MedicalResearch.com Interview with:
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Prof. Margitta Elvers[/caption]
Prof. Margitta Elvers, PhD
Institute of Hemostasis, Hemotherapy and Transfusion Medicine
University Clinic of the Heinrich-Heine-University Düsseldorf
Düsseldorf Germany
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Elvers: Platelets are the main players in hemostasis and thrombosis, but are also recognized to be involved in the pathology of different neurodegenerative diseases. It is well known that amyloid-beta is able to activate platelets and to induce platelet activation. In Alzheimer’s Disease (AD) patients, platelet activation is enhanced and a correlation between AD and vascular diseases such as stroke and atherosclerosis was shown in different studies However, a direct contribution of platelets to the progression of Alzheimer’s disease (AD) was an open question for many years. In the last years our group in Düsseldorf, Germany, provided strong evidence for platelets to play a relevant role in the progression of AD, because AD transgenic mice showed enhanced platelet signaling that translated into almost unlimited thrombus formation in vitro and accelerated carotid artery occlusion in vivo suggesting that these mice are at high risk of arterial thrombosis leading to cerebrovascular and unexpectedly to cardiovascular complications that might be also relevant in AD patients. In the recent study, we analyzed the contribution of platelets, which accumulate at vascular Abeta deposits, to cerebral amyloid angiopathy (CAA), a vascular dysfunction in most of Alzheimer’s disease patients, characterized by deposits of Abeta in the wall of cerebral vessels. We found that synthetic monomeric Abeta is able to bind to integrin alphaIIbbeta3 via its RHDS (Arg-His-Asp-Ser) sequence thereby stimulating the release of adenosine diphosphate (ADP) and clusterin from platelets. ADP enhanced integrin activation via the ADP receptors P2Y1 and P2Y12 and further increased platelet clusterin release and Abeta fibril formation. Clopidogrel, an antiplatelet drug which irreversible inhibits P2Y12, inhibited Abeta aggregation in human and murine platelet cell cultures. Treatment of AD transgenic mice with clopidogrel for three months reduced clusterin plasma levels and the incidence of CAA.
Dr. Halima Amjad[/caption]
Halima Amjad, MD, MPH
Post-doctoral Fellow
Johns Hopkins University School of Medicine
Division of Geriatric Medicine and Gerontology
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Amjad: Safety is an important aspect of dementia care. Dementia is underdiagnosed, however, and there is limited understanding of safety issues in people with undiagnosed dementia. We wanted to better understand potentially unsafe activities and living conditions in all older adults with dementia and specifically examine these activities in undiagnosed dementia. We found that in all study participants with probable dementia, the prevalence of driving, cooking, managing finances, managing medications, or going to physician visits alone was over 20%. The prevalence was higher in older adults with probable dementia without a diagnosis, and even after accounting for sociodemographic, medical, and physical impairment factors, the odds of engaging in these activities was over 2.0 in undiagnosed versus diagnosed probable dementia. Potentially unsafe living conditions including unmet needs and performance on cognitive tests were similar between these groups.
Dr. Zhenmei Zhang[/caption]
Zhenmei Zhang, Ph.D.
Associate Professor
Department of Sociology
Michigan State University
East Lansing, MI48824
MedicalResearch.com: What is the background for this study?
Dr. Zhang: Blacks are especially hard hit by cognitive impairment and dementia. Recent estimates of dementia prevalence and incidence were substantially higher for blacks than whites. Reducing racial/ethnic disparities in dementia has been identified as a national priority by the National Alzheimer’s Project Act, which was signed into law by President Obama in 2011. So I really want to contribute to the ongoing discussion of the origins and pathways through which racial disparities in cognitive impairment is produced. If we have a better understanding of the factors contributing to racial disparities in cognitive impairment in later life, more effective interventions can be conducted to reduce the racial disparities.
Dr. Andrea Wickremasinghe[/caption]
Andrea C. Wickremasinghe, MD
Neonatologist
Kaiser Santa Clara California
MedicalResearch.com: What is the background for this study?
Response: Neonatal jaundice is common and is often treated with phototherapy. Phototherapy is typically considered to be benign. In the past decade, phototherapy use has increased and it is sometimes started at bilirubin levels below recommended treatment thresholds. Beginning in the 1970’s, in-vitro and in-vivo studies have shown phototherapy to be associated with cellular changes implicated in the pathogenesis of cancer. Epidemiologic studies have yielded mixed results, with some studies showing associations between phototherapy and leukemia and other studies failing to show this association. In this study, we used a large statewide administrative dataset to investigate the relationship between neonatal phototherapy and cancer in the first year after birth.
Dr. David Earnest[/caption]
David Earnest, Ph.D.
