguingly, this response is independent of MPYS/STING. Consistent with most NLRP3 inflammasome activators, the response to c-diGMP is dependent on the mobilization of potassium and calcium ions. However, in contrast to other NLRP3 inflammasome activators, this response is not associated with significant changes in mitochondrial potential or the generation of mitochondrial reactive oxygen species. Thus, cyclic dinucleotides activate the NLRP3 inflammasome through a unique pathway that could have evolved to detect pervasive bacterial pathogen-associated molecular patterns associated with intracellular infections.

Medical Library Marketing: An Investigation of Current Definitions and Practices - Preliminary Report of Survey Results

Thu, 10/22/2015 - 12:08pm

Marketing is essential for medical and health science libraries. However, there has been no profession wide analysis of marketing definitions and incorporation for this specific field. A study was undertaken to investigate the current state of marketing understanding and practice in medical and health science libraries. Specifically, this study looks at individual, institutional, and profession wide marketing definitions, practices, trends, and gaps – creating a solid foundation and framework for future work.

This poster reports the preliminary results from a survey looking at current medical/health science library wide opinions and practices concerning medical/health science library marketing. The survey was distributed through various listserves and targeted emails to professional medical/health science librarians. Questions focused on an individual’s perceptions and definitions of marketing for themselves, within their institutions, and for medical librarianship as a whole. Results, explanations, and implications are detailed, as well as plans for further study and resource development based on findings.

A survey of big data research

Wed, 10/21/2015 - 10:15am

Big data create values for business and research, but pose significant challenges in terms of networking, storage, management, analytics, and ethics. Multidisciplinary collaborations from engineers, computer scientists, statisticians, and social scientists are needed to tackle, discover, and understand big data. This survey presents an overview of big data initiatives, technologies, and research in industries and academia, and discusses challenges and potential solutions.

Targeting and Customizing Research Data Management Services (RDM)

Tue, 10/20/2015 - 1:29pm

Designing library services is not new to our field. Service design done right is both challenging and rewarding. In this issue of the Journal of eScience Librarianship, librarians across the country write about the importance of providing a solid Research Data Management (RDM) Service, coupled with targeting institutional partners and solid education practices.

Not just full of hot air: hyperbaric oxygen therapy increases survival in cases of necrotizing soft tissue infections.

Mon, 10/19/2015 - 10:44am

BACKGROUND: The utility of hyperbaric oxygen therapy (HBOT) in the treatment of necrotizing soft tissue infections (NSTIs) has not been proved. Previous studies have been subject to substantial selection bias because HBOT is not available universally at all medical centers, and there is often considerable delay associated with its initiation. We examined the utility of HBOT for the treatment of NSTI in the modern era by isolating centers that have their own HBOT facilities.

METHODS: We queried all centers in the University Health Consortium (UHC) database from 2008 to 2010 that have their own HBOT facilities (n=14). Cases of NSTI were identified by International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes, which included Fournier gangrene (608.83), necrotizing fasciitis (728.86), and gas gangrene (040.0). Status of HBOT was identified by the presence (HBOT) or absence (control) of ICD-9 procedure code 93.95. Our cohort was risk-stratified and matched by UHC's validated severity of illness (SOI) score. Comparisons were then made using univariate tests of association and multivariable logistic regression.

RESULTS: There were 1,583 NSTI cases at the 14 HBOT-capable centers. 117 (7%) cases were treated with HBOT. Univariate analysis showed that there was no difference between HBOT and control groups in hospital length of stay, direct cost, complications, and mortality across the three less severe SOI classes (minor, moderate, and major). However, for extreme SOI the HBOT group had fewer complications (45% vs. 66%; p

CONCLUSION: At HBOT-capable centers, receiving HBOT was associated with a significant survival benefit. Use of HBOT in conjunction with current practices for the treatment of NSTI can be both a cost-effective and life-saving therapy, in particular for the sickest patients.

