MedicalResearch.com Interview with:Gregor Reid, B.Sc. Hons., Ph.D., MBA, ARM, CCM, Dr. HS, FCAHS
Director, Canadian Centre for Human Microbiome and Probiotic Research
Lawson Health Research Institute
London, Ontario, Canada
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Women who breast feed have reduced risk of breast cancer. Human milk has bacteria passed on to the child. These bacteria reach the breast through the nipple and from the gut via the blood. Lactobacilli and Bifidobacteria, beneficial bacteria, grow well in milk. So, I wondered what if women never lactate or breast feed, could bacteria be there? Could bacteria be in the tissue itself and influence whether you got or did not get cancer. Proving there are bacteria in the actual breast tissue itself was an interesting discovery defying previous beliefs.
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MedicalResearch.com Interview with: Albert Shieh, MD
Division of Endocrinology, Diabetes and Hypertension
David Geffen School of Medicine
University of California, Los Angeles
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Whether an individual loses or gains bone mass is dependent on how much bone is being broken down (by osteoclasts) and being formed (by osteoblasts). Both processes occur simultaneously in the human body. At present, we can measure markers of bone breakdown (resorption) and formation. However, we hypothesized that to better predict the amount of bone mass that will be lost in the future, these markers should be combined in an "index" to reflect both processes, rather than being interpreted in isolation. Indeed, we found that the ability of our new bone balance index predicted future bone loss across the menopause transition better than the bone resorption marker alone.
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MedicalResearch.com Interview with:Jinmyoung Cho, PhD
Assistant Investigator
Center for Applied Health Research
Baylor Scott & White Health
Temple, TX 76508
Texas A&M Health Science Center
College Station, Texas
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Early life-course transition experiences to the adult years result in continuing consequences for health in later life. Many veterans have encountered life-threatening environments while they were on military service leading to a higher incidence of physical and mental diseases; greater comorbidity profiles in veterans contribute to higher mortality rate compared to non-veterans.
With increased life expectancy and demographic shifts in our population, the proportion of oldest-old adults, aged over 80 years, continues to increase. The publicly funded Veterans Health Administration (VHA) must care efficiently and effectively for its increasing population of veterans, who are older, sicker, and socioeconomically disadvantaged relative to non-veterans.
Given the large number of veterans over age 80 and the increasing emphasis on managing the aging process, it is important to identify associations between healthcare utilization and survival for VHA’s oldest patients.
We identified protective and risk factors associated with mortality by age group. During a 5-year follow-up period, 44% of patients aged 85 years and over died with survival rates of 59% for 80’s, 32% for 90’s and 15% for 100’s. In the multivariable model, protective effects for veterans 80-99 were female sex, minority race or ethnicity, being married, having certain physical and mental diagnoses (e.g., hypertension, cataract, dyslipidemia, posttraumatic stress disorder, bipolar disorder), urgent care visits, invasive surgery, and few (one to three) prescriptions. Risk factors were lower VHA priority status, physical and mental conditions (e.g., diabetes, anemia, congestive heart failure, dementia, anxiety, depression, smoking, substance abuse disorder), hospital admission, and nursing home care. For those in their 100s, married status, smoking, hospital admission, nursing home care, invasive surgery, and prescription use were significant risk factors; only emergency department (ED) use was protective.
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MedicalResearch.com Interview with:Jared Ellefson, PhD
Postdoctoral fellow
University of Texas Austin's Center for Systems and Synthetic Biology
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Reverse transcriptases (RT) have revolutionized the field of biology - enabling the conversion of RNA into DNA. This initially allowed the cloning of mature messenger RNA into cDNA libraries (e.g. cloning human genes), but has since been finding a more modern role in high throughput RNA-seq which can accurately depict the physiological status of a cell. Despite its critical role, an inherent flaw exists in all known reverse transcriptases. They make many errors while copying RNA - due to the lack of an error-checking (proofreading) domain. Consequently, the errors produced in reverse transcription are propagated into RNA sequencing potentially leading to corrupted data.
