ASCO, Author Interviews, Prostate, Prostate Cancer, Urology / 15.03.2018

MedicalResearch.com Interview with: https://www.churchillpharma.com/ Paul Nemeth, Ph.D. Sr. Vice President, Regulatory Affairs, Clinical Development & Quality Assurance Churchill Pharmaceuticals LLC King of Prussia, PA 19406 MedicalResearch.com: What is the background for this study? Response: In the STAAR study, 53 patients with metastatic castration-resistant prostate cancer (mCRPC) were randomized to receive YONSA, an abiraterone acetate fine particle formulation 500 mg once daily in combination with 4 mg of methylpresnisolone twice daily or 1,000 mg daily of the originator abiraterone acetate (OAA) in combination with 5 mg of prednisone twice daily for a period of 84 days.  Previous studies in healthy volunteers under fasted conditions had shown that single oral doses of 500 mg of YONSA are bioequivalent to single oral doses of 1,000 mg OAA and that a background of 4 mg of methylprednisolone twice daily on a single oral dose of 500 mg of YONSA results in the same extent of absorption as a background of 5 mg of prednisone twice daily on a single oral dose of 1,000 mg of OAA.  (more…)
Author Interviews, Flu - Influenza, Infections, Mental Health Research, Primary Care, Roche / 14.03.2018

MedicalResearch.com Interview with: James W. Antoon, MD, PhD, FAAP Assistant Professor of Clinical Pediatrics University of Illinois at Chicago Associate Medical Director, Pediatric Inpatient Unit Children's Hospital, University of Illinois Hospital & Health Sciences System Chicago, IL 60612  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Oseltamivir, commonly known as Tamiflu, is the only commercially available medication FDA approved to treat the flu.  Since the 2009 H1N1 flu epidemic pediatric prescriptions for Tamiflu have soared.  In the United States, about 40% of Tamiflu prescriptions are given to children less than 16 years of age.  Following reports of abnormal behavior, such as hallucinations, self-injury and suicide attempts in adolescents on Tamiflu, the FDA placed a new warning about these neuropsychiatric symptoms on the drug label.  Whenever the FDA puts out label warning about a drug, doctors and the public take notice. Whether Tamiflu truly causes these side effects is unclear.  For this study we chose to focus on the most consequential of those reports: suicide. The potential link between a drug and suicide is a particularly difficult topic to study for a number of reasons. There are things that happen together or at the same time that can influence someone to attempt suicide and it is very difficult to know which thing is actually having an affect. In our study, other things that can influence suicide are socioeconomic status, mental health, trauma, abuse, among others.  Separating the effects of these confounders can be difficult. It is also possible that the disease itself, which in this case is the flu, causes the effect of suicide. Finally, and luckily, suicide is rare. Our database had 12 million children per year and over five year 21,000 attempted suicide. Of those, only 251 were taking Tamiflu. To get past these issues, we took advantage of a growing drug safety research collaboration between the Departments of Pediatrics and Pharmacy at our institution.  Previous studies have compared those on Tamiflu to those not on Tamiflu to see if there are more side effects in the Tamiflu group.  Our team utilized a novel study method called a case-crossover design. What’s different about this study is that we used each patient as their own comparison.  In other words, we compared each patient to themselves rather than a different group of people.  We essentially studied how patients behaved when the Tamiflu was in their system compared to other l periods where they were not on Tamiflu.  This allowed use to account for the personal differences noted above like mental health and socioeconomic status.   We also compared those children with flu who got Tamiflu and those with flu who did not get Tamiflu to see if the infection itself could be associated with increased suicide. After accounting for all these variables, we did not find any an association between Tamiflu exposure and suicide. Our findings suggest that Tamiflu does NOT increase the risk of suicide in children or teenagers. (more…)
Accidents & Violence, Addiction, Author Interviews, JAMA / 14.03.2018

MedicalResearch.com Interview with: Dr. Laura Dwyer-Lindgren PhD Assistant Professor at IHME Institute for Health Metrics and Evaluation  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This study in the latest in a series of studies IHME has conducted on health and disease on the county level in the United States. We analyzed data provided by the National Center for Health Statistics, the U.S. Census Bureau, and other sources. Main findings include:
  • Nearly 550,000 deaths were attributed to drug use over the 35 years. Nationally, the age-standardized death date increased 238% between 1980 and 2000, and 112% between 2000 and 2014. The death rate from drug use disorders increased in every county, but some counties in Kentucky, West Virginia, Ohio, Indiana, and eastern Oklahoma has increases exceeding 5000%.
  • There were more than a quarter million deaths in the U.S. due to alcohol use; Western counties generally has higher levels than those in other parts of area of the nation, with especially high death rates in Wisconsin, North Dakota, South Dakota, Nebraska, Montana, New Mexico, Arizona, Utah, and Alaska.
  • Neatly 1.3 million suicides were recorded, with especially high rates in Alaska, Nevada, South Dakota, Utah, New Mexico, Arizona, Montana, North Dakota, Oregon, Wyoming and one county in Maryland. While the national death rate due to suicide decreased between 1980 and 2014, there was an increase in the death rate due to suicide in most counties.
  • More than three quarters of a million deaths by homicide occurred in the US between 1980 and 2015. Nationally, the age-standardized death rate due to homicide decreased by about 35% between 1980 and 2000, and by nearly 16% between 2000 and 2014. Counties with the largest decreases were found in Virginia, Florida, Texas, California and New York. 
(more…)
Abuse and Neglect, Neurology / 14.03.2018

