Author Interviews, HIV, Nature, UCLA / 22.12.2014

David Gerberry PhD Center for Biomedical Modeling, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CaliforniaMedicalResearch.com Interview with: David Gerberry PhD Assistant Professor Department of Mathematics and Computer Science Xavier University, Cincinnati, Ohio   Medical Research: What is the background for this study? What are the main findings? Response: In an attempt to control the spread of HIV, governments in sub-Saharan Africa are considering providing antiretroviral drugs to people who do not have the virus but are at risk for becoming infected. Such drugs are known as pre-exposure prophylaxis, or PrEP.  Given the cost of PrEP, an important question is how to maximize the impact of interventions given a fixed level of prevention resources. A common strategy is to target resources to the individuals that are at the highest risk for infection.  This group of people is often referred to as the "core group" and can be thought of as sex workers, clients of sex workers and other individuals that are at very high risk for infection.  While targeting this core group is ideal and would result in the most cost-effectiveness interventions, being able to identify these individuals is difficult in practice and they are often unwilling to participate in the intervention; take pre-exposure prophylaxis or change their behavior for example.  From a mathematical perspective it is also very difficult to quantify their increased level of risk.  For example, is a sex worker at 5 times, 25 times, 100 times or 1000 times the risk for HIV infection?  Without this quantification, it is impossible to estimate the cost-effectiveness of a targeted strategy. In our work, we build an intervention strategy based on geographical targeting.  This takes advantage of the fact that HIV incidence is much higher in certain geographical locations than others.  Therefore, individuals in these areas are at increased risk for HIV infection.  Most importantly, such an intervention is feasible because reliable data exists across much of sub-Saharan Africa for the severity of the HIV epidemic in different regions.  To illustrate our ideas we used mathematical modeling to consider resource allocation in South Africa and found that targeting the provinces with highest HIV incidence would prevent 40% more infections than a plan that ignored geographic variation while using the same amount of resources.
Author Interviews, Infections, PLoS / 22.12.2014

Leonard A. Mermel DO FACP, FIDSA, FSHEA Professor of Medicine, Warren Alpert Medical School of Brown University and Division of Infectious Diseases, Rhode Island Hospital Providence, Rhode IslandMedicalResearch.com Interview with: Leonard A. Mermel DO FACP, FIDSA, FSHEA Professor of Medicine, Warren Alpert Medical School of Brown University and Division of Infectious Diseases, Rhode Island Hospital Providence, Rhode Island Medical Research: What is the background for this study? What are the main findings? Dr. Mermel: While talking to infectious diseases physicians some years ago in Israel, Greece, and Thailand, I learned that unlike my experiene here in the US, most of the bloodstream infections they see are far and away due to Gram-negative bacteria.  So, a hypothesis was generated, namely that the likelihood of Gram-negative bacteremia compared to Gram-positive bacteremia was greater the closer to the equator.  A writing group was formed, colleagues around the world graciously shared their data.  The main finding is that in fact, we unequivocally found that the likelihood of Gram-negative, compared to Gram-positive bacteremia is more common closer to the equator.  This difference was greatest during the warmer months of the year.  We also found that the % GDP spent on healthcare in a given country is also associated with more Gram-negative than Gram-positive bacteremia.  These findings may reflect differences in the human microbiome as one gets closer or farther from the equator as has been recently demonstrated, differences in survival of Gram-negative compared to Gram-positive bacteria under certain environmental conditions, and likely reflects differences in public health and other factors.
Author Interviews, Breast Cancer, JNCI / 21.12.2014

MedicalResearch.com Interview with: Dr Ranjit Manchanda Consultant Gynaecological Oncologist, St Bartholomew’s Hospital, London, UK Honorary Sr Lecturer, Women’s Cancer, EGA Institute for Women's Health, University College London, UK  and Professor Ian Jacobs Vice President, The University of Manchester Dean & Head School of Medicine Faculty of Medical & Human Sciences, Director MAHSC (Manchester Academic Health Science Centre) Medical Research: What is the background for this study? What are the main findings? Dr. Jacobs:  Background- Women carrying a BRCA1/2 gene alteration have a very high risk of developing breast and ovarian cancer and men carrying this alteration have an increased risk of prostate and breast cancer. Approximately 45-65% women who have this inherited genetic change will develop breast cancer and 15-35% ovarian cancer. They also have a 50% chance of passing these genes on to their children. At risk individuals can access available options of screening and prevention through the National Health Service (NHS). Some population groups across the world are known to have a higher frequency of BRCA 1/2 gene alterations than others. One example is Ashkenazi Jews who have a 1 in 40 likelihood of having a BRCA1/2 gene alteration. This is 10-20 times higher than in the general non-Jewish population. At present in the UK, genetic testing is available within the NHS to individuals who have a strong family history of cancer. However, many people are not aware of their family history or its significance and do not seek advice. Many other individuals with BRCA1/2 gene alterations do not have a family history at all. The current approach misses a large number of people at risk who could benefit from knowing about their BRCA 1/2 mutation status and the ability to access opportunities for prevention or screening. In order to address this the GCaPPS study has investigated the best method of screening for risk of inherited (familial) cancer by exploring the alternative approach of offering the genetic test to all men and women >18 years in the Ashkenazi Jewish population. It does so by comparing the benefits and disadvantages of: (i) The current system of testing only those with a family history and (ii) The new option of testing everyone in the population. Main Findings: Over half of the BRCA1/BRCA2 carriers detected did not give a strong family history of cancer and would not have been identified by current family history based testing criteria used in the NHS (National Health Service) in the UK and most health systems internationally. Reassuringly population-based genetic testing in Ashkenazi Jews did not adversely affect short term psychological health or quality-of-life. A health economic analysis indicated that population-based screening for BRCA-mutations in Ashkenazi Jewish women ≥30years would be highly cost-effective compared to the traditional family history based approach. Such an approach if implemented could reduce the incidence of and deaths from breast and ovarian cancer as well as reducing cost and save the NHS funds.
Author Interviews, Endocrinology, JCEM, Menopause, UCLA / 20.12.2014

