Author Interviews, FDA, JAMA / 27.07.2015

Dr. Pinar Karaca-Mandic Ph.D Associate Professor, Health Policy & Management School of Public Health Division of Health Policy & Management Minneapolis MN University of MinnesotaMedicalResearch.com Interview with: Dr. Pinar Karaca-Mandic Ph.D Associate Professor, Health Policy & Management School of Public Health Division of Health Policy & Management Minneapolis MN University of Minnesota Medical Research: What is the background for this study? What are the main findings? Dr. Karaca-Mandic: Drug safety has received a lot of attention recently, and FDA's post-marketing drug surveillance program (FAERS) offers and important opportunity to monitor drug safety and update drug warnings. There has been an increasing trend in reports to FAERS of serious adverse drug events and earlier studies suggested that these trends were primarily driven by increased manufacturer reports of serious and unexpected adverse events. While these studies highlighted the overall increase in adverse event rates, manufacturer timeliness in reporting and compliance with the 15 calendar day regulation for expedited reports was unknown, though some recent media coverage has offered anecdotal examples of delay. My co-authors and I were interested in studying not only the reporting of these events, by manufacturers to FDA, but also their timely reporting as required by the Federal regulation. Delays in reporting can have important public health consequences because the FDA uses this information to update drug warnings. We found that about 10% of serious and unexpected adverse events that are subject to the 15-day regulation were not reported by 15 days. We also found that events that involved a patient death were more likely to be delayed. For example, we found that after adjusting for other characteristics of the report and the patient, about 12% of events that involved patient death, and 9% of those that did not involve patient death were delayed beyond 15 days.
Author Interviews, JACC, Radiology, Stanford / 27.07.2015

MedicalResearch.com Interview with: Patricia Kim Phuong Nguyen MD and Joseph C. Wu, MD, PhD Stanford Cardiovascular Institute Stanford University School of Medicine, Stanford, California Medical Research: What is the background for this study? What are the main findings? Response: The application of CT imaging has greatly increased in the last two decades, raising concern over the effects of low dose radiation exposure from medical imaging. In this study, we recruited 67 patients who underwent CT imaging for various cardiovascular indications including: 1) Pre atrial fibrillation ablation 2) Pre Trans-catheter valve replacement 3) Aortic dissection, and 4) coronary artery disease. A wide range of doses were sampled. We detected damage to DNA and a small percentage of death of T lymphocytes isolated from patients  who were exposed to greater than 7.5 mSv of radiation. No damage was detected in patients exposed to very low doses (less than or equal 7.5 mSv). This study did not look at the relationship between radiation and cancer.
Author Interviews, JAMA, NYU/NYMC, PTSD / 24.07.2015

Charles R. Marmar, MD The Lucius Littauer Professor and Chair, Department of Psychiatry, NYU Langone Medical Center and Director of the Steven and Alexandra Cohen Veterans Center at NYU LangonMedicalResearch.com Interview with: Charles R. Marmar, MD The Lucius Littauer Professor and Chair, Department of Psychiatry, NYU Langone Medical Center and Director of the Steven and Alexandra Cohen Veterans Center at NYU Langone MedicalResearch: What is the background for this study? What are the main findings? Dr. Marmar: Approximately 2.7 million men and women served in Vietnam, and, for those who returned, many have suffered for decades from a variety of psychological problems resulting from their experiences and other injuries such as traumatic brain injury (TBI). The 25-year National Vietnam Veterans Longitudinal Study (NVVLS) was a way we could determine at various points in time how veterans were faring emotionally four decades after their service. While the vast majority are resilient, there are still over 270,000 Vietnam veterans who still have some form of post-traumatic stress disorder (PTSD) and one-third of these veterans have depression. We followed up with veterans who participated in the National Vietnam Veterans Readjustment Study (NVVRS) from 1984 to 1988 who were evaluated for PTSD. The NVVRS group represented a probability sample of those who served in Vietnam. Of the 1,839 participants still alive, 1,409 participated in at least one phase of the NVVLS, which involved a health questionnaire, health interview and clinical interview. The results showed that between 4.5 percent and 11.2 percent of male Vietnam veterans and 6.1 and 8.7 percent of the female veterans are currently experiencing some level of PTSD. About 16 percent of veterans in the study reported an increase of more than 20 points on a PTSD symptom scale compared to 7.6 percent who reported a decrease of greater than 20 points.
Author Interviews, Cancer Research, Genetic Research, MD Anderson / 24.07.2015

