Author Interviews / 13.02.2015

MedicalResearch.com Interview with: Dr. rer. nat. Detlef Bartkowiak Klinik für Strahlentherapie und Radioonkologie Universitätsklinikum Ulm Albert-Einstein-Allee MedicalResearch: What is the background for this study? What are the main findings? Dr. Bartkowiak: After surgery of prostate cancer, the lab marker for prostate specific antigen PSA should fall below detection limits. If the PSA does not decline, this can be a due to residual normal prostate tissue but also due to tumor cells remaining in the patient. If it is tumor cells residing in or near the area of the resected prostate, then this can be treated locally with radiotherapy. If the tumor has already produced metastases at remote sites of the body, irradiating the prostate region is pointless. In our clinical trial into post-operative therapy options, patients who did not achieve an undetectable PSA after radical prostatectomy received additional radiotherapy with 66 Gy. Despite this immediate treatment, the risk of recurrence within 10 years was 37%. Therefore, a more aggressive early treatment should be considered in such patients. (more…)
Addiction, Author Interviews, Methamphetamine / 13.02.2015

MedicalResearch.com Interview with: Kyoon Lyoo, M.D., Ph.D Ewha W. University Seoul, South Korea MedicalResearch: What is the background for this study? What are the main findings? Dr. Lyoo: Recent studies increasingly suggested that the developing brain shows unique characteristics of neuroplasticity to environmental stimuli. Still, it remains unclear whether the adolescent brain would undergo adaptive or dysfunctional changes when exposed to highly neurotoxic substances including methamphetamine. However, despite an increasing prevalence of methamphetamine use in this population, human studies have not yet found clear answers to these questions regarding the effects of methamphetamine exposure on the adolescent brain. This study reports novel in vivo findings in adolescent methamphetamine users, and thus provides a new perspective regarding adolescent-specific brain correlates of methamphetamine-induced neurotoxicity. Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine users compared with adult users. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is much more vulnerable to methamphetamine-induced neurotoxicity than the adult brain. This may help explain why adolescent-onset methamphetamine users show more severe and chronic clinical course than adult-onset users. (more…)
Author Interviews, BMJ, Social Issues / 13.02.2015

MedicalResearch.com Interview with: Professor Khalid Khan Women's Health Research Unit Multi-disciplinary Evidence Synthesis Hub The Blizard Institute Medical Research: What is the background for this study? What are the main findings? Prof. Khan: My co-author talked me into helping him with his online dating and so we embarked on this project. We were fascinated to see if there was any scientific evidence which could help people in their online pursuit of love - and to our surprise there was lots of attraction and persuasion research. There were 86 published studies on attraction and persuasion which met our criteria, and these covered literature in psychology, sociology, and computer behavioural and neurocognitive sciences. Their design features included randomisation in 28 studies, cohort follow-up in 13 studies, cross-sectional evaluation in 37 studies, qualitative analysis in 5 studies and systematic review in 3 studies​. We found that Success in converting initial online contact to a first date is not a complex formula. It relates to simple factors such as a fluent headline, truthfulness of profile, and reciprocity in communication.  Just like when you meet someone in real life, simple actions such as showing interest in the other person (commenting on something in their profile rather than just talking about yourself) goes a long way. (more…)
AHRQ, Author Interviews, Education, NIH, Race/Ethnic Diversity / 13.02.2015

MedicalResearch.com Interview with: Robert M. Kaplan Office of Behavioral and Social Sciences Research National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? What are the main findings? Response: Years of formal education is one of the strongest correlates of life expectancy. The purpose of this study was to examine the relationship between educational attainment and life expectancy with adjustments for other social, behavioral, and biological factors. Using data from a large cohort of nearly 30,000 adults, we found that education was a very strong predictor of survival and that biological and behavioral factors only partially explained the relationship. (more…)
Author Interviews, Genetic Research, Personalized Medicine / 13.02.2015

Prof. Jozef GECZMedicalResearch.com Interview with: Prof. Jozef Gecz NH&MRC Senior Principal Research Fellow Professor of Human Genetics School of Paediatrics and Reproductive Health Faculty of Health Sciences The University of Adelaide at the Women's and Children's Hospital North Adelaide, SA Medical Research: What is the background for this study? What are the main findings? Prof. Gecz: Cerebral palsy is the most frequent movement disorder of children for many years considered to be due to brain injury. Given that cerebral palsy incidence has not changed dramatically over many years while medical care is constantly improving, we look for other causes and specifically genetic mutation. By investigating 183 children with cerebral palsy and for many also one or both of their parents we find that for at least 14% of these we can find plausible explanation in genetic mutation being involved in the causation of their cerebral palsy. Importantly, we find that 10% of these mutations are de novo, which means that these mutations are not present in the parents (specifically in their blood as that is the tissue source we tested). 4% of mutations were inherited from unaffected mothers to affected sons. Previous estimates suggested 2% genetic contribution to Cerebral palsy. We now know that it is at least 14% and likely more. If you are looking for compensation for this condition, contact an Indiana cerebral palsy lawyer. (more…)
Author Interviews, Cost of Health Care / 13.02.2015