The reason for the low fidelity of reverse transcriptases is due to their evolutionary heritage. All RTs are evolved from polymerase enzymes which lack the proofreading domain. This is in stark contrast to certain DNA polymerases which have extreme fidelity. The idea was, what if you could take a high fidelity DNA polymerase and transform it into a high fidelity RT. To do this we developed directed evolution techniques that would enrich these DNA polymerases for reverse transcriptase activity. After a monumental engineering effort, we were left with the world's first reverse transcriptase that could error-check during polymerization. We found that this increased the fidelity of RNA sequencing, in addition to a number of other interesting properties (for instance this single enzyme can do both reverse transcription and PCR).
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MedicalResearch.com Interview with:Amanda Paschke, MD
Director, Infectious Disease Clinical Research
Merck Research Laboratories
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Relebactam is an investigational beta-lactamase inhibitor being developed as a fixed-dose combination with imipenem/cilastatin, which is a broad-spectrum antibiotic in the carbapenem class. In preclinical studies, this combination demonstrated antibacterial activity against a broad range of multidrug-resistant Gram-negative pathogens, including those producing extended-spectrum beta-lactamases such as Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and AmpC-producing Pseudomonas aeruginosa. Many of the most concerning infections caused by “superbugs” are caused by Gram-negative bacteria. These bacteria have evolved to be resistant to commonly used antibacterials, and even to antibacterials used as “last resort” treatment, which is why finding ways to treat them has become urgent. The addition of relebactam to imipenem is designed to restore activity of imipenem against certain imipenem-resistant strains of Gram-negative bacteria known to cause serious infections among people who often have other underlying medical conditions, which complicates treatment.
This was a Phase 2, multicenter, randomized, double-blind, non-inferiority study. The study looked at the use of relebactam plus imipenem versus imipenem alone for the treatment of adult patients with complicated urinary tract infections. The primary endpoint for the trial was microbiological response at the completion of IV study therapy. The study met its primary endpoint, demonstrating that the combination of relebactam with imipenem was as at least as effective as imipenem alone for the treatment of complicated urinary tract infections. The trial also demonstrated that the combination of relebactam plus imipenem is well-tolerated, with a safety profile similar to that of imipenem alone in this patient.
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MedicalResearch.com Interview with:Eva C. Gombos, MD
Assistant Professor, Radiology
Harvard Medical School
Brigham and Women’s Hospital
MedicalResearch.com: What is the background for this study?Response: Treatment of early stage breast cancer, breast-conserving therapy (BCT), which consists of lumpectomy followed by whole-breast irradiation, requires re-excision 20 %–40% of patients due to positive margins.
Breast MR is the imaging modality with the highest sensitivity to detect breast cancer. However, patients who undergo breast MR imaging have not experienced reduced re-excision or improved survival rates.
Our hypothesis is that supine (performed with patient lying on her back) MR imaging within the operating room can be used to plan the extent of resection, to detect residual tumor immediately after the first attempt at definitive surgery, and to provide feedback to the surgeon within the surgical suite. The aim of this study was to use intraoperative supine MR imaging to quantify breast tumor deformation and displacement secondary to the change in patient positioning from imaging (prone performed the patient lying on her stomach) to surgery (supine) and to evaluate the residual tumor immediately after BCT.
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MedicalResearch.com Interview with:Professor Ellen Meara, PhD
Professor
The Dartmouth Institute for Health Policy and Clinical Practice
MedicalResearch.com: What is the background for this study?
Response: Responding to a fourfold rise in death rates, between 2006 and 2012, states collectively enacted 81 laws restricting prescribing and dispensing of prescription opioids. Jill Horwitz, PhD, JD, said “states hoped passing a range of laws might help. So they are enacting small fixes — forbidding patients from “doctor-shopping,” and requiring doctors to use tamper-resistant prescription forms. They are also implementing major efforts such as prescription drug monitoring programs (PDMPs) — online databases that allow law enforcement and clinicians to monitor prescriptions.”