Eduardo Vilar-Sanchez, MD, PhD Assistant Professor, Department of Clinical Cancer Prevention Division of OVP, Cancer Prevention and Population Science The University of Texas MD Anderson Cancer Center Houston, TX 77030MedicalResearch.com Interview with: Eduardo Vilar-Sanchez, MD, PhD Assistant Professor, Department of Clinical Cancer Prevention Division of OVP, Cancer Prevention and Population Science The University of Texas MD Anderson Cancer Center Houston, TX 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Vilar-Sanchez: I am a physician scientist at The University of Texas MD Anderson Cancer Center (MDA), a medical oncologist specializing in cancer genetics, especially colorectal cancer (CRC) syndromes. At MD Anderson, I have medical practice consisting primarily of colorectal cancer, as part of the clinical cancer arm of MD Anderson. I became interested in this topic because it is now well recognized that colorectal cancer is increasing in prevalence in young individuals. CRC is the third most common cancer in the US with 90% diagnosed in patients older than 50. While most CRC patients develop cancer in their 60s or 70s, the incidence is now rising in individuals younger than 50. Over the next two decades, it is projected that the incidence of CRC in young adults under 35 will double. Only 5% of all CRC patients have a known hereditary predisposition cancer syndrome. Patients diagnosed at or under age 35 represent an extreme phenotypic presentation, constituting only 1.5% of all CRC cases. We retrospectively reviewed all patients with CRC patients age 35 or under, who were evaluated by the Genetic Services group at MD Anderson. In this group, a surprising 30% had a recognized hereditary cancer syndrome, a marked increase compared to the general CRC population.
Author Interviews, Cancer Research, NIH / 24.07.2015

Dr. Pam Marcus PhD Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute National Institutes of Health Bethesda, MD 20892MedicalResearch.com Interview with: Dr. Pam Marcus PhD Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute National Institutes of Health Bethesda, MD 20892 MedicalResearch: Why do we need to consider targeted cancer screening? Dr. Marcus: Cancer screening, the routine testing of asymptomatic individuals without a history of the disease of interest, is an important approach to cancer prevention and control. There is compelling evidence that screening for at least four cancers reduces disease-specific mortality, but population-based cancer screening also leads to unfavorable events. Only a minority of those screened will benefit, and many will have false-positive exams. Some screenees will experience undesirable sequelae, ranging from minor inconveniences to serious adverse events due to the exam itself or diagnostic evaluation. MedicalResearch: What is the goal of targeted cancer screening in average-risk individuals? Dr. Marcus: Targeted cancer screening attempts to segregate those who will benefit from screening from those who will not through use of information on disease risk. Average risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without co-morbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. The goal of targeted cancer screening in average risk individuals is to reduce the number of individuals who need to be screened while preserving the overarching benefit of reduced cancer-specific mortality in the general population. Targeted cancer screening is an example of precision medicine; visit http://www.nih.gov/precisionmedicine/goals.htm to learn more about the National Institute of Health’s Precision Initiative.
Author Interviews, Breast Cancer, Journal Clinical Oncology, NIH / 24.07.2015

Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780MedicalResearch.com Interview with: Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780 Medical Research: What is the background for this study? Dr. Gail: In the United States, breast cancer survival following diagnosis has been improving since the 1970s. We wanted to understand what might explain these shifts, to fully characterize the changes over time, and to explore whether tumor size and estrogen receptor status could help explain the  trends in age- and stage-specific breast cancer death rates after diagnosis. We evaluated survival from breast cancer from the date of diagnosis of all women diagnosed with invasive breast cancer in the US SEER Cancer Registries between 1973 and 2010. We excluded women with ductal or lobular carcinoma in situ.  We analyzed separate age groups (<50, 50-69, 70+ years) and SEER stage of disease (local, regional, distant). Medical Research: What are the main findings? Dr. Gail: Between 1973 and 2010, breast cancer death rates after diagnosis in the United States have fallen for each age group of women diagnosed with local or regional stage disease, not only in the first five years after diagnosis, but also thereafter.  For women under age 70, rates also fell for women with distant disease. Changes in tumor size or estrogen-receptor status do not explain much of the improvement among women under age 70 years, but do explain roughly half the improvement in 70+ year old women in the first five years after diagnosis.
Author Interviews, Heart Disease, JCEM, University of Pittsburgh, Women's Heart Health / 24.07.2015

Samar R. El Khoudary, Ph.D., M.P.H. Assistant professor Graduate School of Public Health Department of Epidemiology University of Pittsburgh MedicalResearch.com Interview with: Samar R. El Khoudary, Ph.D., M.P.H. Assistant professor Graduate School of Public Health Department of Epidemiology University of Pittsburgh Medical Research: What is the background for this study? Dr. El Khoudary: Cardiovascular disease is the leading cause of death in women, and it increases after age 50 - the average age when a woman is going through menopause. Weight gain in women during and after menopause has long been attributed to aging, rather than menopause itself. However, recent research identified changes in body fat composition and distribution due to menopause-related hormonal fluctuations. No previous study had evaluated whether those changes in fat distribution during menopause affect cardiovascular fat. Increased and excess fat around the heart and vasculature can be more detrimental than abdominal fat, causing local inflammation and leading to heart disease. Doubling certain types of cardiovascular fat can lead to a more than 50 percent increase in coronary events. My team and I investigated whether there may be a link between menopause and cardiovascular fat using data from 456 women from Pittsburgh and Chicago enrolled in the Study of Women's Health Across the Nation (SWAN). The women averaged about 51 years of age and were not on hormone replacement therapy. Medical Research: What are the main findings? Dr. El Khoudary: Our study is the first to find that  late- and post-menopausal women have significantly greater volumes of fat around their hearts than their pre-menopausal counterparts. As concentrations of the sex hormone estradiol - the most potent estrogen - declined during menopause, greater volumes of cardiovascular fat were found. The finding held even after my colleagues and I took into account the effects of age, race, obesity, physical activity, smoking, alcohol consumption, medication use and chronic diseases.
Author Interviews, Brain Injury, JAMA, Outcomes & Safety, UCLA / 23.07.2015