Carolyn J. Crandall, MD, MS Professor of Medicine David Geffen School of Medicine at University of California, Los Angeles UCLA Medicine/GIM Los Angeles, CA 90024MedicalResearch.com Interview with: Carolyn J. Crandall, MD, MS Professor of Medicine David Geffen School of Medicine UCLA Medicine/GIM Los Angeles, California 90024 Medical Research: What is the background for this study? What are the main findings? Dr. Crandall: In a large group of postmenopausal women aged 50-79, we found that women who reporting having hot flashes at baseline had increased risk of hip fracture during the subsequent 8 years of observation, nearly double the risk compared with women who did not have hot flashes at baseline.
Author Interviews, Diabetes, Diabetologia / 20.12.2014

MedicalResearch.com Interview with: Dr Guy Fagherazzi Center for Research in Epidemiology and Population Health INSERM, Villejuif, France, and colleagues. Medical Research: What is the background for this study? What are the main findings? Dr. Fagherazzi: Our work has been based on previous findings regarding the associations between blood type and the risk of stroke or coronary heart disease, where people with the O blood group seamed to have lower risk of developping the disease. The suggested mechanisms could be also be involved with type 2 diabetes. And our results were in agreement with our first hypothesis. We have followed more than 80 000 women from the E3N cohort study, during 18 years and we have found that individuals with the O blood type had lower risk of type 2 diabetes than the others (people with groups A, B and AB).
AHA Journals, Author Interviews, Stroke / 20.12.2014

Jeff Perry, MD, MSc, CCFP-EM Associate Professor, Department of Emergency Medicine Senior Scientist, Ottawa Hospital Research Institute Research Chair in Emergency Neurological Research, University of Ottawa Emergency Physician, The Ottawa Hospital Epidemiology Program, F6 The Ottawa Hospital, Civic Campus Ottawa, OntarioMedicalResearch.com Interview with: Jeff Perry, MD, MSc, CCFP-EM Associate Professor, Department of Emergency Medicine Senior Scientist, Ottawa Hospital Research Institute Research Chair in Emergency Neurological Research, University of Ottawa Emergency Physician, The Ottawa Hospital Epidemiology Program, The Ottawa Hospital, Ottawa, Ontario Medical Research: What is the background for this study? What are the main findings? Dr. Perry: Currently it is not well known which patients with a TIA or a non-disabling stroke will have a subsequent stroke or die within the days to weeks following their initial event.  This study found that patients with acute ischemia, especially if it is associated with an old infarction or microangiopathy, are at a much higher risk for an early subsequent stroke.
Author Interviews, CMAJ, Pharmacology / 19.12.2014

MedicalResearch.com Interview with: Naveen Poonai MSc MD FAAP FRCPC Paediatric Emergency Physician Children's Hospital, London Health Sciences Center Assistant Professor Paediatrics and Internal Medicine Schulich School of Medicine and Dentistry London, Ontario, Medical Research: What is the background for this study? What are the main findings? Dr. Poonai: We found that in children discharged home with a fracture, both ibuprofen and oral morphine were effective at relieving pain. However, there were no significant differences in efficacy between the two agents and oral morphine was associated with more side effects. MedicalResearch.com: What was most surprising about the results? Dr. Poonai: The most surprising findings for us were that over 70% of children experienced pain significant enough to require analgesia once they were discharged home.  Furthermore, we were surprised to find that the anecdotally more potent agent morphine, was equivalent to ibuprofen for post-fracture pain relief in children.
Author Interviews, NEJM / 19.12.2014

