Antibiotic Resistance, Author Interviews, Infections, Science / 04.01.2015

Melanie Blokesch PhD Assistant Professor (tenure-track) Laboratory of Molecular Microbiology Global Health Institute, School of Life Sciences Swiss Federal Institute of Technology Lausanne (EPFL) Lausanne SwitzerlandMedicalResearch.com Interview with: Melanie Blokesch PhD Assistant Professor (tenure-track) Laboratory of Molecular Microbiology Global Health Institute, School of Life Sciences Swiss Federal Institute of Technology Lausanne (EPFL) Lausanne Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Blokesch: We have been studying the cholera-causing bacterium Vibrio cholerae for many years in my laboratory. Our main focus has always been on elucidating how this pathogen acquires new genetic material that allows it to evolve. This is often accomplished through a mechanism known as horizontal gene transfer (HGT). There are three main modes of horizontal gene transfer in bacteria and the one we are primarily interested in is called natural competence for transformation. When the bacterium enters the state of natural competence it can take up free genetic material from its surrounding and in case it recombines this new material into its own genome the bacterium is considered to be naturally transformed. Notably, natural competence/transformation was first described in 1928 by Fred Griffith, who showed that transformation can render harmless bacteria pathogenic. These early experiments can be considered a milestone in molecular biology as it later led to the discovery of DNA as the carrier of genetic information. Medical Research: What are the main findings? Dr. Blokesch: The main finding of our study is that the pathogen V. cholerae does not solely rely on free DNA floating around but that it actively kills neighbouring bacteria followed by the uptake of their DNA. Indeed, we were able to show that the two processes - killing of other bacteria and DNA uptake - are co-regulated by the same proteins within the bacterial cell. We also used imaging techniques to visualize the killing of other bacteria by V. cholerae, followed by the release of their genetic material, which the predator then pulled into its own cell. We further quantified these HGT events by following the transfer of an antibiotic resistance gene from the killed bacterium to the predatory V. cholerae cell. Notably, the spread of antibiotic resistances is a major health concern and HGT is a major driver of it. (more…)
Author Interviews, CHEST, Hospital Readmissions, Pulmonary Disease / 03.01.2015

Tina Shah, MD University of Chicago Medicine Department of Pulmonary and Critical Care University of ChicagoMedicalResearch.com Interview with: Tina Shah, MD University of Chicago Medicine Department of Pulmonary and Critical Care University of Chicago Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The reason why we undertook this study is to better understand the Medicare COPD population that falls under the purview of the CMS Hospital Readmissions Reduction Program (HRRP). This program places up to a 3% penalty on all Medicare revenues for hospitals that take care of beneficiaries should a hospital exceed its “expected readmission rate.” Previously 30 day readmissions after index admissions for congestive heart failure, acute myocardial infarction and pneumonia fell subject to the HRRP. As of October 2014, COPD has been added to the list, despite minimal evidence to guide hospitals in how to curb COPD readmissions. The goal of this research was to provide an epidemiological background for this population and identify trends as a hypothesis generating first step to predict who is most likely to be readmitted and to identify targets for successful future interventions on this group. Our study population is unique in that we longitudinally look at about 1/2 of all Medicare admissions for COPD exacerbations, using the CMS guideline definition which is based on discharge ICD-9 codes. As described in previous literature, there is a large discrepancy between identification of COPD by provider versus coding algorithm, however since the Hospital Readmissions Reduction Program is based on discharge coding it is important to examine this particular group. (more…)
Author Interviews, Breast Cancer, Mayo Clinic, NEJM / 03.01.2015

MedicalResearch.com Interview with: Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined. As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them. Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up. This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort). This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women. Medical Research: What should clinicians and patients take away from your report? Dr. Hartmann: There are about 100,000 US women each year diagnosed with atypical hyperplasia via breast biopsy. Although strictly speaking, atypical hyperplasia is a benign finding, it is associated with a sizable risk of a later breast cancer. Physicians from numerous disciplines care for women with high-risk benign breast issues, including gynecologists, family physicians, internists, surgeons and oncologists. These practitioners, and the patients themselves, need information about the absolute risk of breast cancer occurring over time after a diagnosis of atypical hyperplasia. This information is provided in the NEJM report. Also, current guidelines should be updated to include this high-risk population and specifics about their absolute risk, and that the risk level qualifies these patients for screening MRI. Moreover, from the standpoint of risk reduction, four previously conducted breast cancer prevention trials included women with atypical hyperplasia. These trials used hormonal therapies (anti-estrogens) and showed that, in women with atypical hyperplasia, the use of such medications could lower the risk of a later breast cancer by 50% or more. Yet, other research has shown that women are quite reluctant to take such medications, primarily because of fear of side effects. In the NEJM report, we detail specific numbers of side effects that actually occurred in women who used these anti-estrogens (as opposed to the number of side effects seen in women taking placebo) and show that most of the side effects occurred quite uncommonly. Thus, we hope that the combination of information provided in this report on (i) actual risks of breast cancer and (ii) actual risks of side effects will help patients and practitioners make informed decisions on the best treatment approaches for women with atypical hyperplasia. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Hartmann: First, women with atypical hyperplasia should be included in future prospective trials of novel imaging strategies (they were not included in trials of MRI, which had been limited to women with hereditary risk). Second, efforts should continue to predict which women with atypical hyperplasia are at highest risk, especially in the first 5-10 years after their biopsy, so they can be cared for optimally. Our research team, and others, continue to study the underlying molecular pathways that drive the progression from atypical hyperplasia to cancer; identifying such processes would not only aid in risk prediction but also identify driving pathways that could be blocked pharmaceutically. Citation: upcoming NEJM publication discussing: Women with Atypical Hyperplasia are at Higher Risk of Breast Cancer MedicalResearch.com Interview with: Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern  – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined.  As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them.  Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up.  This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort).  This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women. (more…)
Author Interviews, Journal Clinical Oncology, Lung Cancer, Radiation Therapy, UT Southwestern / 03.01.2015

