Author Interviews, JAMA, Mental Health Research, OBGYNE, Pediatrics / 11.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41081" align="alignleft" width="133"]Jiook Cha, PhD Assistant Professor Division of Child and Adolescent Psychiatry  Columbia University Medical Center  New York, NY 10032 Dr. Jiook Cha[/caption] Jiook Cha, PhD Assistant Professor Division of Child and Adolescent Psychiatry Columbia University Medical Center New York, NY 10032 MedicalResearch.com: What did we already know about the connection between maternal SSRI use during pregnancy and infant brain development, and how do the current study findings add to our understanding? What’s new/surprising here and why does it matter for mothers and babies? Response: Prior studies have shown mixed results in terms of the associations between maternal SRI use during pregnancy and offspring’s brain and cognitive development. Neurobiological studies with animal models suggest that SSRI use perturbs serotonin signaling and that this has important effects on cognitive development (a study conducted an author of this paper, Jay Gingrich, MD, PhD: Ansorge et al., 2004, Science). The human literature has been more mixed in terms of the associations of prenatal exposure to SSRI with brain and cognitive development. In our study, we used neonatal brain imaging because this is a direct, non-invasive method to test associations between SSRI use and brain development at an early developmental stage, limiting the effects of the post-natal environment. In our study, we had two different control groups, that is, a non-depressed SSRI-free group (healthy controls), and depressed but SSRI-free (SSRI controls) group. Also, in our study we used rigorous imaging analytics that significantly improve the quantitative nature of MR-derived signals from the brain structure using two of the nation’s fastest supercomputers (Argonne National Laboratory and Texas Advanced Computing Center) and allows robust reconstruction of brain’s grey and white matter structure in the infants’ brains. We report a significant association of prenatal exposure to SSRI with a volume increases within many brain areas, including the amygdala and insula cortex, and an increase in white matter connection strength between the amygdala and insular cortex. We were surprised by the magnitude of the effects (or the statistical effect size), compared with other brain imaging studies in psychiatry with children or adults’ brains. Importantly, it should be noted that our estimates of brain structure are still experimental and for research-purpose only. This means that our data need to be replicated and rigorously tested against confounders in order to make a firm conclusion. While our study suggests a “potential” association between prenatal exposure to SSRI and a change in fetal or infant brain development, we still need more research.  tracts_in_the_brain
Author Interviews, Epilepsy, JAMA / 10.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41045" align="alignleft" width="183"]Dr Hayley Gorton PhD MPharm MRPharmS FHEA Research Associate Centre for Pharmacoepidemiology and Drug Safety Research Division of Pharmacy & Optometry| Faculty of Biology, Medicine & Health University of Manchester Dr. Gorton[/caption] Dr Hayley Gorton PhD MPharm MRPharmS FHEA Research Associate Centre for Pharmacoepidemiology and Drug Safety Research Division of Pharmacy & Optometry| Faculty of Biology, Medicine & Health University of Manchester MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is already known that people with epilepsy are at a higher risk of death than those without epilepsy but we didn’t know much about the risks of different types of death. Unnatural death (mainly accident and suicide) accounts for a very small number of all deaths but, compared to people without epilepsy, people with epilepsy are three times more likely to die by accident and twice as likely to die by suicide. Within these broad categories, persons with epilepsy are five times more likely to die specifically by accidental poisoning with medication, and three times more likely to die by intentionally poisoning themselves with medication. Opioid painkillers and medicines for mental illness were the ones most commonly used in poisoning deaths among people with epilepsy and those without epilepsy. Antiepileptic drugs were taken relatively infrequently-they were involved in about 10% of poisoning deaths in people with epilepsy. 
Author Interviews, Cancer Research, Cost of Health Care, JAMA, Pharmaceutical Companies / 09.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41105" align="alignleft" width="133"]Aaron Mitchell, MD Division of Hematology/Oncology, Department of Medicine,  Lineberger Comprehensive Cancer Center The Cecil G. Sheps Center for Health Services Research The University of North Carolina at Chapel Hil Dr. Mitchell[/caption] Aaron Mitchell, MD Division of Hematology/Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center The Cecil G. Sheps Center for Health Services Research The University of North Carolina at Chapel Hill MedicalResearch.com: What is the background for this study? What are the main findings? Response: Financial relationships between physicians and the pharmaceutical industry are very common. However, we are just beginning to figure out whether these relationships may lead to potentially concerning changes in physician behavior - whether physicians tend to prescribe more of the drugs made by a company that has given them money. We decided to ask whether oncologists who receive money from drugmakers are more likely to use the cancer drugs made by companies that have given them money in the past. In studying two specific groups of cancer drugs, one for kidney cancer and one for chronic myeloid leukemia (CML), we found that oncologists who had received payments such as meals, consulting fees, travel & lodging expenses from the manufacturer of one of these drugs tended to use that drug more. When looking at oncologists who received payments for research, we found increased prescribing among the kidney cancer drugs but not the CML drugs.
