Author Interviews, Dermatology, JAMA, Melatonin, Pediatrics, Sleep Disorders / 23.11.2015 Interview with: Prof. Bor-Luen Chiang Vice Superintendent, National Taiwan University Hospital Professor of Graduate Institute of Clinical Medicine and Pediatrics National Taiwan University Attending Physician, Department of Medical research National Taiwan University Hospital and Yung-Sen Chang, MD MPH Attending physician, Department of Pediatrics, Taipei City Hospital Renai Br. Adjunct Attending Physician, Department of Pediatrics National Taiwan University Children’s Hospital Adjunct Instructor, School of Medicine, National Yang-Ming University Medical Research: What is the background for this study? Prof. Chang: Sleep disturbance is a common disorder in the children with atopic dermatitis (AD) (reported in 47 to 60%), but no effective way of managing this problem had been established. In our preceding study, we found that lower nocturnal melatonin level was significantly associated with sleep disturbance in the patients with AD. Melatonin is a hormone secreted by the pineal gland which plays an important role in sleep regulation. In addition to sleep-inducing effects, melatonin also has anti-inflammatory and immunomodulatory properties which might be helpful for the management o fatopic dermatitis. Furthermore, melatonin has an excellent safety profile with minimal adverse effects, making it a good choice for children. Therefore, we aimed to evaluate whether melatonin is effective for improving the sleep problems and the dermatitis severity in children with atopic dermatitis. Medical Research: What are the main findings? Prof. Chang: From our double-blind, placebo-controlled crossover study, we found that after melatonin treatment, the sleep onset latency shortened by 21.4 minutes compared with placebo (from a mean of 44.9 minutes to 21.6 minutes). The Scoring Atopic Dermatitis Index (higher scores representing more severe dermatitis) also decreased by 9.9 compared with placebo (from a mean of 49.1 to 40.2). No adverse events were reported throughout the study. (more…)
Author Interviews, Depression, JAMA / 20.11.2015 Interview with: Raymond W. Lam, MD, FRCPC Professor and Associate Head for Research Department of Psychiatry, University of British Columbia Director, Mood Disorders Centre, Djavad Mowafaghian Centre for Brain Health Executive Chair, Canadian Network for Mood and Anxiety Treatments (CANMAT) Vancouver, BC, Canada Medical Research: What is the background for this study? Dr. Lam: Our multicentre team studied the effects of bright light therapy for nonseasonal depression. Light therapy is a non-pharmacological approach that has been studied as a treatment for seasonal affective disorder (SAD, or "winter depression"), but only a small number of studies has explored the use of light therapy in treating nonseasonal depression. Clinical depression, known formally as Major Depressive Disorder (MDD) is the most common psychiatric disorder and one of the most common medical conditions worldwide. At any given time, at least 1 person in 20 (5% of the general population) is experiencing MDD, which will become the second-leading cause of disability worldwide by 2020, according to the World Health Organization.  (more…)
Author Interviews, JAMA, Outcomes & Safety, Urinary Tract Infections, Urology / 19.11.2015 Interview with: Jerome A. Leis, MD MSc FRCPC Staff physician, General Internal Medicine and Infectious Diseases Physician Lead, Antimicrobial Stewardship Team Staff member, Centre for Quality Improvement and Patient Safety Sunnybrook Health Sciences Centre Assistant Professor, Department of Medicine, University of Toronto Medical Research: What is the background for this study? What are the main findings? Dr. Leis: Overuse of urinary catheters leads to significant morbidity among hospitalized patients.  In most hospitals, discontinuation of urinary catheters relies on individual providers remembering to re-assess whether patients have an ongoing reason for a urinary catheter.  We engaged all of the attending physicians to agree on the appropriate reasons for leaving a urinary catheter in place and developed a medical directive for nurses to remove all urinary catheters lacking these indications.  This nurse-led intervention resulted in a significant reduction in urinary catheter use and catheter-associated urinary tract infections, compared with wards that continued to rely on usual practice. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Pancreatic, Race/Ethnic Diversity, Surgical Research / 18.11.2015 Interview with: Jason S. Gold MD FACS Chief of Surgical Oncology, VA Boston Healthcare System Assistant Professor of Surgery, Harvard Medical School Brigham and Women’s Hospital Medical Research: What is the background for this study? Dr. Gold: Pancreas cancer is a lethal disease. While advances in the best available care for pancreas cancer are desperately needed, improvements can be made in addressing disparities in care. This study aimed to evaluate associations of social and demographic variables with the utilization of surgical resection as well as with survival after surgical resection for early-stage pancreas cancer. Medical Research: What are the main findings? Dr. Gold: The main findings are the following: 1:     We found that less than half of patients with early-stage pancreas cancer undergo resection in the United States. Interestingly, the rate of resection has not changed with time during the eight-year study period. 2.  We also found significant disparities associated with the utilization of surgical resection for early-stage pancreas cancer in the United States. African American patients, Hispanic patients, single patients, and uninsured patients were significantly less likely to have their tumors removed. There were regional variations in the utilization of surgical resection as well. Patients in the Southeast were significantly less likely to have a pancreas resection for cancer compared to patients in the Northeast. 3. Among the patients who underwent surgical resection for early-stage pancreas cancer, we did not see significant independent associations with survival for most of the social and demographic variables analyzed. Surprisingly, however, patients from the Southeast had worse long-term survival after pancreas cancer resection compared to those in other regions of the United States even after adjusting for other variables. (more…)
