Medicine and Health Sciences Commons^™

Time From Infection To Disease And Infectiousness For Ebola Virus Disease, A Systematic Review, Gustavo E Velásquez, Omowunmi Aibana, Emilia J Ling, Ibrahim Diakite, Eric Q Mooring, Megan B Murray

Journal Articles

We systematically reviewed the literature to estimate the incubation and latent periods of Ebola virus disease. We found limited epidemiological data from individuals with discrete 1-day exposures. Available data suggest that the incubation and latent periods may differ, and mathematical models may be improved by distinguishing between the two periods.

The Axillary View Typically Does Not Contribute To Decision Making In Care For Proximal Humeral Fractures, Marschall B Berkes, Joshua S Dines, Jacqueline F Birnbaum, Lionel E Lazaro, Tristan C Lorich, Milton T M Little, Joseph T Nguyen, Dean G Lorich

Journal Articles

BACKGROUND: Convention dictates that an axillary view be obtained when evaluating proximal humerus fractures (PHF). However, the axillary view is frequently omitted because of pain and technical considerations. Furthermore, its diagnostic utility is unclear in this setting.

QUESTIONS/PURPOSES: The purpose of this study was to (1) determine the rate of obtaining an adequate axillary X-ray and complete shoulder series at a level I trauma center, (2) understand the cost of ordering and attempting an axillary radiograph, and (3) determine if axillary radiographs influence the management of PHF.

PATIENTS AND METHODS: PHF treated between 2009 and 2011 that were ordered for …

Successful Treatment Of Peritoneal Dialysis Catheter-Related Polymicrobial Peritonitis Involving Clostridium Difficile, A Case Report And Review Of The Literature, S. Bharti, P. Malhotra, S. Juretschko

Journal Articles

Clostridium difficile is one of the most common nosocomial pathogens and the cause of pseudomembranous colitis in cases of prior antimicrobial exposure. Extra intestinal manifestations of C. difficile are uncommon and rarely reported. We report the first successfully treated case of catheter-related C. difficile peritonitis in a patient undergoing peritoneal dialysis.

The Role Of Factor Xa Inhibitors In Venous Thromboembolism Treatment, K. P. Cabral, J. E. Ansell

Journal Articles

Three factor Xa inhibitors have been studied in the treatment of venous thromboembolism, both for acute therapy and as extended therapy to prevent recurrent events. Rivaroxaban, apixaban, and edoxaban have all proven to be effective in Phase III clinical trials for this indication when compared to current standard of therapy with similar or less bleeding. Nevertheless, the agents all offer different pharmacological profiles, which have an impact on patient selection and potential advantages in clinical practice.

Target-Specific Oral Anticoagulants-New Approaches In The Field Of Oral Anticoagulation, H. Mani, J. Douxfils, J. Ansell

Journal Articles

No abstract provided.

Malignancies, Particularly B-Cell Lymphomas, Are A Frequent Cause Of Mortality In Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy, D. O. Griffin, M. Metzger, K. Poeth, K. Deng, A. Dharsee, J. C. Rico, J. Mcgowan

Journal Articles

Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival ofdiagnosis.

Multicenter Randomized Controlled Trial On Duration Of Therapy For Thrombosis In Children And Young Adults (The Kids-Dott Trial): Pilot/Feasibility Phase Findings, N. A. Goldenberg, T. Abshire, P. J. Blatchford, L. Z. Fenton, J. L. Halperin, W. R. Hiatt, C. M. Kessler, J. M. Kittelson, A. C. Spyropoulos, S. Schulman, +4 Additional Authors

Journal Articles

BACKGROUND: Randomized controlled trials (RCTs) on pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS: The Kids-DOTT trial is a multicenter RCT investigating non-inferiority of a 6-week (shortened) versus 3-month (conventional) duration of anticoagulation in patients aged < 21 years with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded-endpoint, parallel-cohort RCT design. RESULTS: No eligibility violations or randomization errors occurred. Of the enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in prespecified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Interobserver agreement between local and blinded central determination of venous occlusion by imaging at 6 weeks after diagnosis was strong (k-statistic = 0.75; 95% confidence interval [CI] 0.48-1.0). The primary efficacy and safety event rates were 3.3% (95% CI 0.3-11.5%) and 1.4% (95% CI 0.03-7.4%). CONCLUSIONS: The P/F phase of the Kids-DOTT trial has demonstrated the validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention and endpoint rates to inform the fully powered RCT.