MedicalResearch.com Interview with: Veljko Dubljević, Ph.D., D.Phil. Assistant Professor of Philosophy, Department of Philosophy and Religious Studies, and Science Technology and Society Program, North Carolina State University Raleigh, NC 27607  MedicalResearch.com: What is the background for this study? Response: There is considerable controversy about the interpretation of data of the neuroscientific studies done by Benjamin Libet. On the one hand, Libet claimed that his work disproves certain metaphysical conceptions of free will (Libertarianism), whereas it does not disprove others (e.g., Compatibilism). In a nutshell, the reason for these claims is that Libet found preparatory brain activity (Readiness Potentials or RPs) some 500ms before the conscious decision to act was felt by study participants. That seemed to exclude the possibility that mental causation was taking place. At the same time, the onset of movement left a time-window for a 'veto-decision'. This led Libet to conclude that there is no 'free will', but that there is a 'free won't'. On the other hand, there were many criticisms of the study - methodological or substantive. Most notably, Patrick Haggard argued that it is not RPs that are correlates of a decision to act, but Lateralized Readiness Potentials (LRPs). Haggard agreed with many critics of Libet in that RPs could be connected to a range of other phenomena, and that preparatory brain activity that is most important for a decision to act already has to be 'lateralized'. Namely, the decision to move the left or right arm is critical in this regard, and will lead to RP being focused in one or the other hemisphere, thus making LRPs the point of interest for any conscious decision to act. All in all, Haggard claimed to have replicated Libet's major findings, with the caveat that timing of LRPs excludes the time-frame for a 'veto-decision'. This Haggard claimed makes the evidence more in line with the metaphysical doctrine of 'hard determinism', which excludes agency and responsibility. Many other neuroscientists followed Libet's (and Haggard's) lead and these experiment became part of 'lore' in neuroscience education - many other labs performed similar experiments and claimed to basically replicate the findings. Our study was the first to review all available evidence. (more…)
Author Interviews, Diabetes, Duke, Heart Disease / 14.03.2018

MedicalResearch.com Interview with: Stephen J. Greene, MD Division of Cardiology Duke University Medical Center Durham, NC MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2008, the United States FDA issued an industry guidance specifying that diabetes drugs should routinely be tested in large cardiovascular outcome trials to confirm cardiovascular safety. The guidance specifically mentioned cardiovascular safety in terms of MACE, or major adverse cardiac events, including cardiovascular death, myocardial infarction, and stroke.  Largely because of this, these trials have traditionally had a focus on cardiovascular disease in terms of atherosclerotic events. Heart failure was not mentioned in the FDA document and these trials have had a lesser focus on it. As the years have gone by, we have learned more and more about the connection between diabetes and heart failure. There is tremendous overlap between the two patient populations. Also, as more and more of the large cardiovascular outcome trials have been completed, we have seen multiple examples of various glucose lowering therapies either increasing or decreasing risk of heart failure events. Given all these data on heart failure/ diabetes interactions, the goal of our research was to carefully examine all of the completed large cardiovascular outcome trials of diabetes therapies to systematically describe the type of heart failure-related data they capture. As an initial step in improving heart failure characterization in these trials, we wanted to first describe what trials have already been doing and where the gaps in understanding heart failure in these trials exist. Overall, we found major gaps in the amount and quality of the heart failure data capture in these trials. We looked at 21 large trials, including over 150,000 patients. Rates of patients with baseline heart failure were inconsistently provided, and among those trials that did provide it, heart failure patients tended to be underrepresented compared to the general population. Patients with baseline heart failure were also poorly characterized, with minimal data on functional status, ejection fraction, or heart failure medications. Only 6 trials reported rates of new-onset heart failure and the definitions used were non-specific. Most trials tended to report rates of heart failure hospitalization, but did not include data on fatal or other types of heart failure events. Only 2 trials included heart failure events within the primary study endpoint. More details are included in our full manuscript, which was published in the Journal of the American College of Cardiology to coincide with our presentation at the ACC conference. (more…)
Author Interviews, Primary Care, Prostate Cancer / 14.03.2018

MedicalResearch.com Interview with: Dr. Jason Profetto, MD, CCFP Family and Academic Medicine Chair, Clinical Skills Undergraduate Medical Education McMaster University MedicalResearch.com: What is the background for this study?  Response: The main reason that prompted me to investigate the issue of digital rectal exams in primary care for prostate screening was that it appeared to be rather dogmatic practice (continually practiced by many despite updated data suggesting a lack of benefit).  I was very curious to see if there was any data that suggested the digital rectal exams was indeed a useful indicator in primary practice (ie. Family Medicine) in detecting prostate cancer in asymptomatic men.  Intuitively, I didn’t believe the DRE was accurate mainly because in medical school it’s generally under-represented in clinical skills teaching and poorly taught and assessed (not just in Ontario, but also Canada).  As a result, it seemed bizarre to me that this specific clinical skills was being used as a routine measure in family medicine to screen for prostate cancer.  Also, for me this was a big issue as many men in my practice were used to having yearly “rectal exams” done and I thought it was time to really take a closer look at the research to see whether or not we can support this practice. MedicalResearch.com: What are the main findings? Response: The main findings suggest that the digital rectal exam is not helpful/accurate in detecting prostate cancer in asymptomatic men in family practice or primary care. (more…)
Author Interviews, Diabetes, Microbiome, Nutrition, Science / 13.03.2018