Plasma microRNAs are associated with atrial fibrillation and change after catheter ablation (the miRhythm study)

Mon, 10/19/2015 - 10:19am

BACKGROUND: MicroRNAs (miRNAs) are associated with cardiovascular disease and control gene expression and are detectable in the circulation.

OBJECTIVE: The purpose of this study was to test the hypothesis that circulating miRNAs may be associated with atrial fibrillation (AF).

METHODS: Using a prospective study design powered to detect subtle differences in miRNAs, we quantified plasma expression of 86 miRNAs by high-throughput quantitative reverse transcriptase-polymerase chain reaction in 112 participants with AF and 99 without AF. To examine parallels between cardiac and plasma miRNA profiles, we quantified atrial tissue and plasma miRNA expression using quantitative reverse transcriptase-polymerase chain reaction in 31 participants undergoing surgery. We also explored the hypothesis that lower AF burden after ablation would be reflected in the circulating blood pool by examining change in plasma miRNAs after AF ablation (n = 47).

RESULTS: Mean age of the cohort was 59 years; 58% of participants were men. Plasma miRs-21 and 150 were 2-fold lower in participants with AF than in those without AF after adjustment (P ≤.0006). Plasma levels of miRs-21 and 150 also were lower in participants with paroxysmal AF than in those with persistent AF (P

CONCLUSION: Cardiac miRs-21 and 150 are known to regulate genes implicated in atrial remodeling. Our findings show associations between plasma miRs-21 and 150 and AF, suggesting that circulating miRNAs can provide insights into cardiac gene regulation.

Open Access: Considerations for Accessing and Using Scholarly Literature

Fri, 10/16/2015 - 10:01am

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Dialogue Education, Parts 1 & 2

Thu, 10/15/2015 - 3:17pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Improving Performance: Facts, Flowcharts, Fishbones, Five Whys, and the Failure

Thu, 10/15/2015 - 3:17pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Evaluation in Times of Change or Crisis

Thu, 10/15/2015 - 3:17pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Cardiovascular Risk Factors and In-Hospital Mortality in Acute Coronary Syndromes: Insights From the Canadian Global Registry of Acute Coronary Events

Thu, 10/15/2015 - 10:21am

BACKGROUND: There are conflicting data regarding the relationship between the number of modifiable traditional risk factors and prognosis in acute coronary syndromes (ACS). This controversy might in part be explained by the differential use of prehospital medications.

METHODS: Using data from the Canadian, multicentre Global Registry of Acute Coronary Events (GRACE) (1999-2008), we stratified 13,686 ACS patients into 3 groups (0, 1-2, vs 3-4 risk factors) and compared their baseline characteristics, in-hospital treatments, and outcomes. Multivariable logistic regressions were performed to adjust for the components of the GRACE risk score and preadmission statin and acetylsalicylic acid (ASA) use.

RESULTS: Among these patients (ST-elevation myocardial infarction 28.3%), 14.5%, 62.6%, and 22.9% had 0, 1-2, and 3-4 risk factors, respectively. Patients with fewer risk factors were less likely to be on ASA, statin, and other prehospital medications. Unadjusted in-hospital mortality was significantly different across risk factor groups (4.9%, 3.0%, and 3.1% for 0, 1-2, and 3-4 risk factor groups, respectively, P for trend = 0.002). This difference was no longer significant after adjusting for the components of the GRACE risk score (P for trend = 0.088) and further adjusting for preadmission statin and ASA use (P for trend = 0.96). For in-hospital mortality, there was no significant interaction between risk factor categories and ACS type (P = 0.26).

CONCLUSIONS: The lower mortality observed in patients with ACS with more risk factors may be partially attributed to the protective effect of prehospital ASA and statin use. The number of risk factors does not provide incremental prognostic value beyond the validated GRACE risk score.

