Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, JAMA, NEJM / 26.08.2016

MedicalResearch.com Interview with: Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: MINDACT was designed to involve only patients with node negative and 1 to 3 positive lymph node breast cancer. Node negative breast cancer is a cancer that has not spread to the surrounding lymph nodes and therefore has a lower risk of recurrence. Scientists have also demonstrated that breast cancer which has spread to 1 to 3 lymph nodes may behave like node negative breast cancer. Patients with either node negative cancer or with a cancer that involves 1-3 lymph nodes are often prescribed chemotherapy, although physicians believe that approximately 15% of them do not require such treatment. MINDACT provides the highest level of evidence to show that using MammaPrint® can substantially reduce the use of chemotherapy in patients with node-negative and 1-to-3 node positive breast cancer – in other words, it can identify patients with these types of breast cancer who can safely be spared a treatment that may cause significant side effects, and will offer no to very little benefit. (more…)
Author Interviews, Diabetes, NEJM, OBGYNE, Technology / 19.08.2016

MedicalResearch.com Interview with: Professor Helen Murphy and Dr Zoe Stewart Institute of Metabolic Science University of Cambridge MedicalResearch.com: What is the background for this study? Response: Controlling blood glucose levels is a daily challenge for people with Type 1 diabetes and is particularly crucial during pregnancy. Previous research shows that women with type 1 diabetes spend only 12 hours per day within the recommended glucose target levels, leading to increased rates of complications including preterm delivery and large for gestational age infants. National surveys show that one in two babies suffer complications related to type 1 diabetes in the mother. The hormonal changes that occur in pregnancy make it difficult for women to predict the best insulin doses for every meal and overnight. Too much insulin causes low glucose levels harmful for the mother and too little causes problems for the developing baby. The artificial pancreas automates the insulin delivery giving better glucose control than we can achieve with currently available treatments. Previous studies show that the closed-loop system also known as artificial pancreas can be used safely in children and adults and our study aimed to investigate whether or not it was helpful for women with type1 diabetes during pregnancy. (more…)
Asthma, Author Interviews, Brigham & Women's - Harvard, NEJM, Pediatrics / 18.08.2016

MedicalResearch.com Interview with: Wanda Phipatanakul, MD, MS Associate Professor of Pediatrics Harvard Medical School Director, Asthma Clinical Research Center Boston Children's Hospital Asthma, Allergy and Immunology Boston, MA 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Acetaminophen (e.g., Tylenol, Panadol) and ibuprofen (e.g., Advil, Motrin) are the only available treatments for pain and fever in toddlers and the most commonly utilized medications worldwide. Recently there has been controversy and even alarm with suggestive observational data that acetaminophen makes asthma worse. This has led some experts to recommend the avoidance of acetaminophen in children with asthma. We sought to find the answer to this burning question through the first prospective, double-blind, randomized clinical trial comparing acetaminophen versus ibuprofen head to head for use when clinically indicated for fever or pain. Is there a difference in asthma morbidity (exacerbations) in young children between the age of 12-59 months, who have asthma? (more…)
Author Interviews, Hepatitis - Liver Disease, NEJM / 17.08.2016

MedicalResearch.com Interview with: Prof. Dr. F. Nevens, MD, PhD Professor of Medicine Hepatology and liver transplantation University Hospitals KU Leuven, Belgium Prof. Dr. F. Nevens, MD, PhD Professor of Medicine Hepatology and liver transplantation University Hospitals KU Leuven, Belgium MedicalResearch.com: What is the background for this study? Response: Primary biliary cholangitis (PBC) is a rare, autoimmune cholestatic liver disease that puts patients at risk for life-threatening complications. PBC is primarily a disease of women, affecting approximately one in 1,000 women over the age of 40. If left untreated, survival of PBC patients is significantly worse than the general population. The POISE trial evaluated the safety and efficacy of once-daily treatment with Ocaliva® (obeticholic acid) in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, ursodeoxycholic acid (UDCA), the current standard of care. Ocaliva is the first PBC therapy that targets the farnesoid X receptor (FXR), a key regulator of bile acid, inflammatory, fibrotic and metabolic pathways. The trial’s primary endpoint was an alkaline phosphatase (ALP) level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a total bilirubin level at or below the upper limit of the normal range after 12 months of obeticholic acid therapy. These liver biomarkers have been shown to predict progression to liver failure and resulting liver transplant or premature death in patients with PBC. (more…)
Author Interviews, NEJM, Neurological Disorders, Surgical Research / 12.08.2016