Author Interviews, Depression, JAMA, Neurological Disorders / 18.11.2015

Claudia van Borkulo, MSc University of Groningen, University Medical Center Groningen Department of Psychiatry, Research School of Behavioural and Cognitive Neurosciences, Interdisciplinary Center for Psychopathology and Emotion Regulation, Groningen, the Interview with: Claudia van Borkulo, MSc University of Groningen, University Medical Center Groningen Department of Psychiatry, Research School of Behavioural and Cognitive Neurosciences, Interdisciplinary Center for Psychopathology and Emotion Regulation, Groningen, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: We consider psychiatric disorders as complex dynamical systems in which symptoms can interact with each other. This novel network approach to psychopathology – that is new to psychiatry – implies that a more densely connected network of symptoms of a disorder might be indicative of worse prognosis. Having one symptom can easily lead to developing more symptoms in a densely connected network, in which more symptoms reinforce each other. Reversely, a symptom in a less densely connected network will rarely turn on other symptoms. A densely connected network can theoretically be related to an increased vulnerability; because of the high level of mutual reinforcement, a small external stressor can induce a quicker transition from a healthy state to a depressed state for people with a more densely connected network. In our study, we investigated the association between baseline network structure of depression symptoms and longitudinal course of depression. We compared the baseline network structure of persisters (defined as patients with MDD at baseline and depressive symptomatology at 2-year follow-up) and remitters (patients with MDD at baseline without depressive symptomatology at 2-year follow-up). While both groups have similar symptomatology at baseline, persisters have a more densely connected network compared to remitters. More specific symptom associations seem to be an important determinant of persistence of depression. (more…)
Author Interviews, JAMA, Pediatrics, Respiratory / 17.11.2015 Interview with: Leonard B. Bacharier, MD Professor of pediatrics Clinical Director, Division of Allergy, Immunology and Pulmonary Medicine St Louis School of Medicine Washington University St Louis, Missouri  Medical Research: What is the background for this study? What are the main findings? Dr. Bacharier: Oral corticosteroids such as prednisone have become the standard of care for children whose colds tend to progress and lead to severe wheezing and difficulty breathing. “But there are some studies that suggest these treatments don’t consistently work for young children. That’s why we want to find ways to prevent upper respiratory infections from progressing to lower respiratory tract illnesses. Once the episode gets going, standard interventions are less effective than would be desired”​​​​​​​​​​​​​​​​, reported Dr. Bacharier. (more…)
Author Interviews, Genetic Research, JAMA, Neurological Disorders / 17.11.2015 Interview with: Kevin M. Biglan, M.D., M.P.H Professor of Neurology and the Associate Chair for Clinical Research Department of Neurology and the Center for Human Experimental Therapeutics University of Rochester School of Medicine and Dentistry Rochester, New York  Medical Research: What is the background for this study? What are the main findings? Dr. Biglan: A therapeutic goal of research in Huntington Disease (HD) is the identification of treatments that delay the progression of disease and onset of illness in individuals at risk for developing manifest HD. Designing such efficacy trials is challenging. A major hurdle is the lack of practical primary outcome measures to assess the effect of an intervention on delaying disease onset. Use of the dichotomous endpoint of clinical diagnosis as the primary outcome requires large sample sizes and long duration of follow up in order to show a significant therapeutic effect on delaying disease onset. Continuous measures that can reliably distinguish cytosine-adenine-guanine (CAG) expanded individuals in the pre-manifest period may allow for the identification of potential disease modifying therapies using relatively smaller cohorts followed for shorter periods of time. The Prospective Huntington At-Risk Observational Study (PHAROS) represents the largest observational study to clinically evaluate pre-manifest Huntington Disease wherein both research participants and investigators were unaware of Huntington Disease mutation status. Accordingly, PHAROS was uniquely designed to address, in an unbiased manner, those clinical features most associated with the CAG expansion during the prodromal phase in  Huntington Disease.  The identification of continuous outcome measures that are associated with HD in the pre-manifest period may facilitate the design and powering of future studies of potential disease modifying therapies prior to traditional motor diagnosis. (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology / 16.11.2015 Interview with: Adam R. Glassman, MS Jaeb Center for Health Research Tampa, FL 33647 Medical Research: What is the background for this study? What are the main findings? Response: Diabetic retinopathy is a complication of diabetes that affects blood vessels in the retina. When diabetic retinopathy worsens to proliferative diabetic retinopathy, blood vessels in the retina can leak fluid or bleed, distorting vision. Diabetic retinopathy is the most common cause of vision loss among people with diabetes and the leading cause of blindness among working-age adults. Scatter laser treatment, also called panretinal photocoagulation, has been standard therapy for the treatment of proliferative diabetic retinopathy since the 1970s. While effective in preserving central vision, laser therapy can reduce side vision and cause swelling in an area of the retina that is important for central vision. This study aimed to find an alternative therapy that avoided these undesirable side effects. Eyes in this study were assigned randomly to treatment with intraocular anti-VEGF injections of Lucentis® or scatter laser treatment. The results of this study demonstrate that eye injections of Lucentis® are as effective for vision outcomes at 2 years as laser therapy. On average, vision among eyes treated with Lucentis® improved by about half a line on an eye chart, with virtually no improvement among eyes treated with laser therapy. Compared with laser-treated eyes, eyes treated with Lucentis injection on average had less side vision loss, less frequent development of swelling in the central retina, and fewer complex retina surgeries for retinal bleeding or retinal detachment. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA / 14.11.2015 Interview with: Samuel Klempner, M.D. Assistant Professor Division of Hematology/Oncology UC Irvine Health Orange, CA 92868  Medical Research: What is the background for this study? What are the main findings? Dr. Klempner: The background for our series is the concept that little is known about the genetic landscape of rare tumors such as acinic cell tumors, and that understanding genetic changes in tumors can identify treatment options.  This paradigm can, and should, be extended beyond rare tumor types and many researchers are currently studying various tumor types.  Another important background idea is that tumor genomic alterations may be more important than that anatomic site of origin. For example, I would argue that a breast cancer that harbors an EGFR mutation common to lung cancer could be treated similar to a lung cancer based on the genomic changes. In our study we found another way that the BRAF protein and its downstream signaling may become activated through duplicating part of the protein called the kinase domain.  This genetic event causes the pathway to be always "on" which is not normal, and likely drives cancer growth.  However, BRAF kinase domain duplication appears sensitive to currently available drugs that target the BRAF pathway, as evidenced by the response in our patient.  Thus, finding this change is important and may be able to guide a more personalized therapy choice.  Importantly, we found BRAF kinase domain duplication across multiple different tumor types, suggesting this may be a recurrent event in some cancers.  A very similar finding, involving duplication of the EGFR kinase domain, was also just reported (Cancer Discovery 2015;5:1155-1163) lending further validation to this mechanism of pathway activation in cancer. (more…)
Author Interviews, JAMA, Mental Health Research, Primary Care / 13.11.2015

Shahrzad Mavandadi, PhD Research Health Science Specialist and Investigator Veterans Integrated Services Network 4 Mental Illness Research, Education, and Clinical Center Corporal Michael J. Crescenz Veterans Affairs Medical Center Philadelphia, Interview with: Shahrzad Mavandadi, PhD Research Health Science Specialist and Investigator Veterans Integrated Services Network 4 Mental Illness Research, Education, and Clinical Center Corporal Michael J. Crescenz Veterans Affairs Medical Center Philadelphia, Pennsylvania  Medical Research: What is the background for this study? Dr. Mavandadi: Mental health (MH) conditions are underidentified and undertreated in later life.  This is particularly true among subgroups of older adults who are more vulnerable to developing mental health issues, have poor access to specialty care, and are less responsive to treatment and therapy.  Thus, we sought to evaluate longitudinal MH outcomes among low-income, community-dwelling older adults enrolled in an evidence-based, collaborative mental health care management service (i.e., the SUpporting Seniors Receiving Treatment And INtervention (SUSTAIN) program).  The SUSTAIN program integrates mental health with primary care (which is where the majority of behavioral health conditions in later life are managed) and provides standardized, measurement-based, software-aided MH assessment and connection to community resources to older adults by telephone. While there is a strong evidence base for the efficacy of collaborative care models for me conditions, little is known about the amount or level of patient and provider support that is needed to achieve optimal behavioral health outcomes.  Thus, we specifically examined outcomes among older adults randomized to one of two program arms of varying intensity: MH symptom monitoring alone or mental health symptom monitoring plus MH care management.   MH care management involved care managers who provided education, counseling, and decision support to patients and their primary care providers, a licensed mental health clinician who supervised the care managers, and the use of an algorithm to help guide pharmacological and non-pharmacological treatment plans.  The sample consisted of 1018 older adults prescribed an antidepressant or anxiolytic by their non-behavioral health providers who presented with clinically significant symptoms at intake. (more…)
Author Interviews, JAMA, Mental Health Research, Pediatrics / 13.11.2015 Interview with: Dr. Mai-Britt Guldin PhD Department of Public Health Aarhus University  Medical Research: What is the background for this study? Dr. Guldin: The background for this study is that death of a parent in childhood is experienced by 3-4% of children in Western societies, and we know such a loss is one of the most stressful and potentially harmful events in childhood. Therefore, we aimed to investigate how parental death may influence the long-term risk of suicide and how this risk differes by cause of parental death, age at loss, sex of child, socioeconomic factors and parental history of psychiatric illness.The sample size in this study is unparalleled by other studies on risk of suicide. Medical Research: What are the main findings? Dr. Guldin: The main findings were that in a population of 7.302,033 (in three Scandinavian countries), we identified 189,094 persons who lost a parent before the age of 18. Of these bereaved persons, 265 died from suicide. Compared to a control group of persons matched by age and sex, but who did not lose a parent