Cell Size Control in the Fission Yeast Schizosaccharomyces pombe: A Dissertation

Wed, 10/14/2015 - 2:57pm

The coordination between cell growth and division is a highly regulated process that is intimately linked to the cell cycle. Efforts to identify an independent mechanism that measures cell size have been unsuccessful. Instead, we propose that size control is an intrinsic function of the basic cell cycle machinery.

My work shows that in the fission yeast Schizosaccharomyces pombe Cdc25 accumulates in a size dependent manner. This accumulation of Cdc25 occurs over a large range of cell sizes. Additionally, experiments with short pulses of cycloheximide have shown that Cdc25 is an inherently unstable protein that quickly returns to a size dependent equilibrium in the cell suggesting that Cdc25 concentration is dependent on size and not time. Thus, Cdc25 can act as a sizer for the cell. However, cells are still viable when Cdc25 is constitutively expressed suggesting that there is another sizer in the case that Cdc25 expression is compromised.

Cdc13 is a likely candidate due to the similar characteristics to Cdc25 and the ability to activate Cdc2. Cdc13 accumulates during the cell cycle in a manner similar to Cdc25. I show that in the absence of Cdc2 tyrosine phosphorylation, the cell size is sensitive to Cdc13 activity showing that Cdc13 accumulation can determine when cells enter mitosis. These results suggest a two sizer model where Cdc25 is the main sizer with Cdc13 acting as a backup sizer in the event of Cdc25 expression is compromised.

Additionally, in the absence of Cdc2 phosphorylation by the kinases Wee1 and Mik1, mitotic entry is regulated by the activity of Cdc2. In the absence of Cdc2 phosphorylation, this activity is regulated by binding of cyclins to Cdc2. Under these circumstances, the activity of Cdc13 can regulate mitotic entry provide further evidence that Cdc13 could be a sizer of the cell in the case where Cdc25 expression is compromised.

The results I present in this dissertation provide the groundwork for understanding how cells regulate size and how this size regulation affects cell cycle control in S. pombe . The results show how the intrinsic cell cycle machinery can act as a sizer for the G2/M transition in S. pombe . Interestingly, this mitotic commitment pathway is well conserved suggesting a general solution for size control in eukaryotes at the G2/M transition. Understanding the mechanism of how protein concentration is regulated in a size dependent manner will give much needed insight into how cells control size. Elucidating the mechanism for size control will capitalize on decades of research and deepen our understanding of basic cell biology.

MicroRNAs Protect the Robustness of Distal Tip Cell Migrations from Temperature Changes in Caenorhabditis elegans: A Dissertation

Wed, 10/14/2015 - 2:57pm

MicroRNAs play an important role in protecting biological robustness during development. Biological robustness is the ability to maintain a consistent output despite variation in input, such as transcriptional noise or environmental stresses. Here, we show that the conserved microRNAs mir-34 and mir-83 promote the robust migration of the distal tip cells in Caenorhabditis elegans when stressed by changing environmental temperature.

Our results show that distal tip cell migration is sensitive to temperature changes occurring within a two hour period during the first larval stage. mir-34 and mir-83 protect distal tip cell migration by regulating potential targets cdc-42, pat-3, and peb-1. cdc-42 and pat-3 are known components of the integrin signaling network controlling pathfinding during migration, while the involvement of peb-1 is a novel finding. Additionally, loss of the two microRNAs leads to a reduction in both fecundity and lifespan, suggesting that the loss of developmental robustness leads to a decrease in fitness.

mir-34 and mir-83 are not only conserved in higher organisms, but duplicated. Both have been implicated as tumor suppressor genes in mammalian work. Our work has found a role for both microRNAs in integrin-regulated cell migrations that is potentially conserved in higher organisms. Additionally, our work supports the growing appreciation for the role of microRNAs in both stress response and promoting developmental robustness.

