AHA Journals, Author Interviews, Duke, Exercise - Fitness, Heart Disease, Social Issues / 18.11.2015

[caption id="attachment_19231" align="alignleft" width="200"]Lauren Cooper, MD Fellow in Cardiovascular Diseases Duke University Medical Center Duke Clinical Research Institute Dr. Cooper[/caption] MedicalResearch.com Interview with: Lauren Cooper, MD Fellow in Cardiovascular Diseases Duke University Medical Center Duke Clinical Research Institute Medical Research: What is the background for this study? Dr. Cooper: The HF-ACTION study, published in 2009, showed that exercise training is associated with reduced risk of death or hospitalization, and is a safe and effective therapy for patients with heart failure and reduced ejection fraction. Subsequently, Medicare began to cover cardiac rehabilitation for patients with heart failure. However, many patients referred to an exercise training program are not fully adherent to the program. Our study looked at psychosocial reasons that may impact participation in an exercise program. Medical Research: What are the main findings? Dr. Cooper: We found that patients with higher levels of social support and fewer barriers to exercise exercised more than patients with lower levels of social support and more barriers to exercise. And patients who exercised less had a higher risk of cardiovascular death or heart failure hospitalization compared to patients who exercised more.
Annals Internal Medicine, Author Interviews, Critical Care - Intensive Care - ICUs, Technology / 18.11.2015

MedicalResearch.com Interview with: Daniel Niven MD, MSc, FRCPC Department of Critical Care Medicine Department of Community Health Sciences O'Brien Institute for Public Health Cumming School of Medicine, University of Calgary  Medical Research: What is the background for this study? Dr. Niven: Fever (temperature 38.0 degrees Celsius or higher) and hypothermia (temperature less than 36.0 degrees Celsius) are commonly included in diagnostic criteria for certain disorders, influence clinical decision making, and are associated with an increased risk for death in select patient populations. Therefore, accurately measuring body temperature is important. Unfortunately, the accuracy of many commonly employed thermometers is not well defined.  Medical Research: What are the main findings? Dr. Niven: This systematic review and meta-analysis examined the accuracy of thermometers measuring temperature from peripheral sites (for example, forehead measurement devices) relative to central sites (for example, the bladder) in adults and children. From 75 studies and 8,682 patients, this meta-analysis found that the majority of commonly used peripheral thermometers do not have clinically acceptable accuracy among adults and children. This was especially the case for patients with fever and hypothermia, where peripheral temperature measurements may be as much as 1 to 2 degrees higher or lower than actual body temperature. Sensitivity for detection of fever was low (64%), whereas specificity was high (96%).
Author Interviews, JAMA, Pediatrics, Respiratory / 17.11.2015

[caption id="attachment_19443" align="alignleft" width="140"]Leonard B. Bacharier, MD Professor of pediatrics Clinical Director, Division of Allergy, Immunology and Pulmonary Medicine St Louis School of Medicine Washington University St Louis, Missouri Dr. Bacharier[/caption] MedicalResearch.com Interview with: Leonard B. Bacharier, MD Professor of pediatrics Clinical Director, Division of Allergy, Immunology and Pulmonary Medicine St Louis School of Medicine Washington University St Louis, Missouri  Medical Research: What is the background for this study? What are the main findings? Dr. Bacharier: Oral corticosteroids such as prednisone have become the standard of care for children whose colds tend to progress and lead to severe wheezing and difficulty breathing. “But there are some studies that suggest these treatments don’t consistently work for young children. That’s why we want to find ways to prevent upper respiratory infections from progressing to lower respiratory tract illnesses. Once the episode gets going, standard interventions are less effective than would be desired”​​​​​​​​​​​​​​​​, reported Dr. Bacharier.
Accidents & Violence, Author Interviews, Mental Health Research, PLoS / 17.11.2015

MedicalResearch.com Interview with: Simone Ullrich, PhD Senior Lecturer in Forensic Mental Health Violence Prevention Research Unit Queen Mary University of London Medical Research: What is the background for this study? What are the main findings? Dr. Ullrich: There are currently thought to be more than three hundred risk assessment instruments used by professionals such as psychiatrists, psychologists, and probation officers to assess the risks of violence and sexual offending among psychiatric patients, prisoners, and the general population. In some mental health services the hospital does not get paid unless staff have carried out a risk assessment on their patients. Producing risk assessment instruments has become an ‘industry’ and new instruments are being produced annually, on every form of violence and criminal activity. The Queen Mary research group believe that none of these instruments have any advantage over those produced before. Furthermore, their best predictions for future violence get 30% wrong. Professor Coid and colleagues believe that no further progress can be made because researchers have been too obsessed with predicting the future of whether a patient will be violent rather than looking for the causes of why they become violent. All previous studies have used special statistical techniques which are designed to measure predictive accuracy. The Queen Mary research group say there is nothing wrong with being accurate or measuring accuracy, but there is no point in trying to develop new instruments which can never improve on getting it right more than 70% of the time. It may be helpful to know that your patient has a high or low risk of being violent if you release them from hospital, but this is not going to tell you what you should do to stop them being violent. Furthermore, if the risk assessment says that their risk is high then it is likely that you will not release them. The problem is that professionals will always play safe and, although there is a good chance (around 30%) that they are totally wrong, the patient will not be released. This is probably one of the most important reasons why patients are staying longer and longer in secure mental health services. These instruments achieve little more than making healthcare professionals risk averse. The National Institute for Health Research (NIHR) funded a study where 409 male and female patients who were discharged from medium secure services in England and Wales were followed up after release into the community. They received assessments with two ‘state of the art’ assessment instruments, the HCR-20 which aims to guide clinicians in their assessment of violence, and the SAPROF, another instrument aimed to guide clinicians on which factors protect patients from becoming violent. Both instruments were developed on the basis of predictive statistics. Measures were taken with these instruments prior to release into the community, then after 6 and 12 months following discharge. Information on violence was gathered via individual case notes and a search of the police national computer. By 6 months following discharge, 54 (14%) had committed a violent act, between 6 and 12 months 43 (13%) had been violent. The authors used two methods to investigate the associations between these risk/ protective factors and violence. They first tested the standard approach of risk assessment for the factors that occurred in the past 6 months which were then used to statistically predict violence in the following 6 months (predictive model). They then used a second approach which looked at the co-occurrence of the risk/ protective factors and violence within the same 6 month time window (causal model). Using the traditional approach and looking at accuracy, the predictive model produced statistical coefficients of low size, suggesting that the risk and protective factors were poor in identifying who would be violent and who would not. Because many associations between the factors and violence were weak, few appeared useful in identifying those which should be targeted to manage future violence. Surprisingly, symptoms of major mental disorder did not show an association with violence, even though most of the patients in the study suffered from major mental disorder. It might have been expected that some patients would relapse, with more symptoms, leading to violence. When the researchers used a causal approach aiming to confirm which risk and protective factors resulted in violence, the findings were very different. Symptoms of major mental disorder, the patients’ living condition, and whether they were taking medication were highly important factors. Secondly, the effects of risk and protective factors on violence were much bigger using the causal approach. For example, the effects of violent thoughts and ruminations, being in an unstable life situation, were about 3 times stronger using the causal model. The effects of being under stress and unable to cope were more than 4 times stronger than using the traditional predictive approach. They concluded that the causal approach was much better in identifying the key factors that need to be considered in the assessment and management of violence.
Author Interviews, Genetic Research, JAMA, Neurological Disorders / 17.11.2015