Aaron J. Dawes, MD Fellow, VA/RWJF Clinical Scholars Program Division of Health Services Research, University of California Los Angeles Los Angeles, CA 90024MedicalResearch.com Interview with: Aaron J. Dawes, MD Fellow, VA/RWJF Clinical Scholars Program Division of Health Services Research, University of California Los Angeles Los Angeles, CA 90024 Medical Research: What is the background for this study? What are the main findings? Dr. Dawes: In the fall of 2013, we formed the Los Angeles County Trauma Consortium, building upon a prior administrative relationship between LA County’s 14 trauma centers. We added health research researchers from UCLA and USC, and shifted the focus of the group from logistical issues to quality improvement. As a first project, our hospitals wanted to know if there was any variation in how traumatic brain injury patients are cared for across the county. Traumatic brain injury accounts for over 1/3 of all injury-related deaths in the U.S. and is the number one reason for ambulance transport to a trauma center in LA County. When we looked at the data, we found widespread variation in both how these patients were cared for at different hospitals and what happened to them as a result of that care. After adjusting for important differences in patient mix, we found that mortality rates varied by hospital from roughly 25% to 55%. As we tried to explain this variation, we looked into how often hospitals complied with two evidence-based guidelines from the Brain Trauma Foundation, hoping that we could eventually develop an intervention to boost compliance with these recommended care practices. While compliance rates varied even more widely than mortality—from 10 to 65% for intracranial pressure monitoring and 7 to 76% for craniotomy—they did not appear to be associated with risk-adjusted mortality rates. Put simply, we found no connection between how often hospitals complied with the guidelines and how likely their patients were to survive.
Author Interviews, Brigham & Women's - Harvard, Diabetes, Nutrition, Pediatrics / 22.07.2015

Prof. Lu Qi, Assistant Professor, Department of Nutrition Harvard School of Public Health and Channing Division of Network Medicine Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MAMedicalResearch.com Interview with: Lu Qi, MD, PhD, FAHA Associate Professor of Medicine Harvard Medical School Assistant Professor of Nutrition HarvardSchool of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Lu Qi:  Most previous studies focus on the effects of either lifestyle or prenatal malnutrition on diabetes risk; no study has assess these two types of risk factors in combination.
Author Interviews, Duke, Education, Heart Disease, JAMA / 22.07.2015

Carolina Malta Hansen, M.D Duke Clinical Research InstituteMedicalResearch.com Interview with: Carolina Malta Hansen, M.D Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Hansen: Approximately 300,000 persons in the United States suffer an out-of-hospital cardiac arrest every year and under 10% survive. Cardiopulmonary resuscitation (CPR) and defibrillation within the first few minutes of cardiac arrest can increase the chance of survival from under 10% to over 50%. In 2010, the HeartRescue program in North Carolina initiated statewide multifaceted interventions to improve care and outcomes for cardiac arrest patients in North Carolina. The project included public training programs in defibrillators and compression-only CPR at schools, hospitals and major events such as the N.C. State Fair, plus additional instruction for EMS and other emergency workers on optimal care for patients in cardiac arrest. We found that following these four years of initiatives to improve care and outcomes for cardiac arrest patients, the proportion of patients who received bystander CPR and first responder defibrillation increased by more than 25% to approximately 50%, the combination of bystander CPR and first responder defibrillation increased from 14% to 23%. Survival with favorable neurologic outcome increased from 7% to 10% and this increase was only observed among patients who received bystander CPR. Finally, we found that compared to patients who received CPR and defibrillation by emergency medical services (EMS), patients who received bystander and/or first responder CPR, defibrillation, or both, were more likely to survive. The combination of bystander CPR and bystander defibrillation was associated with the best survival rates but remained low during the study period with no increase over time.
Alzheimer's - Dementia, Author Interviews, NYU/NYMC / 21.07.2015

