Author Interviews, Chemotherapy, Lung Cancer, NEJM, UT Southwestern / 11.10.2015

David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TXMedicalResearch.com Interview with: David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TX Medical Research: What is the background for this study? What are the main findings? Dr. Gerber: In this trial, we compared an immunotherapy and a chemotherapy drug in patients with non-squamous non-small cell lung cancer (NSCLC) whose disease continued to progress after first-line chemotherapy. We found that nivolumab immunotherapy improved overall survival compared to docetaxel chemotherapy and was generally well tolerated. These results are significant because options for patients whose lung cancer progresses after initial treatment are limited. Nivolumab is an immunotherapy drug that works by inhibiting the cellular pathway known as PD-1 protein on cells that block the body’s immune system from attacking cancerous cells.  The idea behind nivolumab and other immunotherapy drugs is to kick-start the body’s natural immune response to a cancer. Cancer develops and grows in part because it has put the brakes on the immune response. These drugs take the foot off the brake, allowing the immune system to accelerate and attack the cancer. The phase 3 clinical trial followed more than 500 patients who had non-squamous non-small cell lung cancer (NSCLC): 287 received nivolumab and 268 received the chemotherapy drug docetaxel. The one-year survival rate was 51 percent in the nivolumab arm versus 39 percent in the docetaxel arm. The most common reported side effects with nivolumab were fatigue, nausea, decreased appetite, and weakness, and they were less severe than with docetaxel treatment. In a minority of cases, patients treated with nivolumab also developed autoimmune toxicities affecting various organs. In addition to studying safety and efficacy, the trial examined the protein biomarker PD-L1, which is believed to play a role in suppressing the immune system. The study results suggested that patients with a higher level of PD-L1 in their cancers may experience the greatest benefit from nivolumab, which targets the related molecule PD1. Using a biomarker helps oncologists predict which patients will do best on which treatment, and plan their treatment accordingly. Other promising predictive biomarkers for cancer immunotherapies include the degree of immune cell infiltration within a tumor and the number of mutations a tumor has. Specifically, the more mutations a cancer has, the more foreign it appears to the body, thus marking it for immune attack. With lung cancer, we see the greatest number of tumor mutations – and perhaps the greatest benefit from immunotherapy – among individuals with the heaviest smoking history. (more…)
Author Interviews, OBGYNE, Toxin Research / 11.10.2015

Joan A. Casey, PhD, MA Health and Society Scholar Robert Wood Johnson Foundation UC San Francisco/UC Berkeley MedicalResearch.com Interview with: Joan A. Casey, PhD, MA Health and Society Scholar Robert Wood Johnson Foundation UC San Francisco/UC Berkeley  Medical Research: What is the background for this study? What are the main findings? Dr. Casey: ​Eighteen percent of global gas production now comes from unconventional sources. Pennsylvania, in particular, has seen huge increases in unconventional natural gas development (i.e., "fracking") over the past decade. In 2006, there were fewer than 100 unconventional wells, by 2013, there were over 7,000. Developing a single unconventional well takes hundreds to thousands of diesel truck trips to bring in materials, millions of gallons of water mixed with chemicals and sand, and hydraulic fracturing and production, which can release air pollutants and create noise and other community disturbances. We evaluated whether exposure to unconventional natural gas development activity in Pennsylvania was associated with adverse birth outcomes in those living nearby. Mothers who lived near active natural gas wells operated by the fracking industry in Pennsylvania were at an increased risk for preterm birth and for having a high-risk pregnancy. (more…)
Accidents & Violence, Author Interviews, Emergency Care / 10.10.2015

Tracy Mehan, MA Manager of translational research Center for Injury Research at Policy The Research Institute at Nationwide Children’s Hospital Columbus, OH MedicalResearch.com Interview with: Tracy Mehan, MA Manager of translational research Center for Injury Research at Policy The Research Institute at Nationwide Children’s Hospital Columbus, OH   Medical Research: What is the background for this study? What are the main findings? Response: We noticed an increasing number of ziplines popping up all over the United States and wanted to see if there were any potential safety concerns.  In 2001 there were only 10 commercial ziplines. By 2012, there were more than 200. If you include the number of ziplines now seen in backyards and in places like outdoor education programs and camps, the number skyrockets to over 13,000. We found that from 1997 through 2012, there were just under 17,000 non-fatal zipline-related injuries treated in US emergency departments. Almost 70 percent of these injuries occurred in the last four years of the study indicating that this is a growing problem. In 2012 alone, there were more than 3,600 zipline-related injuries, nearly 10 a day. The majority of the injuries were the result of a fall (77 percent) or a collision (13 percent) into a tree, a support structure, or another person. Close to half of the injuries were broken bones (46 percent) and one of every ten (11.7 percent) patients were admitted to the hospital. (more…)
Author Interviews, Cancer Research, Genetic Research / 10.10.2015