MedicalResearch.com Interview with: Gil I. Wolfe, MD, FAAN Irvin and Rosemary Smith Professor and Chair Dept. of Neurology/Jacobs Neurological Institute Univ. at Buffalo Jacobs School of Medicine and Biomedical Sciences/SUNY Buffalo General Medical Center Buffalo, NY 14203-1126 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thymectomy has been used in myasthenia gravis (MG), in particular those patients who do not have a tumor of the thymus gland, known as a thymoma, for over 75 years without randomized data to support its use. A practice parameter in 2000 on behalf of the American Academy of Neurology stated that the benefits of thymectomy in this population of non-thymomatou smyasthenia gravis patients remained uncertain, classified thymectomy as a treatment option in this group, and called for rigorous, randomized studies. What we found is that compared to an identical prednisone protocol alone, that extended transsternal thymectomy confers significant benefits to non-thymomatous MG patients over a period of three years after the procedure. The benefits include better disease status, reduced prednisone requirements, fewer hospitalizations to manage  myasthenia gravis worsenings, and a lower symptom profile related to side effects from medications used to control the disease state. (more…)
Author Interviews, Exercise - Fitness, Hematology, NEJM, Stanford / 08.08.2016

MedicalResearch.com Interview with: D. Alan Nelson, MPAS, PhD Postdoctoral research fellow Stanford Medicine MedicalResearch.com: What is the background for this study? Response: The study was inspired by the uncertainty surrounding sickle cell trait (SCT) and its association with serious exertional collapse events and mortality in active populations. I conducted initial, exploratory analyses on these topics in 2014-15 while examining a range of military readiness predictors and outcomes. The early work indicated that the risk of mortality, rhabdomyolysis and other exertional events arising from SCT might be substantially lower than that suggested by prior work in the research literature. Dr. Lianne Kurina and I decided to conduct further, focused study at the Stanford University School of Medicine to confirm or refute these findings. In considering best approaches, we noted that there was an absence of prior research in which the  sickle cell trait status of an entire, large, physically-active study population was known. This limitation could introduce bias to inflate the apparent impact of a theorized predictive factor. Aside from the challenges in studying the impact of SCT on exertional outcomes, with respect to prevention, a further concern is that  sickle cell trait is a non-modifiable trait. If it were a serious risk factor for rhabdomyolysis and/or mortality, despite careful exertional injury precautions such as those employed by the Army, this might present great challenges for prevention efforts. To maximize the potential for new research to provide actionable prevention information, our interests included examining a range of modifiable risk factors for rhabdomyolysis. Dr. Kurina and I have employed large, longitudinal military datasets for about five years to examine critical military health outcomes, making this study a natural progression of our joint work. The research proceeded with the support of the Uniformed Services University of the Health Sciences, and in cooperation with a distinguished group of experts who co-authored the paper and advised the project. The study was conducted using de-identified records of all SCT-tested African American US Army soldiers on active duty during 2011 - 2014 (N = 47,944). (more…)
Asthma, Author Interviews, NEJM, Pediatrics / 04.08.2016

MedicalResearch.com Interview with: Donata Vercelli, MD Professor of Cellular and Molecular Medicine, University of Arizona Director, Arizona Center for the Biology of Complex Diseases Associate Director, Asthma and Airway Disease Research Center The BIO5 Institute Tucson, AZ 85721 MedicalResearch.com: What is the background for this study? Response: By probing the differences between two farming communities—the Amish of Indiana and the Hutterites of South Dakota—our interdisciplinary team (which included, among others, Erika von Mutius from Ludwig-Maximilians University in Munich, Carole Ober and Anne Sperling from the University of Chicago, and myself) found that substances in the house dust from Amish, but not Hutterite, homes shape the innate immune system in ways that may prevent the development of allergic asthma. Growing up in a microbe-rich farm environment has been known to protect against asthma. Our current study extends these findings by showing that in both humans and mice protection requires engagement of the innate immune system. The Amish and Hutterite farming communities in the United States, founded by immigrants from Central Europe in the 18th and 19th centuries, provide textbook opportunities for comparative studies. The Amish and the Hutterites have similar genetic ancestry and share lifestyles (e.g., family size, diet, lack of exposure to indoor pets) known to affect asthma risk. However, their farming practices differ. The Amish have retained traditional methods, live on single-family dairy farms and rely on horses for fieldwork and transportation. In contrast, the Hutterites live on large communal farms and use modern, industrialized farm machinery. This distances young Hutterite children from the constant daily exposure to farm animals. (more…)
Author Interviews, Endocrinology, Genetic Research, NEJM, Weight Research / 21.07.2016

MedicalResearch.com Interview with: Dr. Peter Kühnen MD Institute for Experimental Pediatric Endocrinology Charité–Universitätsmedizin Berlin Berlin, Germany MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Kühnen: The patients, which were included in this study, are suffering from a genetic defect in a gene called POMC. This gene is cleaved into different hormones as e.g. MSH (melanocyte stimulating hormone). MSH is very important for the regulation of satiety by activation of the MC-4 receptor. For this reason these patients are persistent hyperphagic due to the lack of MSH and they gain weight very fast in the first months of their life. Setmelanotide activates the MC-4 receptor, which is important for the activation of satiety. By restoring the lost function Setmelanotide leads to a reduction of hyperphagia and to a reduction of body weight in this POMC deficient patients. (more…)
Author Interviews, Infections, NEJM, Vaccine Studies / 20.07.2016