Author Interviews, JAMA, Mental Health Research, OBGYNE, Pediatrics / 09.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41072" align="alignleft" width="200"]Claudia I. Lugo-Candelas, PhD Postdoctoral Research Fellow Columbia University Medical Center/ New York State Psychiatric Institute Dr. Lugo-Candelas[/caption] Claudia I. Lugo-Candelas, PhD Postdoctoral Research Fellow Columbia University Medical Center/ New York State Psychiatric Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have seen, in the last decade, an increase in the amount of mothers being prescribed SSRIs during pregnancy. While we know that untreated prenatal maternal depression has adverse consequences for both the mother and child, it’s not really clear what, if any, are the consequences of prenatal SSRI exposure on infant’s brain development. There have been some studies finding increased depression and anxiety in children prenatally exposed to SSRIs, but not all studies find these associations. We thus looked at 2-4 week old infants’ brains, using neuroimaging.  We found increased gray matter volume within the amygdala and insula, and increased white matter connectivity between these two structures in infants prenatally exposed to SSRIs. Of note, the statistical significance and the size of the effects we detected are quite large, even greater than the brain changes that we usually observe in our studies of children and adults with psychiatric disorders. Further, because these structures are involved in emotion processing, and alterations in volume and connectivity are sometimes seen in clinical populations, or in people at risk for anxiety, it important to learn more about what these volume and connectivity differences could mean for these infants.
ALS, Alzheimer's - Dementia, Author Interviews, JAMA / 09.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41048" align="alignleft" width="137"]Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis Dr. Karch[/caption] Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nearly half of all patients with amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disorder, develop cognitive problems that affect memory and thinking. Why a disease that primarily affects movement also disrupts thinking has been unclear. Our findings suggest that genetic connections between the two disorders may explain why they share some of the same features and suggest that some drugs developed to treat ALS also may work against frontotemporal dementia and vice versa. We used a statistical method in almost 125,000 individuals with ALS, frontotemporal dementia (FTD), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease and Parkinson’s disease to determine whether there are common genetic variants that increase risk for multiple neurodegenerative diseases. We found that common variants near the MAPT gene, which makes the tau protein, increases risk for ALS. MAPT has previously had been associated with diseases including frontotemporal dementia and Alzheimer’s disease. But the gene hadn’t been linked to ALS. We also identified variations in a second gene, BNIP1, which normally plays an important role in protecting against cell death, increased the risk of both ALS and frontotemporal dementia. ImportantlyBNIP1 mRNA levels were altered in people who had ALS and in patients with frontotemporal dementia, suggesting the BNIP1 may be a potential therapeutic target for both disorders.
Author Interviews, Cancer Research, Lung Cancer, PNAS / 08.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41075" align="alignleft" width="132"]Nada Kalaany, PhD Harvard Medical School Boston Children's Hospital  Boston, MA 02115 Dr. Kalaany[/caption] Nada Kalaany, PhD Harvard Medical School Boston Children's Hospital Boston, MA 02115 MedicalResearch.com: What is the background for this study? Response: ​ Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and the leading cause of cancer death in the US and worldwide. Over a quarter of NSCLC harbors activating mutations in the KRAS oncogene, which despite decades of attempts, has proven to be very difficult to target. KRAS has previously been demonstrated to directly bind to and activate the pro-proliferative kinase PI3K, which is typically activated by insulin/insulin-like growth factor1 (IGF1) signaling. KRAS-PI3K binding is required for KRAS-driven lung cancer formation and progression. However, whether this interaction is sufficient for lung tumor formation and whether additional input is required from insulin/IGF1 signaling, has remained largely controversial.
Author Interviews, JAMA, Mental Health Research / 07.04.2018

MedicalResearch.com Interview with: [caption id="attachment_40941" align="alignleft" width="200"]Dr. Aideen Maguire Centre of Excellence for Public Health Queen's University Belfast Institute of Clinical Sciences B Royal Hospitals Site, Belfast Dr Aideen Maguire[/caption] Dr. Aideen Maguire Centre of Excellence for Public Health Queen's University Belfast Institute of Clinical Sciences B Royal Hospitals Site, Belfast MedicalResearch.com: What is the background for this study?   Response: Consanguineous Marriage is the marriage between second or first cousins. Although not common practice in the Western world approximately 1 in 10 children worldwide are born to consanguineous parents. It is legal in all countries worldwide except the United States of America, North Korea and China. Cousin-marriage is associated with an increased risk of autosomal recessive genetic disorders in offspring but the association between cousin-marriage and the mental health of offspring has not been extensively studied. MedicalResearch.com: What are the main findings? Response: Children of consanguineous parents are over 3 times more likley to be in receipt of medications for common mood disorders (antidepressant and/or anxioltyic medication) compared to children of non-related parents and over twice as likley to be in receipt of antipsychotic medication compared to children of non-related parents. 