natalie_walkerMedicalResearch.com Interview with: Natalie Walker, Ph.D. National Institute for Health Innovation School of Population Health, University of Auckland Auckland, New Zealand Medical Research: What is the background for this study? What are the main findings? Dr. Walker: Cytisine is a plant-based alkaloid and is structurally similar to nicotine.  It is found in various plants from the Legume Family (Fabaceae), the third largest plant family on earth.  Cytisine is currently manufactured by Sopharma Ltd, Bulgaria (Tabex®) and Aflofarm Pharma, Poland (Desmoxan®) as a smoking cessation treatment, with the cytisine used in the tablets taken from a plant called Golden Rain (Laburnum anagyroides).  Cytisine has been available with and without prescription for smoking cessation since the 1960s, largely in Eastern Europe.   Cytisine is not currently registered for use in any Western countries (although regulatory approval is currently been sought for the USA , UK and Japan).             We know from trial evidence that cytisine is better than a placebo for helping people quit smoking.  Cytisine is also one of the most affordable smoking cessation medicines available. It is much cheaper than nicotine patches, gum and/or lozenges and other smoking cessation medicine such as varenicline. This means smokers and governments are more likely to afford cytisine, especially those from low and middle income countries. However, we don’t know if cytisine is as good as nicotine patches and/or gum or lozenges, one of the most commonly used smoking cessation treatments in many western countries. We therefore undertook a pragmatic non-inferiority trial to answer this question, with recruitment of 1310 adult daily smokers who were motivated to quit, undertaken using the New Zealand national Quitline. Smokers were randomised to receive the standard 25 days of cytisine treatment or 8 weeks of nicotine patches and/or gum or lozenges.  Both groups received standard Quitline behavioural support.  Follow-up occurred at one week and one, two, and six months. At all time points, cytisine was found to be better at helping people quit smoking than nicotine patches and/or gum or lozenges.  This finding was consistent irrespective of ethnicity, age, alcohol consumption, degree of cigarette dependence or whether participants smoked factory-made cigarettes or roll-your-owns. For reasons unknown, cytisine helped more women quit smoking than nicotine patches, gum and/or lozenges.  For men the effectiveness of the two products was similar.  Cytisine use made people less likely to relapse back to smoking. Those who did smoke when using cytisine didn’t enjoy smoking as much, and reduced the number of cigarettes they smoked.  Self-reported, non-medically verified adverse events were more common in those that used cytisine. Three out of every 10 people who used cytisine reported an adverse event, compared to 2 out of every 10 that used nicotine patches, gum and/or lozenges.  However the majority of reported side effects were mild and self-limiting. More people in the cytisine group experienced nausea, vomiting and sleep disturbances (e.g. bad dreams).
Author Interviews, Biomarkers, Brigham & Women's - Harvard, Critical Care - Intensive Care - ICUs, PLoS / 19.12.2014

Daniel Irimia, M.D., Ph.D. Assistant Professor Division of Surgery, Science & Bioengineering Massachusetts General Hospital and Harvard Medical School Associate Director, BioMEMS Resource Center Boston, MA 02129MedicalResearch.com Interview with: Daniel Irimia, M.D., Ph.D. Assistant Professor Division of Surgery, Science & Bioengineering Massachusetts General Hospital and Harvard Medical School Associate Director, BioMEMS Resource Center Boston, MA 02129 Medical Research: What is the background for this study? What are the main findings? Response: Sepsis is affecting more than half of the patients with major burn injuries (20 percent of body surface) and is the leading cause of death among these patients.  Sepsis is also a significant complication for other critically ill patients. More than one million Americans are affected and it has been estimated that approximately 30% of these people die, despite significant advances in life support and antibiotics.  Early diagnosis is essential, and it has been calculated that every 6 hours of delay in a sepsis diagnosis decreases the chances of survival by 10 percent. We have found that the motility of the white blood cells called neutrophils, inside a microfluidic device, is significantly altered two to three days before sepsis develops.
Author Interviews, Cancer Research, Nature / 19.12.2014

Dr Catherine Olsen | Senior Research Officer QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, QLD 4029MedicalResearch.com Interview with: Dr Catherine Olsen  |  Senior Research Officer QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, QLD 4029 Medical Research: What is the background for this study? What are the main findings? Response: Squamous cell carcinomas (SCCs)are the second most common skin cancer occurring in white skinned populations. They cause significant morbidity as they can invade local structures (often the nose or ears) and they also have the potential to metastasize although most are successfully treated before any spread occurs. They are also very expensive cancers to treat because they are so common, posing a significant burden on health care budgets. NSAIDS have been shown to be protective for other cancers (e.g. colorectal and oesophageal cancer). This prompted use to evaluate all of the available evidence on NSAIDs use and SCC by conducting a systematic review and meta-analysis of the association.
Author Interviews, Dermatology, JAMA, Melanoma, Occupational Health, UCSF / 18.12.2014

Martina Sanlorenzo, MD Department of Dermatology Mount Zion Cancer Research Center University of California, San FranciscoMedicalResearch.com Interview with: Martina Sanlorenzo, MD Department of Dermatology Mount Zion Cancer Research Center University of California, San Francisco Medical Research: What is the background for this study? Dr. Sanlorenzo: We recently performed a meta-analysis and found an increased risk of melanoma in pilots and cabin crew. One of the possible occupational hazards responsible for this risk is UV radiation. Medical Research: What are the main findings? Dr. Sanlorenzo: We performed UV measurements in airplane cockpits during flight and we found that windshields blocked UV-B but allowed UV-A transmission. We compared the UV-A dose in airplanes with the UV-A dose in tanning beds, whose use is a known risk factor for melanoma. Pilots flying for 56.6 minutes at 30,000 feet received the same amount of UV-A carcinogenic effective radiation of a 20-minute tanning beds session.
Author Interviews, Heart Disease, JACC / 18.12.2014