MedicalResearch.com Interview with: Nicole E. Basta, PhD MPhil Assistant Professor Division of Epidemiology and Community Health School of Public Health University of Minnesota MedicalResearch.com: What is the background for this study? Response: Meningococcal disease is a serious and often life-threatening condition. In the past several years, multiple outbreaks caused by meningococcal serogroup B (MenB) have occurred on college campuses in the US. Recently, a new meningococcal B vaccine known as 4CMenB or Bexsero was developed. The FDA granted special approval to use the vaccine to control an outbreak at a University in New Jersey prior to its licensure. We took advantage of this unique opportunity to investigate the impact of Bexsero during the outbreak. In doing so, we conducted the first clinical study of Bexsero among teens and young adults in the US. (more…)
Author Interviews, Education, NEJM / 09.07.2016

MedicalResearch.com Interview with: Marsha Regenstein, Ph.D, Professor From the Department of Health Policy and Management Milken Institute School of Public Health George Washington University Washington, DC MedicalResearch.com: What is the background for this study? Response: Despite the billions of dollars in public spending on graduate medical education (GME) in the United States, little is known about the true cost of training a resident, with the few studies that exist showing wide variation in their methods and results. At the same time, the U.S. appears to be producing too few primary care physicians to meet the health care needs of the population, and especially those who live in underserved areas with high health care needs and shortages of health professionals. The Teaching Health Center (THC) Graduate Medical Education funding program was established under the Affordable Care Act to increase the number of medical and dental residents training in six primary care specialties in underserved areas. The Teaching Health Center funding supports community-based residency training in settings such as Federally-qualified health centers, rural clinics, mental health clinics and other non-profit community-based organizations. Hospitals commonly serve as training partners, but THC funding goes directly to the community-based partner, bringing funding and training closer to the communities where underserved patients live. The Health Resources and Services Administration (HRSA), which manages and funds the program, set an interim payment of $150,000 per resident; currently, 59 THCs are training 690 residents in 27 states and the District of Columbia. The interim payment rate was based on the best available information at the time and was meant to cover the full cost of training a resident. (more…)
Author Interviews, Cancer Research, Leukemia, NEJM, Stanford / 29.06.2016

MedicalResearch.com Interview with: Jason R. Gotlib, MD The Clinical Investigator Pathway Hematology Division Stanford University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background is that advanced forms of systemic mastocytosis, which are blood cancers characterized by accumulation of abnormal mast cells in the bone marrow and additional organs, represent a group of orphan diseases with a large unmet need. Approximately 90% of patients harbor the acquired KIT D816V mutation, a mutated receptor tyrosine kinase on the surface of mast cells which a primary driver of disease pathogenesis. Only 1 drug is approved for patients with one form of advanced systemic mastocytosis, termed ‘aggressive systemic mastocytosis, or ‘ASM’. This therapy is imatinib (Gleevec), but it is only approved for patients without the KIT D816V mutation, or with KIT mutation status unknown because the KIT D816V mutation is resistant to imatinib. Therefore, this drug may only be useful for approximately 10% of patients. Other drugs that have been used off-label for systemic mastocytosis (but are not approved for this indication) include interferon-alpha or cladribine, which show some activity, but their evaluation to date has been primarily limited to small case series which are usually retrospective in nature, and include mixed populations of systemic mastocytosis patients who have both early stage disease without organ damage (e.g. indolent systemic mastocytosis) and and advanced stage patients, as included in this trial, who have one or more findings of organ damage. Also, those trials employed differing response criteria and no central adjudication of eligibility and response assessments was undertaken. Midostaurin is a multikinase inhibitor with activity against both wild-type KIT, but most importantly, KIT D816V (in contrast to imatinib). Prior work demonstrated that cell lines transformed with the KIT D816V mutation can be inhibited at relatively low concentrations of midostaurin. These concentrations could also be achieved in vivo (e.g. at concentrations achievable in the blood of patients). Cell lines transformed by KIT D816V could not be inhibited by imatinib. (more…)
Author Interviews, Infections, NEJM, Vaccine Studies / 29.06.2016