Professor in the Department of Neuroscience and Experimental Therapeutics
Texas A&M Health Science Center College of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Earnest: When body clocks are disrupted, as they are when people engage in shift work or go to bed and get up at radically different times every few days, more severe ischemic strokes can result.
MedicalResearch.com: What should readers take away from your report?
Dr. Earnest: Whenever possible, go to bed and get up at the same time each day and keep regular mealtimes. If you do need to keep an irregular schedule, it is especially important to be mindful of stroke risk and try especially hard to eliminate other risk factors, such as hypertension and obesity.
Dr. Yann Klimentidis[/caption]
Dr. Yann C. Klimentidis PhD
Assistant Professor
Epidemiology and Biostatistics Department
The University of Arizona
Tucson, AZ 85724
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Klimentidis: There is a large gender disparity in obesity rates among African-Americans. African-American women have much higher rates of overweight and obesity as compared to African-American men. We hypothesized that genetic factors may partly explain this difference. So we tested whether the influence of West-African genetic ancestry on obesity differed among men and women. We found that greater West-African genetic ancestry was associated with protection against central obesity in men, but no such effect was observed in women.
Dr. Sanjay Saint[/caption]
MedicalResearch.com Interview with:
Sanjay Saint, MD, MPH
Chief of Medicine
VA Ann Arbor Healthcare System
George Dock Professor of Internal Medicine & Senior Associate Chair -
Department of Internal Medicine
University of Michigan Medical School
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Saint: Catheter-associated urinary tract infection (CAUTI) is a common, costly, and morbid complication of hospitalization. Urinary tract infection (UTI) is one of the most common device-related infections in the United States. CAUTI rates rose nationally between 2009 and 2013.
We put in place a national program to reduce CAUTI. Specifically, we enrolled 926 intensive care unit (ICU) and non-ICU hospital units in 603 hospitals spread over 32 states, the District of Columbia and Puerto Rico between March 2011 and November 2013.
By the end of the 18-month program, UTI rates among hospital patients in general wards had dropped by a third. Specifically:
• The rate of CAUTIs dropped from 2.40 per 1000 days of catheter use to 2.05 (a ~14 percent overall drop).
• Nearly all of the decrease in CAUTI rates was due to changes in infection rates in non-ICUs, which went from 2.28 to 1.54 infections per 1,000 catheter-days – a drop of 32 percent. In non-ICUs, the overall use of catheters decreased by 7%.
• ICUs didn’t see a substantial change in either CAUTI or catheter use, likely because the nature of patients treated in ICUs means more frequent urine output monitoring and culturing of urine, so UTIs are more likely to be spotted.
Prof. Neil Carragher[/caption]
Professor Neil Carragher
Principal Investigator Drug Discovery
Institute of Genetics and Molecular Medicine
University of Edinburgh
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Carragher: The aim of the study was to generate novel small molecule inhibitors that target breast cancers using a strategy which we named: "dual ligand based phenotypic screening". From initial derivation of a small chemical library based on a promiscuous kinase inhibitor PP1, iterative screening across a suite of breast cancer phenotypic assays guided chemical design towards the novel compound eCF506. eCF506 is a highly potent, orally bioavailable and specific inhibitor of Src Kinase.
Dr. W.H.Wilson Tang[/caption]
Dr. W.H. Wilson Tang M.D.
Department of Cellular and Molecular Medicine (NC10)
Cleveland Clinic Lerner Research Institute
Cleveland, Ohio 44195
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Our group has recently described the mechanistic link between intestinal microbe-generated phosphatidylcholine metabolite, trimethylamine N-oxide (TMAO), and the pathogenesis of atherosclerotic coronary artery disease (CAD) and its adverse clinical outcomes. Here in a separate, independent, contemporary cohort of patients undergoing coronary angiography, we demonstrated the association between elevated fasting TMAO levels and quantitative atherosclerotic burden (as measured by SYNTAX and SYNTAX II scores) in stable cardiac patients and is an independent predictor for the presence of diffuse (but not focal) lesion characteristics.
Ettje Tigchelaar[/caption]
Ettje Tigchelaar MSc
PhD student from department of Genetics
University of Groningen, Groningen
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: A gluten-free diet is used by celiac disease patients to alleviate their symptoms. Previous research in these patients has shown differences in gut microbiota composition when on habitual gluten containing diet (HD) compared to a gluten-free diet (GFD). Recently more and more individuals without celiac disease also started to adopt a gluten-free diet to improve their health and/or control weight. We studied changes in gut microbiota composition in these healthy individuals on a gluten-free diet.