MedicalResearch.com Interview with: Dexter Canoy, PhD Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, United Kingdom Medical Research: What is the background for this study? What are the main findings? Response: Over a million middle-aged women in the UK who took part in our study between 1996 and 2001 provided information regarding their health and lifestyle, including their reproductive history such as age when they had their first menstruation. We followed them for over 10 years and identified those who developed heart disease (and other vascular diseases) by obtaining information on hospitalizations and death records. Our study demonstrates that on average, women with menarche before age 13 or after this age have slightly increased risks of developing heart disease, stroke and hospital admissions associated with hypertension. The increased risks for these vascular diseases were highest in women with menarche at age 10 years or younger, or age 17 years or older. This U-shaped association was consistently found among lean, overweight and obese women, among never, past or current smokers, or among women in low, middle or high socioeconomic group.
Author Interviews, JAMA, Pharmacology / 17.12.2014

Dong Wook Shin, MD, MBA, DrPH Assistant Professor, Center for Health Promotion/Dept.of Family Medicine Seoul National University HospitalMedicalResearch.com Interview with: Dong Wook Shin, MD, MBA, DrPH Assistant Professor, Center for Health Promotion/Dept.of Family Medicine Seoul National University Hospital Medical Research: What is the background for this study? What are the main findings? Response: In South Korea, the National Health Insurance provides universal coverage and the Health Insurance Review & Assessment Service (HIRA) oversees claims reviews. HIRA has reported the rates of antibiotic prescriptions for upper respiratory tract infections in each clinic via web site since 2006. We assessed the effect of public disclosure. The main findings are that decreases of antibiotic uses were observed since the public disclosure of the prescription rates regardless of hospital level.
Author Interviews, CDC, Dermatology, Emergency Care, JAMA / 16.12.2014

Gery P. Guy Jr., PhD, MPH Health economist Division of Cancer Prevention and Control’s Epidemiology and Applied Research Branch CDCMedicalResearch.com Interview with: Gery P. Guy Jr., PhD, MPH Health economist Division of Cancer Prevention and Control’s Epidemiology and Applied Research Branch CDC Medical Research: What is the background for this study? What are the main findings? Dr. Guy: Indoor tanning exposes users to intense UV radiation and is associated with an increased risk of skin cancer. However, little is known about the more immediate adverse outcomes of indoor tanning. This study provides the first national estimates of visits to emergency departments related to indoor tanning. We examined cases from the Consumer Product Safety Commission’s National Electronic Injury Surveillance System (NEISS), a national probability sample of hospitals in the U.S. and its territories. Patient information is collected from each NEISS hospital for every emergency visit involving an injury associated with consumer products. From this sample, the total number of product-related injuries treated in hospital emergency rooms nationwide can be estimated.
Author Interviews, Breast Cancer, NEJM / 16.12.2014

Prudence A. Francis, M.D Associate Professor , Peter MacCallum Cancer Centre Melbourne, AustraliaMedicalResearch.com Interview with: Prudence A. Francis, M.D Associate Professor, Peter MacCallum Cancer Centre Melbourne, Australia Medical Research: What is the background for this study? What are the main findings? Response: The background for this study was the observation that premenopausal women diagnosed with hormone receptor positive breast cancer under age 35, had an increased risk of recurrence, as compared with older premenopausal women. We postulated that this might be because this age group was less likely to enter menopause after receiving chemotherapy, and so their ovaries were continuing to produce estrogen, which might have the effect of stimulating any remaining cancer cells. The main findings were that while not all premenopausal women benefit from the addition of treatment with ovarian function suppression to , the women who underwent chemotherapy and remained premenopausal (median age 40) did have improved breast cancer outcomes. This same group of women had even further improvement in recurrence rates if the ovarian suppression was combined with an aromatase inhibitor exemestane, as compared with tamoxifen. The effects of including ovarian suppression were particularly striking in women under 35 years of age. Those premenopausal women who did not receive chemotherapy (median age 46) after discussion with their doctor, did well with tamoxifen alone and do not appear to benefit from ovarian suppression currently.
Author Interviews, FASEB, Weight Research / 15.12.2014

Dr. Richard Phipps PhD Department of Environmental Medicine and Flaum Eye Institute, School of Medicine and Dentistry, University of Rochester, Rochester, New YorkMedicalResearch.com Interview with: Dr. Richard Phipps PhD Department of Environmental Medicine and Flaum Eye Institute, School of Medicine and Dentistry, University of Rochester, Rochester, New York Medical Research: What is the background for this study? What are the main findings? Response: Obesity has risen dramatically over the past 30 years in the United States and throughout the world. Obesity increases morbidity and mortality by increasing health problems such as Type 2 diabetes, cardiovascular disease and cancer. Thus, obesity is one of our greatest challenges worldwide. Our laboratory has been studying a protein called Thy-1 for several decades. Until now its’ true function was unknown. The main finding from our research is that when cells express this protein on their surface, they are inhibited from becoming fat cells. We show in a mouse model system that mice, which lack Thy-1, and given a high fat diet, increase weight much faster than mice that express Thy-1. These mice that lack Thy-1, also have increased levels of many proinflammatory mediators in their blood. In human cells, those that express high levels of Thy-1 are blocked in their ability to become fat cells, unlike the human cells from different tissues that do not express Thy-1. Thus, the main finding is that learning how to manipulate Thy-1 expression could lead to reduced fat cells and reduced fat production. Not only is this an important finding for obesity, but there are many human diseases that are caused by excess fat production in organs, such as, the orbit of the eye, the liver, and the bone marrow.
Author Interviews, Flu - Influenza, PLoS, Vaccine Studies / 15.12.2014