MedicalResearch.com Interview with: Dr. Puneeth Iyengar, MD, PhD. Assistant Professor Director of Clinical Research Dept of Radiation Oncology Co-leader, Thoracic Disease Oriented Team Harold Simmons Cancer Center UT Southwestern Medical Center  Dallas, TX Medical Research: What is the background for this study? What are the main findings? Response: Stage IV Non-small cell lung cancer (NSCLC) remains a disease of limited survival, in the range of one year for a majority of patients who historically have gone on to receive systemic therapy only. Disease in this patient population most often recurs in the sites of original gross disease. With greater understanding of the biology and patterns of failure that occur in stage IV NSCLC, it is becomingly increasingly obvious that there are subsets of patients, those with limited sites of metastatic disease, who may benefit with more aggressive local therapy in addition to systemic agents to effectuate longer progression free survival (PFS) and potentially overall survival (OS). Since failures of treatment occur most commonly in original gross deposits, local non-invasive therapy in the form of stereotactic body radiation therapy (SBRT) may offer a means to curtail the recurrences, perhaps as a way to shift the time to and patterns of failure. To address these concepts, a multi institutional single arm phase II study was conducted at UT Southwestern Medical Center in Dallas and University of Colorado Medical Center. Twenty-four patients with limited metastatic NSCLC (fewer than or equal to six sites of disease including the primary) who had progressed through at least one systemic therapy regimen were treated with SBRT to all sites of gross disease and the EGFR inhibitor erlotinib with progression free survival the primary end point. The results of the study were very significant, with a PFS in this study cohort of 14.7 months, compared to historical ranges of 2-4 months, and an OS of 20.4 months, compared to historical ranges of 6-9 months for this same patient population. The SBRT treatments were found to be very safe and efficacious – only 3 out of 47 measurable lesions irradiated recurred with a concomitant shift in failure patterns from local to distant sites. As importantly, EGFR status was evaluated in 13 patient tumors, with none harboring the most common mutations. One could, therefore, predict that with a mutation enriched population, the combination of EGFR inhibitor and SBRT may have offered even greater PFS and OS benefits. Our observations also suggest that the SBRT treatments probably contributed the most to the dramatic PFS and OS outcomes. These findings were published in the Journal of Clinical Oncology in the December 1, 2014 print issue with an accompanying editorial. (more…)
Author Interviews, Brigham & Women's - Harvard, Diabetes, JAMA / 02.01.2015

Seth A. Berkowitz, MD, MPH Division of General Internal Medicine Massachusetts General Hospital, BostonMedicalResearch.com Interview with: Seth A. Berkowitz, MD, MPH Division of General Internal Medicine Massachusetts General Hospital, Boston Medical Research: What is the background for this study? What are the main findings? Dr. Berkowitz: Prior studies had looked the association between single unmet basic material needs and diabetes control, but hadn't necessarily looked at multiple things people may not be able to afford, which more closely mirrors real-life. Also, prior studies had been done in a 'pre-Affordable Care Act' setting, while, by being in Massachusetts, our study was conducted in a setting of near-universal healthcare coverage that is similar to what the rest of the US is moving towards. We found that difficulties meeting basic material needs, such as difficulties affording food, known as food insecurity, and having financial barriers to taking medications, called cost-related medication underuse, are associated with worse diabetes control and increased use of costly health services in diabetes patients, despite near-universal health insurance coverage (more…)
Author Interviews, Erasmus, NEJM, Stroke / 02.01.2015

Diederik Dippel MD, PhD Senior Consultant in Neurology Erasmus MC University Medical Center Rotterdam The NetherlandsMedicalResearch.com Interview with: Diederik Dippel MD, PhD Senior Consultant in Neurology Erasmus MC University Medical Center Rotterdam The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Dippel: MR CLEAN is the first randomized clinical trial to show that intra-arterial treatment of ischemic stroke to get the clot out, really works. It leads to more recovery and less handicap. Previous studies had shown that intra-arterial treatment leads to recanalization, but the final proof that the treatment leads to recovery more often than standard treatment was lacking. With standard treatment, less than 1 out of 5 recovers without handicap, but with this new treatment, this will be 1 out of 3. The treatment did not lead to more complications than standard treatment. The rate of symptomatic intracranial hemorrhage was similar in both arms. Our study differs from previous, neutral trials.
  • First, we required patients to have an intracranial arterial occlusion confirmed by neuro-imaging.
  • Second, we used third generation thrombectomy devices, such as retrievable stents in most of the cases.
  • Third, our trial was conducted in a country with a very good infrastructure, which allowed rapid transfer to intervention centers, which are spread throughout the country. Our rate of iv tPA in Dutch hospitals is over 11% on average.
  • Last, all intervention centers participated, and almost no patients were treated outside the trial. Moreover, reimbursement of the treatment was conditional on participation in the trial. (more…)
Annals Thoracic Surgery, Author Interviews, Heart Disease, Surgical Research, Yale / 02.01.2015

Karthik Murugiah MBBS Fellow in Cardiovascular Medicine Yale School of Medicine Center for Outcomes Research and Evaluation (CORE) New Haven, CT 06510MedicalResearch.com Interview with: Karthik Murugiah MBBS Fellow in Cardiovascular Medicine Yale School of Medicine Center for Outcomes Research and Evaluation (CORE) New Haven, CT 06510 Medical Research: What is the background for this study? What are the main findings? Response: Aortic valve disease is common among older people and frequently requires valve replacement. 1-year survival after open surgical aortic valve replacement is high (9 in 10 survive the year after surgery). Our study focuses on the experience of these survivors in terms of the need for hospitalization during the year after surgery. Among patients >65 years of age enrolled in Medicare who underwent surgical replacement of their aortic valve and survived at least one year, 3 in 5 were free from hospitalization during that year. Both, the rates of hospitalization and the average total number of days spent in the hospital in the year following surgery have been decreasing all through the last decade (1999 to 2010). (more…)
Accidents & Violence, Author Interviews, JAMA, Mental Health Research, Pediatrics / 01.01.2015