[caption id="attachment_19384" align="alignleft" width="168"]Kevin M. Biglan, M.D., M.P.H Professor of Neurology and the Associate Chair for Clinical Research Department of Neurology and the Center for Human Experimental Therapeutics University of Rochester School of Medicine and Dentistry Rochester, New York Dr. Biglan[/caption] MedicalResearch.com Interview with: Kevin M. Biglan, M.D., M.P.H Professor of Neurology and the Associate Chair for Clinical Research Department of Neurology and the Center for Human Experimental Therapeutics University of Rochester School of Medicine and Dentistry Rochester, New York  Medical Research: What is the background for this study? What are the main findings? Dr. Biglan: A therapeutic goal of research in Huntington Disease (HD) is the identification of treatments that delay the progression of disease and onset of illness in individuals at risk for developing manifest HD. Designing such efficacy trials is challenging. A major hurdle is the lack of practical primary outcome measures to assess the effect of an intervention on delaying disease onset. Use of the dichotomous endpoint of clinical diagnosis as the primary outcome requires large sample sizes and long duration of follow up in order to show a significant therapeutic effect on delaying disease onset. Continuous measures that can reliably distinguish cytosine-adenine-guanine (CAG) expanded individuals in the pre-manifest period may allow for the identification of potential disease modifying therapies using relatively smaller cohorts followed for shorter periods of time. The Prospective Huntington At-Risk Observational Study (PHAROS) represents the largest observational study to clinically evaluate pre-manifest Huntington Disease wherein both research participants and investigators were unaware of Huntington Disease mutation status. Accordingly, PHAROS was uniquely designed to address, in an unbiased manner, those clinical features most associated with the CAG expansion during the prodromal phase in  Huntington Disease.  The identification of continuous outcome measures that are associated with HD in the pre-manifest period may facilitate the design and powering of future studies of potential disease modifying therapies prior to traditional motor diagnosis.
Author Interviews, Diabetes, JAMA, Ophthalmology / 16.11.2015

MedicalResearch.com Interview with: Adam R. Glassman, MS Jaeb Center for Health Research Tampa, FL 33647 Medical Research: What is the background for this study? What are the main findings? Response: Diabetic retinopathy is a complication of diabetes that affects blood vessels in the retina. When diabetic retinopathy worsens to proliferative diabetic retinopathy, blood vessels in the retina can leak fluid or bleed, distorting vision. Diabetic retinopathy is the most common cause of vision loss among people with diabetes and the leading cause of blindness among working-age adults. Scatter laser treatment, also called panretinal photocoagulation, has been standard therapy for the treatment of proliferative diabetic retinopathy since the 1970s. While effective in preserving central vision, laser therapy can reduce side vision and cause swelling in an area of the retina that is important for central vision. This study aimed to find an alternative therapy that avoided these undesirable side effects. Eyes in this study were assigned randomly to treatment with intraocular anti-VEGF injections of Lucentis® or scatter laser treatment. The results of this study demonstrate that eye injections of Lucentis® are as effective for vision outcomes at 2 years as laser therapy. On average, vision among eyes treated with Lucentis® improved by about half a line on an eye chart, with virtually no improvement among eyes treated with laser therapy. Compared with laser-treated eyes, eyes treated with Lucentis injection on average had less side vision loss, less frequent development of swelling in the central retina, and fewer complex retina surgeries for retinal bleeding or retinal detachment.
Annals Internal Medicine, Asthma, Author Interviews, Pharmacology / 16.11.2015