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MedicalResearch.com Interview with:Dr. Ir. Gerda Pot PhD
Universitair Docent Gezondheid en Leven| Assistant Professor Health and Life
Faculteit Aard- en Levenswetenschappen | Faculty of Earth and Life Sciences
MedicalResearch.com: What is the background for this study?Response: I was inspired to start this work by my grandmother. She was a stickler for timekeeping of her meals and I wondered whether this was her secret for healthy aging.
It seems common wisdom but surprisingly very little scientific evidence exist. Therefore we conducted this review to see all the studies out there before setting out doing our own research.
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MedicalResearch.com Interview with:Lindsay Kohler MPH
Mel and Enid Zuckerman College of Public Health
Tucson, Arizona
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Several studies have reported that following health promotion guidelines for diet, physical activity, and maintenance of a healthy body weight may reduce the risk of getting cancer or dying from cancer. We performed a systematic review to examine the associations between established cancer prevention guidelines for diet and physical activity and cancer outcomes. We found that adhering to cancer prevention guidelines set forth by the American Cancer Society or the World Cancer Research Fund/American Institute for Cancer Research consistently reduced the risk of overall cancer incidence and mortality (10-61%) in the studies included in this review. In addition, higher adherence to the guidelines consistently reduced the risk of breast, colorectal, and endometrial cancers. Adherence to a pattern of healthy behaviors may significantly reduce cancer incidence and mortality.
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MedicalResearch.com Interview with: Dr. Stefan Toggweiler, MD
Heart Center, Luzerner Kantonsspital
Lucerne, SwitzerlandMedicalResearch.com: What is the background for this study?Response: Transcatheter aortic valve replacement (TAVR) is increasingly used for the treatment of aortic stenosis in inoperable and high-risk patients. It is well known that TAVR is associated with acute and delayed occurrence of conduction disorders. Namely, delayed high-degree atrioventrcular block is a feared complication. Thus, patients are usually monitored by telemetry for a few days, but there is currently no consensus on the duration of telemetry. In this study, we evaluated how the postprocedural ECG determines the need for permanent pacemaker implantation in patients undergoing TAVR.
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MedicalResearch.com Interview with:Peter Johnson MA, MD, FRCP
Professor of Medical Oncology
Cancer Research UK Centre
Southampton General Hospital
Southampton
MedicalResearch.com: What is the background for this study? What are the main findings?Prof. Johnson: Based upon retrospective series looking at the ability of interim PET to predict the outcomes of treatment, we aimed to test the idea of modulating treatment in response to an early assessment of the response to ABVD: could we safely reduce the amount of treatment by omitting bleomycin in the group who had responded well? Although the risk of severe toxicity from bleomycin is generally low, for the small number of patients who experience it, it can be life-changing or even fatal. We also wanted to test whether it might be possible to reduce the use of consolidation radiotherapy by comparison to our previous trials, and this seems to have worked too: we used radiotherapy in less than 10% of patients in RATHL, as compared to around half in our previous trials. We have seen better survival figures than in our previous studies with less treatment overall, so it feels as though we are on the right track.
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MedicalResearch.com Interview with:Mirna Becevic, PhD, MHA
Assistant Research Professor
University of Missouri - Department of Dermatology
Missouri Telehealth Network
MedicalResearch.com: What is the background for this study?Response: Psychiatry is, by far, the biggest utilizer of telemedicine services on the Missouri Telehealth Network (MTN). MTN supports an average of 4000 tele-psychiatry appointments every month, and 10% of those are provided by the University of Missouri Department of Psychiatry. Since we are all aware of the ever-increasing demand for child and adolescent psychiatry, but also the stigma that goes along with it, we wanted to examine more closely the actual usage of those services at the University of Missouri.
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MedicalResearch.com Interview with:
Sunita Sah MD PhD
Management & Organizations
Johnson Graduate School of Management
Cornell University
MedicalResearch.com: What is the background for this study? What are the main findings?Dr. Sah: Physicians often recommend the treatment they specialize in, e.g., surgeons are more likely to recommend surgery than non-surgeons. Results from an observational study and a randomized controlled laboratory experiment found that when physicians revealed their bias toward their own specialty, patients were more likely to report increased trust in the physician’s expertise and take the treatment in accordance with the physician’s specialty. (more…)
MedicalResearch.com Interview with:Dr Stéphanie Kermorgant PhD
Barts Cancer Institute
Queen Mary University of London
MedicalResearch.com: What is the background for this study? What are the main findings?Response: There is an urgent need to better understand how cancer spreads around the body (a process called metastasis). Often it is metastasis that kills cancer patients and not the primary tumour.