MedicalResearch.com Interview with: Philip Bejon, Ph.D. Professor of Tropical Medicine, Director of the Wellcome-KEMRI-Oxford Collaborative Research Programme, Group Head / PI, Consultant Physician and Unit Director Kilifi, Kenya MedicalResearch.com: What is the background for this study? Response: According to the latest World Health Organisation (WHO) estimates more than 400,000 people died from malaria in 2015, with over 90% of these deaths occurring in sub-Saharan Africa. The vast majority who die are children under 5, and almost all cases are caused by the P. falciparum strain of malaria transmitted by female Anopheles mosquitoes. RTS,S, which protects only against P. falciparum, was developed by GlaxoSmithKline with support from the PATH Malaria Vaccine Initiative (MVI) and with grant funds from the Bill & Melinda Gates Foundation to MVI. In July 2015, it received a positive opinion from the European Medicines Agency. Earlier this year, the WHO recommended further evaluation of the four-dose regimen of RTS,S in a pilot implementation programme in sub-Saharan Africa, to address several knowledge gaps before the vaccine might be rolled out more widely. (more…)
Author Interviews, NEJM, OBGYNE, University Texas, Zika / 26.06.2016

MedicalResearch.com Interview with: Abigail R.A. Aiken, MD, MPH, PhD Assistant Professor LBJ School of Public Affairs University of Texas at Austin Austin, TX, 78713 MedicalResearch.com: What is the background for this study? Response: As Zika began to emerge as an epidemic in Latin America and its links with microcephaly began to be realized, we were aware that women in the region who were already pregnant or who would become pregnant would have a very limited set of reproductive options. Research and media attention about the possible biological effects of Zika in pregnancy began to appear rapidly. But much less attention was been paid to the impacts of Zika on women. We followed the responses of governments and health organizations and when they began to issue advisories warning women to avoid pregnancy, we knew it would be important to investigate the impacts of those advisories. A country-wide policy that is impossible to follow if you are pregnant or cannot avoid pregnancy is an unusual and important public issue. Accurate data on abortion are very difficult to obtain in Latin America because in most countries, abortion is highly restricted. We wanted to provide a window on the issue of how women were responding to the risks of Zika and its associated advisories, so we worked with Women on Web (WoW), an online non-profit telemedicine initiative that provides safe medical abortion to women in countries where safe, legal abortion is not universally available. (more…)
Author Interviews, NEJM, Occupational Health, Opiods / 24.06.2016

MedicalResearch.com Interview with: Professor Ellen Meara, PhD Professor The Dartmouth Institute for Health Policy and Clinical Practice MedicalResearch.com: What is the background for this study? Response: Responding to a fourfold rise in death rates, between 2006 and 2012, states collectively enacted 81 laws restricting prescribing and dispensing of prescription opioids. Jill Horwitz, PhD, JD, said “states hoped passing a range of laws might help. So they are enacting small fixes — forbidding patients from “doctor-shopping,” and requiring doctors to use tamper-resistant prescription forms. They are also implementing major efforts such as prescription drug monitoring programs (PDMPs) — online databases that allow law enforcement and clinicians to monitor prescriptions.” (more…)
Author Interviews, Cancer Research, CT Scanning, Lymphoma, NEJM / 23.06.2016

MedicalResearch.com Interview with: Peter Johnson MA, MD, FRCP Professor of Medical Oncology Cancer Research UK Centre Southampton General Hospital Southampton MedicalResearch.com: What is the background for this study? What are the main findings? Prof. Johnson: Based upon retrospective series looking at the ability of interim PET to predict the outcomes of treatment, we aimed to test the idea of modulating treatment in response to an early assessment of the response to ABVD: could we safely reduce the amount of treatment by omitting bleomycin in the group who had responded well? Although the risk of severe toxicity from bleomycin is generally low, for the small number of patients who experience it, it can be life-changing or even fatal. We also wanted to test whether it might be possible to reduce the use of consolidation radiotherapy by comparison to our previous trials, and this seems to have worked too: we used radiotherapy in less than 10% of patients in RATHL, as compared to around half in our previous trials. We have seen better survival figures than in our previous studies with less treatment overall, so it feels as though we are on the right track. (more…)
Author Interviews, Genetic Research, Heart Disease, NEJM / 23.06.2016

MedicalResearch.com Interview with: Professor Chris Semsarian MBBS PhD MPH FRACP FAHMS FAHA FHRS FCSANZ Professor of Medicine, University of Sydney Cardiologist, Royal Prince Alfred Hospital NHMRC Practitioner Fellow Head, Molecular Cardiology Program Centenary Institute, Newtown NSW Australia MedicalResearch.com: What is the background for this study? Response: Sudden cardiac death is a tragic and devastating event at all ages, and especially in the young (aged under 35 years). Understanding the causes and circumstances of SCD in the young is critical if we are to develop strategies to prevent SCD in the young. Our study represents the first prospective, population-based study of SCD in the young across two nations, Australia and New Zealand. (more…)
Author Interviews, Blood Pressure - Hypertension, NEJM, Stroke / 09.06.2016