MedicalResearch.com Interview with: Liping Zhao PhD, Professor Department of Biochemistry and Microbiology School of Environmental and Biological Sciences Rutgers University-New Brunswick NJ MedicalResearch.com: What is the background for this study? Response: Microbes in the human gut (collectively known as the gut microbiota) provide many functions that are important for human health. A notable example is that some gut bacteria are able to ferment non-digestible carbohydrates in our diet, e.g. dietary fibers, to produce short-chain fatty acids (SCFAs). These SCFAs nourish our gut epithelial cells, reduce inflammation, and play a role in appetite control. Deficiency of SCFAs has been associated with many diseases including type 2 diabetes. Many gut bacteria have the genes (and therefore the capacity) to produce SCFAs from carbohydrate fermentation. However, we know little about how these bacteria, as individual strains and as a group, actually respond to an increased supply of carbohydrates. This is key to improve clinical efficacy of dietary fiber interventions to improve human health. (more…)
Author Interviews, Breast Cancer, JAMA, Schizophrenia / 13.03.2018

MedicalResearch.com Interview with: Chuanjun Zhuo, MD, PhD Department of Psychiatric Laboratory Department of Psychiatric Neuroimaging Faculty Tianjin Mental Health Center Tianjin, China  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: According to previous epidemiological studies, women with schizophrenia may be associated with significantly increased risk of breast cancer. However, the results of these studies were not always consistent. In view of the fact that medical care for patients with schizophrenia is becoming multidisciplinary, we aimed to evaluate the risk of breast cancer in women with schizophrenia via a meta-analysis of relevant cohort studies. We included twelve cohorts and adopted the recently proposed prediction interval to evaluate the heterogeneity among the included studies. We found that schizophrenia was associated with about 30% increased risk of breast cancer incidence in women. However, significant heterogeneity existed of the included studies, which indicates that more extensive researches into the potential mechanisms underlying the associations between schizophrenia and breast cancer risk are needed. (more…)
Author Interviews, Heart Disease, Women's Heart Health / 13.03.2018

MedicalResearch.com Interview with: Dr. Somwail Rasla, MD Primary Care Center Brown University, Pawtucket, RI MedicalResearch.com: What is the background for this study? What are the main findings? Response: Heart failure (HF) is a major global epidemic. The risk of heart failure rises with age, It triples for women above age 60. Studies have found an inverse relationship between the risk of heart failure hospitalization and midlife fitness.Walking is the most common form of physical activity reported in women and older adults. T his study aims at exploring the association of walking pace (speed), walking frequency and duration with the risk of incident acute hospitalized HF (HHF). (more…)
Author Interviews, Biomarkers, Rheumatology, Vanderbilt / 13.03.2018

MedicalResearch.com interview with: Dr. Chase Spurlock, PhD CEO, IQuity, Specialty Diagnostic Technologies Faculty, Vanderbilt University Medical Center Dr. Spurlock discusses IQuity's release of IsolateFibromyalgia, the first RNA-based blood test to detect fibromyalgia. MedicalResearch.com: What is the background for this test? Would you briefly explain what fibromyalgia is, whom it affects and why it has been difficult to definitely diagnosis?  Dr. Spurlock: We developed the IsolateFibromyalgia™ test using our established RNA assay platform, IQIsolate™, to help clinicians receive timely and accurate information. This technology has evolved from over a decade of research at Vanderbilt University and continues at IQuity funded by both the National Institutes of Health (NIH) as well as private investors. We discovered that differences in RNA expression patterns could be detected in patients with a variety of human conditions spanning infection to more complex inflammatory diseases. With our focus on autoimmune disease, we identified and validated RNAs capable of distinguishing multiple sclerosis, IBS, Crohn’s, ulcerative colitis and fibromyalgia syndrome. In the case of fibromyalgia, our research involved almost 600 subjects including healthy individuals, patients with endocrine conditions, dermatologic conditions and rheumatologic diseases — rheumatoid arthritis, Sjogren’s syndrome and systemic lupus erythematosus. Reported sensitivity and specificity of this assay is 92 percent and 96 percent, respectively. Fibromyalgia syndrome is characterized by widespread musculoskeletal pain often initially localized to the neck and shoulders. Patients typically describe pain throughout the muscles but may also report pain in the joints. Furthermore, fibromyalgia is usually accompanied by fatigue as well as cognitive disturbance. Patients most afflicted are women between ages 20 and 55. Fibromyalgia affects approximately as many as 6-10 million people in the U.S. The difficulty in reaching a definitive diagnosis lies in two important issues. First, the cause of the syndrome is unknown, and the way the condition presents and progresses can vary among patients. Secondarily, fibromyalgia syndrome mimics many other conditions due to the multiple nonspecific symptoms associated with fibromyalgia. Patients look well, there are no obvious abnormalities on physical examination other than tenderness, and laboratory and radiologic studies are normal. With no discernable abnormalities in routine clinical laboratory testing or imaging, the diagnosis is based on subjective reporting of symptoms. The difficulties and complex nature of receiving a correct fibromyalgia diagnosis are apparent. Despite improved awareness among primary care clinicians, many continue to be uncomfortable with making this diagnosis. Fibromyalgia patients on average wait almost a year after experiencing symptoms before seeing a physician and end up visiting on average 3.7 different physicians before a diagnosis. The diagnostic journey can take years. IsolateFibromyalgia provides the clinician and patient actionable information with 94 percent accuracy. (more…)
Author Interviews, Brain Injury, JAMA / 12.03.2018