MedicalResearch.com Interview with: Michael Miligkos, MD, MS Laboratory of Biomathematics, University of Thessaly School of Medicine Larissa, Greece Medical Research: What is the background for this study? What are the main findings? Dr. Miligkos: Asthma is one of the most common chronic diseases with and has considerable social and economic burdens. Although inhaled corticosteroids constitute the current gold standard of maintenance treatment, leukotriene-receptor antagonists (LTRAs) have the advantages of oral once- or twice- daily dosing and, apparent avoidance of the adverse effects associated with long-term corticosteroid therapy. In addition, their mechanisms of action theoretically predicts a good response in patients with specific asthma “phenotypes”. This systematic review investigated the use of all marketed LTRAs in usual licensed doses as asthma controller medications compared with placebo and found that administration of a LTRA to adults and adolescents with asthma significantly reduced the risk for an exacerbation. In trials of LTRA monotherapy, LTRAs significantly improved asthma control compared with placebo, whereas only some measures of asthma control were significantly improved in trials of LTRAs used as add-on use therapy to ICSs.
Author Interviews, Blood Clots, Orthopedics, PLoS / 16.11.2015

MedicalResearch.com Interview with: Banne Nemeth, MD and  Suzanne C. Cannegieter MD PhD Leiden University Medical Center The Einthoven Laboratory for Experimental Vascular Medicine Clinical Department of Epidemiology and Orthopedic Surgery Medical Research: What is the background for this study? What are the main findings? Dr. Nemeth: Clinicians cannot currently accurately predict who will develop venous thrombosis, but it would be very helpful to be able to identify individuals at high risk for venous thrombosis because the condition can be prevented by giving anticoagulants before a clot forms (thromboprophylaxis). The ability to predict venous thrombosis would be particularly useful in patients who have had a lower limb immobilized in a cast after, for example, breaking a bone. These patients have an increased risk of venous thrombosis compared to patients without cast immobilization. We developed and validated a prediction model to identify patients with plaster cast of the lower extremity who are at high risk to develop venous thrombosis. A clinical risk score named, L-TRIP(cast) score (Leiden Thrombosis Risk Prediction for patients with cast immobilization score), was developed containing 14 clinical risk factors such as age, sex, BMI, use of oral contraceptives and location of plaster cast. Patients that score 9 points or higher are classified as being at high risk for venous thrombosis. Clinicians may decide to prescribe thromboprophylaxis therapy for these patients.
Author Interviews, Columbia, Heart Disease, JACC, Transplantation / 14.11.2015

[caption id="attachment_19394" align="alignleft" width="149"]Raymond Givens MD PhD Columbia University Medical Center Dr. Givens
(photo Seth Wenig)[/caption] MedicalResearch.com Interview with: Raymond Givens MD PhD  Columbia University Medical Center  Medical Research: What is the background for this study? What are the main findings? Dr. Givens: Multiple listing- i.e., simultaneous placement on multiple organ transplant waiting lists- is allowed by the United Network for Organ Sharing (UNOS). Because insurance generally does not pay for the costs of transportation between multiple centers or of temporary housing, there has been concern that the multiple-listing policy gives an unfair advantage to wealthier patients. We examined the UNOS database from 2000-2013 and identified 33,928 patients who were listed for a first-time single-organ heart transplant, 2% of whom met our definition of multiple-listing. Compared to single-listed patients, multiple-listed patients lived in ZIP codes with significantly higher median incomes, and were more likely to have private insurance and less likely to be supported by Medicaid. They were also significantly more likely to have blood type O and to live in areas with higher predicted waiting times. Despite having lower listing priority at the start of the primary listing and lower predicted mortality, the multiple-listed patients were often upgraded at secondary listing and had a higher eventual transplant rate (74.4% vs 70.2%) and lower mortality rate while listed (8.1% vs 12.2%). When the multiple-listed cohort was compared against a propensity-score-matched single-listed subset the relative rare of transplant was 3.02. There were no differences in post-transplant survival.
AHA Journals, Author Interviews, Heart Disease / 14.11.2015

[caption id="attachment_19398" align="alignleft" width="148"]Susan Marzolini, R.Kin, PhD Scientific Associate, TRI-REPS Supervisor Toronto Rehab/UHN Cardiovascular Prevention and Rehabilitation Program Dr. Marzolini[/caption] MedicalResearch.com Interview with: Susan Marzolini, R.Kin, PhD Scientific Associate, TRI-REPS Supervisor Toronto Rehab/UHN Cardiovascular Prevention and Rehabilitation Program Medical Research: What is the background for this study? What are the main findings? Dr. Marzolini: Coronary artery bypass graft (CABG) surgery is a leading revascularization procedure for treating coronary artery disease. Despite effective revascularization, cardiovascular risk factor control through intensive lifestyle and pharmacological treatment is essential to prevent graft deterioration and progression of atherosclerosis following surgery. Outpatient cardiac rehabilitation (CR) programs offer structured exercise, education, interdisciplinary support, counselling, and risk reduction to promote secondary prevention. These programs have been shown to improve fitness, psychosocial well-being, and significantly reduce morbidity and mortality after CABG surgery. However, while Canadian and international guidelines endorse “early” referral to CR post-cardiac event, actual practice is variable and delays are common_ENREF_9_ENREF_9_ENREF_7. Delayed entry is of concern, as there is emerging evidence that later referral and initiation of cardiac rehabilitation is associated with negative consequences on cardiovascular fitness, however this has not been examined in the post-CABG population. Therefore, we conducted a retrospective analysis of 6497 consecutively enrolled post CABG participants in a single cardiac rehabilitation program in Toronto, Canada from January 1995 to October 2012. Our objective was to examine the effects of later entry on CR outcomes (i.e., CR use, anthropometrics, and functional capacity) while accounting for demographic, environmental, and physiological correlates of longer wait-time. We found that longer wait-time to start a cardiac rehabilitation program was associated with poorer outcomes including less improvement in cardiopulmonary fitness and lower program attendance, which have been shown to confer a mortality disadvantage. Longer wait time was also associated with less improvement in body fat percentage as well as poorer completion rates. We identified that bypass patients predisposed to longer wait times, and subsequently poorer participation and outcomes, are women, those who are older, from a lower socioeconomic neighborhood, people with a more complex medical history, who are employed, have a longer drive-time to cardiac rehabilitation, and people with less social support.
Author Interviews, Cancer Research, Genetic Research, JAMA / 14.11.2015

