Author Interviews, Education, JAMA / 09.12.2015 Interview with: Henry Sondheimer, MD Senior director of student affairs American Association of Medical Colleges Medical Research: What is the background for this study? What are the main findings? Dr. Sondheimer: The background for this study in JAMA's Med Ed issue of December 8th is that a group of the medical schools' deans asked us (AAMC staff) in 2014 whether there was a differential in placement of African-American, Hispanic, and Native American graduates into Graduate Medical Education at the time of their graduation from medical school. In fact, as shown in this short paper, there is a difference with more current graduates from the under-represented in medicine graduates not beginning their GME immediately post-graduation. However, over time this difference diminishes substantially but does not disappear completely. (more…)
Author Interviews, Education, Electronic Records, JAMA / 08.12.2015 Interview with: David Ouyang MD Department of Internal Medicine Stanford University School of Medicine Stanford, California Medical Research: What is the background for this study? What are the main findings? Dr. Ouyang: In American teaching hospitals, trainee resident physicians are an integral part of the medical team in performing procedures, writing notes, and coordinating care. As more care is being facilitated by electronic medical record (EMR) systems, we are just now finally able to understand how much residents work and how residents spend their time. In our study, we examined the types and timing of electronic actions performed on the EMR system by residents and found that residents spend about a third (36%) of their day in front of the computer and frequently perform many simultaneous tasks across the charts of multiple patients. Additionally, residents often do work long hours, with a median of 69.2 hours per week when on the inpatient medicine service. (more…)
Author Interviews, Cleveland Clinic, Emergency Care, JAMA, Stroke, Telemedicine / 08.12.2015 Interview with: Ken Uchino, MD FAHA FANA Director, Vascular Neurology Fellowship Research Director, Cerebrovascular Center, Cleveland Clinic Associate Professor of Medicine (Neurology) Cleveland Clinic Lerner College of Medicine of CWRU Cleveland, OH 44195 Medical Research: What is the background for this study? What are the main findings? Dr. Uchino: Treatment for acute ischemic stroke is time dependent. Multiple studies have reported strategies to improve time to treatment after arrival in the hospital. Mimicking pre-hospital thrombolysis of acute myocardial infarction pioneered 30 years ago, two groups in Germany have implemented pre-hospital ischemic stroke thrombolysis using mobile stroke unit (“stroke ambulance”) that includes CT scan and laboratory capabilities. These units have been demonstrated to provide stroke treatment earlier than bringing patients to the emergency departments. Our report extends the concept mobile stroke unit further by using telemedicine for remote physician presence. The other mobile stroke units were designed to have at least one physician on board. This allows potential multiple or geographically distant units to be supported by stroke specialists. The study demonstrates that after patient arrival in the ambulance, the time to evaluation (CT scanning and blood testing) and to thrombolytic treatment is as quick or better as patient arrival in emergency department door. We are reporting the overall time efficiency after emergency medical service notification (911 call) in a separate paper. (more…)
Anemia, Author Interviews, Brigham & Women's - Harvard, JAMA, Transfusions / 07.12.2015 Interview with: Dr. Walter H. Dzik MD Associate Pathologist, Massachusetts General Hospital Associate Professor of Pathology Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Dzik: Millions of Red Blood Cell transfusions are given each year.  To maintain adequate blood inventories worldwide, Red Blood Cell units are stored under refrigerated conditions.  Previous animal and laboratory research has highlighted the fact that red cells undergo biochemical, morphologic, and biophysical changes during prolonged refrigerated blood storage.    Researchers and clnicians have questioned whether the changes that occur during storage would impair the ability of transfused Red Cells to delivery oxygen to tissues. Our study was a randomized controlled trial conducted in patients with extreme anemia and insufficient global tissue oxygenation.    We randomly assigned children with severe anemia and lactic acidosis to receive Red Blood Cells stored 1-10 days versus Red Blood Cells stored 25-35 days.   We measured the recovery from lactic acidosis in response to transfusion in the two groups.   We also measured cerebral tissue oxygenation using a non-invasive tissue oximeter.    We found that the proportion of patients who achieved reversal of lactic acidosis was the same in the two RBC storage-duration groups.   The rate of decline of lactic acidosis was also equal.   There was also no difference in cerebral oxygenation, resolution of acidosis, correction of vital signs, clinical recovery, survival and 30-day followup.    (more…)