MedicalResearch.com Interview with: Christopher Abeare, Ph.D. Associate Professor Clinical Neuropsychology Department of Psychology University of Windsor Windsor, Ontario MedicalResearch.com: What is the background for this study? What are the main findings?  Response: In this study, we examined the prevalence of invalid performance on baseline neurocognitive testing in sport concussion. Baseline testing is a commonly employed practice in which the cognitive abilities of athletes are assessed pre-season. These baseline test results are then used as a point of comparison against which post-injury neurocognitive test results can be compared, thereby creating a more individualized approach to the assessment of neurocognitive functioning. However, there has been growing concern about the validity of baseline test results, meaning that there is concern over the degree to which the scores on these baseline tests actually reflect an athlete’s true cognitive ability. There are many reasons why their test scores might not reflect their actual ability, ranging from inattentiveness during testing and lack of appreciation of the importance of doing their best on testing to intentional underperformance (aka “sandbagging” or malingering). As a result of these concerns, 4 different validity measures have been developed. We compared these 4 validity measures, head to head, in a sample of 7897 athletes aged 10 to 21 years. We found that 56% of athletes failed at least 1 of these validity measures, suggesting that as many as 56% of  athletes have scores that may not reflect their true ability level. We then tested the hypothesis that age would be related to the proportion of athletes with invalid performance. Our findings supported this hypothesis in that nearly 84% of 10-year-olds failed at least one validity measure and 29% of 21-year-olds failed at least one.  (more…)
Author Interviews, Cost of Health Care / 12.03.2018

MedicalResearch.com Interview with: Dr. Samuel Cho, MD Associate Professor of Orthopaedics Icahn School of Medicine at Mount Sinai   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Anterior cervical discectomy and fusion (ACDF), first implemented in 1957, has been considered the “gold standard” for decades for the treatment of cervical degenerative disc disease after conservative options have been exhausted. For patients presenting with neck and radiating arm pain, motor weakness, and sensory loss due to cervical disc herniation or compressive pathologies, ACDF has been shown to be generally well-tolerated and associated with a high clinical success rate. Despite the proven long-term radiographic and clinical success of ACDF, however, our literature has shown the procedure to be associated with certain drawbacks including neurological complications, rapid development of adjacent segment disease, and decreased range of motion owing to solid bony arthrodesis. More recently, cervical disc replacement (CDR) has also become an acceptable surgical option for similar cervical spine pathologies as ACDF. CDR was developed as a motion-sparing alternative to ACDF with purported advantages including minimization of adjacent segment disease and obviation of pseudoarthrosis. Multiple large investigational device exemption (IDE) studies showing the non-inferiority of cervical disc replacement, the cost-effectiveness of this procedure has increasingly become a topic of interest. For this reason, we sought to determine the seven-year cost-effectiveness of single level ACDF versus CDR for the treatment of cervical disc degeneration. (more…)
Author Interviews, JAMA, University of Michigan, Urinary Tract Infections / 12.03.2018

MedicalResearch.com Interview with: Keith S. Kaye, MD, MPH Professor of Medicine, Division of Infectious Diseases University of Michigan Medical School Ann Arbor MI  MedicalResearch.com: What is the background for this study? Response: Complicated complicated urinary tract infections (cUTI), including acute pyelonephritis, are a major cause of hospital admissions, and are associated with significant morbidity and mortality and can be difficult to treat. While the most common pathogen is Escherichia coli, the more problematic pathogens are multidrug-resistant (MDR) gram-negative organisms including other Enterobacteriaceae species. The prevalence of cUTI due to MDR gram-negative bacteria has risen. In some instances, MDR gram-negative bacteria isolated from the urinary tract can cause bacteremia. Vabomere was approved by the U.S. Food and Drug Administration (FDA) in August 2017 for the treatment of adult patients with cUTI, including pyelonephritis, caused by designated susceptible Enterobacteriaceae: Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae species complex.   Vabomere is a fixed-dose (2g/2g) combination product of a carbapenem and a β-lactamase inhibitor with potent in vitro activity against Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE), an important MDR organism associated with serious infections. The Targeting Antibiotic Non-susceptible Gram-negative Organisms (TANGO I) trial was the pivotal Phase 3 study that compared the efficacy and safety of Vabomere to piperacillin-tazobactam in the treatment of patients with cUTI and acute pyelonephritis. (more…)
Author Interviews, Brigham & Women's - Harvard, Diabetes, Heart Disease / 12.03.2018