Huma Q. Rana, MD Clinical Director, Cancer Genetics and Prevention Dana-Farber Cancer Institute in BostonMedicalResearch.com Interview with: Huma Q. Rana, MD Clinical Director, Cancer Genetics and Prevention Dana-Farber Cancer Institute in Boston Medical Research: What is the background for this study? What are the main findings? Dr. Rana: -        Li-Fraumeni syndrome (LFS) is thought to be a rare, inherited condition that  causes high lifetime risks for multiple cancers.  It is caused by mutations in the TP53 gene.  Traditionally, only people with striking personal or family histories of cancer underwent genetic testing for TP53 mutations, as there are well-established testing criteria.   This gene was usually tested for in isolation, meaning not combined with testing of other genes.  Due to technological advances, namely multi-gene panels (MGP), many more people are having their TP53gene analyzed.    This included a patient of mine who somewhat surprisingly  tested positive for a TP53 mutation.    This led us to investigate whether people who test positive for TP53 mutations on MGPs are different from ones who test positive on traditional or single-gene (SG) testing. We compared individuals tested for TP53 single gene versus multigene panel testing to determine if there were differences in the percent of mutation carriers meeting current testing criteria for LFS.   Our data showed that 73% of individuals sent in for single gene testing of TP53 met Classic or Chompret (2009) criteria for LFS, whereas only 30% of those sent in for multi-gene panel testing met criteria (p=0.0000001).  When we looked at the most up-to-date testing criteria, which includes Classic, Chompret, or a personal diagnosis of early-onset breast cancer (age at ≤35), 85% of individuals in the single gene group who were positive met criteria, while only 53% of the mutation carriers identified on a multi-gene panel did.   These data suggest that multi-gene panel testing enables us to identify TP53 mutation carriers who may not have otherwise been identified if testing were limited to those who meet established LFS criteria. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, Pancreatic, Surgical Research / 09.10.2015

MedicalResearch.com Interview with: Andrew P. Loehrer, MD David Torchiana Fellow in Health Policy and Management Massachusetts General Physicians Organization Research Fellow Codman Center for Clinical Effectiveness in Surgery Department of Surgery Massachusetts General Hospital Andrew P. Loehrer, MD David Torchiana Fellow in Health Policy and Management Massachusetts General Physicians Organization Research Fellow Codman Center for Clinical Effectiveness in Surgery Department of Surgery Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Loehrer: The incidence of pancreatic cancer is increasing and is on pace to become the second leading cause of cancer mortality by the year 2020. While surgery remains the only chance for long-term survival, significant and persistent disparities in evaluation for and receipt of surgery remain for underinsured patients across the United States. The Affordable Care Act aims to increase access to care through expansion of health insurance coverage and was modeled on previous reform in the Commonwealth of Massachusetts. We evaluated the impact of the 2006 Massachusetts health reform on rates of surgery for pancreatic cancer. We found the insurance expansion to be independently associated with a 67% increased rate of resection for pancreatic cancer. While disparities in resection rates by insurance status decreased after the health reform, significant gaps remain between privately-insured patients and government-subsidized/self-pay patients. (more…)
Asthma, Author Interviews, Menopause / 09.10.2015

Kai Triebner, MSc Department of Clinical Science University of Bergen Bergen, Norway MedicalResearch.com Interview with: Kai Triebner, MSc Department of Clinical Science University of Bergen Bergen, Norway

Medical Research: What is the background for this study? Response: During the last decades female life expectancy has risen far beyond 50 years worldwide. This means that the quality of life after menopause is highly relevant today. Menopause implies profound hormonal and metabolic changes leading to higher risk of diabetes and cardiovascular diseases. Although researchers are increasingly aware that hormonal status and inflammation may also deteriorate respiratory health, our knowledge is very scarce. So far, no prospective study had investigated whether menopause increases the risk of asthma in the general population. Medical Research:? What are the main findings? Response: We studied the association between menopausal status and newly diagnosed  asthma, after the age of 44. We found that the odds of getting asthma were more than twice as high for women going through the menopausal transition or after menopause, compared to non-menopausal women. The risk was particularly high for overweight and obese women. These results were not due to general aging and were independent of smoking and geographical location. (more…)
Author Interviews, Fertility, Genetic Research / 09.10.2015

Rajiv McCoy, PhD Dept. of Genome Sciences Univ. of WashingtonMedicalResearch.com Interview with: Rajiv McCoy, PhD Dept. of Genome Sciences Univ. of Washington Medical Research: What is the background for this study? What are the main findings? Dr. McCoy:  Aneuploidy—the inheritance of extra or missing chromosomes compared to the typical 46-chromosome set—is extremely common in human embryos. The vast majority of aneuploidies result in preclinical pregnancy loss, often before the pregnancy is even recognized by the mother. This is thought to be the primary reason why only ~30% of all conceptions result in successful live birth. Many aneuploidies arise during egg formation, with the frequency increasing with maternal age. In addition to meiotic errors, a large proportion of aneuploidies affecting cleavage-stage embryos are mitotic in origin, arising during the initial post-fertilization cell divisions. These initial divisions are controlled by machinery contributed by the mother in the egg (before the embryo's genome has been activated). While these mitotic errors are frequent in cleavage-stage embryos, we found that they are rare in embryos at day-5 of development (the blastocyst stage), suggesting that embryos and/or cells with extensive mitotic errors do not survive to day 5. We discovered that some women have a greater propensity to produce embryos with mitotic errors than others, and our idea was that maybe differences in the mitotic machinery could help explain this. Using data from in vitro fertilized embryos screened by our collaborators at Natera, we found that women who have a particular version of a gene called PLK4 tend to produce more aneuploid embryos, regardless of age. This genetic variant is actually very common—more than half of people carry at least one copy—and is present in nearly all populations. PLK4 has a well-known role in ensuring the proper distribution of chromosomes. We also found that patients referred for embryo screening due to previous IVF failure had higher rates of mitotic error, which underscores the clinical importance of this form of whole-chromosome abnormality. (more…)
Author Interviews, JAMA, Ophthalmology / 08.10.2015