MedicalResearch.com Interview with: Joseph A Simonetti, MD MPH Research Fellow Harborview Injury Prevention & Research Center University of Washington Seattle, WA, USA Medical Research: What is the background for this study? What are the main findings? Dr. Simonetti: Studies have consistently shown that children living in households where firearms are stored safely have a lower risk of suffering firearm injuries, including lethal firearm injuries, compared to those living in households where firearms are stored unlocked and/or loaded. Safe firearm storage is widely recommended by public health experts, professional medical societies, and gun rights organizations, especially for households where children might be suffering from mental heath and substance abuse issues that put them at increased risk for suicide or unintentional injury. Our goal was to find out if those recommendations were being effectively implemented in the community. To do this, we used survey data that assessed mental health conditions and firearm access among a nationally representative sample of US adolescents. Medical Research: What are the main findings? Dr. Simonetti: First, we confirmed previous findings that a large proportion of US adolescents have access to a firearm in the home. Of those who reported living in a home with a firearm, 40% said they could immediately access and shoot the firearm. Second, the prevalence of most mental health diagnoses was similar between adolescents who did and did not report firearm access. However, a greater proportion of adolescents with firearm access had drug and alcohol disorders compared to adolescents who reported living in a home with a firearm but did not have access to the firearm. The main finding was that children with mental health risk factors for suicide were just as likely to report in-home firearm access as those without identified risk factors. This finding held true even when comparing firearm access between children with no identified risk factors and those who reported a recent suicide attempt, who arguably have the highest suicide risk in this sample. (more…)
Author Interviews, Compliance, Flu - Influenza, Pediatrics, Pediatrics, Vaccine Studies / 31.12.2014

Melissa Stockwell, MD, MPH, FAAP Florence Irving Assistant Professor of Pediatrics and Population and Family Health Columbia University - College of Physicians & Surgeons and Mailman School of Public Health Medical Director, New York-Presbyterian Hospital Immunization Registry (EzVac) Co-Director, Primary Care Clinician Research Fellowship in Community Health New York, NY 10032MedicalResearch.com Interview with: Melissa Stockwell, MD, MPH, FAAP Florence Irving Assistant Professor of Pediatrics and Population and Family Health, Columbia University - College of Physicians & Surgeons and Mailman School of Public Health Medical Director, New York-Presbyterian Hospital Immunization Registry (EzVac); Co-Director, Primary Care Clinician Research Fellowship in Community Health Medical Research: What is the background for this study? What are the main findings? Response:  Influenza can be a very serious disease and is more than just a bad cold.  Some children who are 6 months through 8 years need two doses of the influenza vaccine in a season depending on if and when they received previous influenza vaccine doses. We know that only about half of these families who want to vaccinate their children against the flu and get the first dose, come back to get the second dose. (more…)
Author Interviews, JAMA, Multiple Sclerosis / 31.12.2014

Dr. Richard Nash MD Colorado Blood Cancer InstituteMedicalResearch.com Interview with: Dr. Richard Nash MD Colorado Blood Cancer Institute   Medical Research: What is the background for this study? What are the main findings? Dr. Nash: Multiple sclerosis is an autoimmune disease of the central nervous system which causes significant disability and in some cases results in patients being wheel-chair bound or bed-ridden. It is a significant medical problem amongst young adults. We undertook this study because current Multiple sclerosis therapies were not adequate for effective long-term control of the disease in the majority of the patients. High-dose immunosuppressive therapy followed by autologous hematopoietic cell transplantation is an effective treatment for many hematological malignancies. It causes a profound immunosuppression. Based on this effect on the immunological system, we initiated a clinical trial of this treatment modified for autoimmune disorders. The study was supported by the Immune Tolerance Network and NIAID, NIH. In a phase 2 clinical trial of 25 patients all of whom were followed for at least 3 years, we demonstrated that 80% of patients had no evidence of disease activity. No other Multiple sclerosis treatments were given after the study treatment. Adverse events were similar to what we have observed for this treatment in patients with hematological malignancies. No significant acute neurological adverse events were observed. (more…)
Author Interviews, Cancer Research, PNAS, UCSD / 31.12.2014

MedicalResearch.com Interview with: Annie Samraj and Ajit Varki MDDr. Annie Samraj MD Postdoc Fellow Varki Lab and Ajit VAjit Varki MD Distinguished Professor of Medicine and Cellular & Molecular Medicine Co-Director, Center for Academic Research and Training in Anthropogeny (CARTA) Co-Director, Glycobiology Research and Training Center (GRTC) University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0687.arki MD Distinguished Professor of Medicine and Cellular & Molecular Medicine , Co-Director, Center for Academic Research and Training in Anthropogeny, Co-Director, Glycobiology Research and Training Center University of California, San Diego, La Jolla, CA Medical Research: What is the background for this study? What are the main findings? Dr. Varki: For the past decade, there has been increasing evidence that people who consume red meat (beef, pork, lamb) are at a higher risk for certain kinds of cancers. Although red meat is a high quality source of protein, iron and vitamins, too much consumption may be harmful to humans. While there are other hypotheses under consideration, we focused on a non-human sugar molecule called Neu5Gc in red meat that could explain the link to cancer risk. We extensively studied various foods and concluded that red meat (particularly beef) is rich in Neu5Gc. In contrast poultry, fish steaks and hen eggs have little or no Neu5Gc. From previous studies, we knew that animal-derived Neu5Gc could be incorporated into human tissues. In this study, we hypothesized that eating red meat could lead to inflammation if the body’s immune system targets the foreign Neu5Gc. Chronic inflammation is also known to instigate or promote tumor progression. To test this hypothesis, we used mice engineered to be similar to humans in that they lacked Neu5Gc, and also produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Tumor formation increased fivefold and Neu5Gc accumulated in the tumors, proving the hypothesis. None of the various control groups of mice showed this effect. (more…)
Author Interviews, JAMA, Surgical Research, Weight Research / 31.12.2014