MedicalResearch.com Interview with: Muthiah Vaduganathan, MD MPH Heart and Vascular Center Brigham and Women's Hospital  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The prevalence of heart failure with preserved ejection fraction (HFpEF) is rising globally, yet no medical therapies are currently available to alter its natural history and its progression remains incompletely understood. Sudden death may represent a target for therapy in this disease entity. In 1,767 patients with HFpEF enrolled in the Americas region of the TOPCAT trial, we found that sudden death accounts for ~20% of all deaths. Male sex and insulin-treated diabetes mellitus identify patients at higher risk for sudden death. Sudden death was numerically lower but not statistically reduced in those randomized to spironolactone. (more…)
Author Interviews, Infections / 12.03.2018

MedicalResearch.com Interview with: Michael Durkin, MD MPH Washington University School of Medicine St. Louis MedicalResearch.com: What is the background for this study? What are the main findings? Response: The aim of this study was to evaluate overall national outpatient antibiotic prescribing trends using a pharmacy benefits manager (Express Scripts). We wanted to evaluate if antibiotic prescribing had decreased as a result of increase physician awareness of antibiotic prescribing. Specifically, the ABIM choosing wisely campaign overlapped with our study period. We did not see any significant reductions in antibiotic prescribing during the 3-year study period. This is a little disappointing given that the CDC estimates that 30% of outpatient antibiotic prescriptions are inappropriate. We also saw some seasonal variation in antibiotic prescribing. This isn’t particularly novel. But it is important to note, as some of these prescriptions represent providers writing antibiotics for likely viral conditions. (more…)
Aging, Author Interviews, Cancer Research, Johns Hopkins / 12.03.2018

MedicalResearch.com Interview with: Hariharan Easwaran, PhD Assistant Professor of Oncology The Sidney Kimmel Comprehensive Cancer Center The Johns Hopkins University School of Medicine Bunting/Blaustein Cancer Research Building 1 Baltimore, MD 21287 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The interpretation of the information encoded in our DNA by the various cells in our body is mediated by a plethora of modifications of DNA and proteins that complex with DNA. DNA methylation is one such important modification, which is normally established in a very orchestrated fashion during development. All normal cells have a defined pattern of DNA methylation, which may vary by tissue type, but is consistent within tissues. This normal pattern is disrupted in all known cancers, and is considered a hallmark of cancers. (more…)
Author Interviews, Dermatology, JAMA, Melanoma / 11.03.2018

MedicalResearch.com Interview with: Aimilios Lallas, PhD First Department of Dermatology, School of Medicine Aristotle University Thessaloniki, Greece MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Our goal today is to recognize melanoma at the earliest stage, ideally before it invades the dermis and acquires metastatic potential. Melanoma-specific dermoscopic criteria have been tested mainly in the context of invasive melanoma. Although they were proven valid melanoma predictors, the question still remains if they are strong enough to diagnose melanoma in situ (MIS). Our aim was to investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of melanoma in situ. We identified 5 main positive dermoscopic indicators of MIS: atypical network, regression, irregular hyperpigmented areas, prominent skin markings and angulated lines.  (more…)
Author Interviews, Parkinson's / 11.03.2018

MedicalResearch.com Interview with: Prof. Jeffrey Hausdorff PhD Director of the Center for the Study of Movement, Cognition and Mobility Full Professor in the Sackler School of Medicine and Sagol School of Neuroscience Tel Aviv Medical Center MedicalResearch.com: What is the background for this study?  Response: Many people with Parkinson’s disease suffer from a disturbing symptom referred to as “freezing of gait”. When freezing occurs, the person’s feet inexplicably become stuck to the floor and he or she is unable to move forward, despite efforts to walk. Initially, the problem can last just a few seconds and occur very infrequently. As the problem progresses, however, freezing can last many seconds, occurring frequently throughout the day. This can lead to a very frustrating situation that may also be dangerous. People with freezing of gait have an increased risk of falls and reduced health-related quality of life. The behavioral manifestation of freezing of gait is a problem with walking, i.e., it is a “motor” symptom. However, there is also evidence that deficits in specific aspects of cognitive function (i.e., executive function) may also contribute to freezing of gait. The goals of the present work were to use non-invasive brain stimulation to better understand if these cognitive deficits are indeed in the causal chain and if non-invasive brain stimulation that simultaneously targets both motor and cognitive brain areas that are believed to involved with freezing have a better impact on freezing and related symptoms than stimulation that targets only motor brain areas or sham stimulation. (more…)
Author Interviews, Heart Disease, Weight Research / 11.03.2018