Fernando Goni, PhD MS Adjunct associate professor Department of Neurology, Center for Cognitive Neurology NYU School of Medicine NYU Langone Medical CenterMedicalResearch.com Interview with: Fernando Goni, PhD MS Adjunct associate professor Department of Neurology, Center for Cognitive Neurology NYU School of Medicine NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Goni: It has been established that most neurodegenerative diseases including Alzheimer's, Lewy Body and other dementias, Parkinson's and prion diseases develop and progress along similar paths. In each disease, a particular protein undergoes a change in its shape from a soluble, physiologically functional protein to a protein that has lost the ability to perform its required tasks in the brain, starting off a chain reaction of binding to each other with little control. These aggregates become toxic to brain cells. We raised antibodies in mice against the common beta-sheet structures present in toxic oligomers of many neurodegenerative diseases including amyloid and tau in Alzheimer's; oligomeric forms of prions and oligomerized alpha-synuclein in Parkinson's. From that response, we produced monoclonal antibodies of the same characteristics. At least three of the monoclonals recognize pathological structures in histological samples of human brains from Alzheimer's disease, Parkinson's disease and GSS (human prionosis). They also recognized in vitro the oligomeric forms particular for each disease. In old animals of a mouse model of Alzheimer's, that already had pathology, the monoclonal antibodies could rescue behavior and reduced significantly the oligomers of Tau and Abeta.
Author Interviews, Probiotics, UC Davis / 20.07.2015

Maria L Marco, PhD Associate Professor Department of Food Science & Technology Davis, CA 95616MedicalResearch.com Interview with: Maria L Marco, PhD Associate Professor Department of Food Science & Technology Davis, CA  95616 Medical Research: What is the background for this study? What are the main findings? Dr. Marco: Probiotics encompass certain strains of bacteria and yeast that when administered alive and in sufficient amounts can confer specific health benefits. Probiotics are increasingly added to foods, beverages, and intestinal supplements for delivery to the digestive tract. (Fermented) dairy products are currently the most popular food carriers for probiotic strains in clinical studies and commercial products. Although microorganisms generally respond quickly and adapt to their surrounding environments (e.g. in foods), the importance of the carrier format on probiotic function in vivo has yet to be systematically and mechanistically investigated. To address this need, we performed a couple studies in rodents to (i) examine whether probiotic Lactobacillus casei produces different proteins during low temperature (refrigeration) incubation in milk and (ii) measure whether incubation in milk is required for L. casei protection against inflammation. We found by shot-gun proteomics that L. casei does adapt for growth and survival in milk by producing a variety of (extra)cellular proteins, even at low-temperatures used to store dairy products prior to consumption. Such exposure of L. casei to milk was also essential for reducing the severity of disease in a mouse model of Ulcerative Colitis (UC), an inflammatory bowel disease characterized by continuous inflammation in the large intestine. Consuming milk alone also provided some protection against weight loss and intestinal inflammation in the Ulcerative Colitis mouse model but was not as effective as L. casei and milk in combination. Lastly, the importance of dairy for L. casei in preventing Ulcerative Colitis was confirmed by our findings that L. casei mutants lacking the capacity to synthesize proteins which are selectively produced during low-temperature incubation in milk were also impaired in preventing inflammatory responses in the intestine.
Author Interviews, Genetic Research, Heart Disease, McGill / 20.07.2015

Christopher Labos MD CM, MSc FRCPC Division of Epidemiology, Biostatistics and Occupational Health McGill University Montreal, Quebec CanadaMedicalResearch.com Interview with: Christopher Labos MD CM, MSc FRCPC Division of Epidemiology, Biostatistics and Occupational Health McGill University Montreal, Quebec Canada Medical Research: What is the background for this study? What are the main findings? Response: There have been great advances in the field of genetics in recent years. Especially in cardiology, a number of genetic variants have been identified that are associated with cardiovascular disease. But it is not clear how useful these variants are in terms of predicting future evens in patients that have already suffered a myocardial infarction. What we found in our study is that a genetic risk score composed of the 30 most common genetic variants associated with cardiovascular diseases was not useful in predicting recurrent events in the first year after a patient suffered a myocardial infarction.
Author Interviews, Beth Israel Deaconess, Diabetes, Heart Disease, University of Michigan / 18.07.2015

MedicalResearch.com Interview with: Venkatesh L. Murthy, MD, PhD, FACC, FASNC University of MichiganVenkatesh L. Murthy, MD, PhD, FACC, FASNC University of Michigan Dr. Ravi Shah MD Beth Israel Deaconess Medical Centerand Dr. Ravi Shah MD Beth Israel Deaconess Medical Center   MedicalResearch: What is the background for this study? Response: Recent changes recommend statin therapy for cardiovascular risk reduction in an increasingly large number of Americans. Conversely, a number of studies have identified an increased risk of diabetes with statin treatment. Thus, there is increasing need for tools to target statin therapy to those with a favorable risk-benefit profile. MedicalResearch: What are the main findings? Response: In our study, we analyzed data from 3,153 individuals from the Multi-Ethnic Study of Atherosclerosis who underwent CT scanning at baseline for assessment of calcium score. The CT scans were analyzed to assess liver attenuation as a measure of the amount of liver fat. We demonstrated that high liver fat doubled the risk of diabetes over a median of 9 years of follow-up. Importantly, statin therapy also doubled the risk of diabetes. The two together had an additive effect, even after adjusting for BMI, age, gender, family history of diabetes, waist circumference, lipids, hsCRP and exercise habits. As in prior studies, the risk of cardiovascular disease (CVD) events increased with increasing calcium score, as has previously been shown in MESA and in other studies. We then divided the cohort into six groups based on calcium score (0, 1-100 and >100) and liver fat (low/high). Using published data from meta-analyses of statin trials, we computed the number needed to treat to prevent one hard CVD event for statin therapy. Using data from our study, we computed the number needed to harm to cause one additional case of diabetes from statin therapy. The numbers needed to treat with ranged from 29-40 for calcium score of >100 to 218-252 for calcium score of 0. Conversely, the numbers needed to harm were approximately 63-68 for those with low liver fat versus 22-24 for those with high liver fat. Thus the combination of calcium score and liver fat assessment, from a single standard calcium score scan, allows for physicians to provide better assessment of risk and benefit of statins in discussion with their patients.
Author Interviews, Education, Electronic Records, PLoS, UCSF / 17.07.2015