before the age of 18, suicide was twice as common in the bereaved cohort (IRR = 2.02; 95% CI, 1.67-2.44). The risk remained high for at least 25 years of follow-up. The risk was particularly high for children who lost a parent due to suicide, but was also high for children who lost a parent due to other causes. The risk tended to be particularly high for boys who lost a mother and children losing a parent before the age of six. (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, JAMA, Neurological Disorders, Schizophrenia / 12.11.2015 Interview with: Frederick W. Vonberg, MA, MBBS Research Fellow in Neurocritical Care Boston Children's Hospital and Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Response: An association between schizophrenia and epilepsy has long been suspected, ever since people noticed similarities in some aspects of the presentation of the two conditions, and in their epidemiology. For example, people with epilepsy are thought to be more at risk of developing schizophrenia. Furthermore, a psychosis resembling schizophrenia can characterize some forms of epilepsy. Whether this link reflected an overlap in the genetics of the two conditions has remained a mystery, however. In this study, we used a recently developed computational technique to show that there is a significant positive correlation between the genetic variants that are associated with epilepsy and with those that are associated with schizophrenia. (more…)
Author Interviews, Duke, JAMA, Pharmacology, Stroke / 10.11.2015 Interview with: Ying Xian, PhD Assistant Professor of Medicine. Member in the Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Xian: Intravenous tissue plasminogen activator (tPA) is the only FDA approved medical therapy to reduce disability and improve outcomes for patients with acute ischemic stroke. But treatment with tPA also carries the risk of symptomatic intracranial hemorrhage (sICH), which is often fatal. Nearly half of ischemic stroke patients are taking antiplatelet drugs such as aspirin and/or clopidogrel prior to stroke. We found these patients had higher risk for sICH when treated with tPA. But the risk is relatively small. For every 147 patients on aspirin treated with tPA, only 1 more symptomatic intracranial hemorrhage as compared with those treated with tPA without prior antiplatelet therapy. The risk is slightly higher among those on dual antiplatelet therapy of aspirin and clopidogrel (number needed to harm 60). Despite the higher bleeding risk, patients treated with tPA on prior antiplatelet therapy appeared to have better functional outcomes in terms of ambulatory status and modified Rankin scale than those not on prior antiplatelet therapy. Therefore, overall the benefits of thrombolytic therapy may outweigh the risks. (more…)
Author Interviews, Diabetes, JAMA, Pediatrics, Probiotics / 10.11.2015

Dr. Ulla Uusitalo PhD University of South Florida, Interview with: Dr. Ulla Uusitalo PhD University of South Florida, Tampa Medical Research: What is the background for this study? What are the main findings? Dr. Uusitalo: The TEDDY Study is an international prospective cohort study with the primary goal to identify environmental causes of Type 1 Diabetes (T1D). It is carried out in six clinical research centers, in four countries: University of Colorado Health Science Center (US), Georgia Regents University (US), Pacific Northwest Diabetes Research Institute (US), Turku University Hospital (Finland), Institute of Diabetes Research (Germany), and Lund University (Sweden), since 2004. One possible environmental factor related to Type 1 Diabetes etiology is diet. Dietary supplements including probiotics as well as various types of infant formulas including probiotic fortified infant formula are studied. The microbial composition of gut has been shown to be associated with the development of  Type 1 Diabetes. Colonization of the infant gut starts already in utero and early microbial exposures have been found to be important in defining the trajectory of colonization. Probiotics have been demonstrated to induce favorable immunomodulation and it has been suggested that probiotic treatment could prevent T1D. Therefore we wanted to study the early exposures of probiotic and risk of islet autoimmunity, a condition often preceding Type 1 Diabetes. This study produced very interesting results. The main finding was that we found 60% decrease in the risk of islet autoimmunity among children with HLA genotype of DR3/4 (high risk), who were exposed to probiotics during the first 27 days of life. (more…)
Author Interviews, Diabetes, Heart Disease, JAMA, Mental Health Research / 10.11.2015 Interview with: Dr. Christina Mangurian MD Associate Professor of Clinical Psychiatry UCSF School of Medicine and the UCSF Department of Psychiatry's first Director of Diversity Medical Research: What is the background for this study? What are the main findings? Dr. Mangurian: People with severe mental illness (SMI, e.g., schizophrenia and bipolar disorder) die 25 years earlier than the general population, often from cardiovascular disease.  The ADA and APA guidelines recommend annual diabetes screening of this population when taking certain antipsychotic medications.  Despite these guidelines, nearly 70% of this population remain unscreened.  This has huge public health implications and likely costs our public health system a tremendous amount in undiagnosed disease. (more…)
Author Interviews, Heart Disease, JAMA, PAD / 09.11.2015 Interview with: Farzin Fakhry, MD PhD Candidate Depts. of Epidemiology & Radiology Erasmus MC Rotterdam, the Netherlands and Myriam Hunink MD, PhD Professor Professor of Radiology and Clinical Epidemiology Erasmus University Medical Center Rotterdam Adjunct Professor of Health Decision Science Harvard T.H. Chan School of Public Health, Boston Medical Research: What is the background for this study? What are the main findings? Response: Intermittent claudication is the classical symptomatic form of peripheral arterial disease (PAD) and affects approximately 20-40 million people worldwide. These patients experience significant functional disability resulting in a sedentary lifestyle and reduced quality of life. In the Endovascular Revascularization And Supervised Exercise (ERASE) study we compared a combination therapy of endovascular revascularization plus supervised exercise versus the recommended care of supervised exercise only as first-line treatment for patients with intermittent claudication. Results from the ERASE study showed that after one year follow up patients in both groups showed significant improvements in their treadmill walking distance and disease specific quality of life. Yet, patients receiving the combination therapy had more rapid and significantly greater improvement in their walking performance and disease specific quality of life compared to the patients following a supervised exercise program only. (more…)