During metastasis, cancer cells detach from the primary tumour and are able to survive detached, allowing them to enter in blood vessels and colonize different parts of the body.
Integrins and growth factor receptors are two classes of cell surface molecules that have been known to cooperate to promote cancer metastasis. However how they communicate is poorly understood. They have mostly been shown to exert their function at the surface of the cells.
Our study reveals that one growth factor receptor, called c-Met, and one integrin, beta1-integrin, in fact communicate inside the cancer cell to increase its survival when detached.
Moreover, this communication occurs in an anusual place in the cell, that we have called “Autophagy Related Endomembrane” (ARE). Autophagy is normally a process that degrades and recycles cellular material, making new building blocks for the cell. Our study reveals that intracellular structures related to the autophagy process can also help membrane receptors to communicate. Thus they may also function as “signalling platforms”.
One other key finding in this study is that integrins normally have been recognized to function as “adhesion molecules”, connecting the cells to their surrounding environment, the “extracellular matrix”. Their role in metastasis has been mostly linked to their adhesive function. Our exciting study reveals a new function of integrins, a “signalling function”, which is independent from their adhesion function.
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MedicalResearch.com Interview with:Professor Chris Semsarian
MBBS PhD MPH FRACP FAHMS FAHA FHRS FCSANZ
Professor of Medicine, University of Sydney
Cardiologist, Royal Prince Alfred Hospital
NHMRC Practitioner Fellow
Head, Molecular Cardiology Program
Centenary Institute,
Newtown NSW Australia
MedicalResearch.com: What is the background for this study?Response: Sudden cardiac death is a tragic and devastating event at all ages, and especially in the young (aged under 35 years). Understanding the causes and circumstances of SCD in the young is critical if we are to develop strategies to prevent SCD in the young. Our study represents the first prospective, population-based study of SCD in the young across two nations, Australia and New Zealand.
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MedicalResearch.com Interview with:Maria-Luisa Alegre, MD, PhD
Professor of medicine
University of Chicago
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Most of the research that investigates why/how transplanted organs are rejected has focused on the genetic disparities between the donor and the recipient. Foreign proteins in the donor organ are recognized by the immune system of the host, which becomes activated to reject the transplanted organ. This is why transplant recipients need to take immunosuppressive medications for the rest of their lives.
Whether environmental factors, in addition to genetic factors, can also affect how the immune system is activated by the transplanted organ is much less understood. In particular, the microbiota, the communities of microbes that live on and in our body, is distinct in each individual and is known to affect the function of the immune system in diseases ranging from autoimmunity to cancer.
Using mouse models of skin and heart transplantation, we investigated if the microbiota was an environmental factor that could affect the speed at which the immune system rejects a transplanted organ.
We found that the microbial communities that colonize the donor and the host fine-tune the function of the immune system and control the strength with which the immune system reacts to a transplanted organ.
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MedicalResearch.com Interview with:Guang Yang, Ph.D.
Assistant Professor
NYU Langone School of Medicine
Alexandria Center for Life Sciences
New York, NY 10016
MedicalResearch.com: What is the background for this study? How common is the problem of long-lasting behavioral deficits after repeated anesthesia exposure in neonates?Response: Each year, in the United States alone, more than 1 million children under 4 years of age undergo surgical procedures that require anesthesia. Many lines of evidence from animal studies have shown that prolonged or repeated exposure to general anesthesia during critical stages of brain development leads to long-lasting behavioral deficits later in life. The results from human studies are less clear, although some studies suggest a higher incidence of learning disabilities and attention-deficit and hyperactivity disorders in children repeatedly exposed to procedures requiring general anesthesia. To date, there has been no effective treatment to mitigate the potential neurotoxic effects of general anesthesia.