Author Interviews, Blood Pressure - Hypertension, Nature / 06.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41036" align="alignleft" width="149"]Dr. Charles Brenner, PhD Chief Scientific Advisor ChromaDex Dr. Charles Brenner[/caption] Dr. Charles Brenner, PhD Chief Scientific Advisor ChromaDex MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nicotinamide adenine dinucleotide (NAD) is the central regulator of metabolism. NAD is under attack in multiple conditions of metabolic stress and declines in human aging. Thus, using supplements to maintain NAD has emerged as an important strategy to support healthy aging. There are three vitamin precursors of NAD. However, two of those forms (niacin and nicotinamide) have unwanted side effects and/or inhibit some of the metabolic regulators that can be stimulated by higher NAD. Nicotinamide riboside (NR) is the most recently discovered NAD precursor vitamin. Research has shown that NR boosts NAD more than the other precursors, doesn’t cause flushing, doesn’t inhibit sirtuin enzymes, and that the pathway that converts NR to NAD is turned on in tissues undergoing stress and damage. Commercialized as NIAGEN®, NR has been clinically proven to significantly increase NAD levels in people as an oral supplement. NIAGEN® is the only NR with published human safety, efficacy and tolerability studies. The University of Colorado study is the first clinical trial showing that not only does NIAGEN® boost NAD levels, it also may have a beneficial effect on cardiovascular health and function.
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA / 06.04.2018

MedicalResearch.com Interview with: Dr. Alvin Chandra  MD first author  and Dr. Scott David Solomon M.D. Director, Noninvasive Cardiology Professor, Harvard Medical School Cardiovascular Medicine Brigham and Women’s Hospital Boston, Massachusetts MedicalResearch.com: What is the background for this study? What are the main findings? Response: In general, the quality of life of heart failure with reduced ejection fraction patients is quite impaired, and  similar to that of patients on dialysis. PARADIGM-HF was the largest trial of heart failure patients and showed that sacubitril/valsartan was superior to the gold-standard enalapril in reducing cardiovascular death, heart failure hospitalization and all-cause mortality. In addition, patients on sacubitril/valsartan, when compared to enalapril, showed significant improvement in overall quality of life. In this study we looked in more detail at the individual components of “quality of life” and found that in virtually all domains and activities, patients who were randomized to sacubitril/valsartan reported improvement in their limitations  compared to those who were randomized to enalapril. These activities included jogging, doing hobbies, and household chores, with the largest improvement seen in  sexual activities limitations.
Author Interviews, Genetic Research, Heart Disease, JAMA / 06.04.2018

MedicalResearch.com Interview with: [caption id="attachment_40958" align="alignleft" width="150"]Stella Aslibekyan, PhD Associate Professor PhD Program Director Department of Epidemiology University of Alabama at Birmingham Dr. Aslibekyan[/caption] Stella Aslibekyan, PhD Associate Professor PhD Program Director Department of Epidemiology University of Alabama at Birmingham MedicalResearch.com: What is the background for this study? What are the main findings? Response: When the human genome was sequenced in 2003, there were somewhat unrestrained expectations of unraveling all etiologic mysteries and discovering breakthrough treatments. Needless to say, that did not happen, in part because individual genetic variants can only account for a small fraction of trait variability. Since then, epigenetics-- the study of mitotically heritable changes in gene expression-- has emerged as another promising avenue for understanding disease risk. The best studied epigenetic process in humans is DNA methylation, and earlier studies (including some from our group) have shown interesting associations between changes in methylation in specific genomic regions and cardiovascular disease traits, e.g. plasma cholesterol levels. In this project, we have combined DNA methylation data on thousands of individuals from multiple international cohorts and interrogated epigenetic contributions to circulating tumor necrosis factor alpha (TNFa), a marker of systemic inflammation. We identified and replicated several epigenomic markers of TNFa, linked them to variation in gene expression, and showed that these methylation changes (which were located in interferon pathway genes) were predictive of coronary heart disease later in life. Interestingly, the variants we discovered were not sequence-dependent (in other words, they were not associated with any genetic mutations), highlighting the role of the environment.
