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…)
Author Interviews, Blood Pressure - Hypertension, Heart Disease, JAMA, Surgical Research / 05.10.2015

Mads Emil Jørgensen Copenhagen University Hospital..., MedicalResearch.com Interview with: Mads E. Jørgensen, MB Cardiovascular Research Center Gentofte Hospital University of Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Response: For many years there has been a wide use of beta blockers in the non-cardiac surgery setting with the intent to protect the heart. Within recent years, this field of research has opened up to new studies evaluating in detail which patient subgroups do benefit from this therapy and which may actually be at increased risk. The current study evaluated chronic beta blocker use and risks of perioperative complications in a rather low risk population of patients with hypertension, but without cardiac, kidney or liver disease. Among 55,000 patients receiving at least two antihypertensive drugs, we found that patients treated with a beta blocker were at increased risks of complications during surgery and 30-day after surgery, compared to patients treated with other antihypertensive drugs only. In various subgroup analyses (by age, gender, diabetes, surgery risk etc.) the findings were consistent although challenged in power. (more…)
Author Interviews, Flu - Influenza, JAMA, Vanderbilt / 05.10.2015

Carlos G. Grijalva, MD MPH Associate Professor Department of Health Policy Vanderbilt University Medical Center Nashville, TN 37212MedicalResearch.com Interview with: Carlos G. Grijalva, MD MPH Associate Professor Department of Health Policy Vanderbilt University Medical Center Nashville, TN 37212  Medical Research: What is the background for this study? Dr. Grijalva: Influenza is an important cause of disease. Every year influenza causes more than 200,000 hospitalizations in the US. The most effective strategy to prevent influenza infections is vaccination. Several studies have shown that influenza vaccines can prevent fever or respiratory symptoms caused by influenza. However, whether influenza vaccines can prevent more serious complications of influenza such as pneumonia, remains unclear This was a multicenter collaboration between academic institutions and the centers for disease control and prevention. We used data from the Etiology of Pneumonia in the community or EPIC study, a large prospective study of hospitalizations for pneumonia conducted between 2010 and 2012. The EPIC study enrolled patients from Chicago, IL, Salt Lake City, UT, and Memphis and Nashville, TN. The main goal of the EPIC study was to determine the causes of pneumonia in children and adults hospitalized with pneumonia. Medical Research:? What are the main findings? Dr. Grijalva: We conducted a case-control study using data from EPIC. Our study included more than 2700 patients hospitalized for pneumonia, including both children and adults. Approximately 6% of these patients had influenza pneumonia and were identified as cases. Other patients hospitalized for pneumonia that was not caused by influenza were the controls. We compared the history of influenza vaccination between cases and controls. We found that influenza vaccination was associated with a reduced risk of influenza pneumonia that required hospitalization. The estimated vaccine effectiveness was 57%. This means that about 57% of hospitalizations due to influenza-associated pneumonia could be prevented through influenza vaccination. (more…)
Author Interviews, Genetic Research, Nutrition, Weight Research / 05.10.2015

Jacqueline Alvarez-Leite MD, Ph.D Full Professor, UFMG Moore Laboratory Massachusetts General HospitalMedicalResearch.com Interview with: Jacqueline Alvarez-Leite  MD, Ph.D Federal University of Minas Gerias in Brazil Medical Research: What is the background for this study? What are the main findings? Dr. Alvarez-Leite : Obesity is now a global epidemic and bariatric surgery is now the main therapeutic option for those individuals with extreme obesity in which clinical treatments failed. However, a significant proportion of those patients regain the weight lost 3-4 years after surgery. Therefore, some metabolic or genetic trait may be related to weight regain. The rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity- associated (FTO) gene is one of the most studied genes involved in obesity. However, few studies have been conducted on patients who underwent bariatric surgery. In our study, we evaluated the influence of  this FTO SNP on body weight and composition, and weight regain in 146 patients during a 60-mo follow-up period after bariatric surgery. We observed that there was a different evolution of weight loss in individual with obesity carriers of the FTO gene variant after bariatric surgery. However, this pattern is evident at only 2 y post bariatric
 surgery, inducing a lower proportion of surgery success (percentage of excess weight loss >50%) and greater and earlier weight regain after 3-y of follow-up. Multiple regression 
analyses showed that the variation in rs9939609 was a significant and independent predictor for regaining weight during the 
5-y follow-up period. (more…)
Author Interviews, Kaiser Permanente, Pediatrics, Weight Research / 05.10.2015