Dr. Courtney Lyles Ph.D. Assistant Professor UCSF School of MedicineMedicalResearch.com Interview with: Dr. Courtney Lyles Ph.D. Assistant Professor UCSF School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Lyles: In our commentary (http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001852), we describe the Meaningful Use program sponsored by the federal government to incentivize healthcare systems to implement electronic health records (EHRs).  This Meaningful Use program also includes financial incentives for healthcare systems who can get substantial proportions of their patient population to access their electronic health records – that is, by logging into an online patient portal website to view medical information like lab results or immunization lists or to perform a healthcare task like requesting a medication refill or messaging their provider.  Because there are billions of dollars at stake in this program for EHR implementation, there is a lot of attention on this issue right now.  Many thought leaders are discussing how we can transform healthcare by digitizing medical information and connecting with patients in their everyday life outside of office or hospital visits.  Portals are key to a lot of changes we might make in healthcare delivery in an attempt to increase convenience and satisfaction for patients.  Perhaps most importantly, these online portal websites are also one of the first health technologies that will be relatively uniformly distributed across healthcare settings, from private doctor’s offices to public clinics/hospitals serving vulnerable patient populations. However, our main message is that we in the medical and healthcare fields should be paying more attention to how patients are able to understand and use the information provided through portal websites.  There is a lot of evidence that patients who have lower education/income, are from racial/ethnic minority groups, or have limited health literacy are significantly less likely to use the existing portal websites.  There is also evidence that portal websites are not extremely usable or accessible, which is an additional barrier for those with communication barriers like lower literacy or limited English proficiency.  Therefore, we don’t want widespread EHR implementation to result in only the most well-resourced individuals gaining the potential benefits of portal access.
Author Interviews, PLoS, Toxin Research, University of Pennsylvania / 17.07.2015

Reynold A. Panettieri, Jr., M.D. Robert L. Mayock and David A. Cooper Professor of Medicine Pulmonary, Allergy & Critical Care Division Director, Airways Biology Initiative Deputy Director, Center of Excellence in Environmental Toxicology Adjunct Professor, Wistar Institute Philadelphia, PA 19104-3413MedicalResearch.com Interview with: Reynold A. Panettieri, Jr., M.D. Robert L. Mayock and David A. Cooper Professor of Medicine Pulmonary, Allergy & Critical Care Division Director, Airways Biology Initiative Deputy Director, Center of Excellence in Environmental Toxicology Adjunct Professor, Wistar Institute Philadelphia, PA  19104-3413 Medical Research: What is the background for this study? What are the main findings? Dr. Panettieri: Over the past ten years in the US, unconventional gas and oil drilling (hydraulic fracturing) to generate natural gas has markedly increased.  In areas with hydraulic fracturing, there is a large increase in truck traffic, noise and potential air and water pollution.  Accordingly, residents may experience health consequences from such exposures.  We questioned whether proximity to active wells increases hospitalization rates in residents.  To address this question, we reviewed all hospitalizations in two counties in Pennsylvania, namely, Bradford and Susquehanna Counties, that experienced a meteoric increase in active wells.  In comparison, Wayne County, where there is a moratorium on hydraulic fracturing, is demographically identical to Bradford and Susquehanna Counties and served as a control population.  Having examined the 25 most common reasons for admission to the hospital, we determined that cardiovascular hospitalizations as well as neurologic, dermatologic and cancer hospitalizations were associated with living closer to active wells.  These data represent some of the first studies to associate active well drilling with hospitalizations in the United States.
Author Interviews, Genetic Research, Surgical Research, Yale / 17.07.2015