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MedicalResearch.com Interview with:Pei-Jung Lin, Ph.D.
Assistant Professor
Center for the Evaluation of Value and Risk in Health
Institute for Clinical Research and Health Policy Studies
Tufts Medical Center
Boston, MA 02111
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Alzheimer’s disease (AD) is a slow, progressive disease. Many people with AD may live for years with the disease left unrecognized or untreated, in part because the early symptoms are mild and often mistaken as part of normal aging. In this study, we found that Alzheimer’s patients may use more health care services and incur higher costs than those without dementia even before they receive a formal diagnosis. For example, total Medicare expenditures were 42% higher among Alzheimer’s patients than matched controls during the year prior to diagnosis ($15,091 vs. $10,622), and 192% higher in the first year immediately following diagnosis ($27,126 vs. $9,274). We also found similar trends among Medicare patients with mild cognitive impairment (MCI)— a prodromal stage of AD and associated with higher dementia risk.
Our study suggests that an Alzheimer’s disease or MCI diagnosis appears to be prompted by other health problems such as cardiovascular and cerebrovascular diseases, pneumonia, renal failure, urinary tract infections, and blood and respiratory infections. This finding likely reflects a failure of ambulatory care related to the impact of cognitive impairment on other chronic conditions.
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MedicalResearch.com Interview with:Thomas Andrew Gaziano, MD, MSc
Department of Cardiology
Assistant Professor
Harvard Medical School
MedicalResearch.com: What is the background for this study?Response: Heart failure (HF) is the leading cause of admissions to hospitals in the United States and the associated costs run between $24-47 billion annually. Targeting neurohormonal pathways that aggravate the disease has the potential to reduce admissions. Enalapril, an angiotensin converting enzyme-inhibitor (ACEI), is more commonly prescribed to treat HF than Sacubitril/Valsartan, an angiotensin-receptor/neprilysin inhibitor (ARNI). The latter was shown to reduce cardiovascular death and hospitalizations due to heart failure in a multi-country, randomized clinical (PARADIGM-HF), compared to Enalapril. In order to assess the cost-effectiveness of Sacubitril/Valsartan, compared to Enalapril, in the United States, we created a model population with population characteristics equivalent to the population in the PARADIGM-HF trial. Using a 2-state Markov model we simulated HF death and hospitalizations for patients with a left ventricular ejection fraction (LVEF) of 40% or less.
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MedicalResearch.com Interview with:Dr. Ying Bao Sc.D., M.D
Assistant Professor of Medicine
Channing Division of Network Medicine
Department of Medicine
Brigham and Women's Hospital
Harvard Medical School,
Boston, MA
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Nuts are rich in bioactive macronutrients, micronutrients, tocopherols and phytochemicals. Current epidemiological evidence has consistently linked increased nut consumption to reduced risk of several chronic conditions including cardiovascular diseases, type 2 diabetes, and inflammation. In contrast, evidence on nut consumption and cancer risk has been insufficient and equivocal.
Prostate cancer is the leading cancer among U.S. men, with approximately 220,800 new cases diagnosed in 2015. However, very few studies have investigated the association between nut intake and prostate cancer. Thus, in the current study, we followed 47,299 US men from 1986-2012, and examined
(1) whether consuming more nuts prevents getting prostate cancer, and
(2) whether consuming more nuts reduces death rates among non-metastatic prostate cancer patients.
During 26 years of follow-up, 6,810 men were diagnosed with prostate cancer, and 4,346 of these patients were without metastasis at diagnosis. We found no association between nut intake and being diagnosed with prostate cancer. However, among non-metastatic prostate cancer patients, those who consumed nuts 5 or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month.
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MedicalResearch.com Interview with:Dr. Richard Leigh MD
Neuro Vascular Brain Imaging Unit
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Bethesda, MD
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Patients who suffer an ischemic stroke have limited treatment options. One of the reasons for this is that our treatments can sometimes make the stroke worse by transforming the ischemic stroke into a hemorrhagic stroke. In our study we identified a new piece of information that we can extract from the patient’s MRI scan that informs us on the risk of having a hemorrhage.