[caption id="attachment_19304" align="alignleft" width="160"]Samuel Klempner, M.D. Assistant Professor Division of Hematology/Oncology UC Irvine Health Orange, CA 92868 Dr. Klempner[/caption] MedicalResearch.com Interview with: Samuel Klempner, M.D. Assistant Professor Division of Hematology/Oncology UC Irvine Health Orange, CA 92868  Medical Research: What is the background for this study? What are the main findings? Dr. Klempner: The background for our series is the concept that little is known about the genetic landscape of rare tumors such as acinic cell tumors, and that understanding genetic changes in tumors can identify treatment options.  This paradigm can, and should, be extended beyond rare tumor types and many researchers are currently studying various tumor types.  Another important background idea is that tumor genomic alterations may be more important than that anatomic site of origin. For example, I would argue that a breast cancer that harbors an EGFR mutation common to lung cancer could be treated similar to a lung cancer based on the genomic changes. In our study we found another way that the BRAF protein and its downstream signaling may become activated through duplicating part of the protein called the kinase domain.  This genetic event causes the pathway to be always "on" which is not normal, and likely drives cancer growth.  However, BRAF kinase domain duplication appears sensitive to currently available drugs that target the BRAF pathway, as evidenced by the response in our patient.  Thus, finding this change is important and may be able to guide a more personalized therapy choice.  Importantly, we found BRAF kinase domain duplication across multiple different tumor types, suggesting this may be a recurrent event in some cancers.  A very similar finding, involving duplication of the EGFR kinase domain, was also just reported (Cancer Discovery 2015;5:1155-1163) lending further validation to this mechanism of pathway activation in cancer.
AHA Journals, Author Interviews, McGill, Stroke / 14.11.2015

MedicalResearch.com Interview with: Sophie Vincent, Medical Student McGill University and Kristian Filion, PhD FAHA Assistant Professor of Medicine Division of Clinical Epidemiology Jewish General Hospital/McGill University Medical Research: What is the background for this study? What are the main findings? Response: Patients with carotid atherosclerosis causing vascular stenosis are at increased risk of stroke, which is the third leading cause of death in the United States and in Canada. Carotid artery stenting and carotid endarterectomy are the primary surgical options for the treatment of carotid stenosis. With the assumption that an endovascular approach would offer a more favorable safety profile than open surgical procedure, the use of stenting increased significantly following its entry into the market in the 1990s. However, despite this observed increase in use, the long-term safety and efficacy of stenting relative to endarterectomy remained unclear, which is why we decided to conduct this study. Although carotid artery stenting has more favorable periprocedural outcomes with respect to myocardial infarction, hematoma, and cranial nerve palsy, the observed increased risk of stroke throughout follow-up with stenting suggests that endarterectomy remains the treatment of choice for the management of carotid stenosis.
Author Interviews, JAMA, Mental Health Research, Primary Care / 13.11.2015

Shahrzad Mavandadi, PhD Research Health Science Specialist and Investigator Veterans Integrated Services Network 4 Mental Illness Research, Education, and Clinical Center Corporal Michael J. Crescenz Veterans Affairs Medical Center Philadelphia, PennsylvaniaMedicalResearch.com Interview with: Shahrzad Mavandadi, PhD Research Health Science Specialist and Investigator Veterans Integrated Services Network 4 Mental Illness Research, Education, and Clinical Center Corporal Michael J. Crescenz Veterans Affairs Medical Center Philadelphia, Pennsylvania  Medical Research: What is the background for this study? Dr. Mavandadi: Mental health (MH) conditions are underidentified and undertreated in later life.  This is particularly true among subgroups of older adults who are more vulnerable to developing mental health issues, have poor access to specialty care, and are less responsive to treatment and therapy.  Thus, we sought to evaluate longitudinal MH outcomes among low-income, community-dwelling older adults enrolled in an evidence-based, collaborative mental health care management service (i.e., the SUpporting Seniors Receiving Treatment And INtervention (SUSTAIN) program).  The SUSTAIN program integrates mental health with primary care (which is where the majority of behavioral health conditions in later life are managed) and provides standardized, measurement-based, software-aided MH assessment and connection to community resources to older adults by telephone. While there is a strong evidence base for the efficacy of collaborative care models for me conditions, little is known about the amount or level of patient and provider support that is needed to achieve optimal behavioral health outcomes.  Thus, we specifically examined outcomes among older adults randomized to one of two program arms of varying intensity: MH symptom monitoring alone or mental health symptom monitoring plus MH care management.   MH care management involved care managers who provided education, counseling, and decision support to patients and their primary care providers, a licensed mental health clinician who supervised the care managers, and the use of an algorithm to help guide pharmacological and non-pharmacological treatment plans.  The sample consisted of 1018 older adults prescribed an antidepressant or anxiolytic by their non-behavioral health providers who presented with clinically significant symptoms at intake.
Author Interviews, JAMA, Mental Health Research, Pediatrics / 13.11.2015