John Romley Ph.D Economist at the Leonard D. Schaeffer Center for Health Policy and Economics Research Assistant Professor Sol Price School of Public Policy University of Southern California, Los Angeles.MedicalResearch.com Interview with: John Romley Ph.D Economist at the Leonard D. Schaeffer Center for Health Policy and Economics Research Assistant Professor Sol Price School of Public Policy University of Southern California, Los Angeles. MedicalResearch: What is the background for this study? What are the main findings? Dr. Romley: The need for better value in US health care is widely recognized. Existing evidence suggests that improvement in the productivity of American hospitals—that is, the output that hospitals produce from inputs such as labor and capital—has lagged behind that of other industries. However, previous studies have not adequately addressed quality of care or severity of patient illness. Our study, by contrast, adjusts for trends in the severity of patients’ conditions and health outcomes. We studied productivity growth among US hospitals in treating Medicare patients with heart attack, heart failure, and pneumonia during 2002–11. We found that the rates of annual productivity growth were 0.78 percent for heart attack, 0.62 percent for heart failure, and 1.90 percent for pneumonia. (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, University of Pennsylvania / 13.02.2015

Ezekiel Jonathan Emanuel MD PhD Department of Medical Ethics and Health Policy Perelman School of Medicine and Department of Health Care Management The Wharton School University of Pennsylvania Philadelphia, PAMedicalResearch.com Interview with: Ezekiel Jonathan Emanuel MD PhD Department of Medical Ethics and Health Policy Perelman School of Medicine and Department of Health Care Management The Wharton School University of Pennsylvania Philadelphia, PA Editor’s note: Dr. Emanuel is a medical oncologist as well as director of the department of Medical Ethics and Health Policy at the University of Pennsylvania. Dr. Emanuel was kind enough to answer several questions regarding his most recent study, published in the new JAMA Oncology journal, Patient Demands and Requests for Cancer Tests and Treatments. Medical Research: What is the background for this study? What are the main findings? Dr. Emanuel: The genesis for this study is twofold. One, the first referenced article, by John Tilbert1 discussed how physicians explain US health care costs. In this study, physicians felt patients, insurance companies, drug companies, government regulations and malpractice lawyers...all were more to blame than doctors themselves for the high cost of US health care. Secondly, I give lots of presentations to doctors who offer two explanations for escalating health care costs: fear of malpractice litigation, and demanding patients, who request extensive testing and drugs. We decided to see whether the impression doctors frequently held of patients’ demands driving up health care costs, had been previously investigated. We could find no article to substantiate this belief. In addition, demanding patients were not common in my medical experience. In our study we included 5050 patient encounters. We asked the clinician coming out of the encounter, did the patient make a demand or request? (By asking immediately after the doctor left the examination room, there was little risk of inaccurate recall of the specifics of visit). In 8.7% there was a patient request and of these, over 70% were deemed clinically appropriate as determined by the physician (i.e. a request for pain medication, palliative care or imaging to address a new symptom or finding). In only 1% of all encounters (50/5050) was a clinically inappropriate request made as determined by the doctor, and the doctors hardly filled any of these inappropriate requests (total of 7 of 5050 encounters). We concluded that it is pretty rare for patients to make demands or requests, at least in this oncology setting, and even less common for the demands to be complied with by the doctor. Therefore it seems unlikely to us that health care costs are significantly driven by inappropriate patient requests. It is possible that there are more or different patient demands in other health care settings but we were very surprised to find no difference in patient requests based on patient-income, i.e. wealthier, more educated patients made no more demands than patients of lesser means. (more…)
Annals Internal Medicine, Author Interviews, Lung Cancer, NIH, Radiology / 13.02.2015

MedicalResearch.com Interview with: Paul F. Pinsky, PhD MPH Acting Chief Early Detection Research Group National Cancer Institute Bethesda, MD, 20892 Medical Research: What is the background for this study? What are the main findings? Response: The National Lung Screening Trial (NLST) reported, in 2011, a 20% reduction in lung cancer mortality with low-dose CT screening. However, there was a high false positive rate, around 25% in the first two screening rounds, and somewhat lower in the final round. In order to reduce the high false positive rate, and also to standardize the reported system for low-dose CT screening, analogous to the use of BIRADS for mammography screening, the American College of Radiology (ACR) developed the Lung-RADS classification system. It was released in May, 2014. Although it was developed based on published summary data from several studies, including the NLST, it was never applied to a large group of screened subjects on an individual basis. Therefore, we retrospectively applied Lung-RADS to previously collected, detailed screening data from the National Lung Screening Trial . The major findings were that the false positive rate decreased very substantially using Lung-RADS instead of the original National Lung Screening Trial criteria. At the baseline screen, it decreased by 50% and at subsequent screens it decreased by 75%. There was also, however, a modest decrease in the sensitivity rate, from 93% to 85% at baseline and from 93% to 79% at subsequent screens. (more…)
Author Interviews, JAMA, Mental Health Research, UCSF / 12.02.2015