John A. Elefteriades, MD William W.L. Glenn Professor of Surgery Chief of Cardiothoracic Surgery Director, Aortic Institute at Yale-New Haven Yale University School of MedicineMedicalResearch.com Interview with: John A. Elefteriades, MD William W.L. Glenn Professor of Surgery Chief of Cardiothoracic Surgery Director, Aortic Institute at Yale-New Haven Yale University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Elefteriades: The race to map the human genome was declared completed in 2003, at a cost of 3 billion dollars for the international collaborative university group and 300 million dollars for Craig Venter at Celera. Whole exome sequencing can now be performed at a cost of only several thousand dollars per individual. So, whole exome sequencing (also called Next Generation Sequencing) can now be applied to understand and treat diseases of many organ systems. In this study, we applied whole exome sequencing to study over 100 patients with thoracic aneurysm. In the late 1990s, both Dr. Diana Milewicz in Texas and our group at Yale had determined that many thoracic aortic aneurysms were genetically transmitted. Dr. Milewicz went on to identify many of the causative mutations. In this study, we were able to look, by whole exome sequencing performed on saliva, for all 21 mutations known to cause thoracic aortic aneurysm--all at one time in one comprehensive genetic test. We were able to protect patients with the most serious discovered mutations by early surgery, the need for which could not otherwise have been apparent. 
Author Interviews, Compliance, Cost of Health Care, Emergency Care, Primary Care, UCSD / 15.07.2015

Nadereh Pourat, PhD Professor, Department of Health Policy and Management, UCLA Fielding School of Public Health Adjunct Professor, UCLA School of Dentistry Director of Research, UCLA Center for Health Policy ResearchMedicalResearch.com Interview with: Nadereh Pourat, PhD Professor, Department of Health Policy and Management, UCLA Fielding School of Public Health Adjunct Professor, UCLA School of Dentistry Director of Research, UCLA Center for Health Policy Research Medical Research: What is the background for this study? What are the main findings? Dr. Pourat: We have succeeded to insure most of the uninsured population in the U.S., but now have to figure out how to reduce costs while improving health. We had the opportunity to examine the role of continuity with a primary care provider, which is one of the pathways that looked promising in improving health and reducing costs. We were evaluating a major demonstration program in California called the Health Care Coverage Initiative (HCCI) and one of the participating counties implemented a policy to increase adherence by only paying for visits if patients went to their assigned providers. We examined what happened to patients who always or sometimes adhered to their provider versus those who never adhered. We found that adherence or continuity reduced emergency department use and hospitalizations. This would lead to savings because of the high costs of these services. Medical Research: What should clinicians and patients take away from your report? Dr. Pourat: The study shows that both patients and clinicians would benefit from continuity with the primary care provider. Clinicians can actually make a difference in helping patients: they can teach patients about self-care and help them manage their conditions better. Patients would benefit from following through with treatment plans and experience less medical error and duplication of services which are potentially harmful. Continuity fosters rapport and trust between patients and providers and can be beneficial to both.
Author Interviews, Emergency Care, FDA, Opiods, Pharmacology / 15.07.2015

MedicalResearch.com Interview with: Christopher M. Jones, Pharm D., M.P.H Senior advisor, Office of Public Health Strategy and Analysis Office of the Commissioner, Food and Drug Administration Medical Research: What is the background for this study? Dr. Jones: Opioid analgesics and benzodiazepines are the two most common drug classes involved in prescription drug overdose deaths. In 2010, 75% of prescription drug overdose deaths involved opioid analgesics and 29% involved benzodiazepines. Opioid analgesics and benzodiazepines are also the most common drugs associated with emergency department visits due to nonmedical use of prescription drugs. Combined opioid and benzodiazepine use has been suggested as a risk factor for overdose death. Opioids and benzodiazepines have complex drug interactions and in combination can result in synergistic respiratory depression, but the exact mechanisms by which benzodiazepines worsen opioid-related respiratory depression are not fully understood. Widespread co-use of benzodiazepines and opioids has been documented in both chronic pain and addiction treatment settings. Studies suggest that among patients who receive long-term opioids for chronic non-cancer pain, 40% or more also use benzodiazepines. Among patients who abuse opioids, benzodiazepine abuse also is prevalent, and co-users report using benzodiazepines to enhance opioid intoxication. This study builds on the prior literature by analyzing trends on how the combined use of opioids and benzodiazepines in the U.S. contributes to the serious adverse outcomes of nonmedical use–related ED visits and drug overdose deaths. A better understanding of the consequences of co-use of these medications will help identify at-risk populations, inform prevention efforts, and improve the risk–benefit balance of these medications. Medical Research: What are the main findings? Dr. Jones: From 2004 to 2011, the rate of nonmedical use–related Emergency Department visits involving both opioid analgesics and benzodiazepines increased from 11.0 to 34.2 per 100,000 population. During the same period, drug overdose deaths involving both drugs increased from 0.6 to 1.7 per 100,000. Statistically significant increases in Emergency Department visits occurred among males and females, non-Hispanic whites, non-Hispanic blacks, and Hispanics, and all age groups except 12–17-year-olds. For overdose deaths, statistically significant increases were seen in males and female, all three race/ethnicity groups, and all age groups except 12–17-year-olds. Benzodiazepine involvement in opioid analgesic overdose deaths increased each year, increasing from 18% of opioid analgesic overdose deaths in 2004 to 31% in 2011.
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Statins / 14.07.2015