Adrian Egli, MD PhD Research Group leader Infection Biology Laboratory Department of Biomedicine University of Basel and University Hospital Basel Basel, SwitzerlandMedicalResearch.com Interview with: Adrian Egli, MD PhD Research Group leader Infection Biology Laboratory Department of Biomedicine University of Basel and University Hospital Basel Basel, Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Egli: Infections with influenza viruses are associated with a high morbidity and mortality. In particular, people with a weak immune system are at danger for more severe complications. This includes elderly people, pregnant women, patients after transplantation, patients with HIV infection, chronic diseases such as diabetes and many more. In these high-risk groups, annual vaccination is clearly recommended. However, due to the immunsuppressive condition the immune response to the influenza vaccine is often reduced. The seroconversion rate - a 4-fold antibody titer increase upon vaccination - is one of the key markers for a successful vaccination. In young adults the seroconversion rate is normally >85%; however, in patients with immunosuppression, this can be lower than 40%. Improving vaccine efficacy is one of the key focuses of my research group. We try to understand, how to improve vaccines and better protect the people at the highest risks for influenza-associated complications. In this study, we could show that an important cytokine, called Interferon lambda, is clearly associated with the vaccine induced antibody response upon influenza vaccination. We could show that genetic polymorphisms, in one of the Interferon lambda gene family (IFNL3), are modulating the expression of this gene. This strongly affects the cross talk between the innate and adaptive immune response in the context of vaccination. We observed that, the more Interferon lambda is present, the lower the antibody response is. People with a lower expression of Interferon lambda had a significant higher response to the vaccine. Therefore, we developed substances to block the effect of Interferon lambda. We could show in vitro, that due to the Interferon lambda blockade, the antibody production was improved.
Author Interviews, Dermatology, Nature, Sleep Disorders / 14.12.2014

Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, IllinoisMedicalResearch.com Interview with: Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, Illinois Medical Research: What is the background for this study? What are the main findings? Dr. Silverberg: Chronic itch related to childhood eczema has been shown to cause worsened sleep quality with shorter sleep duration, more frequent and prolonged awakening, and overall lower sleep efficiency. However, little is known about the sleep disturbances that occur in adults with eczema.
Author Interviews, CMAJ, HPV, McGill, Vaccine Studies / 14.12.2014

Leah M. Smith PhD Department of Epidemiology, Biostatistics, and Occupational Health (Smith, Kaufman, Strumpf) McGill University, Montréal, QuebecMedicalResearch.com Interview with: Leah M. Smith PhD Department of Epidemiology, Biostatistics, and Occupational Health  (Smith, Kaufman, Strumpf) McGill University, Montréal, Quebec   Medical Research: What is the background for this study? What are the main findings? Dr. Smith: The human papillomavirus (HPV) vaccine protects against types of HPV that cause cervical cancer and anogenital warts. The vaccine first became available in 2006. Since then, it has faced a great deal of controversy surrounding, in part, some of the unanswered questions about the real-world effects of the vaccine, especially on the young girls targeted for immunization. One issue that has received a great deal of public attention has been the concern that HPV vaccination might give girls a false sense of protection against all sexually transmitted infections that might lead them to be more sexually active than they would otherwise. As a result, some parents have been reluctant to have their daughters vaccinated. It is also reason why some religious groups have spoken out against the vaccine. This question is further important from a public health perspective because increases in risky sexual behaviour would inevitably also lead to increases in teen pregnancy and sexually transmitted infections (excluding anogenital warts), which would of course undermine the potential health benefits of the vaccine.  In this study, we directly addressed the question of whether HPV vaccination has led to increases in pregnancy and non-HPV-related sexually transmitted infections (both of which are proxies for risky sexual behaviour) among adolescent girls. In our study of over 260,000 girls, we did not find any evidence that the HPV vaccine had a negative impact on these outcomes.
Author Interviews, BMJ, Surgical Research / 14.12.2014