Author Interviews, Diabetes, NEJM, Pediatrics, Weight Research / 05.04.2018

MedicalResearch.com Interview with: [caption id="attachment_40992" align="alignleft" width="166"]Lise Geisler Bjerregaard PhD Dr. Geisler Bjerregaard[/caption] Lise Geisler Bjerregaard PhD Postdoc, PhD, M.Sc. Public Health Center for Klinisk Forskning og Sygdomsforebyggelse/ Center for Clinical Research and Disease Prevention Sektion for Klinisk Epidemiologi Frederiksberg Hospital, Frederiksberg MedicalResearch.com: What is the background for this study? What are the main findings? Response: Being overweight in childhood and early adulthood is associated with an increased risk of developing type 2 diabetes in adulthood. We wanted to know whether or not remission of overweight before early adulthood can reduce the risks of type 2 diabetes later in life. We studied the associations between different combinations of weight status in childhood, adolescence and early adulthood, and later development of type 2 diabetes. We found that men who had been overweight at 7 years of age but normalised weight by age 13 years and were normal weight as young men had similar risks of type 2 diabetes as men who were never overweight. Men who normalised weight between age 13 years and early adulthood had increased risks of type 2 diabetes, but lower risks than men who were overweight at all ages. 
Author Interviews, Infections, Science, Vaccine Studies / 05.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41013" align="alignleft" width="300"]This Gram-stained photomicrograph depicts numbers of Bordetella pertussis bacteria, which is the etiologic pathogen for pertussis, also known as whooping cough. This Gram-stained photomicrograph depicts numbers of Bordetella pertussis bacteria, which is the etiologic pathogen for pertussis, also known as whooping cough.
CDC image[/caption] Matthieu Domenech de Cellès PhD Department of Ecology and Evolutionary Biology University of Michigan, Ann Arbor, MI, USA. Biostatistics, Biomathematics, Pharmacoepidemiology, and Infectious Diseases Unit Institut Pasteur, Inserm, University of Versailles St-Quentin-en-Yvelines, Versailles, France. MedicalResearch.com: What is the background for this study? What are the main findings?   Response: Our main motivation was to elucidate an apparent paradox: Why has the US experienced a resurgence of pertussis (whooping cough) since the mid-1970s, despite persistently high vaccine coverage? A variety of hypotheses have been proposed to explain this resurgence, but most attention has focused on the potential shortcomings of the new generation of pertussis vaccines (called acellular pertussis vaccines). However, there remains considerable uncertainty about the degree and the mechanisms of protection conferred by pertussis vaccines. Via a collaboration with the local department of public health, we used detailed surveillance data in the state of Massachusetts to test a number of hypotheses about pertussis vaccines. We found that, although pertussis vaccines are imperfect (in the sense that they do not provide lifelong, 100% protection to 100% of children vaccinated), they are still highly efficacious. Specifically, we estimated that vaccine protection wanes over time, but slowly, with about 85% of children still protected 10 years after vaccination. Despite this high vaccine efficacy, we showed that the resurgence of pertussis was, in fact, to be expected. What happens is that the introduction of routine vaccination leads to an overall reduction in transmission, not only in vaccinated children but also in the population at large. Accordingly, those who escaped vaccination as children (as a consequence of incomplete vaccine coverage or imperfect vaccine protection) increasingly age having also avoided natural infection. As a result, the number of individuals susceptible to contract pertussis gradually increases. Because such people are the “fuel” of epidemics, this sets the stage for pertussis’ resurgence, with increasing incidence among older individuals. This overall effect is called the “end-of-honeymoon” and means that resurgence is therefore a predictable consequence of incomplete vaccination with efficacious, but imperfect, vaccines. Importantly, these results show that recent trends do not necessarily reflect recent changes in the epidemiology of pertussis. Rather, they may be interpreted as a legacy of past immunization practices, with long-to-manifest effects. This is a significant shift of perspective about pertussis epidemiology. 
Author Interviews, JNCI, Lung Cancer, UT Southwestern / 04.04.2018

MedicalResearch.com Interview with: [caption id="attachment_40982" align="alignleft" width="142"]Amyn Habib, M.D. Associate Professor, Neurology & Neurotherapeutics UT Southwestern Medical Center Dr. Amyn Habib[/caption] Amyn Habib, M.D. Associate Professor, Neurology & Neurotherapeutics UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? Response: The epidermal growth factor receptor (EGFR) is expressed in most lung cancers and could play an important role in driving the growth of lung cancer.  Drugs are available that can block the activity of the EGFR. However, EGFR inhibitors are successful in only a small subset of lung cancers that have a mutant form of the EGFR, and do not work in the majority of lung cancers that have the normal form of the EGFR. 
Author Interviews, BMJ, Heart Disease, Pain Research, Stroke / 04.04.2018

MedicalResearch.com Interview with: [caption id="attachment_40974" align="alignleft" width="133"]Islam Elgendy MD Division of Cardiovascular Medicine University of Florida   Dr. Elgendy[/caption] Islam Elgendy MD Division of Cardiovascular Medicine University of Florida   MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Migraine headache is a prevalent medical condition, often being chronic and debilitating to many. Previous studies have shown that migraine, particularly migraine with aura, is associated with an increased risk of cardiovascular events. Recently, a number of these studies have reported long-term follow up data. To better understand the long-term morbidity that is associated with migraines, we performed a systematic evaluation to study the link between migraine and risk of cardiovascular and cerebrovascular events. This study demonstrated that migraine is associated with an increased risk of major adverse cardiovascular and cerebrovascular events, which was driven by an increased long-term risk of myocardial infarction and stroke. This effect was predominantly observed in migraineurs who have aura. 