Author Interviews, Heart Disease, JAMA, Kidney Disease / 05.12.2015 Interview with: Girish N. Nadkarni, MD, MPH Division of Nephrology, Department of Medicine Icahn School of Medicine at Mount Sinai New York, New York What is the background for this study? What are the main findings? Dr. Nadkarni: Cardiovascular disease is one of the major causes of morbidity and mortality in patients with kidney disease. Moreover, there is a lack of good quality evidence in kidney disease patients. In addition, previous studies have shown that cardiovascular trials exclude patients with kidney disease. We wanted to analyze all of the clinical trials on acute myocardial infarctions and heart failure in the last decade and see if they continued excluding patients with kidney disease. We discovered that in 371 trials including close to six hundred thousand patients, the majority (57%) excluded patients with kidney disease. A large proportion of the trials excluded patients for non-specific reasons, rather than a prespecified threshold of kidney function and did not report kidney function at baseline. Finally, in trials that did include kidney patients and reported outcomes by kidney function, only 13% showed an interaction or suggestion of harm. (more…)
Abuse and Neglect, Author Interviews, JAMA, OBGYNE / 04.12.2015 Interview with: Alex Haynes, MD, MPH Assistant Professor of Surgery, Harvard Medical School Assistant in Surgery, Massachusetts General Hospital Division of Surgical Oncology Associate Program Director, Safe Surgery, Ariadne Labs Research Associate Harvard School of Public Health and George Molina, MD, MPH Surgical Research Resident Massachusetts General Hospital  Medical Research: What is the background for this study? What are the main findings? Response: We have previously done work looking at the global volume of operations, and in particular the surgical volume at a country level. This work was based on the hypothesis that a certain level of surgical care is necessary for healthy populations. In doing this work, we found that cesarean delivery makes up a large proportion of all operations that happen globally. In the mid-1980’s, based on existing data the World Health Organization made the recommendation that at a country-level, the cesarean delivery rate should not exceed 10 to 15 per 100 live births. We wanted to see if this recommendation was still applicable using current data. In order to answer this question, we used multiple imputation to estimate country-level cesarean delivery rates for all 194 countries in the world in 2012 to investigate the association between country-level cesarean delivery rates and maternal and neonatal mortality. We found that at a population level, as the cesarean delivery rate increased up to about 19 per 100 live births, there was a decrease in country-level maternal and neonatal mortality. However, as country-level cesarean delivery rates rose above this level there were no associated changes in maternal or neonatal mortality. (more…)
Author Interviews, Cognitive Issues, Exercise - Fitness, JAMA, Lifestyle & Health / 02.12.2015 Interview with: Tina Hoang MSPH Staff Research Associate Northern California Institute for Research and Education, Veterans Affairs Medical Center Dr. Kristine Yaffe MD Professor of Psychiatry, Neurology, and Epidemiology University of California San Francisco, CA  94121 Medical Research: What is the background for this study? What are the main findings? Response: We assessed physical activity and TV watching in young adults over 25 years to see if there was an association with cognitive function in middle age.  Most previous studies have only considered this association in older adults. We found that both low physical activity and high TV watching over time were associated with worse cognitive function. (more…)
Author Interviews, JAMA, Lung Cancer, Radiation Therapy / 02.12.2015 Interview with: Benjamin Movsas, MD Chairman of Radiation Oncology Henry Ford Hospital Detroit, Michigan  Medical Research: What is the background for this study? What are the main findings? Dr. Movsas: The background is that a recent randomized lung cancer trial (RTOG 0617) showed a lower (rather than a higher) survival among the patients who received a higher dose of radiation (RT).  This unexpected finding was puzzling as there were few differences in toxicity between the radiation dose arms noted by health care providers. The main finding of the quality of life (QOL) analysis was that there was indeed a large difference in QOL as reported by the patients themselves (with lower QOL on the high RT dose arm at 3 months).  Moreover, while this study was not randomized for RT technique, about half of the patients received intensity modulated RT (IMRT), a more sophisticated approach than the alternative (3D conformal RT), which can better protect normal tissues.  Despite the fact that patients with larger tumors received IMRT, their self reported QOL one year later was significantly better (ie, much less decline in QOL) relative to patients who received 3D conformal RT.  Finally, higher QOL at baseline significantly predicated for better survival. (more…)