Author Interviews, Gender Differences, Heart Disease, JAMA / 09.11.2015 Interview with: Dr. David Bluemke MD, PhD, MsB Director of Radiology and Imaging Sciences NIH Clinical Center Bethesda, MD  Medical Research: What is the background for this study? What are the main findings? Dr. Bluemke: Heart disease is the most common reason for death and disability of adults in the United States and worldwide. This study evaluated 1,840 adults in six communities throughout the United States, ages 45-84. In normal adults, the heart is a muscle, but various injuries to the heart (the most severe being a myocardial infarction/ heart attack) occur over an individual’s lifetime. These injuries result in heart muscle being replaced by a scar composed of fibrous tissue. The main finding is that even in healthy, middle and older adults, about 1 in 12 adults in the U.S. have developed scars in the heart. Most of these (80%) are not detected by their doctor, or by other tests such as ECG. (more…)
Author Interviews, Cancer Research, JAMA, MD Anderson / 05.11.2015 Interview with: William N. William Jr., MD Associate Professor Chief, Head and Neck Section Department of Thoracic / Head and Neck Medical Oncology The University of Texas M. D. Anderson Cancer Center Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. William: Oral pre-malignant lesions are often characterized as white and/or red patches in the mouth and are considered risk factors for oral cancer. This is why it might be best for people to go get oral cancer screening done if they suspect that there might be a problem. However, not all oral pre-malignant lesions will turn into cancer, but when this happens, surgery is usually recommended, many times leading to serious speech and swallowing dysfunction. Chemoprevention is the use of compounds to prevent cancers from happening before they occur. One of the greatest challenges in developing chemopreventive agents is to identify the population at highest cancer risk. The Erlotinib Prevention of Oral Cancer (EPOC) trial involved 379 patients at five sites across the country. All had premalignant lesions in their mouths. Following study enrollment, participants were evaluated for LOH, a chromosomal abnormality characterized by the loss of chromosomal regions, which include tumor suppressor genes. Patients who tested positive for LOH were considered to be at high risk for oral cancer and were randomized to receive either erlotinib (an EGFR inhibitor drug) or a placebo for one year. The study’s primary endpoint was to determine if fewer patients treated with erlotinib would develop oral cancer, compared to those that received placebo. The EPOC study demonstrated that LOH predicted a higher oral cancer risk. LOH-negative patients had a three-year cancer-free survival rate of 87 percent compared to 74 percent for the LOH-positive group. However, patients who took erlotinib showed no statistical difference in terms of cancer-free survival rates after three years: 74 percent for participants given erlotinib compared to 70 percent for those taking placebo. Patients with both LOH and EGFR copy number gains had the highest incidence of cancer, but still did not benefit from erlotinib. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA / 05.11.2015 Interview with: Dr. Brad A. Bryan Ph.D Assistant Professor Biomedical Sciences Texas A&M University Health Science Center, Houston, TX Department of Biomedical Sciences Texas Tech University Health Sciences Center Medical Research: What is the background for this study? What are the main findings? Dr. Bryan: In 2008 it was serendipitously discovered that the beta blocker propranolol was effective in treating a common benign pediatric vascular tumor called infantile hemangioma.  Over the past few years, my lab has been working on elucidating the molecular mechanisms underlying this pediatric tumor and part of this research involved uncovering how propranolol selectively inhibited these tumors.  At the same time these studies were taking place, other members of my lab were working on pre-clinical drug development for a malignant vascular tumor called angiosarcoma.  Patients with angiosarcoma are faced with very few effective treatment options and abysmal survival rates, so we decided to see if the efficacy of beta blockade observed in infantile hemangiomas transferred to angiosarcomas.  Using preclinical in vitro and in vivo assays, we demonstrated that propranolol was very effective at inducing cell death, blocking migration, and inhibiting tumor growth in our angiosarcoma models.  This work was subsequently published in Plos One (Stiles et al., 2013).  I then collaborated with Dr. William Chow from San Francisco to test propranolol off-label (propranolol is FDA approved to treat high blood pressure, heart dysrhythmias, thyrotoxicosis, and essential tremors) in a patient suffering from a rapidly expanding angiosarcoma covering a large portion of his face.  In the window between diagnosis of the tumor and the start of chemotherapy, we placed the patient on oral propranolol.  The redness of the tumor very rapidly lessened and remarkably by only one week of treatment the tumor margins appeared to significantly shrink.  We examined biospies of the tumor before and after only one week of propranolol and found that the proliferation of the tumor cells was markedly decreased following beta blockade.  After a combination of propranolol, chemotherapy, and radiation that lasted several months, the patient had no detectable metabolically active tumor or distant metastases. We published these findings in JAMA Dermatology (Chow et al., 2015). (more…)