Jeffrey A. Gusenoff, MD Associate Professor of Plastic Surgery Co-Director, Life After Weight Loss Program Co-Director, BodyChangers Director, Post-Bariatric Body Contouring Fellowship UPMC Department of Plastic SurgeryMedicalResearch.com Interview with: Jeffrey A. Gusenoff, MD Associate Professor of Plastic Surgery Co-Director, Life After Weight Loss Program Co-Director, BodyChangers Director, Post-Bariatric Body Contouring Fellowship UPMC Department of Plastic Surgery Medical Research: What is the background for this study? What are the main findings? Dr. Gusenoff: With the rise in massive weight loss patients from bariatric surgery or diet and exercise, more patients are choosing to have a thighplasty to remove excess skin of the inner thigh. Many techniques exist for treating this, but there aren't many studies that look into the safety of these procedures in massive weight loss patients. What we found is that  many patients have scars that go all the way down the thigh with a fairly high complication rate of almost 70%. (more…)
Author Interviews, JAMA, Smoking / 31.12.2014

Dr Hayden McRobbie MB ChB PhD Reader in Public Health Interventions Wolfson Institute of Preventive Medicine Barts and The London School of Medicine and Dentistry Queen Mary University of LondonMedicalResearch.com Interview with: Dr Hayden McRobbie MB ChB PhD Reader in Public Health Interventions Wolfson Institute of Preventive Medicine Barts and The London School of Medicine and Dentistry Queen Mary University of London Medical Research: What is the background for this study? What are the main findings? Dr. McRobbi: Varenicline is an effective smoking cessation aid that acts primarily to alleviate the symptoms of tobacco withdrawal discomfort, thereby making quitting easier. It also reduces the rewarding effects of cigarettes smoked which may enhance the drugs smoking cessation effect by reducing the enjoyment of smoking prior to quitting and preventing a lapse, after quitting, progressing to relapse. In some people the standard dose of varenicline (2mg/day) results in a decrease in the enjoyment of smoking prior to quitting and that these people appear to have higher quit rates that those that don’t experience this reaction to smoking. The randomised placebo controlled trial was designed to investigate whether increasing the varenicline dose (up to 5mg/day) in smokers who show no reaction to the standard dose improves treatment outcomes compared to remain on the standard dose. Medical Research: What are the main findings? Dr. McRobbi: Whilst the increased dose, compared with the standard dose, reduced the enjoyment of smoking prior to quitting it had no additional effect on alleviating tobacco withdrawal symptoms or smoking cessation rates at 12 weeks post quit date (26% vs. 23%). (more…)
Author Interviews, Nature, Neurological Disorders / 30.12.2014

György Buzsáki, M.D., Ph.D. Biggs Professor of Neural Sciences NYU Neuroscience Institute New York University Langone Medical Center New York, NY 10016MedicalResearch.com Interview with: György Buzsáki, M.D., Ph.D. Biggs Professor of Neural Sciences NYU Neuroscience Institute New York University Langone Medical Center New York, NY 10016 Medical Research: What is the background for the NeuroGrid device? Dr. Buzsaki: The main form of communication among neurons in the brain occurs through action potentials (‘spikes’). Understanding the mechanisms that translate spikes of individual neurons into perceptions, thoughts, and actions requires the ability to monitor large populations of neurons at the spatial and temporal resolution of their interactions. We developed a novel, organic material-based, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) with neuron-size density electrodes capable of acquiring action potential of individual neurons from the surface of the brain. The NeuroGrid has several innovative characteristics that overcome limitations in current methods of surface recording: (i) light-weight and conformable architecture to establish stable electrical and mechanical contacts, thereby ensuring minimal damage to underlying tissue; (ii) efficient abiotic/biotic interface resulting in a high signal to noise ratio and the ability to resolve spikes. This is achieved by using conducting polymers as the interfacing material. Conducting polymers are mix conductors, they can conduct electronics and ionic currents hence they can efficiently transduce ion based neural activity into electronic signals (iii) scalable neuron-size density electrodes to allow isolation and characterization of multiple individual neurons’ action potential across the cortical surface. (more…)
Annals Internal Medicine, Author Interviews, Colon Cancer, Race/Ethnic Diversity, University of Pennsylvania / 30.12.2014

Jeffrey H. Silber, M.D., Ph.D. The Nancy Abramson Wolfson Endowed Chair in Health Services Research Director, Center for Outcomes Research The Children's Hospital of Philadelphia Professor of Pediatrics, Anesthesiology & Critical Care The Perelman School of Medicine Professor of Health Care Management, The Wharton SchoolMedicalResearch.com Interview with: Jeffrey H. Silber, M.D., Ph.D. The Nancy Abramson Wolfson Endowed Chair in Health Services Research Director, Center for Outcomes Research The Children's Hospital of Philadelphia Professor of Pediatrics, Anesthesiology & Critical Care The Perelman School of Medicine Professor of Health Care Management, The Wharton School The University of Pennsylvania  Philadelphia, PA 19104 Medical Research: What is the background for this study? What are the main findings? Response: Differences in colon cancer survival by race is a well recognized problem among Medicare beneficiaries. We wanted to determine to what extent the racial disparity in survival is due to a racial disparity in presentation characteristics at diagnosis (such as advanced stage and the presence of chronic diseases) versus a disparity in subsequent treatment by surgeons and oncologists. To answer this question, we compared black colon cancer patients to three matched white groups: (1) “Demographics” match controlling age, sex, diagnosis year, and Survey, Epidemiology, and End Results (SEER) site; (2) “Presentation” match controlling demographics plus comorbidities and tumor characteristics including stage and grade; and (3) “Treatment” match including presentation variables plus details of surgery, radiation and chemotherapy. We studied Medicare patients 65 years of age and older diagnosed between 1991-2005 in the SEER-Medicare database. There were 7,677 black patients and 3 sets of 7,677 matched white controls. We found that difference in 5-year survival (black-white) was 9.9% in the demographics match. This disparity remained unchanged between 1991-2005. After matching on presentation characteristics, this difference fell to 4.9%. Finally, after additionally matching on treatment, this same difference hardly changed, moving to only 4.3%. So the disparity in survival attributed to treatment differences comprised only an absolute 0.6% of the overall 9.9% survival disparity. (more…)
Author Interviews, JAMA, OBGYNE / 28.12.2014