Prof-Jeremy-A-GuggenheimMedicalResearch.com Interview with: Professor Jeremy A. Guggenheim School of Optometry & Vision Sciences Cardiff University Cardiff, UK Medical Research: What is the background for this study? Dr. Guggenheim: An increased risk of myopia (nearsightedness) in first-born vs. non-first-born individuals was noticed in a 2013 study, which focused on 4 cohorts of children and young adults. We wanted to know whether the link between birth order and myopia was present in an earlier generation – before the invention of mobile phones and other gadgets. Also, first-born children tend to get slightly higher exam grades than do non-first-born children, an effect that has been attributed to slightly greater investment of time and energy by parents in the education of their first-born child. A high level of education is a well-known risk factor for myopia, therefore we were interested to find out whether the association between birth order and myopia was attributable to the slightly greater educational exposure of first-born individuals  (more…)
Author Interviews, JAMA, PTSD / 08.10.2015

Kathryn Magruder, Ph.D., M.P.H. Johnson Veterans Affairs Medical Center Charleston, S.C.MedicalResearch.com Interview with: Kathryn Magruder, Ph.D., M.P.H. Johnson Veterans Affairs Medical Center Charleston, S.C. Medical Research: What is the background for this study? What are the main findings? Dr. Magruder: There has been lots of attention and concern over PTSD in your younger veterans — both male and female -- and in male Vietnam veterans.  Too often the women who served during the Vietnam Era have been largely overlooked.  We felt like we owed it to them to understand better their responses to their wartime experiences — even if 40 years later.  It’s never too late to do the right thing! Our main finding is that the women who served in Vietnam had high prevalence of PTSD (20% lifetime, 16% current) and this was not attributable to cases that had developed prior to entering the military.  This was higher than the women who served near Vietnam or in the United States.  When we looked at their reported experiences during the Vietnam Era, the women who were in Vietnam reported higher levels of exposure to all of the items on our scale.  It was these experiences — especially sexual harassment, performance pressures, and experiences with triage and death — that explained their higher levels of PTSD. (more…)
Author Interviews, JAMA, Mental Health Research, Surgical Research / 08.10.2015

Dr. Junaid A. Bhatti MBBS PhD Sunnybrook Health Sciences Centre Toronto, ONMedicalResearch.com Interview with: Dr. Junaid A. Bhatti MBBS PhD Sunnybrook Health Sciences Centre Toronto, ON Medical Research: What is the background for this study? What are the main findings? Dr. Bhatti:  Bariatric surgery remains an important option for morbidly obese patients where other obesity management options fail. It is a safe procedure with mortality risk not higher than any other major procedure of this type. Some studies report that some patients may experience psychological stress following surgery. Studies on the long-term outcomes noted that there was a higher suicide risk in bariatric patients as compared to the general population. It was not clear whether these risks increased following surgery. In this study, we used the data of bariatric patients from Ontario who underwent surgery between 2006 and 2011. We assessed their emergency room visits three years before and three years following surgery. We looked into whether these patients had significantly more visits related to suicide attempts before compared to post surgery period. Overall, about 111 patients (1%) of the cohort had suicide attempts during follow-up. What we saw is that suicide risk increased by 50% following surgery than before surgery period. The risks were higher, but not significantly higher than others, if they were 35 years or older or from low-income or rural settings. The emergency services utilization of suicide attempts following surgery was more intense for the visits before surgery. (more…)
Author Interviews, JAMA, Surgical Research / 08.10.2015

Dr-Isam-Atroshi.pngMedicalResearch.com Interview with: Isam Atroshi, MD, PhD Department of Orthopedics Hässleholm-Kristianstad Lund University Lund, Sweden Medical Research: What is the background for this study? Dr. Atroshi: Although carpal tunnel release surgery is a very common operation and we know that, in the short term, the results in most patients are very good, we do not know that much about long-term outcomes. In fact, before our study there have been no reliable data about outcomes beyond 5 years and whether or not the results differ depending on type of surgery. Medical Research: What are the main findings? Dr. Atroshi: In our study patients with carpal tunnel syndrome who had participated in a randomized clinical trial of open versus endoscopic release were evaluated 11 to 16 years after they had the surgery. We were able to follow 124 of the 128 patients (3 had died and only 1 declined); this almost complete follow-up is unique in clinical research and a major strength of the study. Our main findings are that the good short-term results of surgery are durable in the majority of the patients irrespective of the type of surgery whether open or endoscopic. Two-thirds of the patients can expect to continue being completely free of symptoms more than 10 years after surgery. About a third of the patients still experience some numbness or tingling in the fingers but in most of these the symptoms are only mild and do not cause functional difficulties. More than 85% are very satisfied with the results of the surgery after more than 10 years. However, up to 6% of patients who have surgery could need further surgery because of symptom recurrence. (more…)
Author Interviews, BMJ, Breast Cancer, Cancer Research / 07.10.2015