[caption id="attachment_19297" align="alignleft" width="200"]Dr. Mai-Britt Guldin PhD Department of Public Health Aarhus University Dr. Gulden[/caption] MedicalResearch.com Interview with: Dr. Mai-Britt Guldin PhD Department of Public Health Aarhus University  Medical Research: What is the background for this study? Dr. Guldin: The background for this study is that death of a parent in childhood is experienced by 3-4% of children in Western societies, and we know such a loss is one of the most stressful and potentially harmful events in childhood. Therefore, we aimed to investigate how parental death may influence the long-term risk of suicide and how this risk differes by cause of parental death, age at loss, sex of child, socioeconomic factors and parental history of psychiatric illness.The sample size in this study is unparalleled by other studies on risk of suicide. Medical Research: What are the main findings? Dr. Guldin: The main findings were that in a population of 7.302,033 (in three Scandinavian countries), we identified 189,094 persons who lost a parent before the age of 18. Of these bereaved persons, 265 died from suicide. Compared to a control group of persons matched by age and sex, but who did not lose a parent before the age of 18, suicide was twice as common in the bereaved cohort (IRR = 2.02; 95% CI, 1.67-2.44). The risk remained high for at least 25 years of follow-up. The risk was particularly high for children who lost a parent due to suicide, but was also high for children who lost a parent due to other causes. The risk tended to be particularly high for boys who lost a mother and children losing a parent before the age of six.
Author Interviews, FASEB, Metabolic Syndrome, Nutrition, Weight Research / 13.11.2015

[caption id="attachment_19362" align="alignleft" width="200"]Suzan Wopereis, Ph.D. TNO, Microbiology and Systems Biology Group Zeist, The Netherlands Dr. Wopereis[/caption] MedicalResearch.com Interview with: Suzan Wopereis, Ph.D. TNO, Microbiology and Systems Biology Group Zeist, The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Wopereis: For the first time we could demonstrate the very subtle start of negative health effects caused by a high calorie snack diet in healthy men. We already knew about the negative consequences of such diets from so called epidemiologic studies. In such studies, scientists compare large populations (thousands of people) to better understand disease development. For example, by comparing  obese populations to a lean population, scientists could define various steps in the disease development related to obesity, like high cholesterol, onset of inflammation, high blood pressure, high glucose, etc. Yet, the early deviations from health  were difficult to study because human metabolism (the way we digest and metabolize our meals from a biochemical viewpoint)  is very flexible and able to efficiently deal with all kinds of daily stressors, such as a meal or intensive exercise. So, at TNO we decided to exploit  this flexibility by giving our healthy volunteers a ‘challenge test’, in the form of a high-fat milkshake. Next, we studied how multiple aspects of their metabolism react to such a challenge test. We showed that a snack diet for 4 weeks reduced many aspects of  flexibility of our healthy men, thus indicating very early changes in health. Both the high-fat challenge test and the integral study of many different outcomes form a novel approach of what “healthy” really means. In the study we used two groups of male volunteers. One group of 10 healthy male volunteers and one group of 9 male volunteers with Metabolic Syndrome, who had a combination of 2 or more risk factors that raises your risk for heart disease and other health problems (unhealthy cholesterol levels, high blood pressure, high blood sugar, high blood lipids, and abdominal fat). In other words, subjects with Metabolic Syndrome have a suboptimal health condition. Both groups received a high-fat milk-shake, and before and up to 8 hours after consumption of this metabolic challenge-test, blood samples were taken. In these blood samples, 61 different biomarkers were measured, such as cholesterol and blood sugar. These 61 biomarkers were used for a thorough health assessment of these 2 groups in response to the challenge test. We noted that biochemical processes related to sugar metabolism, fat metabolism and inflammation function abnormal in subjects with Metabolic Syndrome. The next step was to provide the 10 healthy male volunteers with a snack diet for 4 weeks. On top of their normal diet they had to consume an additional 1300 kcal per day, in the form of sweets and savory products such as candy bars, tarts, peanuts, and crisps. After these 4 weeks the response of the same 61 biomarkers to the challenge test was evaluated. Here, we observed that signaling molecules such as hormones regulating the control of sugar and fat metabolism and inflammation were changed, resembling the very subtle start of negative health effects. Without the use of the challenge test, we would not have been able to observe that even this short period of overfeeding induces changes in the metabolism of healthy people that resemble what happens in people with metabolic syndrome.
Author Interviews, Dermatology, Melanoma, NEJM, UCSF / 13.11.2015

[caption id="attachment_19293" align="alignleft" width="105"]Boris C. Bastian, MD, PhD Professor of Dermatology and Pathology Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research University of California, San Francisco Dr. Bastian[/caption] MedicalResearch.com Interview with: Boris C. Bastian, MD, PhD Professor of Dermatology and Pathology Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research University of California, San Francisco Medical Research: What is the background for this study? What are the main findings? Dr. Bastian:  The cost of DNA sequencing has dropped substantially since the initial sequencing of the human genome in 2001. As a result, the most common cancer subtypes have now been sequenced, revealing the pathogenic mutations that drive them. A typical cancer is driven by 5-10 mutations, but we still do not understand the order in which these mutations occur for most cancers. Determining the order in which mutations occur is challenging for cancers that are detected at a late stage. Melanomas, however, lend themselves to this type of analysis because they are pigmented and found on the surface of the skin, allowing them to be identified early. Sometimes, melanomas are even found adjacent to their remnant precursor neoplasms, such as benign nevi (also known as common moles). We performed detailed genetic analyses of 37 cases of melanomas that were adjacent to their intact precursor neoplasms. We microdissected and sequenced the surrounding uninvolved normal tissue, the precursor neoplasm, and the descendent neoplasm. By comparing the genetic abnormalities in each of the microdissected areas, we were able to decipher the order of genetic alterations for each case. Our work reveals the stereotypic pattern of mutations as they occur in melanoma. Mutations in the MAPK pathway, usually affecting BRAF or NRAS, occur earliest, followed by TERT promoter mutations, then CDKN2Aalterations, and finally TP53 and PTEN alterations. Benign nevi typically harbor a single pathogenic alteration, whereas fully evolved melanomas harbor three or more pathogenic alterations. We also identified an intermediate stage of neoplasia with some but not all of the pathogenic mutations required for fully evolved melanoma. There has been a longstanding debate whether morphologically intermediate lesions, such as dysplastic nevi, truly constitute biological intermediates or whether they simply represent a gray zone of histopathological assessment. Our data indicates that these neoplasms are genuine biological entities. Finally, we observe evidence of UV-radiation-induced DNA damage at all stages of pathogenesis, implicating UV radiation in both the initiation and progression of melanoma.
AHA Journals, Author Interviews, Blood Pressure - Hypertension, Brigham & Women's - Harvard, Heart Disease / 12.11.2015