MedicalResearch.com Interview with: Dr-Corinna-Koebnick Corinna Koebnick, PhD Research scientist with Research & Evaluation Kaiser Permanente Southern California MedicalResearch: Please describe your study, what you were looking for, and why.  Dr. Koebnick: This study is based on the Kaiser Permanente Southern California Children’s Health Study, which includes all children and adolescents 2–19 years of age in Southern California who are actively enrolled in a large, integrated, managed health care system. We examined the body weight from electronic health records of more than 1.3 million children and adolescents 2-19 years of age from 2008 to 2013. The objective of this study was to investigate recent trends in pediatric obesity in Southern California between 2008 and 2013. Several recent studies have investigated national trends in childhood obesity in the United States and indicated that childhood obesity rates may have reached a plateau, but are not declining. Ours is one of the few studies that is large enough to be able to detect small changes in the prevalence of obesity in time periods of less than 10 years. MedicalResearch: What are the findings of this study?  Dr. Koebnick: Our study provides strong indication that the prevalence of overweight and obesity between 2008 and 2013 has not only plateaued, but also is slowly declining. While the decline in overweight and obesity was less pronounced in girls, adolescents, some minority groups and youth living in low income and low education areas, the decline was remarkably stable across all groups and significant even in minority youth and youth of lower socioeconomic status. We found the prevalence of overweight and obesity decreased overall by 2.2 percent and 1.6 percent, respectively. This change corresponds to a relative decline of 6.1 percent in overweight youth and 8.4 percent in obese youth. Although a decline was seen across all groups, the decrease was not as strong in adolescents aged 12-19 years, in girls compared to boys, and Hispanic and black children compared to non-Hispanic whites. (more…)
Author Interviews, Pediatrics, Technology / 05.10.2015

Ichiro Morioka, M.D. Professor of Pediatrics, Kobe University Graduate School of Medicine Chuo-ku, Kobe, JapanMedicalResearch.com Interview with: Ichiro Morioka, M.D. Professor of Pediatrics, Kobe University Graduate School of Medicine Chuo-ku, Kobe, Japan  Medical Research: What is the background for this study? What are the main findings? Dr. Morioka: Japan has the highest survival rate for preterm infants due to recent advanced medical treatment and the availability of Neonatal Intensive Care Units (NICU). Despite this, cases of cerebral palsy and hearing loss caused by neonatal jaundice continue (kernicterus) to occur, with cases reported for at least 2 in every 1000 infants born before the 30th week of gestation. It has also been established that cases of jaundice can worsen even two weeks after birth and thereafter, meaning that there is a need for continuous long-term jaundice monitoring of infants in the NICU. However, jaundice in preterm infants is difficult to detect through physical observations, and monitoring through a daily blood test is not a realistic option. We focused on transcutaneous jaundice monitoring used in daily health tests for full term infants. The bilirubin levels of 85 infants with a birth weight of under 1500 grams were monitored in NICUs at Kobe University, Kakogawa City Hospital, Hyogo Prefectural Kobe Children’s Hospital, Japanese Red Cross Society Himeji Hospital, and Takatsuki General Hospital, and were taken a total of 383 transcutaneous and blood bilirubin measurements at the same time. Through our results we were able to ascertain that the chest and back areas of preterm infants have the highest levels of sensitivity, and transcutaneous bilirubin levels in those areas were close to bilirubin levels in the blood. In addition to expanding the possibilities for transcutaneous monitoring of jaundice in preterm infants, we discovered the optimum area of skin to monitor it. (more…)
Author Interviews, Genetic Research, Ophthalmology / 05.10.2015