Author Interviews, JAMA, Stroke, Surgical Research / 04.11.2015 Interview with: Saleh A Almenawer, MD Neurosurgeon, Hamilton Health Sciences McMaster University Hamilton, ON Canada  Medical Research: What is the background for this study? Dr. Almenawer: The current standard therapy for acute ischemic stroke is intravenous tissue plasminogen activator (tPA), which improves survival and functional outcomes when administered as early as possible after stroke. However, the use of intravenous tPA is limited by the narrow therapeutic time window (< 4.5 hours) and by important contraindications, including coagulopathy, recent surgery, or stroke or head injury within the past 3 months. This leaves as few as 10% of patients presenting with ischemic stroke eligible for treatment with tPA. Moreover, intravenous tPA is associated with long recanalization times and poor revascularization rates in proximal large vessel occlusion, and the prognosis of these patients remains poor. The limitations of intravenous tPA have spurred interest in endovascular thrombectomy for acute ischemic stroke, analogous to thrombolysis versus percutaneous coronary intervention for myocardial infarction. Several randomized clinical trials (RCTs) have compared clinical outcomes of mechanical thrombectomy to standard medical treatment with intravenous tPA. The current study was a meta-analysis of RCTs that aimed to answer the question of whether endovascular thrombectomy is associated with better clinical outcomes than intravenous tPA, and accordingly, whether endovascular thrombectomy should replace intravenous tPA as the new standard of care for ischemic stroke. (more…)
Author Interviews, Cost of Health Care, JAMA, Pharmacology, Sloan Kettering / 04.11.2015 Interview with: Dr. Elizabeth D. Kantor PhD MPH Assistant Attending Epidemiologist Memorial Sloan Kettering Cancer Center

Medical Research: What is the background for this study? What are the main findings? Dr. Kantor: We know that use of prescription drugs represents a major expenditure in the United States and research suggests that use of prescriptions has increased. However, much of what we know is derived from information on expenditures, is outdated, or is limited to certain populations, such as older adults or those with a given clinical condition. For example, a number of studies have looked at things like use of drugs used to control condition x among persons with condition x, but that doesn't tell us about use of that class of drugs in the population. It’s important that we continue to monitor use of prescription drugs in the population, as practice patterns are continually evolving as the population ages, the health needs of the population change, drugs enter/exit the market, scientific knowledge advances, and policies change. We therefore sought to create an updated comprehensive reference on prescription drug use among US adults using nationally representative data from the National Health And Nutrition Examination Survey, a continuous survey conducted by the Centers for Disease Control and Prevention. We examined trends in use of prescription drugs over 7 cycles, ranging from 1999-2000 to 2011-2012 (the sample size per cycle ranged from 4,861 to 6,212).Participants were asked about use of prescription medications over the prior 30 days, from which we were able to estimate the prevalence of use within each survey cycle. We then looked at trends in prescription drug use, both overall and within drug classes. In our study, we observed that use of any prescription medications increased over the study period, with 51% of adults reporting any prescription medication use in 1999-2000 and 59% reporting any use in 2011-2012. We also observed an increase in polypharmacy (or use of 5 or more prescription drugs) over the study period, with approximately 8% of adults reporting use of 5 or more drugs in 1999-2000, as compared to 15% in 2011-2012. Polypharmacy was much more common among older adults: 24% of adults ages 65 and older reported use of 5 or more drugs in 1999-2000 and 39% reported use of 5 or more drugs in 2011-2012. At first glance, one might take a look at these results and think that this is probably because the US population is aging and people tend to take more drugs as they age. But we found that the increase in overall prescription drug use and polypharmacy persisted even after accounting for the aging of the US population. This means that something else is driving the observed increase in use of prescription drugs. We also found that use of the majority of drug classes increased over the study period. For example, among commonly used drug classes, we observed marked increases in use of drugs taken to control high cholesterol, high blood pressure, and diabetes. We also observed marked increases in some less commonly used drug classes, such as muscle relaxants. Interestingly, if we look at the ten most commonly used drugs in 2011-2012, we can see that most are taken for conditions associated with cardiometabolic disease This raises the question of how much of this increase in prescription drug use may be attributable to overweight/obesity, as we know that the prevalence of obesity has increased among US adults. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, McGill, Pharmacology / 04.11.2015 Interview with: Tewodros Eguale, MD, PhD Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada Research Fellow in Medicine Brigham and Women's Hospital Medical Research: What is the background for this study? Dr. EgualeOff-label prescribing is common and has been identified as a potentially important contributor to preventable adverse drug events (ADE). Significant deleterious effects were reported with off-label use of some drugs. Moreover, studies in children, where drugs are often used without sufficient scientific investigation, have shown that off-label uses increase the risk of ADE.  In adults, there has been no systematic investigation of the effects of off-label use in real world situation. The lack of knowledge is related to the methodological challenges of measuring off-label use and its effects; specifically the lack of link between prescribed drugs and their indication for use. The Medical Office of the XXI Century (MOXXI) electronic health record (EHR), developed by team of researchers at McGill University, facilitates the documentation of treatment indications, reasons for discontinuation of drug orders and adverse drug event. These new features provided the first opportunity to systematically monitor and evaluate off-label use and the occurrence of adverse drug events.  This study took advantage of the use of this new generation of software in a network of primary care practices to systematicaly evaluate the effect of off-label use on ADEs. (more…)