MedicalResearch.com Interview with: Adnan I. Qureshi, M.D Zeenat Qureshi Stroke Research Center University of Minnesota Minneapolis, MN MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Qureshi: An acute hypertensive response in patients with intracerebral hemorrhage is common and may be associated with hematoma expansion and increased mortality. The Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial was designed to determine the efficacy of rapidly lowering systolic blood pressure in patients in an earlier time window after symptom onset than evaluated in previous trials. The trial was based on evidence that hematoma expansion and subsequent death or disability might be reduced with very early and more aggressive reduction in systolic blood pressure in those at higher risk due to presence of high systolic blood pressure at presentation. The trial randomized eligible subjects with intracerebral hemorrhage to test the superiority of intensive (goal 110-140 mmHg) over standard (goal 140-180 mmHg) systolic blood pressure reduction using intravenous nicardipine within 4.5 hours of symptom onset. Of a total of 1000 subjects that were recruited with a mean (standard deviation) baseline systolic blood pressure of 200.6 (27.0) mmHg, 500 were assigned to intensive-treatment and 500 to standard-treatment. Enrollment was stopped following a pre-specified interim analysis because of futility. The primary endpoint of death or disability at 3 months post-randomization was observed in 38.7% (186/481) of subjects receiving intensive treatment and 37.7% (181/480) subjects receiving standard treatment (relative risk: 1.03; 95% confidence interval: 0.85 to 1.27), adjusted for age, initial Glasgow Coma scale, and presence or absence of intraventricular hemorrhage. The rate of renal adverse events within 7 days of randomization was significantly higher among subjects randomized to intensive treatment. Compared to a target systolic blood pressure of 140-180 mmHg, treating subjects with intracerebral hemorrhage to a target systolic blood pressure of 110-140 mmHg did not lower the rate of death or disability. (more…)
Author Interviews, NEJM, Rheumatology / 02.06.2016

MedicalResearch.com Interview with: Chih-Hung Kuo, M.B., B.S. Peter McCluskey, M.D. Clare L. Fraser, M.B., B.S. University of Sydney Sydney, NSW, Australia MedicalResearch.com: What is the background for this study? What are the main findings? Response: Giant cell arteritis is a life and sight threatening systemic inflammatory condition, which remains difficult to diagnose. Jaw claudication (cramping of muscle from ischemia) is a highly specific symptom with significant diagnostic and prognostic (risk of permanent blindness) values. The reporting of jaw symptoms may be affected by many factors, such as diet. There remains no standardized clinical test available for clinicians. We study the use of chewing gum as a standardized test (like a stress test for angina pain) to better characterize this critical symptom. The pilot study of two cases with abnormal results were published in the New England Journal of Medicine. Chewing gum at a rate of 1 chew/second can reproduce the jaw claudication symptom around 2-3 minutes. In one case, the jaw claudication was unmasked by the test with a subsequent positive biopsy result. The test result became negative after corticosteroid treatment. (more…)
Author Interviews, Hospital Acquired, NEJM, Urinary Tract Infections / 02.06.2016

MedicalResearch.com Interview with: Sanjay Saint, MD, MPH Chief of Medicine VA Ann Arbor Healthcare System George Dock Professor of Internal Medicine & Senior Associate Chair - Department of Internal Medicine University of Michigan Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Saint: Catheter-associated urinary tract infection (CAUTI) is a common, costly, and morbid complication of hospitalization. Urinary tract infection (UTI) is one of the most common device-related infections in the United States. CAUTI rates rose nationally between 2009 and 2013. We put in place a national program to reduce CAUTI. Specifically, we enrolled 926 intensive care unit (ICU) and non-ICU hospital units in 603 hospitals spread over 32 states, the District of Columbia and Puerto Rico between March 2011 and November 2013. By the end of the 18-month program, UTI rates among hospital patients in general wards had dropped by a third. Specifically: • The rate of CAUTIs dropped from 2.40 per 1000 days of catheter use to 2.05 (a ~14 percent overall drop). • Nearly all of the decrease in CAUTI rates was due to changes in infection rates in non-ICUs, which went from 2.28 to 1.54 infections per 1,000 catheter-days – a drop of 32 percent. In non-ICUs, the overall use of catheters decreased by 7%. • ICUs didn’t see a substantial change in either CAUTI or catheter use, likely because the nature of patients treated in ICUs means more frequent urine output monitoring and culturing of urine, so UTIs are more likely to be spotted. (more…)
Author Interviews, Disability Research, Genetic Research, NEJM / 29.05.2016