Author Interviews, JAMA, University of Michigan / 01.12.2015 Interview with: Mark D. Peterson, Ph.D., M.S. University of Michigan, Medicine Department of Physical Medicine and Rehabilitation Ann Arbor, MI  Medical Research: What is the background for this study? What are the main findings? Dr. Peterson: Cerebral palsy (CP) is a neurodevelopmental condition caused by a disturbance to the developing fetal or infant brain. While the incidence of CP has remained stable in recent years, the mortality rate of children with Cerebral palsy has declined, suggesting that adults with Cerebral palsy represent a growing population whose healthcare needs are poorly understood.  More than half of children with Cerebral palsy are independently mobile at 8 years of age; however, a large proportion lose mobility in adulthood. These declines are attributed to pain, fatigue, and muscle weakness, and result in chronic inactivity and accelerated aging. Despite this, there have been virtually no specific surveillance efforts or even epidemiologic studies to examine the prevalence of lifestyle-related chronic diseases in adults with Cerebral palsy. Therefore, the purpose of this study was to examine estimates of chronic conditions in a large, U.S. population-representative sample of adults with CP (n=1,015 fromthe Medical Expenditure Panel Survey (MEPS) (2002-2010). We demonstrated that adults with cerebral palsy had significantly greater estimates of chronic diseases, including diabetes, asthma, hypertension and other heart conditions, stroke, emphysema, joint pain, and arthritis as compared with adults without Cerebral palsy. (more…)
Asthma, Author Interviews, JAMA, OBGYNE, Pediatrics / 01.12.2015 Interview with: Dr Mairead Black MBChB, MRCOG, MSc Research Fellow, Wellcome Trust Clinical Lecturer, Obstetrics and Gynaecology School of Medicine and Dentistry, Division of Applied Health Sciences University of Aberdeen Aberdeen Maternity Hospital, Cornhill Road Aberdeen AB25 2ZD  Medical Research: What is the background for this study? Dr. Black: The current thinking is, if a baby is exposed to labour, then it is also exposed to ‘good bacteria’ that mothers pass on during the birth, and they are also exposed to a degree of natural stress at the time of birth that might make them more resistant to developing future illnesses. The World Health Organisation formerly recommended that no more than 15 percent of deliveries should be C-sections. However rates in some countries have soared – China and Brazil have rates in excess of 50%, whilst in the UK the figure is 26% with almost half of these being planned in advance. The main purpose of this study was to explore whether health outcomes in children up to very early adulthood differ according to how they are delivered and whether avoiding labour entirely, i.e. via a planned C-section, could put children at a disadvantage compared to those delivered vaginally or by emergency C-section, where most will have been exposed to labour. The study analysed data from over 300,000 births between 1993 and 2007 across Scotland, using routinely collected data from seven linked databases. (more…)
Author Interviews, JAMA, Prostate Cancer, Radiation Therapy / 30.11.2015 Interview with: Prof Nicholas James STAMPEDE Trial Chief Investigator Director of the Cancer Research Centre Warwick Medical School University of Warwick Coventry and Professor of Clinical Oncology Cancer Centre, Queen Elizabeth Hospital Birmingham Medical Research: What is the background for this study? What are the main findings? Dr. James: The STAMPEDE trial is a multi-arm, multi-stage trials platform testing a range of different therapies in addition to standard of care (SOC) for men commencing long term androgen deprivation therapy (ADT) for newly diagnosed locally advanced or metastatic prostate cancer. These data from the control arm form part of a pair of publications detailing outcomes in the control arm of STAMPEDE and help to make sense of the forthcoming paper on the randomised comparisons currently in press at the Lancet. (more…)
Author Interviews, JAMA, Obstructive Sleep Apnea, Surgical Research, UCLA / 29.11.2015 Interview with: Soroush Zaghi, MD Department of Head and Neck Surgery David Geffen School of Medicine at UCLA University of California, Los Angeles MedicalResearch: What is the central message for clinicians and surgeons from your results? Dr. Zaghi: Multiple studies from different practitioners and institutions agree that Maxillomandibular Advancement (MMA) is a highly effective surgical option for patients with obstructive sleep apnea who cannot tolerate positive pressure therapy and have not found success with other surgical procedures. (more…)