A Novel Engineered Vegf Blocker With An Excellent Pharmacokinetic Profile And Robust Anti-Tumor Activity, L. Liu, H. Yu, X. Huang, H. Tan, S. Li, Y. Luo, L. Zhang, S. Jiang, C. C. Chu, W. Tian, +4 Additional Authors

Journal Articles

BACKGROUND: Relatively poor penetration and retention in tumor tissue has been documented for large molecule drugs including therapeutic antibodies and recombinant immunoglobulin constant region (Fc)-fusion proteins due to their large size, positive charge, and strong target binding affinity. Therefore, when designing a large molecular drug candidate, smaller size, neutral charge, and optimal affinity should be considered. METHODS: We engineered a recombinant protein by molecular engineering the second domain of VEGFR1 and a few flanking residues fused with the Fc fragment of human IgG1, which we named HB-002.1. This recombinant protein was extensively characterized both in vitro and in vivo for …

The Orbit Bleeding Score: A Simple Bedside Score To Assess Bleeding Risk In Atrial Fibrillation, E. C. O'Brien, D. N. Simon, L. E. Thomas, E. M. Hylek, B. J. Gersh, J. E. Ansell, P. R. Kowey, K. W. Mahaffey, P. Chang, E. D. Peterson, +3 Additional Authors

Journal Articles

BACKGROUND: Therapeutic decisions in atrial fibrillation (AF) are often influenced by assessment of bleeding risk. However, existing bleeding risk scores have limitations. OBJECTIVES: We sought to develop and validate a novel bleeding risk score using routinely available clinical information to predict major bleeding in a large, community-based AF population. METHODS: We analysed data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a prospective registry that enrolled incident and prevalent AF patients at 176 US sites. Using Cox proportional hazards regression, we identified factors independently associated with major bleeding among patients taking oral anticoagulation (OAC) over a median …

Healthcare Provider Perceptions Of Clinical Prediction Rules, S. Richardson, S. Khan, L. Mccullagh, M. Kline, D. Mann, T. Mcginn

Journal Articles

Objectives: To examine internal medicine and emergency medicine healthcare provider perceptions of usefulness of specific clinical prediction rules. Setting: The study took place in two academic medical centres. A web-based survey was distributed and completed by participants between 1 January and 31 May 2013. Participants: Medical doctors, doctors of osteopathy or nurse practitioners employed in the internal medicine or emergency medicine departments at either institution. Primary and secondary outcome measures: The primary outcome was to identify the clinical prediction rules perceived as most useful by healthcare providers specialising in internal medicine and emergency medicine. Secondary outcomes included comparing usefulness scores …

Investigation Of Body Image As A Mediator Of The Effects Of Bowel And Gi Symptoms On Psychological Distress In Female Survivors Of Rectal And Anal Cancer, C. Benedict, V. M. Rodriguez, J. Carter, L. Temple, C. Nelson, K. Duhamel

Journal Articles

PURPOSE: Treatment for rectal and anal cancer (RACa) can result in persistent bowel and gastrointestinal (GI) dysfunction. Body image problems may develop over time and exacerbate symptom-related distress. RACa survivors are an understudied group, however, and factors contributing to post-treatment well-being are not well understood. This study examined whether poorer body image explained the relation between symptom severity and psychological distress. METHODS: Participants (N = 70) completed the baseline assessment of a sexual health intervention study. Bootstrap methods tested body image as a mediator between bowel and GI symptom severity and two indicators of psychological distress (depressive and anxiety symptoms), …