We observed changes in the abundance of specific bacteria, for example the abundance of the bacterium family Veillonellaceae was much lower on a gluten-free diet versus HD, whereas it was higher for the family Clostridiaceae. We also looked at the function of the bacteria in the gut and found that many of those bacteria that changed because of the gluten-free diet played a role in metabolism of starch. This makes sense since starch is like gluten highly present in wheat containing products, thus when eliminating gluten from the diet, the intake of starch also changes and the gut bacteria processing this dietary starch change accordingly.
Mark de Jong, MD, Psychiatrist
Yulius Academy, Yulius Mental Health
Barendrecht, the Netherlands
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Compulsory psychiatric admission, defined as admission against the will of the patient, has a strong effect on psychiatric patients and their relatives, and can be traumatic. Compulsory admission also conflicts with human rights, principles of autonomy, shared decision making, and recovery focused care. We also see, that rates of compulsory admissions in several European countries are tending to rise. So, interventions that prevent patients from being compulsory admitted are urgently needed.
We reviewed and meta-analyzed all currently available RCTs, that were designed to reduce compulsory admission rates in adult psychiatric patients with severe mental illnesses in outpatients settings. We found, that advance statements, like crisis plans, showed a significant 23% risk reduction in compulsory admissions. In contrast, community treatment orders and interventions for compliance enhancement showed no significant risk reduction in compulsory admissions. Although RCTs on integrated treatment showed no statistically significant risk reduction, we found a potentially clinically relevant risk reduction of 29%.
Dr. Daniel Murphy[/caption]
Daniel R. Murphy, M.D., M.B.A.
Assistant Professor - Interim Director of GIM at Baylor Clinic
Department of Medicine
Health Svc Research & General Internal Medicine
Baylor College of Medicine
Houston, TX
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Murphy: Electronic health records (EHRs) have improved communication in health care, but they have not eliminated the problem of patients failing to receive appropriate and timely follow up after abnormal test results. For example, after a chest x-ray result where a radiologist identifies a potentially cancerous mass and suggests additional evaluation, about 8% of patients do not receive follow-up imaging or have a visit with an appropriate specialist within 30 days. Identifying patients experiencing a delay with traditional methods, like randomly reviewing charts, is not practical. Fortunately, EHRs collect large amounts of data each day that can be useful in automating the process of identifying such patients.
We evaluated whether an electronic “trigger” algorithm designed to detect delays in follow up of abnormal lung imaging tests could help medical facilities identify patients likely to have experienced a delay. Of 40,218 imaging tests performed, the trigger found 655 with a possible delay. Reviewing a subset of these records showed that 61% were truly delays in care that required action. We also found that the trigger had a sensitivity of 99%, indicating that it missed very few actual delays.
Dr-Aurora-Perez-Cornago[/caption]
Aurora Perez-Cornago, PhD
Cancer Epidemiology Unit
Nuffield Department of Population Health
University of Oxford
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Excessive body size and adiposity have been proposed to influence
several metabolic and hormonal mechanisms that can promote cancer development.
We found that men who have greater adiposity have an elevated risk of
high grade prostate cancer, an aggressive form of the disease, and
prostate cancer death.
Dr. Johannes Neumann[/caption]
Dr. med. Johannes Neumann
Resident physician
University Heart Center Hamburg
Department of General and Interventional Cardiology
Universitätsklinikum Hamburg-Eppendorf
Hamburg
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The early decision making in patients with suspected acute myocardial infarction is important. Current guidelines recommend measurement of cardiac troponin at admission and after 3 hours. In our study we evaluated the performance of a high-sensitivity troponin I assay with a rapid measurement after only 1 hour. We included 1040 patients with new onset chest pain and could show, that a low cutoff concentration of 6 ng/L after 1 hour allows safe rule-out of acute myocardial infarction. The results were comparable to the recommended 3-hour approach and were validated in 2 external cohorts. When using the 99th percentile to rule-out myocardial infarction, as recommended by current guidelines, the negative predictive value was much lower. Furthermore, a troponin I concentration above 6 ng/L in combination with an absolute change of 12 ng/L after 1 hour showed a high positive predictive value for the final diagnosis of myocardial infarction. This allows early decision making after only 1 hour.
Dr. Nicole Pratt[/caption]
Nicole Pratt PhD
Senior Research Fellow
Quality Use of Medicines and Pharmacy Research Centre
Sansom Institute, School of Pharmacy and Medical Sciences
University of South Australia
Adelaide South Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Pratt: The cardiac safety of methylphenidate has been debated. This study aimed to measure the risk of cardiac events in a large population of children treated with these medicines. We found that there was a significantly raised risk of arrhythmia in time periods when children were treated with methylphenidate compared to time periods when they were not. While the relative risk of cardiac events was significant the absolute risk is likely to be low as cardiac events are rare in children.