Author Interviews, Colon Cancer, Genetic Research, JAMA / 03.04.2018

MedicalResearch.com Interview with: [caption id="attachment_40952" align="alignleft" width="200"]Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH  43221 Heather Hampel[/caption] Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH  4322 MedicalResearch.com:  What is the background for this study?  What are the main findings? Response: The background is that we had recently shown that some colorectal cancer patients who underwent traditional screening for Lynch syndrome were eventually found to have double somatic (two acquired) mutations in the MMR genes and they did not have Lynch syndrome at all. This was discovered after their tumor had already had MSI and/or IHC screening test, followed by MLH1 methylation and/or BRAF testing, followed by germline DNA testing on a blood sample from the patient for MMR gene mutations, then finally by sequencing their tumor. This gave us the idea to reverse the sequence and start with tumor sequencing since it might streamline testing, save time, and prevent several other tests. In addition, we knew that all stage IV colorectal cancer are already supposed to have tumor sequencing of the KRAS, NRAS, and BRAF genes and MSI testing for treatment purposes. Our hypothesis was that an upfront tumor sequencing test could replace all these separate tests with similar sensitivity and specificity.
Author Interviews, CMAJ, Heart Disease, Technology / 03.04.2018

MedicalResearch.com Interview with: [caption id="attachment_40936" align="alignleft" width="200"]Benjamin Hibbert MD PhD FRCPCz Interventional Cardiologist Clinician Scientist and Assistant Professor CAPITAL Research Group Vascular Biology and Experimental Medicine Laboratory University of Ottawa Heart Institute Dr. Benjamin Hibbert[/caption] Benjamin Hibbert MD PhD FRCPCz Interventional Cardiologist Clinician Scientist and Assistant Professor CAPITAL Research Group Vascular Biology and Experimental Medicine Laboratory University of Ottawa Heart Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: When we designed the study in 2014 we were routinely using the modified allen's test (MAT) to screen patients for transradial access for coronary angiography and PCI. We all had iPhones and we started using the HeartRate monitoring application as a photoplethysmograph. Quite quickly we found that using the application was simple, worked well and because we always had our iPhone with us we tended to use it more often. That being said - we wanted to test it in a scientifically rigorous method and thus we elected to perform an RCT to evaluate it's diagnostic accuracy. smart app measures blood flowThe current study is the first to use the photoplethysmographic capabilities of smartphones to assess blood flow - in this case in the hand to assess for blockages in arteries before accessing them for a procedure. The hand is supplied by two arteries - the radial artery and the ulnar artery. In many cases in medicine we use the radial artery, whether it be placing a catheter to monitor blood pressure, as a method of getting to the heart for angioplasty and in coronary artery bypass grafting it is removed and used as a bypass to restore blood flow to the heart. In many instances doctors assess the patency of the ulnar artery to decided if they are going to use the radial artery for a procedure - the concept being that if the ulnar is compromised and we use the radial then the hand can develop complications from not enough blood flow. To determine if a patient is eligible doctors would use a bedside physical exam test called the modified Allen's test in which they occlude both arteries to cause the hand to turn white. They then release pressure on the ulnar letting blood only pass through this vessel to see if the hand turns pink. However, there is a lot of variability in what doctors consider to be abnormal and determining if the test is positive can depend on numerous factors including skin tone, the amount of pressure applied and the size of the vessels.
Author Interviews, Cannabis, JAMA, Opiods / 02.04.2018

MedicalResearch.com Interview with: [caption id="attachment_18486" align="alignleft" width="200"]Dr. Italia V. Rolle, PhD and Dr. Tim McAfee, MD Office on Smoking and Health National Center for Chronic Disease Prevention and Health Promotion CDC Marijuana plant[/caption] Hefei Wen, PhD Assistant Professor, Department of Health Management & Policy University of Kentucky College of Public Health  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Marijuana is one of the potential, non-opioid alternatives that can relieve pain at a relatively lower risk of addiction and virtually no risk of overdose. Medical and adult-use marijuana laws, has made marijuana available to more Americans. Yet no study to date has focused on the effect of medical and adult-use marijuana laws on opioid prescribing in particular. Our study provides some of the first empirical evidence that the implementation of medical and adult-use marijuana laws between 2011 and 2016 was associated with lower opioid prescribing rates and spending among Medicaid enrollees.  