MedicalResearch.com Interview with: Dr. Annabel Christ PhD Max-Delbrueck-Center for Molecular Medicine Berlin, Germany Medical Research: What is the background for this study? Dr. Christ: The development and function of the retina in all vertebrate species follow the same principles. Still, there is one important feature that distinguishes the mammalian eye from that of others inasmuch as it does not grow much after birth. In contrast, in fish or reptiles, the retina continuously grows, even in adults. The mechanism that restricts the growth of the mammalian eye remains enigmatic. Yet, understanding this mechanism may offer therapeutic strategies to block eye growth in cases of severe nearsightedness or to induce growth of the retina in patients with retina degeneration. To explore the mechanisms that control human eye growth we studied a genetic form of extreme eye overgrowth (buphthalmia). It is caused by an inherited defect in the gene encoding LRP2, a receptor in the retina. We reasoned that this exceptional form of eye disease might tell us something about the concepts governing eye growth in all humans. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research, JNCI, Mayo Clinic, Race/Ethnic Diversity / 05.10.2015

Harry H. Yoon, MD Mayo Clinic Rochester, MN 55905MedicalResearch.com Interview with: Harry H. Yoon, MD Mayo Clinic Rochester, MN 55905 Medical Research: What is the background for this study? What are the main findings? Dr. Yoon: In the U.S., the survival of patients with colon cancer is known to differ by race, with individuals of black race having worse outcomes than those of white race. However, it has been difficult to tease apart why the differences in survival exist. It is generally believed that social or other non-biologic factors (eg, decreased access to care, suboptimal treatment) contribute to the discrepancy.  It’s also known that differences in the general medical condition of patients could affect how long a patient lives. However, it is unknown whether there are race-based differences in the biology of colon tumors themselves.  This biology can be reflected in the genetic composition of tumors, as well as by whether and how quickly the cancer returns after the patient has undergone surgery and chemotherapy. In addition, it is unknown whether race-based differences in biology may be related to the age of the patient at the time of diagnosis.  Blacks with colorectal cancer typically have an earlier age of onset than whites do. A major barrier to addressing these questions are that there are very few large populations of colon cancer patients where everyone had the same disease stage and received uniform treatment, and where patients were monitored for years afterward specifically to see whether the cancer returned.  It is much harder to measure whether cancer has returned (ie, cancer recurrence), as compared to simply knowing whether a patient is alive or dead.  This difference is important, because knowing about cancer recurrence sheds more light on cancer biology than only knowing about patient survival, since many factors unrelated to cancer biology (eg., heart disease) can affect whether a person is alive or dead. The most reliable data on cancer recurrence (not just patient survival) generally comes from patients who have enrolled in a clinical trial.  In the Alliance N0147 trial, all patients had the same cancer stage (ie, stage III), underwent surgery and received standard of care chemotherapy (ie, “FOLFOX”) after surgery.  Patients had uniform, periodic monitoring after chemotherapy to see if the cancer returned. In other words, examining racial outcomes in this cohort largely eliminates some of the key factors (eg, decreased access to care, suboptimal treatment) that are believed to contribute to racial discrepancies, and provides a unique opportunity to determine if differences in cancer biology between races may exist. This study was done to see if colon cancers are genetically different based on race, and whether race-based differences exist in cancer recurrence rates. The study found that tumors from whites, blacks, and Asians were different in terms of the frequency of mutations in two key cancer-related genes, BRAF and KRAS.  Tumors from whites were twice as likely to have mutated BRAF (14% in whites compared to 6% in Asians and 6% in blacks).  Tumors from blacks had the highest frequency of KRAS mutations (44% in blacks compared to 28% in Asians and 35% in whites).  Tumors from Asians were the mostly likely to have normal copies of both genes (67% in Asians compared to 50% in blacks and 51% in whites). Next, the study found that the colon cancers among blacks had more than double the risk of cancer recurrence, compared to whites.  However, this discrepancy was only evident among young patients (ie, aged less than 50 years).  Almost 50% of younger black patients experienced colon cancer recurrence within 5 years, compared to ~30% of black patients over age 50, or compared to white or Asian patients regardless of age. The worse outcome among young blacks remained evident even after adjusting for many potential confounding factors, such as tumor grade, the number of malignant nodes, or the presence of BRAF or KRASmutations.  Because this question was examined in a clinical trial cohort of uniform stage and treatment, the role of multiple important potential confounders was diminished. To our knowledge, this is the first report indicating that colon cancers from young black individuals have a higher chance of relapsing after surgery and chemotherapy, compared to those from white individuals. (more…)
Author Interviews, Exercise - Fitness / 04.10.2015