Carol Mathews UCSF Professor, Psychiatry UCSF School of MedicineMedicalResearch.com Interview with: Carol Mathews Professor, Psychiatry UCSF School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Mathews: The background for this study is that, as a part of ongoing genetic studies of Tourette Syndrome, the Tourette Syndrome Association International Genetics Collaborative (TSAICG) has collected a wealth of information about commonly co-occurring psychiatric disorders in individuals with Tourette Syndrome and their families, providing us with an opportunity to explore questions about Tourette Syndrome that are relevant to individuals with Tourette Syndrome, their families, and their treating clinicians. (more…)
Author Interviews, Diabetes, Diabetologia, Race/Ethnic Diversity / 12.02.2015

Dr. Therese Tillin Research Fellow, Cardiometabolic Phenotyping Group Institute of Cardiovascular Science Faculty of Pop Health SciencesMedicalResearch.com Interview with: Dr. Therese Tillin Research Fellow, Cardiometabolic Phenotyping Group Institute of Cardiovascular Science Faculty of Pop Health Sciences Medical Research: What is the background for this study? What are the main findings? Dr. Tillin: The global burden of type 2 diabetes is rising rapidly and people of South Asian origins (from the Indian subcontinent)  remain at much higher risk of developing diabetes than people of European origin.  Why is this?  Although it is  thought that increased levels of obesity around the waist level, diet, physical activity levels and genetic factors contribute, no study to date has been able to tease out fully the underlying causes for the added risk in South Asian people.  However, it is likely that complex metabolic disturbances may play an important role. We have been studying a British cohort of people of European and South Asian origin for nearly 20 years and have used nuclear magnetic resonance spectroscopy to build a profile of amino acids in blood samples that were collected at the start of the study between 1988 and 1991.  We found that higher levels of some amino acids, in particular tyrosine, were already present in non-diabetic South Asian individuals back then.  Some of these amino acids, again especially tyrosine, more strongly predicted later development of type 2 diabetes in the South Asian people than in the Europeans in our study, even after adjustment for other risk factors such as obesity and insulin resistance. A given increase (one standard deviation) in tyrosine increased risk of developing diabetes by just 10% in Europeans, while in South Asians the increase in risk was 47%. (more…)
Author Interviews, Cancer Research, JAMA, MD Anderson, Outcomes & Safety / 12.02.2015

Kenneth L. Kehl, MD Division of Cancer Medicine, MD Anderson Cancer Center Houston, TexasMedicalResearch.com Interview with: Kenneth L. Kehl, MD Division of Cancer Medicine, MD Anderson Cancer Center Houston, Texas Medical Research: What is the background for this study? What are the main findings? Response: Prior studies have demonstrated that most patients with cancer wish to participate in their treatment decisions.  We studied a cohort of patients with lung or colorectal cancer and assessed whether patient involvement in decision-making was associated with perceived quality of care or ratings of physician communication.  We found that patients who described a more shared decision-making process gave higher ratings of their care quality and physician communication.  This effect was independent of patients' stated preferences regarding involvement in decision-making. (more…)
Author Interviews, JAMA, Mental Health Research / 12.02.2015

Elizabeth Walker, PhD, MPH, MAT FIRST Postdoctoral Fellow Center for Behavioral Health Policy Studies Rollins School of Public Health, Emory UniversityMedicalResearch.com Interview with: Elizabeth Walker, PhD, MPH, MAT FIRST Postdoctoral Fellow Center for Behavioral Health Policy Studies Rollins School of Public Health, Emory University   Medical Research: What is the background for this study? Response: Mental disorders are a major cause of disability globally and are associated with premature mortality.  Quantifying and understanding excess mortality among people with mental disorders can inform approaches for reducing this burden.  The purpose of this study was to systematically review the literature in order to estimate individual- and population-level mortality rates associated with mental disorders.  We conducted a comprehensive systematic review and meta-analysis, which included 203 studies from 29 countries. Medical Research: What are the main findings? Response: We estimated that 8 million deaths worldwide per year are attributable to mental disorders.  People with mental disorders have over 2 times the risk of mortality compared to the general population or people without mental disorders.  This translates to a median of 10 years of life lost.  In total, 67.3% of people with mental disorders died from natural causes, 17.5% from unnatural causes, and the remainder from unknown causes. (more…)
Author Interviews, NEJM, Stroke / 12.02.2015