[caption id="attachment_19340" align="alignleft" width="135"]Carrie C. Lubitz, MD, MPH Assistant Professor of Surgery, Harvard Medical School Senior Scientist, Institute for Technology Assessment Attending Surgeon, Mass General/North Shore Center for Outpatient Care Danvers, Massachusetts Dr. Lubitz[/caption] MedicalResearch.com Interview with: Carrie C. Lubitz, MD, MPH Assistant Professor of Surgery, Harvard Medical School Senior Scientist, Institute for Technology Assessment Attending Surgeon, Mass General/North Shore Center for Outpatient Care Danvers, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Lubitz: Given reported estimates of resistant hypertension and the proportion of resistant hypertensive patients  with primary hyperaldosteronism (PA) - the most common form of secondary hypertension caused by a nodule or hyperplasia of the adrenal glands – we estimate over a million Americans have undiagnosed PA. Furthermore, it has been shown that patients with PA with the same blood pressure as comparable patients with primary hypertension have worse outcomes. In our study, we found that identifying and appropriately treating patients with PA can improve long-term outcomes in patients in a large number of patients who have resistant hypertension.
Author Interviews, Brigham & Women's - Harvard, Genetic Research, JAMA, Neurological Disorders, Schizophrenia / 12.11.2015

[caption id="attachment_19334" align="alignleft" width="150"]Frederick W. Vonberg, MA, MBBS Research Fellow in Neurocritical Care Boston Children's Hospital and Harvard Medical School Dr. Vonberg[/caption] MedicalResearch.com Interview with: Frederick W. Vonberg, MA, MBBS Research Fellow in Neurocritical Care Boston Children's Hospital and Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Response: An association between schizophrenia and epilepsy has long been suspected, ever since people noticed similarities in some aspects of the presentation of the two conditions, and in their epidemiology. For example, people with epilepsy are thought to be more at risk of developing schizophrenia. Furthermore, a psychosis resembling schizophrenia can characterize some forms of epilepsy. Whether this link reflected an overlap in the genetics of the two conditions has remained a mystery, however. In this study, we used a recently developed computational technique to show that there is a significant positive correlation between the genetic variants that are associated with epilepsy and with those that are associated with schizophrenia.
Author Interviews, BMJ, Diabetes / 12.11.2015

MedicalResearch.com Interview with: Prof. Julia Hippisley-Cox PhD Professor of Clinical Epidemiology & General Practice Faculty of Medicine & Health Sciences The University of Nottingham  Medical Research: What is the background for this study? What are the main findings? ProfHippisley-Cox:          Patients with type 1 or type 2 diabetes are at increased risk of blindness and amputation but generally do not have an accurate assessment of the magnitude of their individual risk. There are currently no tools available to calculate risk of other complications such as amputation or blindness. This is important since these are the complications which patients with diabetes fear most and which most impair quality of life. They are also the complications for which patients are most likely to over-estimate their risk and over-estimate the benefits of intensive treatment.          We have developed and externally validated new risk prediction algorithms which calculates absolute risk of developing these complications over a 10 year period in patients with diabetes, taking account of their individual risk factors.
Author Interviews, Brigham & Women's - Harvard, Cancer Research, PNAS / 12.11.2015

[caption id="attachment_19325" align="alignleft" width="150"]Dr-Lei-Xu.jpg Dr. Lei Xu[/caption] MedicalResearch.com Interview with: Lei Xu, MD, PhD Steele Laboratory of Tumor Biology Radiation Oncology Department Massachusetts General Hospital Medical Research: What is the background for this study? Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing. Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves.
Annals Internal Medicine, Author Interviews, Heart Disease, Surgical Research / 11.11.2015

Dr. Giuseppe Andò University of Messina, Messina, ItalyMedicalResearch.com Interview with: Dr. Giuseppe Andò University of Messina, Messina, Italy Medical Research: What is the background for this study? Dr. Andò: Patients’ preference for radial access for coronary angiography and percutaneous intervention is paralleled by an almost complete abolition of access-site bleeding. Given the deleterious impact of any clinically relevant bleeding event on short- and long-term outcomes, the use of radial access should translate into a reduction in net adverse events, especially in patients with high risk of bleeding such as those with an acute coronary syndrome. Nonetheless, studies conducted over the past decade by pioneers of radial access were relatively small and not sufficiently compelling to affect guidelines and endorse a change in current practice. Medical Research: What are the main findings? Dr. Andò: We have pooled in the present study 4 well-conducted, large, multicenter studies with data from centers with different expertise in radial procedures across America, Europe, Asia and Oceania. We demonstrate that the use of radial access can reduce mortality in patients with acute coronary syndromes undergoing invasive management by a consistent reduction in major bleeding.
Author Interviews, Blood Pressure - Hypertension, JACC, University Texas / 11.11.2015