Dr Aneel Bhangu Clinical Lecturer in Surgery Queen Elizabeth Hospital, Edgbaston, Birmingham UKMedicalResearch.com Interview with: Dr Aneel Bhangu Clinical Lecturer in Surgery Queen Elizabeth Hospital, Edgbaston, Birmingham UK Medical Research: What is the background for this study? What are the main findings? Dr. Bhangu: Randomised clinical trials are widely regarded as the type of evidence in medical research most likely to change practice and improve patient care. However, they are challenging to perform, expensive to deliver and rely on patients’ willingness to participate for the benefit of their wider community. Results of these studies should be disseminated widely in order to promote new medical knowledge. Unfortunately, some clinical trials are terminated early or fail to reach publication after completion. This leads to lost data and wastage of finite resources. Clinical trials within surgical disciplines present unique challenges, which may further impact on dissemination of evidence. We aimed to investigate the fate of surgical trials. Disappointingly, we found that 1 in 5 surgical trials are terminated early before completion, most commonly due to poor recruitment of research participants. Of trials which do reach completion, 1 in 3 are not published, indicating a significant waste of resources. A systematic approach to contact trial investigators during the study proved largely unsuccessful, implicating further hidden barriers to identifying trial data.
Author Interviews, Breast Cancer, JNCI, Mayo Clinic / 14.12.2014

Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo ClinicMedicalResearch.com Interview with: Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Dr. Goetz: There has been conflicting data with regard to the importance of metabolism as measured by CYP2D6 genetic variation.   Two large “negative” studies were reported simultaneously in 2012 and these were referenced by guidelines that CYP2D6 should not be used to select hormonal therapy.   Our findings demonstrated that these studies were flawed in part based on analytical validity issues.  In short, the use of tumor tissue to derive CYP2D6 germline genotype leads to genotyping error in up to 45% of samples.
Author Interviews, MRSA, PNAS, UCLA, Vaccine Studies / 14.12.2014

Dr. Michael Yeaman Ph.D. Professor of Medicine, Infectious Disease Specialist Chief, Division of Molecular Medicine David Geffen School of Medicine at UCLA Los Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterMedicalResearch.com Interview with: Dr. Michael Yeaman Ph.D. Professor of Medicine, Infectious Disease Specialist Chief, Division of Molecular Medicine David Geffen School of Medicine at UCLA Los Angeles Biomedical Research Institute Harbor-UCLA Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Yeaman: In the U.S. and around the globe, skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA) continue to endanger the health and lives of patients and otherwise healthy individuals. Treatment is difficult because MRSA is resistant to many antibiotics, and the infections can recur, placing family members and other close contacts at risk of infection. Infectious disease specialists at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) tested a new investigational vaccine, NDV-3, and found it holds new hope for preventing or reducing the severity of infections caused by the "superbug" MRSA. In the study, which was published Dec. 8 in the Proceedings of the National Academy of Sciences USA, the researchers reported that NDV-3, employing the recombinant protein Als3, can mobilize the immune system to fight off MRSA skin infections in an experimental model. The researchers found the vaccine works by enhancing molecular and cellular immune defenses of the skin in response to MRSA and other S. aureus bacteria in disease models. This is the first published study to demonstrate the effectiveness of a cross-kingdom recombinant vaccine against MRSA skin infections. NDV-3 is unique as it is the first vaccine to demonstrate it can be effective in protecting against infections caused by both S. aureus and the fungus Candida albicans. NDV-3 represents a novel approach to vaccine design that pioneers an approach termed convergent immunity.
Author Interviews, BMJ, Heart Disease, Nutrition, Sugar, Weight Research / 13.12.2014

Dr James J DiNicolantonio PharmD Ithaca, New YorkMedicalResearch.com Interview with: James J. DiNicolantonio, PharmD Associate Editor BMJ Open Heart Cardiovascular Research Scientist Saint Luke's Mid America Heart Institute Medical Research: What is the background for this study? What are the main findings? Dr. DiNicolantonio: Cardiovascular disease is the leading cause of premature mortality in the developed world, and hypertension is its most important risk factor. Controlling hypertension is a major focus of public health initiatives, and dietary approaches have historically focused on sodium. A reduction in the intake of added sugars, particularly fructose, and specifically in the quantities and context of industrially-manufactured consumables, would help not only curb hypertension rates, but would also help address broader problems related to cardiometabolic disease.
Author Interviews, Cognitive Issues, Genetic Research, JAMA / 13.12.2014

David H. Ledbetter, Ph.D., FACMG Executive Vice President & Chief Scientific Officer, Geisinger Health System Danville, PA 17822MedicalResearch.com Interview with: David H. Ledbetter, Ph.D., FACMG Executive Vice President & Chief Scientific Officer, Geisinger Health System Danville, PA 17822 Medical Research: What is the background for this study? What are the main findings? Dr. Ledbetter: One of the biggest challenges in clinical care and research of children with autism and related neurodevelopment disorders is the remarkable clinical variability between individuals. This heterogeneity is reduced, but still significant, when considering individuals who have neurodevelopment disorders due to the identical genetic mutation such as deletion 16p11.2. We proposed that family background, genetic or environmental, may contribute to the variability in cognitive, behavioral and motor performance profiles of children with a sporadic (new) mutation in 16p11.2. Our study confirmed that a significant portion of the clinical variability seen in these children is due to the performance level of their parents and unaffected siblings and suggested that this may be due in part to genetic background effects as these traits are all known to have very high heritability.
Author Interviews, Brain Injury, NEJM / 13.12.2014