Dr. Madeleine M A Tilanus-Linthorst PhD Department of Surgery Erasmus University Medical Centre - Cancer Institute Rotterdam, NetherlandsMedicalResearch.com Interview with: Dr. Madeleine M A Tilanus-Linthorst PhD Department of Surgery Erasmus University Medical Centre - Cancer Institute Rotterdam, Netherlands  Medical Research: What is the background for this study? Medical Research: Why is this study important? Response: This prospective nationwide study  investigates whether  tumor stage (size and axillary nodal involvement)  still has impact on survival of breast cancer in modern times with more effective end more widely used additional systemic therapy . We  take tumour biology, age and the different therapies into account and compare results with our nationwide results from 1999-2005.   
  1. Mortality increased with increasing tumour size and independently with nodal involvement, correcting for age, tumour biology and therapy.
  2. Five year relative survival (this is compared with women without breast cancer of the same ages) was 96% for all 93.569 Dutch breast cancer patients between 2006-2012 and 100% in cancers ≤ 1cm.3.     In 2006-2012 in the Dutch population 65% of the breast cancers were detected ≤2cm.
Medical Research: What should clinicians and patients take away from your report?
  1. First, the general prospect of a woman diagnosed with breast cancer currently in the Western world is very good.
  2. Catching breast cancer early is still highly important.
  3. Surgery is the cornerstone of therapy and maybe breast conserving therapy is even a bit better for survival than mastectomy and certainly not worse. Breast cancer in the other breast did not impact on survival and preventive contralateral mastectomy seems only well advised in high risk gene mutation carriers.
  4. Both additional hormonal therapy and targeted therapy (usual against epidermal growth factor her2neu) are, if indicated by tumour stage and receptor status, beneficial for survival.
  5. Further also patients diagnosed late with large tumors of 5cm and above experienced an improvement in outcome. In the earlier group such patients had a 70% five-year relative survival, while in the recent cohort this increased to 81%. This may be a comforting result for some patients.
  6. Finally our results are informative when considering breast  screening.
(more…)
AHA Journals, Author Interviews, Exercise - Fitness, Heart Disease, JACC, University Texas, UT Southwestern / 07.10.2015

Ambarish Pandey, MD Cardiology Fellow, PGY5 University of Texas Southwestern Medical Center, Dallas, Texas 75390MedicalResearch.com Interview with: Ambarish Pandey, MD Cardiology Fellow, PGY5 University of Texas Southwestern Medical Center, Dallas, Texas 75390 Medical Research: What is the background for this study? What are the main findings? Dr. Berry: Physical inactivity is considered a major modifiable risk factor for coronary artery disease and the current guidelines recommend atleast 150 min/week (~ 500 MET-min/week) of moderate intensity physical activity to reduce the burden of coronary artery disease. In contrast, the role of physical activity in reducing risk of heart failure is not emphasized in the current guidelines. This is particularly relevant considering the increasing burden of heart failure in the community. Against this background, we performed this study to the dose-response relationship between physical activity levels and risk of heart failure. We observed a dose dependent inverse association between physical activity levels and heart failure risk. Furthermore, we observed that the current guideline recommended physical activity levels (500 MET-min/week) are associated with only modest reduction in HF risk (< 10%). In contrast, a substantial reduction in heart failure risk was observed at twice and four times the recommended physical activity levels (19% and 35% risk reduction respectively) (more…)
Author Interviews, Brain Injury, NEJM / 07.10.2015

Prof. Peter JD Andrews Honorary Professor Department of Anaesthesia University of EdinburghMedicalResearch.com Interview with: Prof. Peter JD Andrews Honorary Professor Department of Anaesthesia University of Edinburgh  Medical Research: What is the background for this study? Prof. Andrews: Therapeutic hypothermia has shown considerable promise as a neuro-protective intervention in many species and models of cerebral injury in the laboratory. Clinical trials after neonatal hypoxic ischemic encephalopathy and cardiac arrest (global cereal ischemia) show signal of benefit. The outcome after traumatic brain injury (TBI) has not improved in the last 20 years. Clinical trials of prophylactic therapeutic hypothermia for neuroprotection after traumatic brain injury show a mixed outcome, however, the larger trials are all neutral or have a trend toward harm. Because traumatic brain injury is a heterogeneous pathology it has been suggest that the therapeutic hypothermia intervention should be adjusted according to response of a biomarker, to maximize benefit and limit any harms. The EUROTHERM3235Trial was a trial of therapeutic hypothermia to reduce brain swelling after traumatic brain injury. Brain swelling was measured by an intracranial pressure (ICP) probe directly inserted into the brain. Medical Research: What are the main findings? Prof. Andrews: Hypothermia successfully reduced intracranial pressure, but did not improve outcomes compared to standard care alone, with more than a third achieving a good outcome in the standard care group and one a quarter in the hypothermia group. (more…)
Author Interviews, Cancer Research, End of Life Care, Journal Clinical Oncology / 07.10.2015

Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Director, Center for Research on End of Life Care Weill Cornell Medical College New York Presbyterian Hospital New York City, New YorkMedicalResearch.com Interview with: Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Director, Center for Research on End of Life Care Weill Cornell Medical College New York Presbyterian Hospital New York City, New York 10065 Medical Research: What is the background for this study? What are the main findings? Dr. Prigerson: Research has revealed that a majority of terminally ill cancer patients do not realize that they are dying. We wanted to know if terminally ill patients would report wanting to know their life expectancy, how many oncologists shared their life expectancy estimate for the patient with them, and how that prognostic disclosure affected the patient’s accuracy.  We found that 71% of terminally ill cancer patients wanted to know their life expectancy, but only 17.6% were told it by their oncologist. Those who were told were much more realistic than those who were not told, about 17 months closer to their actual survival time from out baseline assessment. Oncologists who shared the prognosis did not psychologically injure patients (eg make them significantly more anxious or depressed) nor was their relationship harmed. (more…)
Allergies, Author Interviews, CDC, Pharmacology, Vaccine Studies / 07.10.2015

MedicalResearch.com Interview with: Michael M. McNeil, MD, MPH Centers for Disease Control and Prevention Atlanta, GA Medical Research: What is the background for this study? What are the main findings? Dr. McNeil : Anaphylaxis is an uncommon potentially life-threatening allergic reaction which can occur immediately (usually within minutes) after exposures to food, drugs, venom and vaccines. More than 100 million people in the U.S. receive vaccinations each year. Most vaccines have the potential to trigger anaphylaxis, but the rates at which it occurs after vaccination are not well known. The CDC study examined data from the Vaccine Safety Datalink (VSD), a collaborative project between CDC and 9 integrated healthcare organizations, which contains vaccination records on more than 9 million patients. The study sought to determine the rates of anaphylaxis after all vaccines combined and some individual vaccines including seasonal influenza vaccines given to children and adults.  Patients studied received vaccinations between January 1, 2009 – December 31, 2011.  Electronic medical record data was screened for patients with specific diagnostic codes for anaphylaxis or who had received epinephrine prescriptions as a treatment for potential anaphylaxis. Researchers were able to look at data from 25,173,965 vaccinations during 17,606,500 visits to healthcare providers. The researchers identified 33 confirmed vaccine-triggered anaphylaxis cases that occurred after more than 25 million vaccine doses. The rate of anaphylaxis was calculated at 1.31 per million doses for all vaccines, and 1.35 per million for seasonal inactivated influenza vaccines. Patients ranged in age from 4 to 65 with a median age of 17. None of the patients with anaphylaxis were below the age of 4 years old. Only one of the 33 patients was hospitalized, and none died as a result of anaphylaxis. A majority (85%) of the case-patients had pre-existing atopic disease including previous anaphylaxis, asthma, and allergies. (more…)
Author Interviews, Heart Disease, JACC, Metabolic Syndrome, Pediatrics / 07.10.2015

Mark DeBoerMedicalResearch.com Interview with: Mark DeBoer, MD Children's Hospital's Department of Pediatrics University of Virginia  Medical Research: What is the background for this study? What are the main findings? Dr. DeBoer: We have been interested in how the severity of the metabolic syndrome relates to long term risks, both for children and adults.  We formulated a score that takes the different components of the metabolic syndrome (body mass index, blood pressure, fasting blood sugar, triglycerides and high density cholesterol) for an individual and forms a score estimating how severe the metabolic syndrome is in that individual.  When we looked at long-term data from individuals followed for 40 years, we found that children and adults with higher scores were more much likely to develop cardiovascular disease. (more…)
Author Interviews, Heart Disease, Statins / 07.10.2015

Giancarlo Marenzi, M.D. Centro Cardiologico Monzino Milan, ItalyMedicalResearch.com Interview with: Giancarlo Marenzi, M.D. Centro Cardiologico Monzino Milan, Italy  Medical Research: What is the background for this study? What are the main findings? Dr. Marenzi: Pre-treatment with statins in patients with stable angina or non-ST-elevation acute coronary syndromes undergoing elective or urgent percutaneous coronary intervention (PCI) has been shown to reduce myocardial injury and to improve clinical outcomes. Conversely, data on a cardio-protective effect of statin pre-treatment in ST-elevation myocardial infarction (STEMI) patients undergoing primary PCI are more controversial. In this prospective study, we evaluated infarct size and myocardial salvage by cardiac magnetic resonance imaging in a consecutive cohort of 230 STEMI patients undergoing primary PCI, comparing patients on chronic statin with those without. Patients on chronic statin therapy showed an almost 40% lower enzymatic (troponin I) peak value, when compared to patients without. In parallel, a 32% smaller infarct size and a 24% higher myocardial salvage were found in the statin group, as compared to those without. In the entire population, no significant association was found between infarct size and LDL-cholesterol levels at hospital admission. (more…)
Author Interviews, Genetic Research, Lung Cancer, PLoS / 07.10.2015