Dr. Wanpen Vongpatanasin MD Program Director, Hypertension Fellowship Program Professor of Internal Medicine Director of the University of Texas Southwestern Hypertension ProgramMedicalResearch.com Interview with: Dr. Wanpen Vongpatanasin MD Program Director, Hypertension Fellowship Program Professor of Internal Medicine Director of the University of Texas Southwestern Hypertension Program Medical Research: What is the background for this study? What are the main findings? Dr. Vongpatanasin: Home blood pressure measurement may reveal very different number when compared to clinic blood pressure in hypertensive patients.  This difference can manifest as white coat hypertension (White Coat Hypertension; elevated office blood pressure with normal ambulatory or home blood pressure), or masked hypertension (MH; elevated ambulatory or home BP with normal office blood pressure).  Although numerous epidemiological studies from Europe and Asia have shown increased cardiovascular risks associated with White Coat Hypertension and masked hypertension, previous studies have not addressed cardiovascular outcomes associated with White Coat Hypertension and masked hypertension in the general population in the United States. We found that  participants in the Dallas Heart Study, a multiethnic populational-based study in the Dallas County, both White Coat Hypertension and MH are associated with increased aortic stiffness and markers of kidney damage when compared to the group with normal blood pressure both at home and in the clinic. Furthermore, both white coat hypertension and masked hypertension are associated with increased risk of cardiovascular events, including coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death over a median follow-up period of 9 years.
AHA Journals, Author Interviews, Duke, Education, Gender Differences, Heart Disease / 10.11.2015

[caption id="attachment_19201" align="alignleft" width="160"]Pamela S. Douglas, MD, MACC, FASE, FAHA Ursula Geller Professor of Research in Cardiovascular Disease Duke University School of Medicine Dr. Douglas[/caption] MedicalResearch.com Interview with: Pamela S. Douglas, MD, MACC, FASE, FAHA Ursula Geller Professor of Research in Cardiovascular Disease Duke University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Douglas: The impetus for our study was the concern that cardiology as a profession might be enhanced by greater diversity. By not attracting women in larger numbers (9% of FACCs are female), our fellowships have incomplete access to the talent pool of outstanding residents, and we do not have a diverse group of clinicians to care for our increasingly diverse patient population, or of researchers to explore potentially important health care disparities. Our findings were twofold: first, job descriptions for men and women cardiologists are dramatically different. Men are much more likely to do invasive procedures while women are more likely to see patients and perform imaging/noninvasive tests.  While there were slightly more women working part time than men this was still rare, and the difference in number of days worked was just 6, across an entire year. The second finding was that there was a significant difference in compensation. Unadjusted, this was over $110, 000 per year; after very robust adjustment using over 100  personal, practice, job description and productivity measures, the difference was $37, 000 per year, or over a million dollars across a career. A separate independent economic analysis of wage differentials yield a similar difference of $32,000 per year.
Author Interviews, Duke, JAMA, Pharmacology, Stroke / 10.11.2015

[caption id="attachment_19166" align="alignleft" width="137"]Ying Xian, PhD Assistant Professor of Medicine. Member in the Duke Clinical Research Institute Dr. Ying Xian[/caption] MedicalResearch.com Interview with: Ying Xian, PhD Assistant Professor of Medicine. Member in the Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Xian: Intravenous tissue plasminogen activator (tPA) is the only FDA approved medical therapy to reduce disability and improve outcomes for patients with acute ischemic stroke. But treatment with tPA also carries the risk of symptomatic intracranial hemorrhage (sICH), which is often fatal. Nearly half of ischemic stroke patients are taking antiplatelet drugs such as aspirin and/or clopidogrel prior to stroke. We found these patients had higher risk for sICH when treated with tPA. But the risk is relatively small. For every 147 patients on aspirin treated with tPA, only 1 more symptomatic intracranial hemorrhage as compared with those treated with tPA without prior antiplatelet therapy. The risk is slightly higher among those on dual antiplatelet therapy of aspirin and clopidogrel (number needed to harm 60). Despite the higher bleeding risk, patients treated with tPA on prior antiplatelet therapy appeared to have better functional outcomes in terms of ambulatory status and modified Rankin scale than those not on prior antiplatelet therapy. Therefore, overall the benefits of thrombolytic therapy may outweigh the risks.
Author Interviews, Diabetes, JAMA, Pediatrics, Probiotics / 10.11.2015

Dr. Ulla Uusitalo PhD University of South Florida, TampaMedicalResearch.com Interview with: Dr. Ulla Uusitalo PhD University of South Florida, Tampa Medical Research: What is the background for this study? What are the main findings? Dr. Uusitalo: The TEDDY Study is an international prospective cohort study with the primary goal to identify environmental causes of Type 1 Diabetes (T1D). It is carried out in six clinical research centers, in four countries: University of Colorado Health Science Center (US), Georgia Regents University (US), Pacific Northwest Diabetes Research Institute (US), Turku University Hospital (Finland), Institute of Diabetes Research (Germany), and Lund University (Sweden), since 2004. One possible environmental factor related to Type 1 Diabetes etiology is diet. Dietary supplements including probiotics as well as various types of infant formulas including probiotic fortified infant formula are studied. The microbial composition of gut has been shown to be associated with the development of  Type 1 Diabetes. Colonization of the infant gut starts already in utero and early microbial exposures have been found to be important in defining the trajectory of colonization. Probiotics have been demonstrated to induce favorable immunomodulation and it has been suggested that probiotic treatment could prevent T1D. Therefore we wanted to study the early exposures of probiotic and risk of islet autoimmunity, a condition often preceding Type 1 Diabetes. This study produced very interesting results. The main finding was that we found 60% decrease in the risk of islet autoimmunity among children with HLA genotype of DR3/4 (high risk), who were exposed to probiotics during the first 27 days of life.
AACR, Author Interviews, Cancer, Cancer Research, University Texas / 10.11.2015