MedicalResearch.com Interview with: Dr. Brett E. Skolnick PhD Department of Neurosurgery Cushing Neuroscience Institute Hofstra North Shore–LIJ School of Medicine, Manhasset, NY Medical Research: What is the background for this study? What are the main findings? Dr. Skolnick: The experimental evidence for a role of progesterone is based on extensive non-clinical studies in non-primate species (4 animal species such as rat, mice) the majority of which indicate that progesterone has a variety of neuroprotective properties. The animal models of injury in traumatic brain injury (TBI) have included models of blunt trauma, fluid percussion injury, cortical aspiration but similar effects have been seen stroke models and models of spinal cord injury. In these experiments progesterone has been shown to reduce cerebral edema thus limiting the effects or preventing intracranial pressure increases which can lead to secondary injury. Progesterone has also been shown to exert anti-inflammatory, anti-apopotic and perhaps even anti-oxidant effects. All of these effect are postulated to work synergistically to prevent cell death which could result in improved functional outcomes. Two small single center clinical trials provided the support in traumatic brain injury patients that progesterone could have impact on functional outcomes in larger, properly powered trials.  The results of which are summarized in the NEJM article. In the current trial evaluated the Glasgow Outcome Scale and the extended version of the Glasgow Outcome scale at 6 months following injury. These scales are well validated scales that are used to determine the degree of recovery in terms of disability and handicap due to TBI rather than the degree of impairment. The GOS has 5 levels: death, vegetative state, severe disability, moderate disability and good recovery with death and vegetative state typically collapsed because they are considered equally undesirable. The Extended GOS takes the three best levels of recovery and subdivides these into a upper and lower category to increase the granularity of the outcome measure. Progesterone was administered within 8 hour of injury (loading dose followed by continuous infusions) for a total of 120 hours.  Careful assessments were performed to ensure optimal patient management during the trial to provide the best background to evaluate the impact of the addition of progesterone or placebo (1  to 1 randomization).  No effect was seen on the GOS or the extended GOS. In addition a fairly new approach of categorizing patients based on prognostic factors known at time of randomization (such as Age, baseline GCS, pupillary response, hypoxia, hypotension, Marshall Classification or presence/absence of subarachnoid hemorrhage) as developed by Hukkelhoven and colleagues was used. This was expected to tease out improvements, if they existed in subgroups of patients where perhaps progesterone could work better in the most severe or less severe traumatic brain injury patients. But again no effects were seen. The unfavorable outcomes (see NEJM paper for details) were essentially identical between progesterone and placebo groups whether they had the worst prognosis or the best prognosis.
Author Interviews, Genetic Research, NEJM, NIH / 13.12.2014

Dr. Constantine A. Stratakis, M.D., D.Sc National Institutes of Health, Clinical Research Center Bethesda, MD 20892-1862MedicalResearch.com Interview with: Dr. Constantine A. Stratakis, M.D., D.Sc National Institutes of Health, Clinical Research Center Bethesda, MD 20892-1862 Medical Research: What is the background for this study? What are the main findings? Dr. Stratakis: We have been working for years on the genetics of pituitary tumors in association with other conditions. A few years ago (attached), we studied for the first time a series of pediatric giants that we sequenced for then known genes. We found a few MEN1 and AIP mutations but all mutations were present in older kids with gigantism. This left out the youngest among the giants without any genetic defect. This was the first time I realized that I was dealing with a different disease. We started looking for additional genetic defects and when we found the Xq26 microduplications in 3 kindreds. We contacted the custodians of the largest series in the world - Dr. Beckers in Liege. He screened his cases, once we gave him the coordinates, and boom - it was there... The most significant thing here is that this is a new disease really: the early pediatric gigantism is almost exclusively due to Xq26 microduplications unless it is part of a family with another syndrome (AIP, MEN1, Carney complex). If there is no family history and you are dealing with a toddler with gigantism, based in these data, there is a more than 80% chance of having an Xq26 defect. This is pretty amazing! In addition, assuming that GPR101 is the responsible gene (which needs to be confirmed with additional studies) this identifies a new molecular pathway of increasing growth hormone secretion, most likely due to upregulation of GHRH - all of this needs to be confirmed in further human and animal studies. The Xq26 genomic micro-arrangements (which contain the GPR101, but also 3 other genes) is the big news here...
Author Interviews, Erasmus, JACC, Memory, Stroke / 13.12.2014

MedicalResearch.com Interview with: M. Arfan Ikram, MD, PhD,and Ayesha Sajjad, MD Department of Epidemiology Erasmus University Medical Center, Rotterdam Rotterdam, The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: The occurrence of cognitive impairment and dementia after a stroke event are already known. Since these neuro-degenerative processes and stroke share vascular pathways in their pathogenesis such as small vessel disease, we aimed to study whether early cognitive impairment can be predictive of stroke onset in the elderly. We also hypothesized that a higher cognitive reserve (due to higher education attainment) may mask early symptoms of memory loss and thus put these older individuals at a higher risk of stroke. We found that self-reported subjective memory complaints as answered by a single question: “ Do you have memory complaints?” was highly predictive of stroke especially in older persons who were highly educated. In comparison, objective measures of cognitive impairment such as MMSE did not show any association with the risk of stroke.
Author Interviews, Heart Disease, Imperial College, JACC / 13.12.2014