Cds, Ux, And System Redesign - Promising Techniques And Tools To Bridge The Evidence Gap, T. Mcginn

Journal Articles

INTRODUCTION: In this special issue of eGEMs, we explore the struggles related to bringing evidence into day-to-day practice, what I define as the "evidence gap." We are all aware of high quality evidence in the form of guidelines, randomized clinical trials for treatments and diagnostic tests, and clinical prediction rules, which are all readily available online. We also know that electronic health records (EHRs) are now ubiquitous in health care and in most practices across the country. How we marry this high quality evidence and the practice of medicine through effective decision support is a major challenge. ABOUT THE ISSUE: …

Comparison Of Cytologic Accuracy Of Endobronchial Ultrasound Transbronchial Needle Aspiration Using Needle Suction Versus No Suction, K. Harris, R. Maroun, K. Attwood, M. Chalhoub

Journal Articles

BACKGROUND AND OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a relatively new procedure initially used for lung cancer diagnosis, staging and re-staging and extended to benign diseases such as sarcoidosis and other mediastinal lesions. Previously, multiple studies evaluated the use of needle biopsy with no aspiration that did not change the diagnostic accuracy compared with needle biopsy aspiration. MATERIALS AND METHODS: All adult subjects who were scheduled to undergo EBUS-TBNA to sample mediastinal lesions were eligible. We evaluated two methods of sampling mediastinal lesions. The first method was the application of negative pressure syringe for needle suction aspiration. The …

Xanomeline Suppresses Excessive Pro-Inflammatory Cytokine Responses Through Neural Signal-Mediated Pathways And Improves Survival In Lethal Inflammation, M. Rosas-Ballina, S. I. Valdes-Ferrer, M. E. Dancho, M. Ochani, D. Katz, K. F. Cheng, P. S. Olofsson, S. S. Chavan, Y. Al-Abed, K. J. Tracey, V. A. Pavlov

Journal Articles

Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer's disease …

Use And Outcomes Associated With Bridging During Anticoagulation Interruptions In Patients With Atrial Fibrillation: Findings From The Outcomes Registry For Better Informed Treatment Of Atrial Fibrillation (Orbit-Af), B. A. Steinberg, E. D. Peterson, S. Kim, L. Thomas, B. J. Gersh, G. C. Fonarow, P. R. Kowey, K. W. Mahaffey, M. W. Sherwood, J. Ansell, +2 Additional Authors

Journal Articles

BACKGROUND: Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown. METHODS AND RESULTS: The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of …

Anti-C1q Antibodies In Systemic Lupus Erythematosus, A. M. Orbai, L. Truedsson, G. Sturfelt, O. Nived, H. Fang, G. S. Alarcon, C. Gordon, J. Merrill, C. Aranow, M. Petri, +43 Additional Authors

Journal Articles

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% …

Immune Dysregulation In Patients Persistently Infected With Human Papillomaviruses 6 And 11, A. V. Lucs, J. A. Devoti, L. Hatam, A. Afzal, A. L. Abramson, B. M. Steinberg, V. R. Bonagura

Journal Articles

Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent infection that can cause significant morbidity and on occasion mortality. Depending on the site of infection, patients chronically infected with these viruses develop either recurrent, and on occasion, severe genital warts or recurrent respiratory papillomas that can obstruct the upper airway. The HPV-induced diseases described are likely the result of a complex and localized immune suppressive milieu …

Primary Extranodal Marginal Zone Lymphoma Of The Endometrium: Report Of Four Cases And Review Of Literature, F. C. Tahmasebi, S. Roy, J. E. Kolitz, F. Sen, J. Laser, X. Zhang

Journal Articles

Primary extranodal marginal zone lymphoma of the endometrium (PEMZL-EM) is exceedingly rare and has not been well characterized. Herein, we study the clinicopathological, cytogenetic and molecular features of four cases, the largest case series reported to date. The median age of the four patients was 59 years. Clinical presentations included abnormal vaginal bleeding (three cases) and incidental finding (one case). There were no constitutional symptoms in any of the cases. None of the patients had evidence of lymphoma in any other anatomic sites including bone marrow. Histologically, the lymphoma was characterized by a nodular proliferation of small lymphocytes admixed with …