MedicalResearch.com Interview with: Dr. Clara van Karnebeek PhD Certified Pediatrician and Biochemical Geneticist at the BC Children’s Hospital Principal Investigator, University of British Columbia MedicalResearch.com: What is the background for this study? Dr. van Karnebeek: The goal of the study was to diagnose patients with genetic conditions and discover and describe new diseases with potential for treatment. The study included patients with neurodevelopmental conditions that doctors suspected were genetic or metabolic in origin but had not been diagnosed using conventional methods. Our team tested the children and their parents using a combination of metabolomic (large scale chemical) analysis and a type of genomic sequencing called whole exome sequencing. With this state-of-the-art technique, experts analyze and interpret the portion of DNA called genes that hold the codes for proteins. Some people’s intellectual disability is due to rare genetic conditions that interfere with the processes the body uses to break down food. Because of these metabolic dysfunctions, there is an energy deficit and build-up of toxic substances in the brain and body leading to symptoms such as developmental and cognitive delays, epilepsy, and organ dysfunction. Some of these rare diseases respond to treatments targeting the metabolic dysfunction at the cellular level and range from simple interventions like dietary modifications, vitamin supplements and medications to more invasive procedures like bone marrow transplants. Because the right treatment can improve cognitive functioning or slow or stop irreversible brain damage, early intervention can improve lifelong outcomes for affected children and their families. (more…)
Aging, Author Interviews, End of Life Care, NEJM, Social Issues / 24.05.2016

MedicalResearch.com Interview with: Jill Cameron, PhD Canadian Institutes of Health Research New Investigator Associate Professor, Department of Occupational Science and Occupational Therapy Rehabilitation Sciences Institute Faculty of Medicine, University of Toronto MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Cameron: In the world of critical illness, a lot of research has focused on helping people to survive – and now that more people are surviving, we need to ask ourselves, what does quality of life and wellbeing look like afterwards for both patients and caregivers? The aim of our research was to identify factors associated with family caregiver health and wellbeing during the first year after patients were discharged from the Intensive Care Unit. We examined factors related to the patient and their functional wellbeing, the caregiving situation including the impact it has on caregivers everyday lives, and caregiver including their sense of control over their lives and available social support. We used Pearlin’s Caregiving Stress Process model to guide this research. From 2007-2014, caregivers of patients who received seven or more days of mechanical ventilation in an ICU across 10 Canadian university-affiliated hospitals were given self-administered questionnaires to assess caregiver and patient characteristics, caregiver depression symptoms, psychological wellbeing, and health-related quality of life. Assessments occurred seven days and three, six and 12-months after ICU discharge. The study found that most caregivers reported high levels of depression symptoms, which commonly persisted up to one year and did not improve in some. Caregiver sense of control, impact on caregivers’ everyday lives, and social support had the largest relationships with the outcomes. Caregivers’ experienced better health outcomes when they were older, caring for a spouse, had higher income, better social support, sense of control, and caregiving had less of a negative impact on their everyday lives. No patient characteristics or indicators of illness severity were associated with caregiver outcomes. Poor caregiver outcomes may compromise patients’ rehabilitation potential and sustainability of home care. Identifying risk factors for caregiver distress is an important first step to prevent more suffering and allow ICU survivors and caregivers to regain active and fulfilling lives. (more…)
Asthma, Author Interviews, NEJM, NIH, Pediatrics, Pulmonary Disease / 18.05.2016

MedicalResearch.com Interview with: Dr. James P. Kiley Ph.D National Institutes of Health Bethesda Maryland  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Kiley: While a higher proportion of children have asthma compared to adults, the disease is limited to childhood for many individuals who appear to be unaffected as adults. Regardless of whether asthma continues into adulthood or reoccurs during adulthood, the impact of childhood asthma on lung function later in life is unclear. This study demonstrated that in children with chronic persistent asthma at the age of 5-12 years who continued to be followed through their early twenties, 75% of them had some abnormality in the pattern of their lung growth. The study examined the trajectory of lung growth, and the decline from maximum growth, in a large cohort of persons who had persistent, mild-to-moderate asthma in childhood and determined the demographic and clinical factors associated with abnormal patterns of lung growth and decline. (more…)
Asthma, Author Interviews, Brigham & Women's - Harvard, NEJM, Pediatrics, Pulmonary Disease / 15.05.2016

MedicalResearch.com Interview with: Michael McGeachie, PhD Instructor in Medicine Harvard Medical School Channing Division of Network Medicine Brigham and Women's Hospital MedicalResearch.com: What is the background for this study? Dr. McGeachie: In asthma, and in general but particularly in asthma, a person’s level of lung function has a big impact on his or her quality of life, level of respiratory symptoms and complications, and general morbidity. In asthma, low lung function leads to greater severity and frequency of asthma symptoms. Asthma is a common childhood illness, affecting 9-10% of children. Many children grow out of asthma as they become adults, but other asthmatics remain effected through adulthood, which can lead to a lifetime of respiratory symptoms and chronic airway obstruction, including chronic obstructive pulmonary disease (COPD). If you consider lung function longitudinally, throughout development, plateau, and decline, different people and different asthmatics tend to exhibit different patterns of lung function. Healthy, non-asthmatic people tend to have a period of rapid lung function increase in adolescence, a plateau of lung function level in their late teens and early 20s, and starting around 25 or so a slow, gradual decline of lung function that continues throughout old age. We call this Normal Growth of lung function. However, some people exhibit Reduced Growth, where they don’t reach their expected maximum lung function for a person of the same age, sex, height, and race. Others can show Early Decline, who might reach a normal maximum but then begin to decline immediately without a plateau or with a truncated plateau. We hypothesized that these patterns, Reduced Growth and Early Decline, might have different baseline indicators, precursors, outcomes, and risk of developing COPD. (more…)
Author Interviews, NEJM, Stroke / 10.05.2016