MedicalResearch.com Interview with: Keiji Tanimoto, D.D.S., Ph.D Assistant Professor Research Institute for Radiation Biology and Medicine Hiroshima University Hiroshima Japan Medical Research: What is the background for this study? Dr. Tanimoto: Hypoxia-inducible factor-2α (HIF-2αor EPAS1) is important for cancer progression, and its overexpression is considered a putative biomarker for poor prognosis in patients with lung cancer. However, molecular mechanisms underlying EPAS1 overexpression are not fully understood. Recently, several SNPs of EPAS1 have been reported to be associated with the development of various diseases including cancer. Therefore, we focused on SNPs within EPAS1, and examined the roles of these SNPs in regulation of EPAS1 gene expression and the association of these SNPs with prognosis of non-small cell lung cancer (NSCLC) patients by bioinformatics analyses. Medical Research: What are the main findings? Dr. Tanimoto:
  • The SNP within the EPAS1 intron 1 region (rs13419896) may affect EPAS1 gene and protein expression;
  • The fragment with A allele of the SNP showed higher transactivation activity than one with G, especially in the presence of overexpressed c-Fos or c-Jun;
  • The median survival time of NSCLC patients with at least one A allele of rs13419896 was significantly shorter than that with the G/G homozygote (28.0 vs. 52.5 months, P = 0.047, log-rank test);
  • The possession of A allele of rs13419896, along with clinical stage, was an independent variable for risk estimation of overall survival for NSCLC patients [hazard ratio (HR) = 2.31, 95% CI = 1.14-4.81, P = 0.021], after adjustment for age, gender, stage, histology, tumor size, and differentiation.
(more…)
Author Interviews, JAMA, Orthopedics / 07.10.2015

Dr. Anne Moseley Senior Research Fellow, Musculoskeletal Division The George Institute for Global Health Sydney Australia MedicalResearch.com Interview with: Dr. Anne Moseley Senior Research Fellow, Musculoskeletal Division The George Institute for Global Health Sydney Australia  Medical Research: What is the background for this study? What are the main findings? Dr. Moseley: Ankle fracture is a common injury and is treated with reduction (realignment), sometimes with surgical fixation, followed by a period of immobilization while the fracture heals. Rehabilitation addresses the detrimental effects of the ankle fracture and the subsequent immobilization. Supervised exercise programmes are a common form of rehabilitation traditionally offered to some patients. The benefits of supervised exercise after immobilization for ankle fracture has been unclear. We conducted a clinical trial to determine the effectiveness and cost-effectiveness of a supervised exercise programme and advice about self-management ("rehabilitation" group) compared to advice about self-management alone. Contrary to accepted wisdom, we found that a supervised exercise programme did not offer advantages over physical therapist-prescribed self-management. (more…)
Author Interviews, JAMA, Surgical Research / 07.10.2015

MedicalResearch.com Interview with: Johannes Kurt Schultz, MD Department of Gastrointestinal Surgery Akershus University Hospital, Lørenskog, Norway Faculty of Medicine, University of Oslo, Oslo, Norway  Medical Research: What is the background for this study? What are the main findings? Dr. Schultz: Acute perforated diverticulitis is a serious condition requiring urgent surgical attention. Laparoscopic peritoneal lavage has been described as a tempting option in treatment of these patients instead of today’s standard management with resection of the diseased bowel segment. Previous non-randomized studies have suggested that this novel mini-invasive approach is superior to traditional surgery. Our randomized trial is the largest study conducted to investigate these two treatment options. We demonstrate that the new treatment is not superior to the established surgical management. In fact, the reoperation rate in the laparoscopic lavage group was higher and some sigmoid cancers were not identified in the lavage group and thus left in-situ. (more…)
Author Interviews, Eating Disorders, Microbiome / 06.10.2015

Dr. Ian Carroll, PhD Professor of medicine UNC Center for Gastrointestinal Biology and DiseaseMedicalResearch.com Interview with: Dr. Ian Carroll, PhD Professor of medicine UNC Center for Gastrointestinal Biology and Disease  Medical Research: What is the background for this study? What are the main findings? Dr. Carroll: Anorexia nervosa (AN) is a severe psychiatric disorder characterized by extreme weight dysregulation and presents with high rates of comorbid anxiety.Anorexia nervosa carries the highest mortality rate of all psychiatric illnesses and relapse is frequent. Although a prime contributor, genetic factors do not fully account for the etiology ofAnorexia nervosa, and non-genetic factors that contribute to the onset and persistence of this disease warrant investigation. Compelling evidence that the intestinal microbiota regulates adiposity and metabolism, and more recently, anxiety behavior, provides a strong rationale for exploring the role of this complex microbial community in the onset, maintenance of, and recovery from Anorexia nervosa. Our study provides evidence of an intestinal dysbiosis in AN and an association between mood and the enteric microbiota in this patient population. (more…)
Author Interviews, Gastrointestinal Disease, JAMA / 06.10.2015