MedicalResearch.com Interview with: Dr. Sadiya S. Khan, MD MS Division of Cardiology, Department of Medicine Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago, Illinois MedicalResearch.com: What is the background for this study? What are the main findings?  Response: In recent years, controversy has grown regarding findings termed the "obesity paradox" whereby individuals with cardiovascular disease who are obese have "better" outcomes. These findings have led to confusion for patients who are obese. The main findings of our study help clarify the adverse cardiovascular risks for obese individuals with a shorter overall health span and lifespan. Obese participants in our study lived shorter and sicker with more years lived with cardiovascular diseases and greater lifetime risk of developing cardiovascular disease.  (more…)
Author Interviews, Heart Disease, Psychological Science / 11.03.2018

MedicalResearch.com Interview with: Dr. Alexander Fanaroff MD Duke University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Among patients with chronic angina, there are strong associations between depression and clinical outcomes, which illustrates the important interplay between psychosocial symptoms and physical symptoms in this condition. But depressive symptoms are distinct from expectations and optimism regarding recovery and returning to a one’s normal lifestyle. Patients with chronic angina may not be optimistic about their outlook for a number of reasons, including uncertainty about their prognosis or lack of medical knowledge, but for many patients with chronic angina, the outlook is actually quite good. We examined data from RIVER-PCI, a clinical trial that randomized patients with chronic angina and incomplete revascularization to ranolazine or placebo, and were followed for the primary outcome of ischemia-driven hospitalization or revascularization. Patients were asked at baseline, 1 month, 6 months, and 12 months how much they agreed with the phrase, “I am optimistic about my future and returning to a normal lifestyle.” We categorized patients by their responses at baseline – we coded “strongly agree” as very optimistic, “agree” as optimistic, “neutral” as neutral, and “disagree” and “strongly disagree” as not optimistic – and evaluated the association between baseline optimism and the primary outcome over long-term follow-up. We found that most patients were optimistic at baseline – 33% were very optimistic, 42% were optimistic, 19% were neutral, and 5% were not optimistic – and the majority remained optimistic over long-term follow-up. The most optimistic patients had a lower prevalence of prior myocardial infarction, heart failure, diabetes, and chronic kidney disease and less severe angina at baseline than less optimistic patients. The rate of the ischemia-driven hospitalization or revascularization was higher in neutral (32.8%) and not optimistic (35.0%) patients compared with the most optimistic patients (24.4%). Even after adjusting for baseline comorbidities and angina frequency, the most optimistic patients had a 30% lower risk of ischemia-driven hospitalization or revascularization compared with neutral or not optimistic patients. (more…)
Author Interviews, GSK, Herpes Viruses, Infections, Vaccine Studies / 10.03.2018

MedicalResearch.com Interview with: Anthony. L. Cunningham, MD The Westmead Institute for Medical Research Westmead, NSW University of Sydney, Sydney,   MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study examines the reasons why the HZ subunit vaccine candidate (HZ/su vaccine) consisting of a single viral protein, varicella-zoster glycoprotein E, and and adjuvant (immunostimulant) combination AS01B is so effective as a vaccine to prevent shingles (>90%), especially in those over the age of 70 years and 80 years, as published in recent trials i.e. it combats the declining immunity in the aging which usually restricts vaccine efficacy to under 60% in these age groups.  (more…)
Author Interviews, Heart Disease, Lancet, Menopause, Women's Heart Health / 10.03.2018

MedicalResearch.com Interview with: Mihir Sanghvi Academic Junior Doctor Barts Health NHS Trust MedicalResearch.com: What is the background for this study? What are the main findings? Response: The effect of menopausal hormone therapy (MHT), previously known as hormone replacement therapy, on cardiovascular health in post-menopausal women remains controversial and unclear. Extensive observational data had suggested MHT to be cardioprotective, leading to MHT being routinely prescribed for both primary and secondary prevention of coronary heart disease (CHD). However, subsequent data from the Women’s Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study (HERS) studies cast doubt on the beneficial cardiovascular effects of MHT; this was reflected in learned societies’ clinical guidance concerning MHT’s role in CHD prevention. The most recent randomised trial data on the subject arose from the Danish Osteoporosis Prevention Study, which indicated that women taking menopausal hormone therapy had a reduced risk of the composite endpoint of mortality, heart failure and myocardial infarction but the study has been subject to criticism [10]. In more recent work, again from the WHI, there was no difference in cardiovascular mortality in MHT users compared to placebo, although the authors themselves state that cause-specific mortality data should be interpreted “cautiously”. The UK Biobank is an ongoing, large-scale, population-based study designed to examine determinants of health in middle and old age. Besides extensive collection of health questionnaire data, biological samples and physical measurements, it has incorporated cardiovascular magnetic resonance (CMR) imaging – the gold standard for analysis of cardiac structure and function – to provide detailed imaging phenotypes. At present, there is a paucity of data on the effects of  menopausal hormone therapy on left ventricular (LV) and left atrial (LA) volumes and function, alterations in which are markers of subclinical cardiovascular disease and have prognostic implications. We found that in a large, population-based cohort of post-menopausal women free of cardiovascular disease, use of menopausal hormone therapy is not associated with adverse, subclinical changes in cardiac structure and function. Indeed, we demonstrate significantly smaller LV and LA chamber volumes which have been linked to favorable cardiovascular outcomes in other settings. (more…)
Author Interviews, JAMA, Prostate Cancer / 10.03.2018