MedicalResearch.com Interview with: Dr Bruce Campbell MBBS(Hons), BMedSc, PhD, FRACP Consultant Neurologist, Head of Hyperacute Stroke Department of Neurology     Royal Melbourne Hospital NHMRC Early Career Research Fellow Melbourne Brain Centre @ RMH Department of Medicine University of Melbourne Australia MedicalResearch: What is the background for this study? What are the main findings? Dr. Campbell: EXTEND-IA was a randomised trial comparing standard thrombolysis with tPA plus endovascular stent-thrombectomy versus tPA alone in ischemic stroke patients selected for the presence of major vessel occlusion and salvageable brain tissue using CT perfusion imaging. It was designed in 2011 at a time when there was uncertainty about the effectiveness of endovascular therapy which deepened in 2013 with the publication of 3 neutral trials. The recent publication of the Dutch MR-CLEAN study showing improved outcomes with stent-thrombectomy was a major advance and prompted a data safety and monitoring committee review of the EXTEND-IA data leading to early termination of the trial for efficacy.
The key findings from EXTEND-IA were that the addition of stent-thrombectomy to tPA led to a dramatic increase in restoration of blood flow to the brain from 34% to 89%. This translated to markedly improved outcomes at 3 months with 71% of stent-thrombectomy patients compared with 40% of tPA-only patients regaining independence. The 3 trials released today were remarkably consistent in their outcomes and this provides a solid evidence base to recommend stent-thrombectomy as the new standard of care for patients with large vessel ischemic stroke.
Patients who were treated with stent-thrombectomy in EXTEND-IA had more than double the rate of reperfusion (restoration of blood flow to the brain) compared to the standard tPA patients and this translated to a 31% absolute increase in the proportion of patients living independently at 3 months. (more…)
Author Interviews, Cancer Research, Critical Care - Intensive Care - ICUs, Infections / 12.02.2015

Dr. Cornejo-Juárez Department of Infectious Disease, Instituto Nacional de Cancerología Tlalpan MexicoMedicalResearch.com Interview with: Dr. Cornejo-Juárez Department of Infectious Disease, Instituto Nacional de Cancerología Tlalpan Mexico MedicalResearch: What is the background for this study? Dr. Cornejo: Critically ill patients in the intensive care unit are at major risk of hospital-acquired infections. Immunosuppressed patients have a higher risk related with continuous exposure to the hospital setting, mucositis and disruption of skin integrity, presence of indwelling catheters and abnormal immune system because of primary malignancy or chemotherapy. Our aimed was to investigate prevalence and outcome of hospital-acquired infections in an oncology ICU. MedicalResearch: What are the main findings? Dr. Cornejo: We found that hospital-acquired infections are a major problem in the ICU. Hospital-acquired infections are related with higher mortality. Multidrug resistant bacteria are frequently involved in these infections, and are associated with increased mortality. (more…)
Author Interviews, Heart Disease, JCEM, Pediatrics, Vitamin D / 12.02.2015

MedicalResearch.com Interview with: Markus Juonala, MD, PhD University of Turku Finland Medical Research: What is the background for this study? What are the main findings? Response: Earlier studies suggest that low vitamin D levels may be associated with cardiovascular disease. We wanted to study whether low childhood vitamin levels predict carotid intima-media thickness, a marker of early atherosclerosis, in adulthood. We observed that those children with vitamin D in lowest quartile had increased risk for high carotid intima-media thickness. (more…)
Accidents & Violence, Author Interviews, BMJ, Pediatrics / 11.02.2015

MedicalResearch.com Interview with: Joke Kieboom, paediatric intensivist Beatrix Children’s Hospital Medical Center Groningen University of Groningen The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: The aim of the study was to evaluate the outcome of drowned children with cardiac arrest and hypothermia, and to determine distinct criteria for termination of cardiopulmonary resuscitation in drowned children with hypothermia and absence of spontaneous circulation. From 1993 to 2012 in the Netherlands, 160 children presented with cardiac arrest and hypothermia after drowning. In 98 (61%) of these children resuscitation was performed for more than 30 minutes, of whom none had good outcome: 87 (89%) died and 11 (11%) survived for with severe disability or in a vegetative state (at one year after the drowning incident). (more…)
Author Interviews, Genetic Research, Leukemia, NEJM, Personalized Medicine / 11.02.2015

David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of CambridgeMedicalResearch.com Interview with: David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of Cambridge Medical Research: What is the background for this study? What are the main findings? Dr. Kent: Cancers are the result of the sequential acquisition of errors in the genetic code.  Most studies have focused on the sum of these mutations (e.g., A+B+C = cancer) but no study in patients has asked the question of whether or not the order of genetic mutations impacts the disease (e.g., does A to AB equal B to BA).  We studied patients with chronic blood disorders (known as myeloproliferative neoplasms, or MPNs) that are precursors to cancer to access the earliest stages of tumour development and studied whether or not the order of mutation acquisition impacted disease.  We studied patients with mutations in two genes (JAK2 and TET2) and showed that the order of acquisition of these mutations impacted timing of clinical presentation, disease subtype, frequency of thrombotic events, and differed in their response to targeted therapy in the lab. (more…)
Author Interviews, Cancer Research, NEJM, Thyroid / 11.02.2015

Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, FranceMedicalResearch.com Interview with: Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, France   Medical Research: What is the background for this study? What are the main findings? Dr. Schlumberger: Patients with advanced refractory thyroid cancer is rare (4-5 patients/million population) but portends a poor prognosis with a median overall survival of 3-5 years from the diagnosis of metastases. Before the availability of kinase inhibitors there was no effective treatment, and for this reason placebo was used as control in SELECT trial. This trial showed an improvement of PFS lenvatinib vs placebo (hazard ratio: 0.21; 99% CI: 0.14–0.31, P<0.001; median PFS: 18.3 vs 3.6 months, respectively) and objective response rate of 65% with some complete responses. Time to response was short (2 months). Similar benefits were observed in naive patients and in patients who had been treated with another tyrosine kinase inhibitor, demonstrating the absence of cross resistance. Toxicity was significant and could be controlled with dose reduction and symptomatic treatment. Medical Research: What should clinicians and patients take away from your report? (more…)
Author Interviews, Dermatology, JAMA / 11.02.2015

Omar A. Ibrahimi, M.D., Ph.D Connecticut Skin Institute Founding Medical Director Stamford, CT 06905MedicalResearch.com Interview with: Omar A. Ibrahimi, M.D., Ph.D Connecticut Skin Institute Founding Medical Director Stamford, CT 06905 www.ctskindoc.com Medical Research: What is the background for this study? What are the main findings? Dr. Ibrahimi: The delivery of healthcare in a efficient and cost effective fashion is one of the largest themes in medicine today. Malpractice lawsuits have steadily increased with the cost of healthcare delivery. Mohs surgery involves the surgical removal, the tissue analysis and the reconstruction of a skin cancer all in a single visit that bundles multiple procedures in a cost effective manner that is proposed to be the gold standard for treating certain skin cancers. Information regarding malpractice involving Mohs surgery is lacking. The only previous study that has been done was a survey of Mohs surgeons looking at how many had been involved in lawsuits and the reasons for being involved. Our study examined a legal database to identify all the lawsuits involving Mohs surgery and skin cancer. We were surprised to find that the majority of lawsuits involved non-Mohs surgeons as the primary defendant, mostly due to a delay of or failure in diagnosis, cosmetic outcome issues, lack of informed consent, and a delay of or failure in referral to a Mohs surgeon. (more…)
Author Interviews, BMJ / 11.02.2015

Christopher Michael Petrilli MD Division of General Internal Medicine The Department of Medicine University of Michigan, Ann Arbor, MichiganMedicalResearch.com Interview with: Christopher Michael Petrilli MD Division of General Internal Medicine The Department of Medicine University of Michigan, Ann Arbor, Michigan   Medical Research: What is the background for this study? What are the main findings? Dr. Petrilli: Our team took note of the broad spectrum of physician attire that was worn in health care settings. We found a lack of specific guidance with regards to “appropriate” physician attire. Then we began to find anecdotal evidence that physician attire may be an important early determinant of patient confidence, trust and satisfaction. Studies have shown that patients are more compliant with their medications and treatment regimens when they perceive their doctors as being competent, supportive and respectful. Therefore, given the increasingly rushed patient–physician encounter, the ability to gain a patient’s trust and confidence are highly desirable. We hypothesized that if physician attire matched patients’ preferences and expectations, it would improve the overall patient experience. Our findings supported our hypothesis. In general, we found that people prefer their physicians dress on the formal side -- and definitely not in casual wear. Doctors of either gender in suits, or a white coat, are more likely to inspire trust and confidence. But fashion takes a back seat when it comes to emergency, surgical or critical care, where data show clothes don't matter as much -- and patients may even prefer to see doctors in scrubs. In general, Europeans and Asians of any age, and Americans over age 50, trusted a formally dressed doctor more, while Americans in Generation X and Y tended to accept less-dressy physicians more willingly. (more…)
Author Interviews, Breast Cancer / 11.02.2015

Alejandra Valenzuela-IglesiasMedicalResearch.com Interview with: Alejandra Valenzuela-Iglesias Ph.D. candidate Department of Molecular Biology University of Sonora Hermosillo, Sonora MedicalResearch: What is the background for this study? What are the main findings? Response: Breast cancer is one of the leading causes of cancer death in women all around the world. In recent years, there has been great interest in creating new therapies that will help to prevent or stop metastasis, but the therapies developed up until today are not completely effective. Metastasis is the main cause of death for a cancer patient because it implies that tumor cells have detached from the primary tumor and have colonized in one or more vital organs or tissues in the organism. For this to occur, the invasive tumor cells form actin-driven membrane protrusions called invadopodia. These protrusions possess proteolytic activity to degrade the basal membrane and extracellular matrix, which facilitates metastatic cancer cells to enter the bloodstream and spread to distant organs in the body. It has been shown that any dysregulation in the actin cytoskeleton leads to impaired invadopodia formation. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas. Our study was a collaboration between Albert Einstein College of Medicine, University of Pittsburgh, and University of Sonora, lead by Dr. Jose Javier Bravo-Cordero and published in the European Journal of Cell Biology. We showed for the first time the role of profilin1 in invadopodia formation and function in human breast cancer cells MDA-MB-231. By using cell imaging techniques we unveiled the dynamic of the profilin1-depleted cells, finding that profilin1 can act as a negative regulator of breast cancer cell invasion, acting as a break in invadopodia turnover, by modulating the molecules involved in invadopodia maturation. The removal of profilin1 expression accelerates invadopodia maturation rate, explaining the invasive phenotype previously reported for this type of cells. (more…)
Author Interviews, BMJ, Heart Disease, Nutrition / 11.02.2015