Author Interviews, Columbia, Compliance, HIV, JAMA, Pediatrics / 04.11.2015 Interview with: Dr. Louise Kuhn PhD Professor, Epidemiology Sergievsky Center Columbia University  Medical Research: What is the background for this study? What are the main findings? Dr. Kuhn: Ritonavir-boosted lopinavir-based antiretroviral therapy is recommended as first-line treatment for HIV-infected infants and young children while efavirenz is recommended for adults and older children. There are several advantages of transitioning HIV-infected children to efavirenz-based treatment as they get older.  These advantages include the possibility of once-daily dosing, simplification of co-treatment for tuberculosis, avoidance of some metabolic toxicities, preservation of ritonavir-boosted lopinavir for second-line treatment, and alignment of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz-based treatment in children exposed to nevirapine for prevention of mother-to-child transmission.  This is because efavirenz and nevirapine are in the same drug class and the majority of children who become infected despite exposure to nevirapine used for prevention have mutations in their virus that usually predict resistance to this drug class. In this study, we randomized HIV-infected children to two different treatment strategies: In the control strategy they remained on their initial ritonavir-boosted lopinavir regimen; in the alternative strategy they transitioned to an efavirenz-based regimen.  All children had been exposed to nevirapine used (unsuccessfully) to prevent mother to child HIV transmission and were virologically-suppressed (HIV in blood < 50 copies/ml) at the time of enrollment into the study.  We observed excellent virological control in both groups with fewer than 3% of children having levels of HIV in their blood greater than 1000 copies/ml.  Sustained suppression of virus in blood below 50 copies/ml throughout follow-up was achieved in 82% of the children transitioned to efavirenz-based treatment compared to 72% of children remaining on the control treatment. (more…)
Author Interviews, JAMA, Surgical Research / 29.10.2015 Interview with: Luke Rudmik, MD Division of Otolaryngology–Head and Neck Surgery Department of Surgery University of Calgary Calgary, Alberta, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Rudmik: The main findings were that patients with chronic sinusitis who have lower impairments in their quality of life can have their work productivity maintained with continuing medical therapy. Although there were no 'improvements' in the patients productivity with continuing medical therapy, it is important to note that patients in this study had better baseline quality of life and better baseline productivity compared to patients who chose to receive sinus surgery who had worse baseline quality of life and baseline productivity impairment. (more…)
Author Interviews, Cancer, Cancer Research, JAMA / 29.10.2015

Jiemin Ma, PhD, MHS Director of Surveillance and Health Services Research American Cancer Interview with: Jiemin Ma, PhD, MHS Director of Surveillance and Health Services Research American Cancer Society Medical Research: What is the background for this study? What are the main findings? Dr. Ma: This study is an analysis of long-term trends in mortality for all causes combined and for 6 leading causes of death, including heart disease, cancer, stroke, chronic obstructive pulmonary disease (COPD), unintentional injuries, and diabetes, in the United States from 1969 through 2013. We found that death rates for all causes and for five of these 6 leading causes (except COPD) decreased during this time period, although the rate of decrease appears to have slowed for heart disease, stroke, and diabetes. COPD death rates doubled during this time period, although the rate began to decrease in men since 1999. (more…)
Author Interviews, Cancer Research, Education, JAMA / 29.10.2015 Interview with: Vinay Prasad, MD MPH Assistant Professor of Medicine Division of Hematology Oncology in the Knight Cancer Institute Department of Public Health and Preventive Medicine Senior Scholar in the Center for Health Care Ethics Oregon Health and Sciences University Portland, Oregon 97239   Medical Research: What is the background for this study? What are the main findings? Dr. Prasad: We wanted to get some information about when and which cancer drugs were called "game changer" or "breakthrough" or "revolutionary".  What we found was surprising.  The use of these grandiose terms, or superlatives, was common in news articles.  They occurred across many classes of medication, were used for approved and unapproved drugs, and some of the use was questionable. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Race/Ethnic Diversity, Surgical Research / 23.10.2015 Interview with: Dr. Quoc-Dien Trinh MD Assistant Professor of Surgery Harvard Medical School  Brigham and Women's Hospital Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Trinh:  Blacks who undergo radical prostatectomy, e.g. surgical removal of the prostate for cancer, are more likely to experience complications, emergency room visits, readmissions compared to their non-hispanic White counterparts. As a result, the 1-year costs of care for Blacks is significantly higher than non-hispanic Whites. Interestingly, despite these quality of care concerns, the survival of elderly Blacks and Whites undergoing prostatectomy is the same. Medical Research: What should clinicians and patients take away from your report? Dr. Trinh: A possible interpretation of our findings is that the biological differences in tumor aggressiveness among Blacks  (e.g. Blacks have more aggressive prostate cancer than Whites) may have been exaggerated, and that the perceived gap in survival is a result of lack of access or cultural perceptions with regard to surgical care for prostate cancer or other factors that differentiate who makes it to the operating table. (more…)