Author Interviews, Gender Differences, JAMA, Surgical Research / 02.04.2018

MedicalResearch.com Interview with: Neel Mansukhani, MD Department of Surgery Northwestern University and Melina R. Kibbe, MD, FACS, FAHA Colin G. Thomas Jr. Distinguished Professor and Chair Department of Surgery Professor, Department of Biomedical Engineering The University of North Carolina at Chapel Hill Chapel Hill, NC 27599-7050 Editor in Chief, JAMA Surgery  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This study is a follow-up to our previous work that examined sex bias in surgical research. Previously, we examined sex bias in basic and translational science surgical research, as well as in clinical surgical research. We discovered previously that sex bias exists in basic and translational surgical research in the unequal inclusion of male and female research subjects. In clinical research, we found sex bias in the degree of sex matching of included subjects, and in the frequency of sex-based reporting, analysis, and discussion of the data. In this current work, we sought to understand the effect of author gender on sex bias in surgical research. In this work, we found that most authors are male, most authors work with other authors of the same gender, and sex bias is prevalent regardless of author gender. Most importantly, we found that sex inclusive research receives more citations after publication compared to sex-biased research. 
Author Interviews, Cannabis, JAMA, Opiods / 02.04.2018

MedicalResearch.com Interview with “Cannabis sativa” by Manuel is licensed under CC BY 2.0 David Bradford, Ph.D. Busbee Chair in Public Policy Department of Public Administration and Policy University of Georgia Athens, GA 30602 MedicalResearch.com: What is the background for this study? Response: To give you some background, in 2016, part of our research team (Bradford and Bradford) published the first study to directly examine the impact that medical cannabis laws (MCLs) may be having on prescription use. We used yearly physician-level Medicare Part D data, looked at nearly all prescription drugs used to treat 9 broad categories of illness/diagnoses, and found substantial reductions in prescriptions. We published a follow-up study in 2017, this time using data from Medicaid Fee-for-Service. Again, we found significant substitution away from prescription medications. In both of these studies, pain was included in the list of conditions for which cannabis may be used in patients, and in both studies, pain prescriptions fell. One of the unanswered questions from both of those studies, though, was what *type* of pain medications were being reduced.  From a public health standpoint, when we're worried about opioid overdose, it matters whether the substitution away from pain medications is coming from substitutions away from things like NSAIDs or whether there is substitution away from opioids.
Author Interviews, PLoS / 30.03.2018

MedicalResearch.com Interview with: Ksenija Marinkovic and Lauren Beaton Psychology Department - College of Sciences Spatio-Temporal Brain Imaging Lab Center for Clinical and Cognitive Neuroscience San Diego State University San Diego CA MedicalResearch.com: What is the background for this study? What are the main findings? Response: In general, we subjectively perceive our actions to be under our deliberate and voluntary control. However, our results are consistent with other accruing evidence suggesting that a large portion of our behavior is automatic and not accessible to conscious experience. The automatic processing primarily underlies predictable daily routines when we seem to be on an “auto-pilot”. In contrast, situations that are ambiguous or that evoke incompatible response tendencies engage cognitive control which allows conscious override of the preplanned actions and results in flexible behavior. Our study used a multimodal imaging approach that combines perfect time sensitivity of magnetoencephalography (MEG) with structural magnetic resonance imaging (MRI) to investigate spatio-temporal stages of the seamless interplay between automatic and controlled processing. MEG is a highly sensitive method that records magnetic fields generated by the brain’s neural activity in real time. Young, healthy, participants performed a version of the Eriksen Flanker task, which presents two colored squares on either side of a centrally presented target square that appears after a short delay. Participants are instructed to press a button corresponding to the color of the target square in the middle and to pay no attention to the flankers. Although participants know that the flankers are irrelevant, they are unable to disregard them deliberately. Instead, flankers trigger an automatic preparation to respond. This is particularly apparent on mismatch trials on which the flanker color is misleading and it activates the wrong hand. Target appearance overrides the initial automatic response as the response plan is switched to the other hand to make a correct response. This process reflects recruitment of cognitive control or the decision-making capacity which includes a range of functions such monitoring contextual demands, selecting the correct response, and suppressing an automatic but irrelevant action. Our multimodal MEG imaging method has allowed us to track the neural response as the brain prepares an incorrect response to flankers and then “switches” motor preparation between hemispheres. This approach makes it possible to investigate the interplay between automatic and controlled processing and dissect decision making as it unfolds. The addition of a moderate dose of alcohol dysregulates this frontal network involved in motor decision making, which decreases accuracy when response conflict is present and lowers neural activity reflecting cognitive control. Related to this overall decrease, and of clinical importance, is the reduced ability to employ cognitive control to refrain from drinking excessively. However, the underlying patterns of response-switching were preserved under alcohol, suggesting that alcohol primarily induces deficits upstream during decision making and not during executing motor commands. 