Keith P. West, Jr., Dr.P.H., R.D. Professor and Director Program and Center in Human Nutrition Department of International Health Bloomberg School of Public Health Johns Hopkins University Baltimore, Maryland 21205MedicalResearch.com Interview with: Keith P. West, Jr., Dr.P.H., R.D. Professor and Director Program and Center in Human Nutrition Department of International Health Bloomberg School of Public Health Johns Hopkins University Baltimore, Maryland 21205 Medical Research: What is the background for this study? What are the main findings? Dr. West: Deficiencies in vitamins and minerals (micronutrients) that must be provided by the diet, are a major public health concern in undernourished societies.  In rural South Asia, where some 35 million babies are born each year, maternal micronutrient deficiencies are common and may increase risk of adverse pregnancy outcomes such as preterm birth, low birth weight or stillbirth and infant mortality.  Further, a newborn of low birth weight faces higher risks of poor postnatal growth, infection and mortality.  Where prenatal care exists, iron-folic acid supplements are often prescribed as standard care to prevent iron deficiency anemia.  But it is likely that many micronutrient deficiencies emerge from an inadequate diet, raising the possibility that a supplement that provides each day a recommended dietary allowance of most essential vitamins and minerals  could measurably improve the health of the mother, fetus and infant.  Because prenatal multinutrient supplements are rarely taken in low income countries, it is important to assess their potential to  improve health before recommending this practice.  We did this be conducting a large prenatal supplementation trial in rural Bangladesh, randomizing  44,567 pregnant women in their 1st trimester to receive a supplement with 15 vitamins and minerals or only iron and folic acid, followed their pregnancies and survival of their 28,516 infants to 6 months of age. Medical Research: What are the main findings? Dr. West:  The multiple micronutrient supplement had the effect of extending the length of gestation compared to the iron-folic acid supplement, by about 2 days on average.  This was enough to lower risk of preterm birth, below 37 weeks,  by 15%.  The extra time in the womb also allowed the fetus to grow a little larger, increasing birth weight (by 54 grams or about 2 ounces) as well as length and other measures of size, leading to a 12% reduction in low birth weight.  In addition, there was an 11% reduction in risk of stillbirth.  These are all indications of a healthier pregnancy.  Although we observed a 14% lower mortality from all causes in girls, there was not a similar effect in boys, leading to no overall effect.  We are continuing to investigate possible reasons for this difference. (more…)
Author Interviews, HPV, Lancet, Vaccine Studies / 28.12.2014

MedicalResearch.com Interview with: Huachun Zou PhD on behalf of all authors. Melbourne Sexual Health Centre, Alfred Health, Carlton, VIC, Melbourne School of Population and Global Health University of Melbourne, Melbourne, VIC, Australia Medical Research: What is the background for this study? What are the main findings? Response: Anogenital human papillomavirus (HPV) infection and anal cancer are common among men who have sex with men (MSM) and preventable with the HPV vaccine. However, the optimal strategy for vaccinating MSM against HPV requires an accurate understanding of the age specific incidence of early HPV infection. In addition to understanding the optimal age at which to vaccinate young MSM, policy makers also need to know the vaccine coverage required in MSM. In this paper we aimed to provide estimates for the site specific incidence of HPV and to use this to estimate the probability of transmission per partner in a cohort of very young MSM aged 16 to 20 years. These data will assist governments in deciding what HPV vaccination strategy is likely to be the most effective in MSM. (more…)
Author Interviews, Breast Cancer, Johns Hopkins, Journal Clinical Oncology, Leukemia / 28.12.2014

MedicalResearch.com Interview with: Dr. Judy Karp, Dr. Antonio Wolff and  Dr. Kala Visvanathan Breast Cancer Program Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore, MD 21287 Medical Research: What is the background for this study? What are the main findings? Response: The background for this study was the clinical observation from the Johns Hopkins Leukemia Program that a significant number of women with newly diagnosed acute myeloid leukemia had a personal history for breast and/or ovarian cancers.  This observation led to our examination of the large NCCN breast cancer database in a multidisciplinary and multi-institutional study.  The overarching finding in our study is that the risk of developing some form of leukemia following chemotherapy with or without radiation therapy, while small, continues to increase over at least 10 years without a plateau and is roughly twice what we thought it to be from previous breast cancer studies. (more…)
Aging, Author Interviews, Nature, Scripps / 27.12.2014