Author Interviews, Cannabis, Columbia, JAMA / 21.10.2015

Deborah S. Hasin, Ph.D. Professor of Epidemiology Columbia University New York, New York Interview with: Deborah S. Hasin, Ph.D. Professor of Epidemiology Columbia University New York, New York 10032 Medical Research: What is the background for this study? What are the main findings? Dr. Hasin: This study is based on data from two large-scale national surveys conducted over an eleven-year period that are designed to provide information on many health-related conditions in U.S. adults, including use of marijuana and other substances, changes over time in the prevalence of marijuana users, changes over time in the prevalence of disorders such as marijuana abuse and dependence, and the correlates and predictors of those disorders. The main findings of the study are that between 2001-2002 and 2012-2013, the prevalence of marijuana users in the United States adult general population more than doubled, from 4.1% to 9.5%, while the prevalence of adults with marijuana use disorder (abuse or dependence) also increased substantially, from 1.5% to 2.9% of American adults. About three in ten adult marijuana users met criteria for a marijuana use disorder. The findings are consistent with other studies showing increases in rates of marijuana-related harms over the same general time period. This may be to do with how accessible marijuana has become, for example you can even find a purple lotus menu on various websites. This is perfectly safe and fun, but can develop into an addiction later in life. (more…)
Author Interviews, CDC, JAMA, OBGYNE, Vaccine Studies / 21.10.2015 Interview with: Dr.Lakshmi Sukumaran MD, MPH Immunization Safety Office, Centers for Disease Control and Prevention Department of Pediatrics, Emory University School of Medicine Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Dr. Sukumaran: Pertussis (whooping cough) is a vaccine-preventable disease that has been increasing in incidence over the past decade in the United States. Newborns and infants are at increased risk of pertussis-related hospitalization and death compared with older children and adults. The Advisory Committee on Immunization Practices (ACIP) recommends that pregnant women receive a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) during each pregnancy to protect her infant from pertussis disease, regardless of prior immunization status. However, there is limited data on the safety of repeated Tdap vaccines in pregnant women. Our study evaluated medically attended (associated with doctor visit or hospitalization) adverse events in mothers, such as fever, allergy and local reactions, and adverse birth outcomes, such as prematurity and low birth weight in newborns, in women receiving Tdap in pregnancy who had received a prior tetanus-containing vaccine. We found no significant differences in rates of these adverse outcomes in women who received Tdap in pregnancy following a prior tetanus-containing vaccine less than 2 years before, 2 to 5 years before, and more than 5 years before. (more…)
Author Interviews, Breast Cancer, JAMA, Mammograms, UC Davis / 21.10.2015 Interview with: Diana L. Miglioretti, PhD Dean's Professor in Biostatistics Department of Public Health Sciences UC Davis School of Medicine Davis, CA  95616 Medical Research: What is the background for this study? What are the main findings? Dr. Miglioretti: Screening mammography intervals remain under debate in the United States. The US Preventive Services Task Force recommends biennial (every other year) screening, whereas other organizations recommend annual screening. To help inform their updated screening guidelines, the American Cancer Society guideline development group requested that the US Breast Cancer Surveillance Consortium conduct a study comparing cancer outcomes among women screened annually vs. biennially. Prior studies conducted by the consortium used wide intervals for defining annual and biennial mammograms. We wanted to evaluate cancer outcomes for women who more closely adhere to screening intervals. Our goal was to determine if women diagnosed with cancer following biennial screening have tumors with less favorable prognostic characteristics compared to women diagnosed after annual screening. We evaluated outcomes separately by age and by menopausal status because evidence suggests that younger women and premenopausal women may have more aggressive tumors and thus may benefit from more frequent screening. We found from this study that premenopausal women diagnosed with invasive breast cancer following biennial versus annual screening mammography were more likely to have tumors with less-favorable prognostic characteristics (e.g., later stage, larger size). For example, women with an invasive breast cancer diagnosed after a biennial screen had a 28% increased risk of a stage IIB or higher tumor, a 21% increased risk of being diagnosed with a tumor >15 mm, and an 11% higher risk of being diagnosed with a tumor with any less-favorable prognostic characteristic compared women diagnosed with breast cancer following an annual mammogram. In contrast, we found postmenopausal women not using hormone therapy and women 50 years of age or older had similar proportions of tumors with less-favorable prognostic characteristics regardless of screening interval. Relative risk estimates were close to one with no significant differences between biennial and annual screeners. Among postmenopausal women using hormone therapy at the time of the mammogram and women age 40-49, results were less clear. Relative risk estimates for biennial versus annual screeners were consistently above one, but were not as large as for premenopausal women and were not statistically significant. (more…)