Using Experimental and Computational Strategies to Understand the Biogenesis of microRNAs and piRNAs: A Dissertation

Tue, 10/13/2015 - 3:26pm

Small RNAs are single-stranded, 18–36 nucleotide RNAs that can be categorized as miRNA, siRNA, and piRNA. miRNA are expressed ubiquitously in tissues and at particular developmental stages. They fine-tune gene expression by regulating the stability and translation of mRNAs. piRNAs are mainly expressed in the animal gonads and their major function is repressing transposable elements to ensure the faithful transfer of genetic information from generation to generation. My thesis research focused on the biogenesis of miRNAs and piRNAs using both experimental and computational strategies.

The biogenesis of miRNAs involves sequential processing of their precursors by the RNase III enzymes Drosha and Dicer to generate miRNA/miRNA* duplexes, which are subsequently loaded into Argonaute proteins to form the RNA-induced silencing complex (RISC). We discovered that, after assembled into Ago1, more than a quarter of Drosophila miRNAs undergo 3′ end trimming by the 3′-to-5′ exoribonuclease Nibbler. Such trimming occurs after removal of the miRNA* strand from pre-RISC and may be the final step in RISC assembly, ultimately enhancing target messenger RNA repression. Moreover, by developing a specialized Burrow-Wheeler Transform based short reads aligner, we discovered that in the absence of Nibbler a subgroup of miRNAs undergoes increased tailing—non-templated nucleotide addition to their 3′ ends, which are usually associated with miRNA degradation. Therefore, the 3′ trimming by Nibbler might increase miRNA stability by protecting them from degradation.

In Drosophila germ line, piRNAs associate with three PIWI-clade Argonaute proteins, Piwi, Aub, and Ago3. piRNAs bound by Aub and Ago3 are generated by reciprocal cleavages of sense and antisense transposon transcripts (a.k.a., the “Ping-Pong” cycle), which amplifies piRNA abundance and degrades transposon transcripts in the cytoplasm. On the other hand, Piwi and its associated piRNA repress the transcription of transposons in the nucleus. We discovered that Aub- and Ago3-mediated transposon RNA cleavage not only generates piRNAs bound to each other, but also produces substrates for the endonuclease Zucchini, which processively cleaves those substrates in a periodicity of ~26 nt and generates piRNAs that predominantly load into Piwi. Without Aub or Ago3, the abundance of Piwi-bound piRNAs drops and transcriptional silencing is compromised. Our discovery revises the current model of piRNA biogenesis.

Predictors and outcomes of readmission for Clostridium difficile in a national sample of medicare beneficiaries

Tue, 10/13/2015 - 2:36pm

BACKGROUND: Rates of Clostridium difficile (CD) infections are increasing. Elderly patients may be at particular risk of recurrent CD infection. Little is known about the risk for CD readmission specifically in this age group.

METHODS: A 5% random sample of Medicare data (2009-2011) was queried for patients surviving a hospitalization for CD by ICD-9 code. Demographic (age, sex, gender), clinical (Elixhauser index, gastrointestinal comorbidities), and hospitalization (length of stay, ICU admission) characteristics as well as exposure to antibiotics and interim non-CD hospitalization were compared for those with and without a readmission for CD. A multivariable survival analysis was used to determine predictors of readmission.

RESULTS: Of 7,564 patients surviving a CD hospitalization, 8.5% were readmitted with CD in a median of 25 days (interquartile range (IQR) 14-57). In multivariable survival analyses, interim non-CD hospital exposure was the strongest predictor of CD readmission (hazard ration (HR) 3.75 95%, confidence interval (CI) 3.2-4.42). Oral and intravenous/intramuscular (IV/IM) antibiotic use, Elixhauser index, and CD as the primary diagnosis also increased the risk of CD readmission. Discharge to hospice, long-term care or a skilled nursing facility decreased the odds of CD readmission.

CONCLUSION: Hospital exposure and antibiotic use put elderly patients at risk of CD readmission. Exposure to these factors should be minimized in the immediate post discharge period.