Dr. Ankur Pandya Ph.D. Assistant Professor of Health Decision Science Department of Health Policy and Management Harvard T.H. Chan School of Public Health Boston, MA MedicalResearch.com Interview with: Dr. Ankur Pandya Ph.D. Assistant Professor of Health Decision Science Department of Health Policy and Management Harvard T.H. Chan School of Public Health Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Pandya: The American College of Cardiology and the American Heart Association (ACC-AHA) cholesterol treatment guidelines were controversial when first released in November 2013, with some concerns that healthy adults would be over-treated with statins. We found that the current 10-year ASCVD risk threshold (≥7.5%) used in the ACC-AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (incremental cost-effectiveness ratio of $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0%) or $150,000/QALY (≥3.0%).
Author Interviews, Beth Israel Deaconess, Cognitive Issues, Diabetes, Neurology / 11.07.2015

Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MAMedicalResearch.com Interview with: Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MA MedicalResearch: What is the background for this study? Dr. Novak: Diabetes mellitus (DM) is a major contributor to morbidity and mortality. Type 2 diabetes mellitus affects more than 44 million people in the U.S., and its numbers are growing rapidly, affecting up to 27% of older adults. Diabetes mellitus accelerates brain aging by about 5 years1, manifests as a widespread generalized atrophy2, and promotes earlier onset of vascular dementia and Alzheimer’s disease (AD).3,4 Diabetes mellitus -related atrophy manifests as worse cognitive function, memory, and gait, especially during a dual task, 5,6 and even a tight glycemic control did not improve cognitive function in participants of the large clinical trials 7. MedicalResearch: What are the main findings? Dr. Novak: Sixty-five participants (aged 66± 9.2 years) 35 with T2DM and 30 non-diabetic controls participated in this study. After 2 years of follow-up, participants with T2 Diabetes mellitus had diminished vascular reactivity in the brain (an ability to increase blood flow in responses to a task or metabolic demands) and performed worse on multiple cognitive tasks (in particular verbal learning and memory). In T2DM group, lower cerebral vasoreactivity correlated with worse performance on daily living activities. Specifically, the lower vasodilatation (ability to increase blood flow) was associated with worse mental functions. In addition, those with higher markers of inflammation had greater decline in vascular function in the brain.
Author Interviews, Heart Disease, Psychological Science, Sexual Health, University Texas / 11.07.2015

Amelia Stanton, Graduate Student Department of Psychology The University of Texas at Austin Austin, TXMedicalResearch.com Interview with: Amelia Stanton, Graduate Student Department of Psychology The University of Texas at Austin Austin, TX Medical Research: What is the background for this study? What are the main findings? Response: Heart rate variability (HRV) has emerged as a valuable non-invasive test to assess autonomic nervous system (ANS) activity. Several studies have linked low resting Heart rate variability to mental health conditions including depression, anxiety, and alcohol dependence, indicating these disorders may be related to an imbalance in autonomic activity. As Heart rate variability is an index of the balance of sympathetic nervous system (SNS) and parasympathetic nervous system activity (PNS), it has proven a useful tool for examining the relative role of SNS activity in female sexual arousal. Moderate SNS dominance (relative to PNS activity) has been shown to predict women’s genital arousal in the laboratory, while high levels of SNS activation have been shown to inhibit genital arousal. Based on this background evidence and on a growing clinical literature indicating that low HRV (generally indicative of high SNS) is associated with negative health outcomes, we predicted a positive linear relationship between Heart rate variability and sexual arousal function. That is, we predicted that women with autonomic balance indicating moderate or low resting SNS activity (relative to PNS activity) would be less likely than women with autonomic balance indicating high resting SNS to report clinically relevant sexual arousal dysfunction. We also predicted that this relationship would hold for overall sexual function. To test this hypothesis, sexual arousal function, overall sexual function, and resting HRV were assessed in 72 women, aged 18-39. The main finding of the study is that women with below average Heart rate variability were significantly more likely to report sexual arousal dysfunction (p < .001) and overall sexual dysfunction (p < .001) than both women with average HRV and women with above average HRV. Based on these results, we concluded that low HRV may be a risk factor for female sexual arousal dysfunction and overall sexual dysfunction.
Author Interviews, Colon Cancer, Duke, Weight Research / 10.07.2015

S. Yousuf Zafar, MD, MHS Associate Professor of Medicine Duke Cancer Institute Duke Clinical Research InstituteMedicalResearch.com Interview with: S. Yousuf Zafar, MD, MHS Associate Professor of Medicine Duke Cancer Institute Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Zafar: Multiple studies have suggested that obesity and colorectal cancer are related. For instance, obesity has been linked with an increased incidence of colon cancer. Obesity has also been associated with a greater risk of colon cancer recurrence. To date, no study has looked at the role of obesity in outcomes for patients with metastatic colorectal cancer. In our study of over 6000 patients receiving treatment for metastatic olcolorectal cancer, we found that patients with the lowest body mass index (BMI) were at greatest risk for worse survival. This does not mean that obesity is good. More likely, it means that those who are very underweight are least able to tolerate the best treatment, or being very underweight is a biologic marker of poor prognosis.
Author Interviews, Blood Pressure - Hypertension, NYU/NYMC, Pediatrics, Toxin Research / 10.07.2015

