MedicalResearch.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…)
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.
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MedicalResearch.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.
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MedicalResearch.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.
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MedicalResearch.com Interview with:
Dr. Madeleine M A Tilanus-Linthorst PhD
Department of Surgery
Erasmus University Medical Centre - Cancer Institute
Rotterdam, NetherlandsMedical 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.
Mortality increased with increasing tumour size and independently with nodal involvement, correcting for age, tumour biology and therapy.
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?
First, the general prospect of a woman diagnosed with breast cancer currently in the Western world is very good.
Catching breast cancer early is still highly important.
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.
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.
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.
Finally our results are informative when considering breast screening.
MedicalResearch.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)
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MedicalResearch.com Interview with:
Prof. Peter JD Andrews
Honorary Professor
Department of Anaesthesia
University of EdinburghMedical 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.
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MedicalResearch.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…)
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.
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MedicalResearch.com Interview with:
Mark DeBoer, MD
Children's Hospital's Department of Pediatrics
University of VirginiaMedical 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.
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MedicalResearch.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.
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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-2αor 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.
MedicalResearch.com Interview with:
Dr. Anne MoseleySenior Research Fellow, Musculoskeletal Division
The George Institute for Global HealthSydney AustraliaMedical 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.
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MedicalResearch.com Interview with:
Johannes Kurt Schultz, MD
Department of Gastrointestinal Surgery
Akershus University Hospital, Lørenskog, Norway
Faculty of Medicine, University of Oslo, Oslo, NorwayMedical 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.
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MedicalResearch.com Interview with:
Dr. Ian Carroll, PhD
Professor of medicine
UNC Center for Gastrointestinal Biology and DiseaseMedical 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.
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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 diseaseper 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.
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MedicalResearch.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.
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MedicalResearch.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.
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MedicalResearch.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.
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MedicalResearch.com Interview with:
Dr. Paul Jeffrey YoungMDIntensive Care Unit, Wellington Regional Hospital
Wellington South, New ZealandMedical 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.
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MedicalResearch.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.
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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.
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MedicalResearch.com Interview with:
Rodrigo R. Munhoz, MD
Hospital Sírio Libanês
São Paulo, BrazilMedical 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.
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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.
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MedicalResearch.com Interview with:
Carlos G. Grijalva, MD MPH
Associate Professor
Department of Health Policy
Vanderbilt University Medical Center
Nashville, TN 37212Medical 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.
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MedicalResearch.com Interview with:
Jacqueline Alvarez-Leite MD, Ph.D
Federal University of Minas Gerias in BrazilMedical 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.
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MedicalResearch.com Interview with: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.
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MedicalResearch.com Interview with:
Ichiro Morioka, M.D.
Professor of Pediatrics, Kobe University Graduate School of Medicine
Chuo-ku, Kobe, JapanMedical 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.
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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.
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MedicalResearch.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.
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MedicalResearch.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…)