MedicalResearch.com Interview with: Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles MedicalResearch.com: What is the background for this study? Response: Patients with high risk prostate cancer have several curative treatment options: radical prostatectomy, external beam radiotherapy with androgen deprivation therapy, and external beam radiotherapy with a brachytherapy boost, also with androgen deprivation therapy (so-called extremely dose-escalated radiotherapy). Prior attempts at comparing long-term clinical outcomes between these treatment options have been hampered by the fact that standards of care have changed significantly with respect to the appropriate dose of radiation and the usage of androgen deprivation therapy. Therefore, many comparative effectiveness reports are in essence comparing apples with rotten oranges. Further, not all high risk prostate cancers are the same. Gleason score 9-10 disease is a particularly aggressive form of prostate cancer that is much more likely to metastasize and potentially cause death. Thankfully, this is a rarer type of prostate cancer -- but this also means that not much data are available specifically for this type of disease. Therefore, we launched a multi-institutional study of men with Gleason score 9-10 disease, including 1809 men treated across 12 institutions. All men were treated between 2000 and 2013 and therefore were more likely to have treatments that would be commensurate with modern standards.  (more…)
Author Interviews, Infections / 09.03.2018

MedicalResearch.com Interview with: Chih-Chi Andrew Hu, Ph.D. Associate professor in Microenvironment & Metastasis Program Wistar Institute  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: To help our body fight infections, B cells need to differentiate into plasma cells so that they can produce abundant antibodies against pathogens. Antibodies are folded and assembled in the endoplasmic reticulum (ER). Only those perfectly manufactured antibodies are allowed to be released from the ER and delivered to the outside of B cells to fight against the pathogens. IRE1 is a sensor protein that sits on the membrane of the ER, and can respond to B cell differentiation by activating the transcription factor called XBP1s. Activation of XBP1s allows B cells to expand the size of the ER and produce necessary chaperone proteins to help B cells manufacture perfect antibodies. By studying B cells that lack XBP1s, we discovered that these B cells produced dramatically increased levels of IRE1, and such IRE1 acquired phosphorylation at its serine 729 (S729).  (more…)
Asthma, Author Interviews, NEJM, Pulmonary Disease / 09.03.2018

MedicalResearch.com Interview with: “Asthma Inhaler” by NIAID is licensed under CC BY 2.0Timothy Harrison, MBBS, BSc, FRCP, MD, MSc Professor and Honorary Consultant Faculty of Medicine & Health Sciences University of Nottingham MedicalResearch.com: What is the background for this study? What are the main findings? Response: Self management plans are recommend for patients with asthma but previous studies have shown that doubling the dose of inhaled steroids when asthma starts deteriorating is ineffective at preventing the development of an exacerbation. This study shows that quadrupling the dose is effective and in a real-life setting can reduce severe exacerbations by about 20% (more…)
Author Interviews, Orthopedics / 08.03.2018

MedicalResearch.com Interview with: Dr. Charles A. Popkin, MD Orthopedic Surgeon NewYork-Presbyterian/Columbia University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? CAP: Sports participation offers multiple benefits for children and adolescents, but there is growing concern about the rise of early sports specialization (ESS). ESS is defined as intense, sport specific training for greater than 8 months a year at the exclusion of other sports and activities in children younger than 12 years of age (pre-pubescent). ESS has been linked with decreased enjoyment, burnout, injury risk and the impact of specialization on long term athletic success is unknown. The extent to which parents exert influence, both directly and indirectly on the phenomenon of ESS was the major focus of the study. (more…)
Author Interviews, Gastrointestinal Disease, Infections / 08.03.2018

MedicalResearch.com Interview with: Esther Bullitt, Ph.D. Associate Professor Dept. of Physiology & Biophysics Boston University School of Medicine Boston, MA  02118-2526  MedicalResearch.com: What is the background for this study? Response:      We know that saliva has properties that allow us to swallow easily, and to help prevent gum disease and infections in the mouth. But is that really the only use for the 1-2 liters (1-2 quarts) of saliva we produce every day?  We decided to test whether a component of saliva, Histatin-5, can help prevent diarrheal disease (Traveler’s Diarrhea by Enterotoxigenic Escherichia coli (ETEC)) that is caused by bacteria commonly found in contaminated food and water. ETEC are bacteria that have hundreds of thin hair-like fibers on their surface, called pili. These bacteria bind specifically to the surface of the gut using these pili, and the bacteria need to stay bound long enough to initiate disease. Studies by Mike Levine’s group in the 1970’s showed that pili are necessary for enterotoxigenic Escherichia coli (ETEC) to cause disease. No adhesion, no disease. One aid to remaining bound is the unwinding and rewinding of the pili. These helical fibers can unwind up to 8 times their original length, acting as shock absorbers during fluid flow.   (more…)
Author Interviews, Multiple Sclerosis, Ophthalmology, Pharmaceutical Companies / 08.03.2018