MedicalResearch.com Interview with: Teresa M. Attina, MD, PhD, MPH and Leonardo Trasande, MD, MPP Department of Pediatrics NYU Langone Medical Center Medical Research: What is the background for this study? Response: Phthalates are environmental chemicals widely used in consumer and personal care products, and often found in plastic to increase flexibility. Di-2-ethylhexylphthalate (DEHP) is of particular interest because industrial processes to produce food frequently use plastic products containing DEHP. Because recognition of potential health risks related to DEHP exposure has increased, DEHP is being replaced by di-isononyl phthalate (DINP) and di-isodecyl phthalate (DIDP), two phthalates with similar chemical properties. Specifically, DINP is used in plastic products for food packaging, and DIDP is used in furnishings, cookware, medications, and several other consumer products. These alternatives have not been substantially studied for toxicity in laboratory studies because these studies are not required for regulatory approval: unlike the EU, in the US the current regulatory framework assumes that chemicals are safe until proven toxic. Medical Research: What are the main findings? Response: We examined DINP and DIDP levels in urine samples from children and adolescents (6 to 19 years old) who participated in the National Health and Nutrition Examination Survey between 2009 and 2012, to assess if these levels were associated with blood pressure measurements. Diet, physical activity, gender, race/ethnicity, income, and other factors that can contribute to increased blood pressure were also included in the analysis. A significant association was found between high blood pressure and DINP/DIDP levels in study participants. This is not a cause-and-effect relationship but it suggests that phthalates may contribute to increased blood pressure.
Author Interviews, Cost of Health Care, OBGYNE, Yale / 10.07.2015

Xiao Xu, Ph.D. Assistant Professor Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of MedicineMedicalResearch.com Interview with: Xiao Xu, Ph.D. Assistant Professor Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Xiao Xu: While research has shown hospital variation in costs of care for other conditions, we know little about whether and how hospitals differ in costs of childbirth related care. With nearly 4 million births each year, childbirth is the most common reason for hospital admission in the U.S. Understanding the pattern and causes of variation in resource utilization during childbirth among hospitals can help inform strategies to reduce costs. Our study used data from 463 hospitals across the country and analyzed hospital costs of maternity care for low-risk births. We found that hospital varied widely in average facility costs per maternity stay.
Author Interviews, Mayo Clinic, Opiods, Tobacco Research / 10.07.2015

W. Michael Hooten, M.D Professor of Anesthesiology Mayo ClinicMedicalResearch.com Interview with: W. Michael Hooten, M.D Professor of Anesthesiology Mayo Clinic Medical Research: What is the background for this study? Dr. Hooten: The purpose of the study was to investigate a gap in knowledge related to the progression of short-term opioid use to longer-term use. Medical Research: What are the main findings? Dr. Hooten: The main findings are that a history of substance abuse or tobacco use is associated with the progression from short-term to a longer-term pattern of opioid prescribing.
Author Interviews, Cancer Research, End of Life Care, JAMA, Johns Hopkins / 10.07.2015

Amol Narang MD Radiation Oncology Resident Johns Hopkins MedicineMedicalResearch.com Interview with: Amol Narang MD Radiation Oncology Resident Johns Hopkins Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Narang: The care provided to cancer patients at end-of-life can be intense, including frequent ER visit, hospitalizations, and ICU stays in the last month of life, administration of chemotherapy in last two weeks of life, and late referrals to hospice. Providing high-intensity treatments at end-of-life has been associated with reduced patient quality-of-life and increased caregiver bereavement. Advance care planning represents an opportunity for patients to indicate their preferences for end-of-life care to try to ensure that the care that they receive at end-of-life is consistent with their values, and has been endorsed by oncologic professional societies, such as ASCO and the NCCN. As such, we wanted to assess if oncologists’ long-standing recognition of the merits of advance care planning has translated into increased participation in advance care planning by cancer patients, and to determine which forms of advance care planning are associated with intensity of care given at end-of-life. From 2000-12, we found that the only type of advance care planning that increased was the assignment of a power of attorney (52% in 2000 to 74% in 2012). However, having a power of attorney was not associated with receiving less aggressive end-of-life care. On the other hand, having a living wills and engaging in a discussion with a provider or loved one about preferences for end-of-life care were both associated with reduced treatment intensity. However, the frequency with which cancer patients created a living or discussed their preferences for end-of-life care did not increase over the study period; importantly, 40% of patients dying of cancer never communicated their preferences for care at end-of-life with anyone.