AHA Journals, Author Interviews, Stroke, Surgical Research / 29.03.2018

MedicalResearch.com Interview with: J.H.L. Mulder, MD PhD Neurology resident Erasmus MC  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Current information about safety and efficacy of endovascular treatment (EVT) for acute ischemic stroke is primarily derived from patients treated in the setting of a randomized controlled trial. However, inherent to this setting, external validity of the results can be jeopardized by patient selection and intensive monitoring. Therefore, an important question remained unanswered: could the positive effect of endovascular treatment be reproduced in standard clinical practice? 
Author Interviews, JAMA, Schizophrenia / 29.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40862" align="alignleft" width="178"]Silvana Galderisi MD President of the European Psychiatric Association Professor of Psychiatry University of Campania "Luigi Vanvitelli" Italy Dr. Galderisi[/caption] Silvana Galderisi MD President of the European Psychiatric Association Professor of Psychiatry University of Campania "Luigi Vanvitelli" Italy MedicalResearch.com: What is the background for this study? Response: The goal of schizophrenia treatment has gradually shifted from reduction of symptoms and prevention of relapse to improvement of real-life functioning. In fact, these outcomes not always coincide and, in spite of progress in treatments reducing symptoms and preventing relapses, people with schizophrenia live 15-20 years less than the general population, are often unemployed, and show severe disabilities. Enhanced understanding of factors associated with real-life functioning is instrumental to design effective integrated and personalized treatment plans for persons with schizophrenia. To this aim, the Italian Network for Research on Psychoses, including 26 twenty-six Italian university psychiatric clinics and/or mental health departments, has focused on the identification of variables influencing real-life functioning, in particular on the interrelationships among illness-related variables, personal resources, context-related variables and real-life functioning. The number of variables and subjects included in the study was larger than in any other study on this topic, and for the first time the network analysis was used to model the interplay among cognitive, psychopathological and psychosocial variables in a large sample of community dwelling subjects with schizophrenia. The network analysis is a data-driven approach; it does not rely on an a priori model of relationships among variables, provides quantitative measures of variable centrality within the network, thus indicating which variables play a key role in the network, and which ones are instead more peripheral. In addition, by inspecting the network, it is possible to understand the extent to which variables belonging to the same construct are connected, and how different constructs are mutually interacting and reinforcing each other. 
Alzheimer's - Dementia, Author Interviews, JAMA, Parkinson's / 27.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40768" align="alignleft" width="147"]Benjamin Dawson, B.Sc.  MD Candidate 2020 Benjamin Dawson[/caption] Benjamin Dawson, B.Sc. MD Candidate 2020 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Dementia in Parkinson’s Disease is one of its most feared complications, and may happen eventually to most patients if they reached advanced age. Identifying those at especially high risk of dementia has important potential implications - it would facilitate clinical counselling, it has treatment implications (e.g. knowing a person is likely to get dementia in the near future would probably steer you away from certain medications and towards others).  Most critically, it can help select patients for trials to prevent dementia. While several factors that show high risk for dementia in Parkinson’s disease have previously been described, these have yet to shape patient-care, either because they are not very strong predictors, or they are not user-friendly.  So, we designed a very simple clinical screening tool, called the Montreal Parkinson’s Risk of Dementia Scale (MoPaRDS).  It took predictors of dementia that were established from large-scale studies and boiled them down into a simple 8-point scale that uses information that you can get in a simple office visit.  The 8 predictors were being over 70, being male, having a blood pressure drop with standing, showing early mild cognitive changes, having a symmetric bilateral disease (that is, one side not clearly worse than the other), experiencing falls or freezing, having experienced hallucinations, and having symptoms of REM sleep behavior disorder ('acting out' the dreams at night). When we tested the scale in a combined cohort of 607 patients with Parkinson’s (of whom 70 developed dementia over mean follow-up of 4.4-years) a positive MoPaRDS screen (≥4 out of 8 items) identified 14-fold increased risk of dementia compared to a negative screen. We recommend dividing the scale into three categories; low-, intermediate- and high-risk. Those in the highest score group (MoPaRDS, 6-8) had a 14.9% risk of developing dementia each year, while those with the lowest scores (MoPaRDS, 0-3) had only 0.6% annual risk.  So, these simple measures can be pretty powerful predictors of dementia.