Nynne Nyboe Andersen, MD Department of Epidemiology Research Statens Serum Institut Denmark MedicalResearch.com Interview with: Nynne Nyboe Andersen, MD Department of Epidemiology Research Statens Serum Institut Denmark Medical Research: What is the background for this study? Response: The use of TNF-α inhibitors, including infliximab, adalimumab and certolizumab pegol to treat people with inflammatory bowel disease is increasing worldwide and has improved the medical treatment modalities. However, in the post-marketing period, case-reports, data from retrospective cohort studies and spontaneous reporting systems have identified patients with inflammatory bowel disease treated with TNF-α inhibitors, developing a demyelinating event of the central nervous system. It remains unanswered whether this reflect a true association between TNF-α inhibitors and demyelinating diseases or whether these cases are a result of the well-established underlying association between demyelinating diseases and inflammatory bowel disease per se. The rarity of demyelinating diseases has stalled a thorough safety evaluation through analytical studies. Consequently, by use of the nationwide Danish registries, we conducted a large population-based cohort study, aiming to address the risk of demyelinating events of the central nervous system in patients with inflammatory bowel disease treated with TNF-α inhibitors compared to untreated patients. Medical Research: What are the main findings? Response: Using a matched study design, a 2-fold increased risk of demyelinating diseases was observed in patients with inflammatory bowel disease treated with TNF-α inhibitors compared to untreated. The absolute risk was low with less than four additional cases per 10000 person years in those treated compared to untreated. The rarity of demyelinating diseases limited the statistical power and capacity to adjust for or match on potential confounder variables, and therefore findings should be considered preliminary as they could be a result of chance or unmeasured confounding and need confirmation in other studies. (more…)
Author Interviews, Exercise - Fitness, Rheumatology / 06.10.2015

Anja Bye, PhD, Senior Researcher Cardiac Exercise Research Group (CERG) K.G. Jebsen Center of Exercise in Medicine National Council of Cardiovascular Disease Department of Circulation and Medical Imaging Medical Faculty Norwegian University of Science and TechnologyMedicalResearch.com Interview with: Anja Bye, PhD, Senior Researcher Cardiac Exercise Research Group (CERG) K.G. Jebsen Center of Exercise in Medicine National Council of Cardiovascular Disease Department of Circulation and Medical Imaging Medical Faculty Norwegian University of Science and Technology Medical Research: What is the background for this study? What are the main findings? Dr. Bye: The background was that we know that this type of training is superior to exercise at lower intensities in cardiovascular risk reduction in several patients groups. As it was not tested in patients with rheumatic disease, we set out to determine if this type of exercise would be tolerated in these patients, and of they would experience the same benefits on the cardiovascular system as other patients groups, and healthy young and elderly individuals. Hence the main goal was not to treat the rheumatic disease, but to study whether the exercise training would be tolerated, as we assumed they would have equal benefits from this type of exercise as everyone else. I think the most interesting findings were that all of the participants were capable of participating in this type of high-intensity exercise program, without reporting any negative side-effects. Of course the great increase in VO2max, and  the trend towards a reduction in the inflammation after the exercise intervention was very interesting. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, JAMA, Pediatrics / 06.10.2015

Susan Gray MD Division of Adolescent Medicine Boston Children's Hospital Boston, MAMedicalResearch.com Interview with: Susan Gray MD Division of Adolescent Medicine Boston Children's Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Gray: This is a study of the health care costs of 13,000 privately insured adolescents (13 to 21 years old) cared for in an association of pediatric primary care practices. We found that a tiny fraction (1%) of adolescents accounted almost a quarter of the expenses of the whole cohort. Mental health disorders were the most common diagnosis among these high cost adolescents. The characteristics most strongly associated with high cost were complex chronic medical conditions, behavioral health disorders, and obesity, but many high cost adolescents had no chronic conditions. Pharmacy costs, especially orphan drug costs, were a surprisingly large contributor to high costs for these privately insured adolescents. Primary care costs were very small in high cost patients. (more…)
Author Interviews, Cancer Research, Dermatology / 06.10.2015

Nirmala Pandeya, PhD Post Doctoral Research Fellow Faculty of Medicine and Biomedical Sciences, School of Public Health Herston campus The University of QueenslandMedicalResearch.com Interview with: Nirmala Pandeya, PhD Post Doctoral Research Fellow Faculty of Medicine and Biomedical Sciences, School of Public Health Herston campus The University of Queensland Medical Research: What is the background for this study? Dr. Pandeya: Basal cell carcinoma (BCC) is the most common cancer. Although BCC is curable and has low mortality, its high occurrence in the population causes significant healthcare and financial burdens to the community. Hence exploring preventive strategies for this cancer is important in reducing the burden. To date few chemopreventives for BCC have been identified. In many cancer cells, inflammatory biomarkers such as cyclooxygenase-2 (COX-2) and its product prostaglandin E2 are increased and basal cell carcinoma is no exception. Anti-inflammatory drugs, suppressing COX-2 activity, have been shown to reduce the risk of various cancers including squamous cell carcinoma of the skin, so they also have a potential to prevent BCC. But to date research evidence on the benefit of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) on basal cell carcinoma has been inconsistent. So we reviewed and synthesized all published epidemiological studies on NSAIDs and BCC to combine results and estimate the overall pooled effect. Medical Research: What are the main findings? Dr. Pandeya: After thorough evaluation, we identified eleven studies that were relevant and pooling showed a 10% reduction in risk of BCC among those using any kind of NSAIDs. Aspirin and non-aspirin NSAIDs analysed separately suggested a reduced risk of basal cell carcinoma, but were not statistically significant likely due to lack of power. Our research found strongest risk reduction of BCC by the use of NSAIDs among those with either a history of skin cancers or high prevalence of actinic keratosis. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, NEJM / 05.10.2015