MedicalResearch.com Interview with: Professor Craig Anderson Professor of Stroke Medicine and Clinical Neuroscience Sydney Medical School at the University of Sydney Institute of Neurosciences of Royal Prince Alfred Hospital MedicalResearch.com: What is the background for this study? Prof. Anderson: Intravenous use of the clot-busting drug, alteplase (or rtPA), at a dose of 0.9 mg/kg body weight is the only proven medical treatment of acute ischemic stroke.  However, a  major drawback to the treatment is an increased risk of major bleeding in the brain, or intracerebral hemorrhage (ICH), that occurs in about 5% of cases, and can be fatal.  This balance of effectiveness (recovery from disability) and risks (ICH, and bleeding elsewhere and uncommon drug allergic reactions) has led to much of the controversy over the net benefit of the drug.  The optimal dose of the drug has never been established, but the Japanese drug safety regulatory authority, has approved a lower dose (0.6mg/kg) on the basis of a small, non-randomized, open study which showed comparable outcomes and lower risk of ICH than historical controls.  This ‘east-west’ divide over the approved dose of alteplase has led to much variation in the dose of alteplase used in clinical practice in Asia – according to a doctor’s perceived risk of ICH in individual patients and the affordability of this relatively expensive treatment in low resource settings.  Data from the Get-with-the Guidelines Quality Registry in the United States suggests Asian patients are at higher risk of ICH after standard-dose alteplase than non-Asians. Our research aimed to resolve this uncertainty over the optimal dose of alteplase, as an international, active-comparator, open-label, blinded outcome assessed, clinical trial of low-dose (0.6 mg/kg) versus standard-dose (0.9mg/kg) in 3310 patients recruited from over 100 hospitals in 13 countries between 2012 and 2015. (more…)
Author Interviews, Cancer Research, Immunotherapy, NEJM / 02.05.2016

MedicalResearch.com Interview with: Paul Nghiem, MD, PhD Professor & Head, University of Washington Dermatology George F. Odland Endowed Chair Affiliate Investigator, Fred Hutchinson Cancer Research Center Professor, Adjunct, of Pathology and Oral Health Sciences Clinical Director, Skin Oncology, Seattle Cancer Care Alliance UW Medical Center at Lake Union Seattle WA 98109   MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Nghiem: Merkel cell carcinoma (MCC) is about 30 times less common than malignant melanoma, but about 3 times more likely to kill a patient than a melanoma. There is no FDA-approved therapy for this cancer & chemotherapy typically only provides about 90 days prior to the cancer progressing. Because of the strong links between MCC and the immune system, including the fact that most MCCs are caused by a virus, there was interest in trying to use immune checkpoint therapy to treat advanced Merkel cell carcinoma. The response to immune stimulation with anti-PD1 therapy was about as frequent as to chemotherapy (56% of patients responded) but importantly, among the responders, 86% remained in ongoing responses at a median of 7.6 months.  While still early, this appears to be strikingly more durable than responses to chemotherapy. (more…)
Author Interviews, NEJM, Pain Research, Surgical Research / 14.04.2016

MedicalResearch.com Interview with: Zoher Ghogawala MD FACS Department of Neurosurgery Lahey Hospital and Medical Center Burlington, MA 01805 MedicalResearch.com: What is the background for this study? Dr. Ghogawala: There is enormous practice variation around the utilization of lumbar spinal fusion in the United States and across the world.  In the United States, lumbar spinal fusion utilization has increased to 465,000 hospital-based procedures in 2011 according to a report from the AHRQ (published in 2014).  Spinal fusion accounts now for the highest aggregate hospital cost (12.8 billion dollars in 2011) of any surgical procedure performed in US hospitals.  What is problematic is that there are no top tier studies that address the question of whether or not adding a lumbar spinal fusion when performing a simple decompression is necessary or helpful.  The question is whether we perform too many fusions in the United States. The SLIP study is the first class I study that demonstrates that the addition of a lumbar fusion when performing a lumbar laminectomy to decompress spinal nerves improves health-related quality of life for patients suffering from low back pain and sciatica from lumbar stenosis with spondylolisthesis - a very common cause of low back pain caused by nerve compression associated with one spinal bone being slightly out of alignment.  MedicalResearch.com: What are the main findings? Dr. Ghogawala: 1)  Adding a lumbar fusion when performing a lumbar laminectomy results in superior health-related quality of life at 2,3, and 4 years after surgery. 2)  Patients with fusion obtained durable results but 14% required re-operation for problems adjacent to their fusion over the 4 year study period. 3)  Lumbar laminectomy alone provided good results for 70% of patients.  There was less blood loss and faster recovery for these patients.  On the other hand, the outcomes were less durable.  One in three patients who underwent a lumbar laminectomy alone required re-operation within 4 years because their back became unstable.  These patients underwent fusion and their health-related quality of life improved. (more…)
Addiction, Author Interviews, NEJM, NYU / 31.03.2016