Author Interviews, Breast Cancer, Chemotherapy, JAMA, Novartis / 26.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40799" align="alignleft" width="145"]Melanie E. Royce, MD, PhD Division of Hematology/Oncology University of New Mexico Comprehensive Cancer Center Albuquerque Dr. Royce[/caption] Melanie E. RoyceMDPhD Division of Hematology/Oncology University of New Mexico Comprehensive Cancer Center Albuquerque MedicalResearch.com: What is the background for this study? What are the main findings? Response: BOLERO-4 is an open label, single-arm, Phase II study that evaluates the combination of everolimus plus letrozole as a first-line treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor (HER2)-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the BOLERO-4 trial published in JAMA Oncology showed that everolimus in combination with endocrine therapy is an effective first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer. A total of 202 patients received everolimus in combination with letrozole as first-line treatment between March 7, 2013 and December 17, 2014. Median progression-free survival (PFS) in the first-line setting was 22.0 months (95% CI 18.1-25.1) with an overall response rate of 45% (95% CI 38.1-52.2) and clinical benefit rate of 74% (95% CI 67.7-80.1). A total of 152 (75%) discontinued treatment, primarily due to disease progression (51%) or adverse events (16%). Data from a smaller number of patients in BOLERO-4 also show limited efficacy with continued everolimus, combined with exemestane, following disease progression. Second-line treatment was ongoing in 16 (32%) patients, while 34 (68%) had discontinued. The most frequent reason for second-line treatment discontinuation was disease progression (56%). In the second-line setting, median PFS was 3.7 months (95% CI 1.9-7.4) with an overall response of 6% (95% CI 1.3-16.5) and clinical benefit rate of 28% (95% CI 16.2-42.5). Safety findings from BOLERO-4 are consistent with previous studies of Afinitor in advanced breast cancer. The most common (≥ 20% incidence) first-line all-grade adverse events were stomatitis (69%), weight loss (44%), nausea (37%) and anemia (35%). Most were ‘low grade’ in severity (grade 1 or 2) and generally well managed. Safety findings show the most common (≥ 10% incidence) second-line adverse events were stomatitis (20%) and weight loss (20%). Lower rates of stomatitis in second-line were noted. 
Author Interviews, CDC, Infections, JAMA / 26.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40787" align="alignleft" width="125"]Dr. Katherine Fleming-Dutra, MD, senior author Deputy Director Office of Antibiotic Stewardship CDC Dr. Fleming-Dutra[/caption] Dr. Katherine Fleming-Dutra, MD, senior author Deputy Director Office of Antibiotic Stewardship CDC MedicalResearch.com: What is the background for this study? What are the main findings? Response: As noted in a previous study, antibiotics are prescribed more for sinus infections than any other illness in the United States. We found that almost 70% of antibiotic prescriptions were for 10 days or longer, whereas 5-7 days is recommended for most patients when antibiotics are needed. In addition, more than 20% of antibiotic prescriptions for sinus infections were for 5 days of azithromycin, even though guidelines recommend against prescribing azithromycin for sinus infections.
Author Interviews, CMAJ, Opiods / 26.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40728" align="alignleft" width="133"]Andrea Schaffer PhD Research Fellow Centre for Big Data Research in Health UNSW Sydney NSW Australia Dr. Schaffer[/caption] Andrea Schaffer PhD Research Fellow Centre for Big Data Research in Health UNSW Sydney NSW Australia  MedicalResearch.com: What is the background for this study? Response: Use and misuse of opioids has increased dramatically in Australia over the past 20 years. In 2014, Australia introduced tamper-resistant controlled-release (CR) oxycodone, which forms a viscous gel when crushed, and is designed to deter its injection or snorting. However, this formulation does not prevent dependence, and can still be misused orally. Tamper-resistant oxycodone CR was also introduced in the US (2010) and Canada (2012), resulting in reductions in oxycodone CR use. However, no large population-level studies have looked at switching behaviour in individuals using oxycodone CR, either in Australia or abroad.
Author Interviews, Cancer Research, Hepatitis - Liver Disease, JAMA / 26.03.2018

MedicalResearch.com Interview with: Sang Min Park MD, MPH, PhD Chief, Department of Family Medicine, Seoul National University College of Medicine Director, Health Promotion Center, Seoul National University Hospital Professor, Department of Biomedical Science & Family Medicine Seoul National University College of Medicine Seoul, Korea What is the background for this study? What are the main findings? Response: Chronic hepatitis B patients have a higher risk of hepatocellular carcinoma than the general population, which has been well-established and known to be caused by progression of hepatitis B infection into severe liver diseases. However, whether obesity-related carcinogenesis plays a central role in the development of hepatocellular carcinoma in chronic hepatitis B patients remained unclear. Therefore, we assessed the association between body mass index and risk of hepatocellular carcinoma in chronic hepatitis B patients, and stratified all analyses by sex using healthcare big data in the Republic of Korea. We found positive association of trends between body mass index and risk of hepatocellular carcinoma in both men and women with hepatitis B infection. The magnitude of the association in women was stronger than that of men. In the severely obese category, the hazard ratio for hepatocellular carcinoma was significantly higher in women compared to men. Our findings highlight that high body mass index is associated with risk of hepatocellular carcinoma in chronic hepatitis B patients, especially in women, which may be partially explained by higher fat content for the same unit of body mass index in women compared to men.