Paul Schimmel, Ph.D. Professor The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research Department of Molecular and Cell Biology, The Scripps Research Institute, La Jolla, California MedicalResearch.com Interview with: Paul Schimmel, Ph.D. Professor The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research Department of Molecular and Cell Biology, The Scripps Research Institute, La Jolla, California Medical Research: What is the background for this study? What are the main findings? Dr. Schimmel: Resveratrol (RSV) is thought to provide health benefits by activating a protective stress response. In the paper we described a new, previously missed mechanism for its action. This mechanism is activated at much lower concentrations of resveratrol than previously described or imagined. Consequently, other mechanisms, which appear to act at higher concentrations of resveratrol, are layered over a preexisting foundation set by the newly revealed mechanism. (more…)
Author Interviews, Hearing Loss, HIV, JAMA, UCSD / 27.12.2014

dr-peter-torre Dr. Peter Torre III PhD Associate Professor, Audiology Director, Recreational Noise Exposure and Hearing Lab San Diego State UniversityMedicalResearch.com Interview with: Dr. Peter Torre III PhD Associate Professor, Audiology Director, Recreational Noise Exposure and Hearing Lab San Diego State University Medical Research: What is the background for this study? What are the main findings? Dr. Torre: The primary purpose of our study was to evaluate hearing sensitivity in HIV+ and HIV- adults. And subsequently, in HIV+ adults only, to examine whether HIV disease variables or treatment was associated with hearing sensitivity. The main findings were that HIV+ adult had poorer hearing for both the lower and higher frequencies compared with HIV- adults, although we did not find any significant associations between HIV variables and treatment variables with hearing loss. (more…)
Author Interviews, JAMA, Pediatrics / 26.12.2014

Seetha Shankaran MD Director, Neonatal-Perinatal Medicne Children's Hospital of Michigan and Hutzel Women's Hospital Detroit, MIMedicalResearch.com Interview with: Seetha Shankaran MD Director, Neonatal-Perinatal Medicne Children's Hospital of Michigan and Hutzel Women's Hospital Detroit, MI Medical Research: What is the background for this study? What are the main findings? Dr. Shankaran: The background for this study is that term newborn infants born following lack of blood flow and oxygen to the brain are at high risk for death or disability, including motor and developmental handicaps. Hypothermia (lowering the core body temperature to 33-34°C for 72 hours has been shown to decrease the rate of death or disability to 44 to 55%. Hypothermia is currently the only proven therapy to reduce these devastating outcomes. The hypothermia therapy provided to term newborns was based on laboratory experiments that demonstrated that in animal models subjected to hypoxia and ischemia, cooling reduced brain injury. In the NICHD Neonatal Research Network (a group of academic centers across the US), in 2005 we reported the first trial of whole-body cooling to 33.5°C for 72 hours and noted a reduction in death or disability in infancy.  When the infants in the study where followed to childhood, we noted that this reduction in death or disability continued to childhood. Recent laboratory experiments have demonstrated that brain injury continues for days or weeks after the hypoxic-ischemic injury. Other laboratory experiments noted that cooling for a greater depth than 33-34°C (as long as the temperature does not decrease much lower) can reduce brain injury further. Based on this information, in the NICHD Neonatal Research Network we designed a study, among term infants with moderate or severe encephalopathy to compare longer cooling and deeper cooling to see if death or disability can be reduced. Term infants with moderate or severe encephalopathy were randomly assigned at <6 hours of age to 4 groups of therapy; 33.5°C for 72 hours, 32.0°C for 72 hours, 33.5°C for 120 hours and 32.0°C for 120 hours. The  goal was to compare death or disability rates between the 2 durations of cooling (72 hours vs. 120 hours) and 2 depths of cooling (33.5 C vs. 32.0°C) and was designed to recruit 726 infants. A independent data safety and monitoring committee was appointed by the director of NICHD to monitor safety events after the first 50 infants were enrolled and then following the enrollment of every 25 infants. The safety events monitored included mortality in the neonatal intensive care unit (NICU), cardiac arrhythmia, persistent acidosis and major vessel bleeding or thrombosis. The study was started in October 2010. Medical Research: What is the background for this study? What are the main findings? Dr. Shankaran: In November 2013 the study was closed by the data safety and monitoring committee after 8 reviews of study data, following recruitment of 364 neonates because of emerging safety concerns as well as futility analyses. The NICU death rates were 7% (7 of 95) for the 33.5°C for 72 hour group, 14% (13 of 90) for the 32.0°C for 72hr group, 16% (15 of 96) in the 33.5°C for 120 hour group and 17% for the 32.0°C for 120 hour group. The adjusted risk ratio (95% CI) for death for the 120 hour vs. the 72 hour was not significantly different 1.37 (0.92-2.04) nor was it significantly different for the 32.0°C group compared to the 33.5°C group 1.24 (0.69-2.25).  The safety outcomes were similar between the 120 vs. 72 hour groups and the 32.0°C vs. the 33.5°C groups, except that major bleeding occurred among 1% in the 120 group vs. 3% in the 72 hours group, RR 0.25 (0.07-0.91). Futility analyses noted that the probability of detecting benefit of longer cooling, deeper cooling or both for death in the NICU was <2%. The follow -up of infants enrolled into the study for 18 months is on-going. (more…)
Author Interviews, Blood Pressure - Hypertension, Case Western, Dermatology, JAMA, Weight Research / 26.12.2014

Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, IllinoisMedicalResearch.com Interview with: Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, Illinois Medical Research: What is the background for this study? Dr. Silverberg: Previous studies found associations between obesity and atopic dermatitis (AD). However, little was known about the association between AD and metabolic risk factors, such as central obesity and high blood pressure. (more…)
Author Interviews, JACC, Surgical Research / 26.12.2014