MedicalResearch.com Interview with: Sarah A. Morrow MD, MS, FRCPC Associate Professor of Neurology Department of Clinical Neurological Sciences University of Western Ontario (Western) MedicalResearch.com: What is the background for this study? Response: Acute demyelinating optic neuritis, which presents with loss of vision and painful eye movements, is common in multiple sclerosis (MS) occurring 50% of persons with MS. High dose (≥ 1g) corticosteroids administered through an IV became the standard of practice after the landmark Optic Neuritis Treatment Trial as IV administration. However, in that study the IV dose of corticosteroids was much higher (1 gram daily) than the oral dose (1 mg/kg). Thus, it is not clear if IV administration is still better if equivalent doses are used orally. Oral administration is much more convenient for patients and less expensive, and previous studies showed that it is preferred by patients. In this study, we asked the following question: are high dose (≥ 1000mg) IV corticosteroids superior to equivalent doses of oral corticosteroids for the acute treatment of optic neuritis? We randomly assigned fifty-five cases of acute optic neuritis to 1000mg IV methylprednisolone or 1250mg oral prednisone daily for three days and compared recovery of their vision over the next 6 months.  (more…)
Abuse and Neglect, Hematology, Lancet, Medical Imaging, Transplantation / 07.03.2018

MedicalResearch.com Interview with: Kirsten Williams, M.D. Blood and marrow transplant specialist Children’s National Health System  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This study addressed a life-threatening complication of bone marrow transplantation called bone marrow failure. Bone marrow transplantation has provided a cure for patients with aggressive leukemias or acquired or genetic marrow dysfunction. The process of bone marrow transplantation involves giving chemotherapy and/or radiation, which removes the diseased blood cells from the bone marrow. After this, new bone marrow stem cells are infused from a healthy individual. They travel to the bone marrow and start the slow process of remaking the blood system. Because these new cells start from infancy, it takes upwards of four to five weeks for new mature healthy cells to emerge into the blood, where they can be identified. Historically, there has been no timely way to determine if the new cells have successfully repopulated unless they can be seen in the blood compartment. This condition of bone marrow failure is life-threatening, because patients don't have white blood cells to protect them from infection. Once bone marrow failure is diagnosed, a second new set of stem cells are infused, often after more chemotherapy is given. However, for many individuals this re-transplantation is too late, because severe infections can be fatal while waiting cells to recover. We were the first group to use a new imaging test to understand how the newly infused bone marrow cells develop inside the patient. We have recently published a way to detect the new bone marrow cell growth as early as five days after the cells are given. We used an investigational nuclear medicine test to reveal this early cell growth, which could be detected weeks before the cells appear in the blood. This radiology test is safe, does not cause any problems and is not invasive. It is called FLT (18F-fluorothymidine) and the contrast is taken up by dividing hematopoietic stem cells. The patients could even see the growth of their new cells inside the bone marrow (which they very much enjoyed while waiting to see recovery of the cells in their blood). We could use the brightness of the image (called SUV) to determine approximately how many weeks remained before the cells were visible in the blood. Finally, we actually could see where the new cells went after they were infused, tracking their settling in various organs and bones. Through this, we could see that cells did not travel directly to all of the bones right away as was previously thought, but rather first went to the liver and spleen, then to the mid-spine (thorax), then to the remainder of the spine and breastplate, and finally to the arms and legs. This pattern of bone marrow development is seen in healthy developing fetuses. In this case, it occurs in a similar pattern in adults undergoing bone marrow transplant. (more…)
Allergies, Author Interviews, Dermatology, Inflammation, Pediatrics / 07.03.2018

MedicalResearch.com Interview with: elstarNidhi Malhotra PhD Boston Children's Hospital Division of Allergy and Immunology Senior Scientist at Elstar Therapeutics Inc. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Allergies such as Atopic Dermatitis (AD) are rampant in the industrialized nations. Why are we more predisposed to developing hypersensitive reactions to innocuous proteins (allergens) is not well understood. To gain better understanding and to develop better therapies, we need to first delve deeper into how our immune system regulates homeostasis in tissues such as skin. The main cell types that thwart inflammatory reactions are known as regulatory T cells. These cells are generated in thymus and reside in secondary lymphoid tissues but they are also prominent at tissue sites such as in dermal layer of skin. In this study, I focused on understanding how Tregs resident in skin are distinct from the Tregs in secondary lymphoid organs such as lymph nodes (LNs). I uncovered that functioning of Tregs in skin is underpinned by a distinct set of genes. One main gene that I found to be highly expressed in skin Tregs but not in LN Tregs is Rora, which encodes for the transcription factor ROR alpha (RORa). This observation was intriguing as previous studies had elucidated the requirement of RORa in the development of inflammatory type-2 innate lymphoid cells (ILC2s) and it has been considered the antagonizing RORa functioning would curb allergic responses. However, I observed that Tregs require RORa to suppress allergic responses. In particular, RORa regulates the expression of a TNF receptor family member DR3, which binds to the cytokine TL1A. TL1A has a role in enhancing suppressive activity of Tregs while also enhancing type-2 cytokine production from ILC2s. Hence, in the absence of DR3 in Tregs, we believe more TL1A is available to ILC2s resulting in unrestrained allergic responses.  (more…)