MedicalResearch.com Interview with: Dr. Jane A. Mitchell National Heart and Lung Institute Imperial College, London, UK Medical Research: What is the background for this study? What are the main findings? Dr. Mitchell: Anti-inflammatory drugs (NSAIDs) work by inhibiting the enzyme COX-2. COX-2 selective anti-inflammatory drugs, like Vioxx, were introduced to reduce gastrointestinal side effects associated with these drugs. However, COX-2 inhibitors as well as most older NSAIDs are associated with increased risk of heart attacks although the precise mechanisms underlying these side effects are not completely understood. The main findings of this study are: 1) COX-2 is highly expressed in the kidney where its genetic deletion leads to changes in more than 1000 genes. 2) Analysis of these genes revealed changes in 2-3 specific genes that regulate levels of ADMA, an endogenous inhibitor of the nitric oxide released by vessels, that can be reversed by giving more of the substrate for NO, L-arginine. 3) Further studies showed that ADMA was indeed increased in the plasma of mice where COX-2 gene was knocked out or in normal mice given a COX-2 inhibitor. 4) In mice where COX-2 was knocked out the release of nitric oxide from vessels was reduced and this could be reversed by supply L-arginine. 5) ADMA was also increased in human volunteers taking a COX-2 inhibitor
Author Interviews, Education, JAMA / 13.12.2014

MedicalResearch.com Interview with: John Hayes, MD Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin Medical Research: What is the background for this study? What are the main findings? Response: Prominent in the discussions about ABIM MOC and recertification has been an ongoing debate about the evidence that supports a relationship between recertification, MOC and patient care. Since many healthcare organizations use board certification as a criteria for employment consideration, the new status of “certified” but not meeting MOC throws considerable disarray into credentialing and hiring committees. We can now have ABIM labeling a physician who boarded eleven years ago as “not certified” but a physician who boarded 25 years ago as “certified” with an asterisk. And of course discussions like this bring employers and healthcare organizations back to the question: What is the additive value of MOC and recertification on patient care? The integrated Veterans Health Administration electronic health record generates performance reports for primary care physicians at regular intervals. In our study, we were able to observe for any difference based on certification groups. We reviewed ten industry-standard quality care measures in approximately 68,000 patients across 4 VA medical centers and found that internists holding time-unlimited certificates performed just as well as those holding time-limited certificates.
Author Interviews, Diabetes, Nature, Weight Research / 12.12.2014

MedicalResearch.com Interview with: Prof. Dr. Patrice D. Cani PhD, Research Associate FRS-FNRS Louvain Drug Research Instiute, Metabolism and Nutrition WELBIO, Walloon Excellence in Life sciences and BIOtechnology NeuroMicrobiota lab, European Associated Laboratory (INSERM/UCL) and Dr Amandine Everard Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Metabolism and Nutrition Research Group, Brussels, Belgium Medical Research: What is the background for this study? What are the main findings? Response: Our intestine harbors more than 100 trillions of bacteria. This huge number of bacteria permanently interacts with our own human cells. Among the systems involved in this crosstalk, the immune system plays a key role in these interactions. We previously showed that specific gut bacteria are able to control energy metabolism, harmful inflammation associated with obesity, body weight gain and type-2 diabetes. However mechanisms involved these effects of gut bacteria on the host during obesity and type-2 diabetes were poorly understood. We identify the essential role of the intestinal immune system in the onset of obesity and type-2 diabetes both induced by a high dose of fat in the diet. This discovery highlights an unexpected mechanism for the control of energy metabolism during obesity and type-2 diabetes. We demonstrate for the first time that the inactivation of a part of the intestine immune system (more specifically the protein MyD88), which is overstimulated by a diet rich in fat, allows to induce weight-loss and to reduce type-2 diabetes associated with obesity. When we tune the immune system by disabling the protein MyD88 specifically in cells covering the intestine, we are able to limit the adipose tissue development induced by the diet rich in fat, to slow down diabetes, to reduce harmful inflammation associated with obesity, to reinforce gut barrier function assumed by our intestine to avoid the inappropriate translocations of bacteria compounds from our intestine in our body. We reveal various mechanisms explaining the partial protection against obesity induced by the inactivation of this protein of the immune system. Among them, we point out that mice that do not have this protein of the immune system (i.e. MyD88) in their intestine are partially protected against obesity because they spend more energy than other obese mice. Moreover, our study shows that this protein of the immune system is able to shape the composition of the gut microbiota residing in our intestine under a high-fat diet. These changes observed in mice deleted for this protein also explain their protection against obesity because when we transfer intestinal bacteria of these mice into other mice that are axenic (without flora), these latest mice are also partially protected against obesity. In conclusions, our studies published in the scientific journal Nature Communications, demonstrated that during consumption of fat food, the intestinal immune system plays an important role in fat storage regulation in the body and is capable to modify the composition of intestinal bacteria (including some which are still unidentified), confirm the implication of intestinal bacteria in the onset of obesity.