Dr. Mary T. Hawn Center for Surgical, Medical Acute Care Research, and Transitions, Birmingham Veterans Affairs Medical Center University of Alabama at Birmingham, BirminghamMedicalResearch.com Interview with: Dr. Mary T. Hawn MD, MPH Center for Surgical, Medical Acute Care Research, and Transitions, Birmingham Veterans Affairs Medical Center Section of Gastrointestinal Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama Medical Research: What is the background for this study? What are the main findings? Dr. Hawn: Cardiac risk factors and surgical risk factors contribute to the development of postoperative adverse cardiac events, but the relative contribution of each has not been quantified. In this study, we sought to determine the incremental risk of surgery following coronary stent placement on adverse cardiac events. To answer this question we used a retrospective cohort study of VA patients with coronary stents placed during 2000-2010 undergoing non-cardiac surgery within two years of stent placement matched to patients with coronary stents not undergoing surgery.  The patients were matched on stent type (drug-eluting versus bare metal) and cardiac risk factors at the time of stent placement.  Our outcome of interest was a composite variable of myocardial infarction and coronary revascularization occurring within 30 days of surgery.  We calculated adjusted risk differences over time from stent placement using generalized estimating equations. When comparing the two cohorts, we found a higher rate of composite cardiac events in the surgical cohort compared to the cohort not undergoing surgery. The main findings in the study were that the incremental risk of surgery was greatest when the surgery occurred in the first 6 weeks following stent placement and decreased to approximately 1% after 6 months, where it remained stable out to 24 months. Surgical characteristics associated with a significant reduction in the incremental risk after 6 months following stent placement included elective, inpatient procedures, and in the setting of a drug eluting stent. (more…)
Author Interviews, HIV, JAMA / 26.12.2014

Jared Baeten, MD PhD Professor, Departments of Global Health and Medicine Adjunct Professor, Department of Epidemiology University of Washington Seattle, WA 98104MedicalResearch.com Interview with: Jared Baeten, MD PhD Professor, Departments of Global Health and Medicine Adjunct Professor, Department of Epidemiology University of Washington Seattle, WA 98104 Medical Research: What is the background for this study? What are the main findings? Dr. Baeten: The medication tenofovir disoproxil fumarate is used widely for the treatment of HIV-1 infection and, more recently, as pre-exposure prophylaxis (PrEP) to protect against HIV-1 infection for at-risk HIV-1 uninfected persons.  Its use has been associated with declines in the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by HIV-1 infected persons, but limited data are available for risk when used as PrEP for HIV-1 prevention. Using data from the largest randomized, placebo-controlled trial of PrEP, among heterosexual women and men in Africa, eGFR changes were assessed during prospective follow-up in those receiving pre-exposure prophylaxis and compared to those receiving placebo.  PrEP use resulted in a small (-1.59 mL/min/1.73m2, 95% CI -2.44, -0.74) but statistically significant decline in eGFR that was non-progressive over a median of 18 months and a maximum of 36 months of follow-up.  PrEP use was not accompanied by a substantial increase in the risk of clinically relevant (≥25%) eGFR decline. (more…)
Author Interviews, Case Western, Nature, Neurological Disorders / 26.12.2014

Bradley T. Lang, PhD Researcher, Jerry Silver Lab Department of Neurosciences Case Western Reserve University School of MedicineMedicalResearch.com Interview with: Bradley T. Lang, PhD Researcher, Jerry Silver Lab Department of Neurosciences Case Western Reserve University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Lang: In the late 1980’s, Jerry Silver, PhD, discovered the presence of chondroitin sulfate proteoglycans in the developing nervous system, which form barriers to prevent aberrant growth. He has been building on this finding for more than 30 years, attempting to understand why the adult spinal cord is incapable of regenerating, or why axons don’t grow where they don’t. He has found that the glial scar, which surrounds the site of neural trauma, is incredibly rich in proteoglycans, which prevent regeneration in the spinal cord. In 2009 we collaborated with a group at Harvard to discover the very first receptor for chondroitin sulfate proteoglycans, protein tyrosine phosphatase-sigma, or PTPsigma. Medical Research: What are the main findings? Dr. Lang: The findings in this paper are twofold. We first describe a novel mechanism of regeneration failure, where regenerating axons become stabilized within a gradient of chondroitin sulfate proteoglycan, completely preventing motility. This finding helps explain why axons persist in the vicinity of the glial scar after injury indefinitely, with little to no regeneration potential—they are simply embedded within the scar. We were able to model this interaction in a petri dish to screen for drugs that were capable of promoting motility. The second finding in the manuscript is the discovery and characterization of a novel peptide therapeutic that binds to the receptor for chondroitin sulfate proteoglycans and releases inhibition. Most importantly, this drug was given systemically, similar to a daily insulin injection, avoiding complications due to direct nervous system infusion/injection. After several weeks of treatment (which began 1 day after injury), rats with severe spinal cord injury regained coordinated locomotion, bladder control, and/or balance. In total, 21/26 treated animals regained some function. (more…)
Author Interviews, Genetic Research, Neurological Disorders, PNAS, Scripps / 26.12.2014

Elizabeth A. Thomas, Ph.D. Associate Professor Department of Molecular and Cellular Neuroscience The Scripps Research InstituteMedicalResearch.com Interview with: Elizabeth A. Thomas, Ph.D. Associate Professor Department of Molecular and Cellular Neuroscience The Scripps Research Institute   Medical Research: What is the background for this study? What are the main findings? Response: Increasing evidence has demonstrated that epigenetic factors can profoundly influence gene expression, and in turn, influence resistance or susceptibility to disease.  Epigenetic drugs, such as histone deacetylase (HDAC) inhibitors, are finding their way into clinical practice, and are being proposed for therapeutic use in several neurological disorders.  Our previous studies have shown that selective HDAC inhibitors can cause beneficial effects in mouse models of Huntington’s disease, improving symptoms, and reducing severity of the disease.  Our current studies show that one such compound can alter DNA methylation, an epigenetic mark that can be inherited, leading to changes in gene expression that are seen in the parent mouse exposed directly to the drug, as well as in offspring from the drug-treated male mice.  Concurrent with these changes, we observed that offspring from drug-treated males shown improved disease symptoms, showing a delay in disease onset and a reduction of motor and cognitive symptoms that included improved performance in tests of balance, speed and memory. These finding have significant implications for human health as they enforce the concept that ancestral drug exposure may be a major molecular factor that can affect disease outcome in a subsequent generation.  One exciting aspect of our study is that the parental drug treatment made the offspring better, not worse, like other compounds known to cause transgenerational effects. (more…)
Author Interviews, JAMA, Obstructive Sleep Apnea, Pediatrics, University Texas, UT Southwestern / 26.12.2014