Reply To: Nasal Endoscopy To Characterize Sinonasal Disease, A. E. Dixon, M. Castro, R. I. Cohen, L. B. Gerald, J. T. Holbrook, C. G. Irvin, S. Mohapatra, S. P. Peters, S. Rayapudi, R. A. Wise, +1 Additional Author

Journal Articles

No abstract provided.

Perioperative Bridging Anticoagulation In Patients With Atrial Fibrillation, J. D. Douketis, A. C. Spyropoulos, S. Kaatz, R. C. Becker, J. A. Caprini, A. S. Dunn, D. A. Garcia, A. Jacobson, A. K. Jaffer, T. L. Ortel, +4 Additional Authors

Journal Articles

BACKGROUND: It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS: We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or …

A Randomized, Phase 2 Trial Of Docetaxel With Or Without Px-866, An Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, In Patients With Relapsed Or Metastatic Head And Neck Squamous Cell Cancer, A. Jimeno, J. E. Bauman, C. Weissman, D. Adkins, I. Schnadig, P. Beauregard, D. W. Bowles, A. Spira, B. Levy, N. Seetharamu, D. Hausman, L. Walker, C. M. Rudin, K. Shirai

Journal Articles

INTRODUCTION: The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is frequently altered in head and neck squamous cell cancer (HNSCC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. Preclinical models revealed synergy with docetaxel and a phase 1 trial demonstrated tolerability of this combination. This randomized phase 2 study evaluated PX-866 combined with docetaxel in patients with advanced, refractory HNSCC. METHODS: Patients with locally advanced, recurrent or metastatic HNSCC who had received at least one and no more than two prior systemic treatment regimens were randomized (1:1) to a combination of docetaxel (75mg/m(2) IV every …

A Framework For Usable And Effective Clinical Decision Support: Experience From The Icpr Randomized Clinical Trial, J. Kannry, L. Mccullagh, A. Kushniruk, D. Mann, D. Edonyabo, T. Mcginn

Journal Articles

INTRODUCTION: The promise of Clinical Decision Support (CDS) has always been to transform patient care and improve patient outcomes through the delivery of timely and appropriate recommendations that are patient specific and, more often than not, are appropriately actionable. However, the users of CDS-providers-are frequently bombarded with inappropriate and inapplicable CDS that often are not informational, not integrated into the workflow, not patient specific, and that may present out of date and irrelevant recommendations. METHODS: The integrated clinical prediction rule (iCPR) project was a randomized clinical trial (RCT) conducted to determine if a novel form of CDS, i.e., clinical prediction …

Comparison Of An Extended-Release Formulation Of Granisetron (Apf530) Versus Palonosetron For The Prevention Of Chemotherapy-Induced Nausea And Vomiting Associated With Moderately Or Highly Emetogenic Chemotherapy: Results Of A Prospective, Randomized, Double-Blind, Noninferiority Phase 3 Trial, H. Raftopoulos, W. Cooper, E. O'Boyle, N. Gabrail, R. Boccia, R. J. Gralla

Journal Articles

PURPOSE: Subcutaneous APF530 provides controlled sustained release of granisetron to prevent acute (0-24 h) and delayed (24-120 h) chemotherapy-induced nausea and vomiting (CINV). This randomized, double-blind phase 3 trial compared APF530 and palonosetron in preventing acute and delayed CINV after moderately (MEC) or highly emetogenic chemotherapy (HEC). METHODS: Patients receiving single-day MEC or HEC received single-dose APF530 250 or 500 mg subcutaneously (SC) (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg. Primary objectives were to establish APF530 noninferiority to palonosetron for preventing acute CINV following MEC or HEC and delayed CINV following MEC and to determine APF530 superiority …