MedicalResearch.com Interview with: Joshua D. Lee MD, MSc Associate Professor in Medicine and Psychiatry NYU Langone Medical Center MedicalResearch.com: What is the background for this study? Dr. Lee: Opioid use disorders, both from prescription pain medication and heroin use, and related death rates are increasing annually in the US.  Many states, counties, and cities that have previously not had great experience with heroin addiction are now overwhelmed.  This presents unprecedented challenges to affected families and communities, and also health providers and criminal justice systems that have historically not provided high rates of evidence-based treatment for opioid addictions.  Left untreated or inadequately treated, opioid use disorders are chronic, destructive, and often fatal. Extended-release naltrexone, an opioid receptor blocker, is a promising relapse prevention medication intervention, but had not been evaluated in a US criminal justice system (CJS) setting or under real-world conditions. This effectiveness study recruited 308 adults with US criminal justice system involvement (i.e., recent jail or prison incarceration, on parole or probation) and a history of opioid dependence (addiction), who were not currently accessing methadone or buprenorphine maintenance treatment, and were interested in treatment with extended-release naltrexone (XR-naltrexone).  All participants were off opioids (detoxed or recently abstinent) at the time of study start (randomization).  Participants randomized to an open-label, non-blinded evaluation of XR-naltrexone versus treatment-as-usual for six months of treatment.  Long-term follow-up occurred at 12 months and 18 months (6 and 12 months post-treatment).  We estimated rates of opioid relapse and opioid use between the two arms over the course of treatment.  We also tracked other drug and alcohol use, re-incarceration rates, and overdose rates throughout the study. (more…)
Author Interviews, NEJM, Pharmacology / 18.03.2016

MedicalResearch.com Interview with: Prof. Bruce Guthrie Primary Care Medicine and Honorary Consultant NHS Fife University of Dundee Dundee, Scotland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Guthrie: Most drug-related harm is caused by commonly prescribed drugs with moderate risk. This prescribing is not always inappropriate, because risk of harm may be outweighed by benefit in an individual, but we have previously shown that high-risk prescribing like this is common and highly variable between primary care practices, consistent with it being improvable. We therefore developed a complex intervention combining education, informatics to make it easy to identify and review patients, and a small financial incentive to review. We evaluated this intervention in a cluster-randomised trial in 33 Scottish primary care practices, targeting nine measures of high-risk non-steroidal anti-inflammatory drug (NSAID) and antiplatelet prescribing (for example, prescription of an NSAID to someone with chronic kidney disease; prescription of an antiplatelet to someone taking an anticoagulant without also prescribing a gastroprotective drug). The intervention reduced the targeted prescribing by just over one third, and this reduction was sustained in the year after the intervention (including the payment to review) ceased. We also observed reductions in related hospital admissions with gastrointestinal bleeding and heart failure, although not acute kidney injury which was reduced but not statistically significantly. (more…)
Author Interviews, Heart Disease, NEJM, Pharmacology / 25.02.2016

MedicalResearch.com Interview with: Professor Paul Myles MBBS, MPH, MD, FCARCSI, FANZCA, FRCA Director, Dept of Anaesthesia and Perioperative Medicine Alfred Hospital and Monash University, Melbourne, Australia Medical Research: What is the background for this study? What are the main findings? Dr. Myles: When we set up this study 10 years ago there was marked variation in practice for  people taking aspirin waiting for coronary artery bypass surgery.  About half were being told that they must stop their aspirin 5-7 days before surgery, and the other half were told that they should stay on their aspirin. This variation existed across different countries, different cities, and even within a single hospital. Doctors had varied opinions because reliable medical research was sparse; the evidence was contradictory. We thus designed a definitive clinical trial in which half the patients were randomly assigned to receive aspirin and the other half received a placebo. Our study has shown that aspirin is safe (i.e. it does not increase the bleeding risk). We also found that there does not appear to be a benefit during and after surgery, but in view of the clear benefits that exist in daily life, including the preoperative waiting period, we recommend that people should stay on their aspirin if they are having coronary artery surgery. (more…)