Ron B. Mitchell, MD Professor of Otolaryngology and Pediatrics William Beckner Distinguished Chair in Otolaryngology Chief of Pediatric Otolaryngology UT Southwestern and Children's Medical Center Dallas ENT Clinic Dallas, TX 75207MedicalResearch.com Interview with: Ron B. Mitchell, MD Professor of Otolaryngology and Pediatrics William Beckner Distinguished Chair in Otolaryngology Chief of Pediatric Otolaryngology UT Southwestern and Children's Medical Center Dallas ENT Clinic Dallas, TX 75207 Medical Research: What is the background for this study? What are the main findings? Dr. Mitchell: The “gold standard” for the diagnosis of and quantification of obstructive sleep apnea (OSA) is polysomnography (PSG or a ‘sleep study’). However, the majorities of T&A procedures are done without PSG and are based on a clinical diagnosis. This is because PSG is expensive, requires overnight observation and is often unavailable. It is important to diagnose and quantify OSA as it allows for surgical planning and predicts the need and type of treatment after surgery. We used data from the Childhood Adenotonsillectomy (CHAT) study; a large multicenter trial (RCT), to look at the ability of clinical parameters to predict the severity of obstructive sleep apnea in children scheduled for a T&A. The main findings of the study are that certain clinical parameters such as obesity and African American race as well as high scores on certain validated questionnaires (such as the pediatric sleep questionnaire- PSQ) are associated, but cannot predict OSA severity. PSG remains the only way to measure objectively the severity of OSA. (more…)
Author Interviews, Cost of Health Care, JAMA, Pediatrics / 24.12.2014

Dr. Ricardo Mosquera MD Assistant professor of Pediatrics at The University of Texas Health Science Center at Houston Medical School Clinic Director, UT Physicians, of the UTHealth Medical School.MedicalResearch.com Interview with: Dr. Ricardo Mosquera MD Assistant professor of Pediatrics at The University of Texas Health Science Center at Houston Medical School Clinic Director, UT Physicians, of the UTHealth Medical School. Medical Research: What is the background for this study? What are the main findings? Dr. Mosquera: There is not strong scientific evidence to support the use of medical homes.  Medical homes have not been demonstrated to decrease adverse outcomes or costs in children. Such benefits are most likely for high-risk children with chronic illness.  We conducted a rigorous and well designed, randomized controlled trial to determine if an enhanced medical home providing comprehensive care decreases serious illness  (death, prolonged hospitalization>7 days, or intensive care unit admissions) and/or cost among high-risk chronically ill children. An enhanced medical home decreased both adverse outcomes (decreased serious illness, hospitalizations, PICU admissions, and serious illness by ~50%) and cost (~$10.000 less per child/year). (more…)
Author Interviews, PLoS, Weight Research / 22.12.2014

Elina Helander, PhD Personal Health Informatics Department of Signal Processing Tampere University of Technology, Tampere, FinlandMedicalResearch.com Interview with: Elina Helander, PhD Personal Health Informatics Department of Signal Processing Tampere University of Technology, Tampere, Finland Medical Research: What is the background for this study? What are the main findings? Dr. Helander: Frequent or at least regular self-weighing is a part of behavioral therapy in many weight programs. However, self-weighing frequency typically varies over time. We analyzed almost 3,000 weight observations from 40 overweight individuals that participated in a 1-year health promotion program. These individuals were instructed to weigh themselves daily but eventually had varying self-weighing frequencies. We examined how different self-weighing frequencies of the same individual were linked with weight changes. We found that weight loss generally occurred during daily weighing. When there were longer breaks in self-weighing such as one month or more, there was a risk of weight gain.  We also computed a theoretical minimum self-weighing frequency for having no weight gain that was 5.8 days in our study. That corresponds approximately weekly weighing. (more…)
Author Interviews, HIV, Nature, UCLA / 22.12.2014

David Gerberry PhD Center for Biomedical Modeling, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CaliforniaMedicalResearch.com Interview with: David Gerberry PhD Assistant Professor Department of Mathematics and Computer Science Xavier University, Cincinnati, Ohio   Medical Research: What is the background for this study? What are the main findings? Response: In an attempt to control the spread of HIV, governments in sub-Saharan Africa are considering providing antiretroviral drugs to people who do not have the virus but are at risk for becoming infected. Such drugs are known as pre-exposure prophylaxis, or PrEP.  Given the cost of PrEP, an important question is how to maximize the impact of interventions given a fixed level of prevention resources. A common strategy is to target resources to the individuals that are at the highest risk for infection.  This group of people is often referred to as the "core group" and can be thought of as sex workers, clients of sex workers and other individuals that are at very high risk for infection.  While targeting this core group is ideal and would result in the most cost-effectiveness interventions, being able to identify these individuals is difficult in practice and they are often unwilling to participate in the intervention; take pre-exposure prophylaxis or change their behavior for example.  From a mathematical perspective it is also very difficult to quantify their increased level of risk.  For example, is a sex worker at 5 times, 25 times, 100 times or 1000 times the risk for HIV infection?  Without this quantification, it is impossible to estimate the cost-effectiveness of a targeted strategy. In our work, we build an intervention strategy based on geographical targeting.  This takes advantage of the fact that HIV incidence is much higher in certain geographical locations than others.  Therefore, individuals in these areas are at increased risk for HIV infection.  Most importantly, such an intervention is feasible because reliable data exists across much of sub-Saharan Africa for the severity of the HIV epidemic in different regions.  To illustrate our ideas we used mathematical modeling to consider resource allocation in South Africa and found that targeting the provinces with highest HIV incidence would prevent 40% more infections than a plan that ignored geographic variation while using the same amount of resources. (more…)