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MedicalResearch.com Interview with: Dr. David Sebastián
IRB Barcelona and CIBERDEM researcher
MedicalResearch.com: What is the background for this study? What are the main findings?Response: One of the alterations that most affects the quality of life of the elderly is muscle wastage and the resulting loss of strength, a condition known as sarcopenia. At about 55 years old, people begin to lose muscle mass, this loss continues into old age, at which point it becomes critical. However, the underlying causes of sarcopenia are unknown and thus no treatment is available for this condition.
Importantly, we have found that the mitochondrial protein Mitofusin 2 is required to preserve healthy muscles in mice. Mitofusin 2 is a mitochondrial protein involved in ensuring the correct function of mitochondria, and it has several activities related to autophagy, a crucial process for the removal of damaged mitochondria. The loss of Mitofusin 2 impedes the correct function of mitochondrial recycling and consequently damaged mitochondria accumulate in muscle cells.
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MedicalResearch.com Interview with:Sirry Alang PhD
Assistant professor of sociology and anthropology
Lehigh University
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Discrepancies exist between how some Black populations perceive depression and how depression is conceptualized within research and clinical settings. African Americans are exposed to a lot of stress from structural racism, yet, they perceive themselves to be resilient. The context of stress from discrimination and beliefs about depression inform how they express psychological distress. Depression is thought of as a weakness that is inconsistent with notions of strength in the community. Although depression was expressed through classic depressive symptoms such as feeling hopeless, loss of sleep, and losing interests in activities, symptom like anger, agitation, and the frantic need for human interaction were considered to be indicative of depression. Anger, agitation, and the frantic need for human interaction are not consistent with how depression is defined in the latest manual for psychiatric diagnosis- the DSM-V.
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MedicalResearch.com Interview with:Jonathan Hsu, MD, MAS, FACC, FAHA, FHRS
Assistant Professor
Cardiac Electrophysiology, Division of Cardiology
University of California, San Diego (UCSD)
MedicalResearch.com: What is the background for this study?
Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and imparts significant stroke risk. In patients with AF determined to be at intermediate to high risk for thromboembolism, anticoagulation with warfarin (a vitamin K antagonist) or the newer non-vitamin K antagonist oral anticoagulants clearly reduces morbidity and mortality compared to aspirin. We sought to evaluate practice patterns of cardiovascular specialists in the United states to determine how often AF patients at risk for stroke are prescribed aspirin over oral anticoagulation, and predictors of this practice.
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MedicalResearch.com Interview with:Dr. Lan Huang PhD
Co-founder, Chairman and CEO
BeyondSpring Pharmaceuticals, IncMedicalResearch.com: What is the background for this study? What are the main findings?Response: The background for this study is the toxicity of Docetaxel chemotherapy causes inadequate dosing with Docetaxel due to dose delay, reduction or discontinuation, thus leaving the patient with inadequate chemotherapy treatment.
A main finding is a statistically significant p value of 0.002 in lower rates of grade 3 and 4 Neutropenia for patients dosed with a combination of BeyondSpring’s Plinabulin and Docetaxel compared to those patients dosed with Docetaxel alone. As a result, approximately 14 percent more patients stayed on the adequate (dense) dose of Docetaxel in the Docetaxel + Plinabulin arm as compared to Docetaxel alone.
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MedicalResearch.com Interview with:Dr. Álex García-Faura
Scientific Director of the Institut Marquès
Spain
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Our clinical research during the last three years has been focused on the effects of music during the early stages of life; in our preliminary studies, applying music to pregnant patients using abdominal speakers, we discovered that there was no fetal reaction to music and that the fetus would only be able to hear it as a distorted whisper because of the effects of the abdominal wall. We thought that it would be necessary to get the music closer to the fetus, and we decided to try to apply the music vaginally. It was a great decision.
(more…)
MedicalResearch.com Interview with:
Duke Appiah, PhD, MPH
Postdoctoral Fellow
Division of Epidemiology and Community Health
University of Minnesota
Minneapolis, MN 55454
MedicalResearch.com: What is the...