MedicalResearch.com Interview with: Xifeng Wu, M.D., Ph.D, Professor, Epidemiology Stephanie Melkonian, Ph.D University of Texas M. D. Anderson Cancer Center Medical Research: What is the background for this study? What are the main findings? Response: This study examines dietary intake of meat-cooking mutagens and genetic risk factors associated with kidney cancer in a population of 659 kidney cancer patients and 699 matched healthy control subjects from the community. We calculated the intake of several cancer-causing carcinogens that are produced when certain types of meat are cooked over an open flame and at high temperatures resulting in the burning, smoking or charring of the meat (for example, during barbequing or pan-frying). We found that kidney cancer patients consumed more red and white meat when compared to the healthy individuals, and also had higher intake of these cancer-causing chemicals created through the meat cooking process. These results suggest that meat intake, and the way we cook our meat, may potentially be linked to risk of kidney cancer. Additionally, we found that individuals with certain genetic variants were more likely to be susceptible to the harmful effects of the cancer-causing mutagens created during the process of cooking meat.
Author Interviews, Diabetes, Heart Disease, JAMA, Mental Health Research / 10.11.2015

[caption id="attachment_19187" align="alignleft" width="150"]Dr. Christina Mangurian MD Associate Professor of Clinical Psychiatry UCSF School of Medicine and the UCSF Department of Psychiatry's first Director of Diversity Dr. Mangurian[/caption] MedicalResearch.com Interview with: Dr. Christina Mangurian MD Associate Professor of Clinical Psychiatry UCSF School of Medicine and the UCSF Department of Psychiatry's first Director of Diversity Medical Research: What is the background for this study? What are the main findings? Dr. Mangurian: People with severe mental illness (SMI, e.g., schizophrenia and bipolar disorder) die 25 years earlier than the general population, often from cardiovascular disease.  The ADA and APA guidelines recommend annual diabetes screening of this population when taking certain antipsychotic medications.  Despite these guidelines, nearly 70% of this population remain unscreened.  This has huge public health implications and likely costs our public health system a tremendous amount in undiagnosed disease.
Author Interviews, Heart Disease, JAMA, PAD / 09.11.2015

MedicalResearch.com Interview with: Farzin Fakhry, MD PhD Candidate Depts. of Epidemiology & Radiology Erasmus MC Rotterdam, the Netherlands and Myriam Hunink MD, PhD Professor Professor of Radiology and Clinical Epidemiology Erasmus University Medical Center Rotterdam Adjunct Professor of Health Decision Science Harvard T.H. Chan School of Public Health, Boston Medical Research: What is the background for this study? What are the main findings? Response: Intermittent claudication is the classical symptomatic form of peripheral arterial disease (PAD) and affects approximately 20-40 million people worldwide. These patients experience significant functional disability resulting in a sedentary lifestyle and reduced quality of life. In the Endovascular Revascularization And Supervised Exercise (ERASE) study we compared a combination therapy of endovascular revascularization plus supervised exercise versus the recommended care of supervised exercise only as first-line treatment for patients with intermittent claudication. Results from the ERASE study showed that after one year follow up patients in both groups showed significant improvements in their treadmill walking distance and disease specific quality of life. Yet, patients receiving the combination therapy had more rapid and significantly greater improvement in their walking performance and disease specific quality of life compared to the patients following a supervised exercise program only.
Author Interviews, Gender Differences, Heart Disease, JAMA / 09.11.2015

[caption id="attachment_19177" align="alignleft" width="202"]Dr. David Bluemke MD, PhD, MsB Director of Radiology and Imaging Sciences NIH Clinical Center Bethesda, MD Dr. Bluemke[/caption] MedicalResearch.com Interview with: Dr. David Bluemke MD, PhD, MsB Director of Radiology and Imaging Sciences NIH Clinical Center Bethesda, MD  Medical Research: What is the background for this study? What are the main findings? Dr. Bluemke: Heart disease is the most common reason for death and disability of adults in the United States and worldwide. This study evaluated 1,840 adults in six communities throughout the United States, ages 45-84. In normal adults, the heart is a muscle, but various injuries to the heart (the most severe being a myocardial infarction/ heart attack) occur over an individual’s lifetime. These injuries result in heart muscle being replaced by a scar composed of fibrous tissue. The main finding is that even in healthy, middle and older adults, about 1 in 12 adults in the U.S. have developed scars in the heart. Most of these (80%) are not detected by their doctor, or by other tests such as ECG.
Author Interviews, Cancer Research, Endocrinology, Journal Clinical Oncology, Menopause, NIH / 07.11.2015

MedicalResearch.com Interview with: Elizabeth K. Cahoon, PhD Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics, National Cancer Institute National Institutes of Health Department of Health and Human Services Bethesda, MD Medical Research: What is the background for this study? What are the main findings? Dr. Cahoon: Although basal cell carcinoma (BCC) is the most common cancer in the United States, there is relatively little research on risk factors since few population-based cancer registries do not capture information on this malignancy. Sun exposure (in particular ultraviolet radiation) is the primary risk factor for basal cell carcinoma, but less is known about other factors that may affect this risk. A previous study found a relationship between menopausal hormone therapy (MHT) use and increased risk of BCC in a population of Danish women. In our study we looked to see if factors related to estrogen exposure from multiple sources was associated with basal cell carcinoma risk in a large, nationwide, prospective study. These included use of oral contraceptives or menopausal hormone therapy, but also reproductive factors (like age at menarche and menopause). We observed that women who experienced natural menopause later in life were more likely to develop basal cell carcinoma compared to women who had natural menopause at a younger age. In addition, women who reported using menopausal hormone therapy for one year or longer were more likely to develop basal cell carcinoma compared to women who did not report MHT use. Women who reported natural menopause and menopausal hormone therapy use for 10 or more years had the highest risk of basal cell carcinoma, compared to women with no menopausal hormone therapy use.