Dr. Markus Juonala[/caption]
Markus Juonala, MD, PhD
Murdoch Childrens Research Institute, Parkville
Victoria, Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Juonala: This is an epidemiological follow-up study investigating whether childhood infections and socieconomic status are associated with cardiovasular risk factor and early chances in vasculature.
The main finding was that childhood infections were associated with obesity and impaired vascular function in adulthood among those individuals with low socioeconomic status.
Dr. Benjamin Perry[/caption]
Benjamin M. Perry, DO
Silver Falls Dermatology
Salem, OR 97302
MedicalResearch.com: What is the background for this study?
Dr. Perry: Our interest in this subject developed when a patient came into our clinic with concern of multiple new nevi developing on palmoplantar surfaces following initiation of treatment with Rituximab. We conducted a review of the existing literature and found that this wasn’t a known adverse effect. From that point, we wanted to know the pathogenesis, prognosis, and management for eruptive nevi that developed in the setting of medication use. A collective review had not been previously performed on this subject. In essence, we had questions that were unanswered and set out to find the answers.
Dr. Kevin T. McVary[/caption]
Kevin T. McVary, MD, FACS
Chair, Division of Urology
The Pavilion at St. John’s Hospital
Springfield, IL
Chair and Professor of Urology
SIU School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. McVary: Benign Prostatic Hyperplasia (BPH) is a localized enlargement of the prostate gland in aging adult men. It affects approximately 75% of men over the age of 65. This excess growth of tissue compresses and obstructs the urethra, reducing the flow of urine from the bladder and sometimes blocking it entirely. As the symptoms increase, they can greatly impact a man’s quality of life. Both BPH and the existing treatments for it can negatively affect an individual’s sex life.
The Rezūm II IDE pivotal study was a prospective, multicenter, randomized (2:1) controlled trial that enrolled 197 patients across 15 clinical sites in the U.S. The main finding showed that radiofrequency generated convective water vapor thermal therapy provides rapid and sustainable improvement of lower urinary tract symptoms (LUTS) secondary to BPH and urinary flow over a 12-month period without negative effects on erectile and ejaculatory function. These results support the application of convective water vapor energy (WAVE) technology as safe and effective minimally invasive therapeutic alternative for symptomatic BPH. Additionally, no treatment or device related de novo erectile dysfunction occurred after thermal therapy, ejaculatory bother score improved 31% over baseline, and 27% of subjects achieved minimal clinically important differences (MCIDs) in erectile function scores at 1 year, including those with moderate to severe ED.
Dr. Steven Kyle Grinspoon[/caption]
Steven Grinspoon, MD
Professor of Medicine, Harvard Medical School
MGH Endowed Chair in Neuroendocrinology and Metabolism
Director, MGH Program in Nutritional Metabolism
and Nutrition Obesity Research Center at Harvard
MGH
Boston, MA 02114
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Grinspoon: Numerous epidemiologic studies have shown that people living with HIV face a 1.5 to 2-fold increased risk of heart attack, or myocardial infarction, as compared to individuals without the virus. Mechanisms underlying the increased risk of myocardial infarction in HIV are incompletely understood. It is possible that among people living with HIV, increased systemic immune activation fuels arterial inflammation. Arterial inflammation may, in turn, promote the development of high-risk morphology coronary atherosclerotic plaque, which is liable to rupture and result in myocardial infarction.
For people diagnosed with HIV, the overall health benefits of immediate antiretroviral therapy (ART) are clear. However, the effects of newly-initiated antiretroviral therapy on arterial inflammation have not previously been studied. In this study, we set out to assess among a cohort of treatment-naive HIV-infected subjects, the effects of newly-initiated ART with a contemporary regimen on both immune function and arterial inflammation. We found that among treatment-naive HIV-infected individuals without clinical cardiovascular disease, newly initiated combined antiretroviral therapy has discordant effects to restore immune function without reducing the degree of arterial inflammation.
Dr. Kristy Arbogast[/caption]
Kristy Arbogast, PhD
Co-Scientific Director
Center for Injury Research and Prevention
The Children's Hospital of Philadelphia
Research Professor
Division of Emergency Medicine
Department of Pediatrics
University of Pennsylvania
Philadelphia, PA 19104
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Arbogast: The research team looked retrospectively at four recent years of data on children diagnosed with concussion at Children's Hospital of Philadelphia (CHOP) to determine how children access the health system for a concussion. For those 8,000 kids with a CHOP primary care provider, 82% entered the health system via a primary care location, 12% entered through the ER and 5% through a specialist. One-third of concussion diagnoses were to children under age 12.
Many current counts of concussion injury among children are based on emergency room visits or organized high school and college athletics data. Thus, we are vastly underestimating child and youth concussions in the US.