Author Interviews, Breast Cancer, JAMA, Surgical Research / 28.11.2015 Interview with: Katharine Yao, MD Director, Breast Surgical Program NorthShore University HealthSystem Illinois Medical Research: What is the background for this study? What are the main findings? Dr. Yao: A survey of breast surgeons was conducted to determine their knowledge level with contralateral breast cancer and how contralateral prophylactic mastectomy (CPM) affects survival.  Of five knowledge questions, only 60% scored with high knowledge (4 or 5 questions correct) scores.   Surgeons mostly scored low on contralateral cancer risks.  Most surgeons correctly stated that contralateral prophylactic mastectomy  does not provide a survival benefit.  Nonetheless, our knowledge questions did not address other important issues about CPM such as operative complications, or contralateral breast cancer risks for other high risk subgroups.  Higher knowledge was associated with fellowship training and duration of practice. (more…)
Author Interviews, Cost of Health Care, Health Care Systems, JAMA, Outcomes & Safety / 25.11.2015 Interview with: Anup Das Medical Scientist Training Program Department of Health Management and Policy University of Michigan, Ann Arbor Medical Research: What is the background for this study? What are the main findings? Response: The Centers for Medicare & Medicaid Services (CMS) recently added a new measure of episode spending to the Hospital Value Based Purchasing program. Participation in this program allows hospitals to receive a financial bonus if they perform well on the included measures. This is the first spending measure in the program, and this change now incentivizes hospitals to improve their quality as well as their spending. The measure evaluates spending from three days before a hospitalization through 30 days post-discharge. In this study, we find that while high-cost hospitals had higher spending levels in each of the three components of an episode of care (pre-admission, index admission, and post-discharge), differences in post-discharge spending were the main determinants of hospital performance on this measure. High-cost hospitals spent on average $4,691 more than low-cost hospitals in post-discharge care. The majority of post-discharge spending comes from skilled nursing facility or readmission costs. Similarly, hospitals that did worse on this new measure of spending over time did so because of increases in their post-discharge spending. (more…)
Author Interviews, Heart Disease, JAMA, UT Southwestern / 25.11.2015

Ambarish Interview with: Ambarish Pandey M.D. Division of Cardiology University of Texas Southwestern Medical Center Dallas, TX Medical Research: What is the background for this study? What are the main findings? Dr. Pandey: Pulmonary artery (PA) catheters have been used for invasive bedside hemodynamic monitoring for past four decades. The ESCAPE trial, published in October 2005, demonstrated that use of  Pulmonary Artery catheter was not associated with a significant improvement in clinical outcomes of patients with heart failure. Accordingly, the current ACC/AHA guidelines discourage the routine use of PA catheter for routine management of acute heart failure in absence of cardiogenic shock or respiratory failure (Class III). Despite the significant evolution of available evidence base and guideline recommendations regarding use of  Pulmonary Artery catheters, national patterns of PA catheter utilization in hospitalized heart failure patients remain unknown. In this study, we observed that use of PA catheter among patients with heart failure decline significantly in the Pre-ESCAPE era (2001 – 2006) followed by a consistent increase in its use in the Post-ESCAPE era (2007-2012). We also observed that the increase in use of  Pulmonary Artery catheters is most significant among heart failure patients without underlying cardiogenic shock or respiratory failure. (more…)
Author Interviews, Gender Differences, Heart Disease, JAMA, Stroke / 23.11.2015 Interview with: Bob Siegerink PhD Frits R. Rosendaal MD, PhD Department of Clinical Epidemiology Leiden University Medical Center Leiden, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: The rates of death due to arterial thrombosis have been declining in the past years, which means that there are more patients with a high burden of disease. Arterial thrombosis is a uncommon disease in the young, but the burden of the disease might have a profound impact on their lives. We analyzed data form the RATIO study, in which we followed women with a ischemic stroke and myocardial infarction for up to 20 years. During this time, overall mortality was 2-4 times higher compared to the general population. This increase in risk was mainly driven by deaths from acute vascular events and persisted over the whole course of the follow up. (more…)
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…)