Prof. Ismail Laher Department of Anesthesiology Department of Pharmacology and Therapeutics Faculty of Medicine University of British Columbia Vancouver, CanadaMedicalResearch.com Interview with: Prof. Ismail Laher Department of Anesthesiology Department of Pharmacology and Therapeutics Faculty of Medicine University of British Columbia Vancouver, Canada  Medical Research: What is the background for this study? What are the main findings? Dr. Laher: There are several groups based in various parts of the world looking to create an exercise pill. We examined the proposed candidates and summarized how these agents work at the cellular level. The main finding is that each of these agents each acts on a select aspect of physical exercise does in humans —these agents seem to interact with only some of the molecular signals activated by regular physical exercise, for example in skeletal muscle. What they fail to do is to provide all the other benefits of exercise such as improved bone strength, better blood supply to many areas of the body, improved activity of insulin and other glucose lowering drugs. Basically these exercise pills will help some athletes reach their goal of faster and stronger muscles even faster—of course this opens the door to doping in human and animal sporting competitions. (more…)
Author Interviews, Breast Cancer, Surgical Research / 04.10.2015

Kimberly J. Van Zee, MD, FACS Surgical oncologist Memorial Sloan-Kettering Cancer MedicalResearch.com Interview with: Kimberly J. Van Zee, MD, FACS Surgical oncologist Memorial Sloan-Kettering Cancer Medical Research: Why is this study important? Dr. Van Zee: It is very important because the 4 large studies that randomized women with DCIS to radiation or not after they had breast-conserving surgery all began between 1985 and 1990.  Those studies are generally used to help women and clinicians estimate risk of subsequent recurrence in the same breast over time.  This study shows that recurrence rates have significantly fallen over the decades, suggesting that the recurrence rates observed in those studies are higher than what would be expected in the current era.  This is good news for women that want to have breast conservation for DCIS! Medical Research: What are the key findings? Dr. Van Zee:
  1. a)       Recurrence rates have fallen over the years, by about 40% between the early period (1978-1998) and the later period (1999-2010).
  2. b)      The decrease in recurrence rates is only partly explained by factors such as increased screening, wider margins, more frequent use of endocrine therapy (ie, tamoxifen).
  3. c)       The improvement in recurrence rates is mostly due to a decrease in recurrence rates for women NOT undergoing radiation (even though women having radiation continue to have a lower recurrence rate than those not having radiation)
  4. d)      This last point is important because since radiation is given only to reduce local recurrence rates and has never been shown to improve survival (survival is excellent with all treatments).  So a woman treated currently with breast conservation without radiation can expect about a  40% lower recurrence rate than in the earlier decades.
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Author Interviews, Mental Health Research / 04.10.2015

Adam Hanley, Doctoral candidate College of Education's Counseling/School Psychology program Florida State UniversityMedicalResearch.com Interview with: Adam Hanley Doctoral candidate College of Education's Counseling/School Psychology program Florida State University Medical Research: What is the background for this study? What are the main findings? Response: This study emerged from the intersection of my personal dislike of dishwashing, my grandmother’s unquestioned enjoyment of the task, and the inevitability of finding myself neck deep in her sink after holiday meals.  Contrasting my suffering with her cheer while pursuing my interest in informal meditation practices challenged me to revisit my dishwashing technique.  Approaching the dishes mindfully, attending to the full sensory experience and connecting with the task as an act of kindness, shifted my dishwashing experience.  The current study was developed to explore whether my new relationship with dishwashing was an isolated phenomenon or might be more generalizable.  To test this generalizability, 51 undergraduate college students were recruited and randomly assigned to wash a standardized set of dishes after reading instructions on either mindful or “correct” dishwashing procedures. (more…)