James J. DiNicolantonio, PharmD Associate Editor BMJ Open Heart Cardiovascular Research Scientist Saint Luke's Mid America Heart InstituteMedicalResearch.com Interview with: James J. DiNicolantonio, PharmD Associate Editor BMJ Open Heart Cardiovascular Research Scientist Saint Luke's Mid America Heart Institute   Medical Research: What is the background for this study? What are the main findings Response: There were 6 randomized controlled dietary trials performed before the government dietary fat recommendations were released.  When we performed a systematic review and meta-analysis of the available trials at this time, there was no significant difference in all-cause mortality or cardiovascular heart disease mortality.  In essence, there was no support from randomized controlled trials at the time to support a reduction in fat and saturated fat (and there still isn't from recent meta-analysis including newer trials). The reductions in mean serum cholesterol levels were significantly higher in the intervention groups but this did not result in significant differences in cardiovascular heart disease or all-cause mortality. (more…)
Author Interviews, Cancer Research / 11.02.2015

MedicalResearch.com Interview with: Dr. Dixie-Lee Esseltine MD, FRCPC Vice President, Oncology Clinical Research Takeda. MedicalResearch: What is Ixazomib? Dr. Dixie-Lee Esseltine: Ixazomib is an investigational, oral, once-weekly proteasome inhibitor (PI) that is being investigated in multiple Phase 3 trials in multiple myeloma (MM) and systemic light-chain (AL) amyloidosis. It is the first oral  proteasome inhibitor to enter Phase 3 clinical trials. Proteasome inhibition is a mechanism underpinning an established standard of care in the treatment of multiple myeloma. However, the current biweekly parenteral administration of proteasome inhibitors may pose challenges to patients. The ability to demonstrate that an oral, once-weekly PI can extend PFS would be a remarkably important finding in the effort to address these challenges. Early studies suggest ixazomib, has activity in MM patients, both as a single agent in relapsed patients and in combination in frontline patients. Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. It was granted Breakthrough Therapy Designation for AL amyloidosis in the U.S. in 2014. MedicalResearch: What is the design for this study? Dr. Dixie-Lee Esseltine: The TOURMALINE MM-1 study (C16010) is a phase 3, randomized, double-blind study comparing ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Patients were randomized to receive ixazomib 4.0mg days 1,8 and 15 or placebo with  lenalidomide 25mg days 1-21 and dexamethasone 40mg days 1,8,15 and 22. Treatment was given every 28 days until disease progression or unacceptable toxicity. Evaluation was based on the International Myeloma Working Group (IMWG) Uniform Response Criteria. (more…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease / 10.02.2015

MedicalResearch.com Interview with: Wolfgang Sadee, Dr.rer.nat. Felts Mercer Professor of Medicine and Chair, Pharmacology Director and Elizabeth S Barrie, PhD Center for Pharmacogenomics The Ohio State University Columbus OH MedicalResearch: What is the background for this study? What are the main findings? Dr. Sadee and Dr. Barrie: We have determined that two frequent genetic variants can interact in a way that lowers the carrier’s risk for a heart attack. These genetic variants are single nucleotide polymorphisms (SNPs) - single base changes in the DNA sequence - of the dopamine-beta hydroxylase gene (DBH), which converts dopamine to norepinephrine. Both act as hormones in the periphery and as neurotransmitters vital to the brain's activity central nervous system. Numerous studies had tested genetic variants in DBH for effects on brain functions. In contrast to expectations, however, our work demonstrates that our two genetic variants lower DBH activity primarily in the periphery, in tissues with sympathetic innervation mediated by norepinephrine, such as the heart, lung, and liver.  As a result, we searched for genetic influence on risk of various diseases of the cardiovascular system and the lung, metabolic disorders, and more.   Each of the two DBH variants alone was associated with a number of disease states; however, when considering both variants in combination, a strong protective effect on the risk for heart attacks was discovered in several clinical trials. Such combined effects arising from interactions between two genetic variants may be more common than currently realized, possibly providing a path towards effective biomarker panels for personalized medicine. (more…)
Author Interviews, Baylor College of Medicine Houston, Breast Cancer / 10.02.2015

Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, TexasMedicalResearch.com Interview with: Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, Texas   Medical Research: What is the background for this study? What are the main findings? Response: Bone metastases present a major clinical problem for oncologists. They are very painful and unpleasant due to the ability of metastatic cells to dissolve bones, and if they spread to the spine or vertebrate bone they  the spinal cord compression could cause paralysis. There is a gap in our knowledge about bone metastasis in breast cancer. We know a lot about when they are fully established and already dissolving the bone, but little about what happens early on, right after the cancer cells get there but before they start the bone-dissolving process. In the study, we revealed that in the early stages, when there are only a few cancer cells, these cells tend to locate themselves in a microenvironment that is enriched in bone making cells called osteoblasts whose normal job is to help make new bones. The cancer cells appear to be surrounded by these bone-making cells before they acquire the ability to dissolve bones. We also uncovered the pathway that gets activated when the cancer cells lodge into the bone-making cells, and helps them progress to more malignant metastases. The action is mediated by a class of proteins that helps bind the cancer cells to the bone tissue called heterotypic adherens junctions (hAJs) involving the adherens proteins E-cadherin (cancer-derived) and N-cadherin (bone-promoting). This then activates the mTOR pathway in cancer cells, which drives the progression from single cells to metastases. (more…)
Author Interviews, CDC, Vaccine Studies / 10.02.2015

MedicalResearch.com Interview with: Tom Shimabukuro, MD, MPH, MBA Captain, U.S. Public Health Service Deputy Director Immunization Safety Office Centers for Disease Control and Prevention (CDC) Medical Research: What is the background for this study? What are the main findings? Response: CDC conducted a study looking at reports of adverse events (possible side effects) following measles, mumps, and rubella (MMR) vaccination in adults. Researchers reviewed the Vaccine Adverse Event Reporting System (VAERS) database for U.S. reports of adults aged 19 years and older who received MMR vaccine from January 1, 2003 to July 31, 2013. During this period, VAERS received 3,175 U.S. reports after MMR vaccine in adults. The most common signs and symptoms for all reports were fever (19%), rash (17%), pain (13%), and joint pain (13%). The study included adults only, a population for which there is limited safety data for this vaccine. This study further supports the MMR vaccine’s safety.  Researchers did not find any new or unexpected safety concerns. (more…)
Author Interviews, Exercise - Fitness, Gender Differences, Primary Care / 10.02.2015

Molly B. Conroy MD, MPH Assistant Professor of Medicine, Epidemiology, and Clinical and Translational Science University of Pittsburgh, Pittsburgh, PA,MedicalResearch.com Interview with: Molly B. Conroy MD, MPH Assistant Professor of Medicine, Epidemiology, and Clinical and Translational Science University of Pittsburgh, Pittsburgh, PA, Medical Research: What is the background for this study? What are the main findings? Response: The background for the study is the fact that middle-aged women are at high risk for being physically inactive, which puts them at higher risk for heart disease, cancer, and other chronic health problems. We compared an interventionist-led physical activity and weight loss program delivered in coordination with primary care to a booklet that women were asked to use to exercise by themselves at home. We found that women who received the interventionist-led program had significantly greater increases in physical activity at 3 months, compared to women who received booklet. At 12 months, women who received the interventionist-led program were still more active than they were before starting the program, although the difference between the 2 groups was no longer significant. (more…)
Author Interviews, Blood Pressure - Hypertension, Diabetes, JAMA / 10.02.2015

Prof. KAZEM RAHIMI | DM MSc FESC Associate Professor of Cardiovascular Medicine, University of Oxford Deputy Director, The George Institute for Global Health James Martin Fellow in Healthcare Innovation, Oxford Martin School Honorary Consultant Cardiologist, Oxford University Hospitals NHS Trust The George Institute for Global Health Oxford Martin School | University of Oxford Oxford United KingdomMedicalResearch.com Interview with: Prof. Kazem Rahimi  DM MSc FESC Associate Professor of Cardiovascular Medicine, University of Oxford ;Deputy Director, The George Institute for Global Health; James Martin Fellow in Healthcare Innovation, Oxford Martin School; Honorary Consultant Cardiologist, Oxford University Hospitals NHS Trust The George Institute for Global Health Oxford Martin School United Kingdom Medical Research: What is the background for this study? What are the main findings? Dr. Rahimi: Lowering blood pressure (BP) in individuals with diabetes is an area of current controversy. Although it is widely accepted that lowering blood pressure in people with diabetes and elevated blood pressure will reduce the risk of heart and circulatory problems, it is less certain whether diabetics whose blood pressure is not very high should be treated with blood pressure lowering drugs, and how far their blood pressure should be reduced. It is also less well known how blood pressure lowering affects a range of other potential health complications for diabetes patients, such as diabetic eye disease. We found that each 10-mm Hg lower systolic blood pressure led to a lower risk of mortality, cardiovascular disease events, coronary heart disease events, stroke, albuminuria (the presence of excessive protein in the urine), and retinopathy (loss of vision related to diabetes). Although proportional effects of blood pressure lowering treatment for most outcomes studied were diminished below a systolic BP level of 140 mm Hg, data indicated that further reduction below 140 mm Hg led to a lower risk of stroke, retinopathy, and albuminuria, potentially leading to net benefits for many individuals at high risk for those outcomes. (more…)
Author Interviews, MD Anderson / 10.02.2015