MedicalResearch.com Interview with:Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS
Director of Clinical Research
Division of Cardiology
Endowed Professor of Atrial Fibrillation Research
University of California, San Francisco
MedicalResearch.com: What is the background for this study? What are the main findings?Response: We and others have previously demonstrated that, despite the observation that African Americans on average exhibit more risk factors for atrial fibrillation, they demonstrate a substantially reduced risk of the disease. This suggests that, if we could understand the mechanism underlying this apparent paradox, we might learn something fundamentally important to atrial fibrillation that would be relevant to treating or preventing the disease regardless of race.
Building on our previous work demonstrating that, among African Americans, more European ancestry (determined by genomic testing) was a statistically significant predictor of atrial fibrillation, we sought to identify the gene(s) that might underlie this observation. The analysis took two forms.
First, we examined if any differences among several well-established single nucleotide polymorphisms (SNP) associated with atrial fibrillation might mediate the race-atrial fibrillation relationship. One such SNP statistically mediated (rs10824026) up to about a third of the race-atrial fibrillation relationship. It’s important to mention that a causal relationship cannot be proven here.
Perhaps more remarkable was the observation that the disease-associated alleles of the SNPs most closely associated with atrial fibrillation in multiple studies were actually significantly more common among African Americans, pointing to the complex nature of both the race-atrial fibrillation relationship as well as the genetics of atrial fibrillation.
Finally, leveraging the ancestral relationships, we performed a genome wide admixture mapping study with the hope of reducing the penalty for multiple hypothesis testing incurred in conventional genome wide association studies. While several loci revealed associations with atrial fibrillation with small p values, none met our criteria for genome wide significance.
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MedicalResearch.com Interview with:Gregg C. Fonarow, MD, FACC, FAHA
Eliot Corday Professor of Cardiovascular Medicine and Science
Director, Ahmanson-UCLA Cardiomyopathy Center
Co-Chief of Clinical Cardiology, UCLA Division of Cardiology
Co-Director, UCLA Preventative Cardiology Program
David Geffen School of Medicine at UCLA
Los Angeles, CA, 90095-1679
MedicalResearch.com: What is the background for this study? What are the main findings?Dr. Fonarow: Angiotensin receptor neprilysin inhibitors (ARNI) have been demonstrated to reduce mortality in patients with heart failure with reduced ejection fraction. However, to date, the population level impact of optimal implementation of this therapy in the United States has not been evaluated.
This new analysis estimates that as many 28,484 deaths in heart failure with reduced ejection fraction patients annually could be prevented or postponed with optimal use of angiotensin receptor neprilysin inhibitors (with sensitivity analyses demonstrating a range of 18,230 to 41,017).
(more…)
MedicalResearch.com Interview with:Annika Rosengren MD
Department of Molecular and Clinical Medicine, Institute of Medicine
Sahlgrenska Academy
University of Gothenburg,
Gothenburg, Sweden
MedicalResearch.com: What is the background for this study? What are the main findings?Response: In an earlier study we found that while hospitalizations for heart failure decreased among people aged 55 and older in Sweden 1987-2006, there was a clear increase among those younger than 45 years, particularly in young men. We thought that increasing body weight in the population might be a factor behind this.
We used anonymized data from more than 1.6 million Swedish men from the Swedish conscript registry aged on average 18 and followed them from adolescence onwards. Those who were overweight as teenagers were markedly more likely to develop heart failure in early middle age. The increased risk of heart failure was found already in men who were within the normal body weight range (a body mass index of 18.5 to 25) in adolescence, with an increased risk starting in those with a BMI of 20 and rising steeply to a nearly ten-fold increased risk in those who were very obese, with a BMI of 35 or over.
Among men with a BMI of 20 and over, the risk of heart failure increased by 16% with every BMI unit, after adjustments for factors that could affect the findings, such as age, year of enlistment into the Swedish armed forces, other diseases, parental education, blood pressure, IQ, muscle strength and fitness.
(more…)
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