Dr. Paul Jeffrey Young MD Intensive Care Unit, Wellington Regional Hospital Wellington South, New ZealandMedicalResearch.com Interview with: Dr. Paul Jeffrey Young MD Intensive Care Unit, Wellington Regional Hospital Wellington South, New Zealand Medical Research: What is the background for this study? What are the main findings? Response: Fever is a response to infection that is broadly conserved across many animal species and it seems reasonable to presume that the components of the immune response have adapted to function optimally in the physiological febrile range.  We have previously shown that among patients with fever and infection, increasing degrees of fever in the first 24 hours in ICU are generally associated with reducing mortality risk after adjusting for illness severity.  Although acetaminophen (paracetamol) is commonly used to treat fever in the ICU, there are no previous data to demonstrate the safety and efficacy of this practice.  The HEAT trial was designed by a group of ICU clinicians to test the hypothesis that treating fever with acetaminophen in critically ill patients with infections would worsen outcomes, or more specifically that it would reduce the number of days patients spent alive and free from requiring intensive care. Medical Research: What are the main findings? Response: The primary finding was that early administration of acetaminophen to treat fever did not alter the number of ICU-free days in adult ICU patients with infections.  The mortality rates of acetaminophen and placebo patients were similar.  Patients who received acetaminophen had lower body temperature than patients who received placebo and did not have significantly more adverse events.  Acetaminophen use was associated with a shorter ICU stay than placebo among survivors and a longer ICU stay among patients who died. (more…)
Author Interviews, Heart Disease, NEJM, Surgical Research / 05.10.2015

Prof. Dr. med. Patrick Meybohm, MHBA Leitender Oberarzt Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie Universitätsklinikum FrankfurtMedicalResearch.com Interview with: Prof. Dr. med. Patrick Meybohm, MHBAConsultant for Anesthesiology and Intensive Care Medicine University Hospital Frankfurt Dept. Of Anesthesiology, Intensive Care Medicine and Pain Therapy Frankfurt Germany Medical Research: What is the background for this study? What are the main findings? Prof. Meybohm: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-Remote ischemic preconditioning group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. (more…)
Author Interviews, Personalized Medicine, Transplantation, University of Pennsylvania / 05.10.2015

MedicalResearch.com Interview with: Brendan J. Keating, DPhil Assistant professor of Transplant Surgery Penn Medicine Medical Research: What is the background for this study? What are the main findings? Response: Genetic studies in transplantation have been plagued by small samples and very complex phenotypes/outcomes of patients. Transplanted individuals are typically on potent immunosuppression drugs for the rest of their lives, as they have 3.5 million to 10 million variants difference from an unrelated transplanted donor organ. Such populations would certainly benefit from large well-powered genetic studies but only 3 transplant genome-wide genotyping studies comprising a few hundred individuals have been published. The papers outline the resources in hand for the International Genetics & Translational Research in Transplantation Network, comprising 22 studies to date (since the publication it has now expanded to 25 studies and > 32,000 subjects with genome-wide genotyping data). We show significant statistical power in iGeneTRAiN to detect main effect association signals across regions such as the MHC region (which harbors the HLA Class I/II regions which are well established to associate with transplantation outcomes). We also show strong genome-wide power to detect transplant outcomes that span all solid organs including graft survival, acute rejection, new onset of diabetes after transplantation (fast becoming the most common comorbidity post-transplantation), and delayed graft function (to date we have looked at this in kidney transplant patients only). We show that iGeneTRAiN is statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The transplant specific GWAS array that we designed (described in depth in the Genome Medicine paper) show that the coverage in key transplant associated regions is much higher than conventional arrays, and we describe the ‘imputation’ pipeline to expand the 780,000 or so variants examined in any given individual to > 15 millions of variants using whole genome sequencing reference datasets. (more…)
Author Interviews, Cancer Research, Endocrinology, JAMA, Menopause / 05.10.2015

Rodrigo R. Munhoz, MD Hospital Sírio Libanês São Paulo, Brazil MedicalResearch.com Interview with: Rodrigo R. Munhoz, MD Hospital Sírio Libanês São Paulo, Brazil  Medical Research: What is the background for this study? What are the main findings? Dr. Munhoz:  Chemotherapy-induced early menopause and its impact on quality of life is clinically relevant issue that often arises during the treatment with curative intent of premenopausal patients with early breast cancer. The use of neo-/adjuvant chemotherapy is associated with risks of ovarian dysfunction, permanent or transient amenorrhea, infertility and symptoms of menopause with a premature onset. In addition to osteoporosis, loss of libido, increased cardiovascular risk and atrophic vaginitis, early ovarian dysfunction may adversely impact quality of life and result in significant psychosocial burden. Currently available guidelines addressing fertility preservation in young women undergoing treatment for early breast cancer recommend that patients at reproductive ages should be advised about the potential risks of fertility impairment and additional effects of adjuvant chemotherapy and that preservation techniques should be carefully considered. However, “evidence regarding the effectiveness of ovarian suppression” is quoted as “insufficient” and the use GnRH agonists as “experimental” . The current meta-analysis includes a large number of patients and also the results of recently presented clinical trials, and suggest that the use of GnRH agonists is associated a higher rate of recovery of regular menses in patients with breast cancer undergoing chemotherapy.These results summarize the findings of different clinical trials and has immediate clinical implications - this was not clear in the literature, since negative results had been reported across different clinical trials. (more…)