Dihua Yu, M.D., Ph.D. Hubert L. & Olive Stringer Distinguished Chair in Basic Science Professor and Deputy Chair Department of Molecular and Cellular Oncology Co-Director, Center of Biological Pathways The Univ. Texas MD Anderson Cancer Center Houston, TX 77030MedicalResearch.com Interview with: Dihua Yu, M.D., Ph.D. Hubert L. & Olive Stringer Distinguished Chair in Basic Science Professor and Deputy Chair Department of Molecular and Cellular Oncology Co-Director, Center of Biological Pathways The Univ. Texas MD Anderson Cancer Center Houston, TX 77030 Medical Research: What is the background for this study? Dr. Yu: Transforming growth factor β (TGF-β) functions as a tumor suppressor in premalignant cells but may also function as a metastasis promoter in cancer cells. This study aimed to understand how the growth factor makes this switch between tumor suppressor to tumor promoter. Medical Research: What are the main findings? Dr. Yu: We reported that 14-3-3ζ overexpression (14-3-3ζ+++) can switch TGF-β’s function from tumor suppressor to metastasis promoter by changing Smad partners. Specifically, 14-3-3ζ+++ led to destabilization of p53, a Smad determinant in pre-malignant cells, thus disrupting p53/Smad complex, and consequently inhibiting TGF-β-induced p21 expression and cytostatic function in non-malignant human mammary epithelial cells (HMECs). On the contrary, 14-3-3ζ+++ stabilized Gli2, a Smad partner in cancer cells, and Gli2 complexed with Smads to promote TGF-β-induced parathyroid hormone-related protein (PTHrP) expression, which enhanced breast cancer bone metastasis. Remarkably, both transcriptomic analyses and clinical pathology data indicated that 14-3-3ζ+++ is associated with the loss of TGF-β’s tumor suppressor function and the gain of its metastasis promoter function by changing contextual partners of Smads. Taken together, we have identified 14-3-3ζ as a novel molecular switch of TGF-β’s function by altering Smad partners from p53 in pre-malignant cells to Gli2 in cancer cells. The study provided important answers to the long-standing questions of how and when TGF-β switches its functional roles from a tumor suppressor to a metastasis promoter. The findings established a scientific base for a new strategy of selectively targeting TGF-β signaling in cancer by inhibiting the cancer-specific Smad partner without blocking TGF-β’s tumor suppressor function in normal tissues. (more…)
Author Interviews, Mental Health Research, Occupational Health / 10.02.2015

Prof.dr. Judith K. Sluiter Principal Investigator Manager KMKA: Kenniscentrum Medische Keuringen in Arbeid Nationaal secretaris voor ICOH (International Commission on Occupational Health) Coronel Instituut voor Arbeid en Gezondheid, Academisch Medisch Centrum / UvA Meibergdreef AmsterdamMedicalResearch.com Interview with: Prof.dr. Judith K. Sluiter Principal Investigator Manager KMKA: Kenniscentrum Medische Keuringen in Arbeid Nationaal secretaris voor ICOH (International Commission on Occupational Health) Coronel Instituut voor Arbeid en Gezondheid, Academisch Medisch Centrum / UvA Meibergdreef Amsterdam Medical Research: What is the background for this study? Prof. Sluiter: Professional footballers contain a group of employees working in a job with specific job demands. The occupational guidance and prevention of decreased work functioning of workers in these kinds of jobs should receive more attention. The mental health of professional footballers receive less attention compared to their physical health. We studied the prevalence of self-reported mental health problems and psychosocial difficulties in a group of current and former professional footballers, and we explored the association between having had psychosocial stressors and the health conditions under study. Medical Research: What are the main findings? Response: The response rate was 29% with available data from 253 footballers. In current players, the prevalence of mental health complaints ranged from 5% (burnout) to 26% (anxiety/depression). In former players, the prevalence ranged from 16% (burnout) to 39% (anxiety/depression). A small percentage of players had low self-esteem (3-5%). One quarter to two-fifth of the players showed adverse nutrition behaviour. Small but significant association between experiencing lower social support (OR=1.1) and having had recent life events (OR=1.4-1.6) and mental health complaints were found in current players. Having had severe injuries was associated with better nutrition behavior. In former players, having had life events showed a preventive effect on smoking (OR=0.4) and having had previous surgery was significantly associated with current smoking behavior (OR=1.9). (more…)