Author Interviews, Brigham & Women's - Harvard, Diabetes, Diabetes Care, Nutrition / 19.01.2015

Jinnie J. Rhee Department of Epidemiology, Harvard School of Public Health, Boston, MAMedicalResearch.com Interview with: Jinnie J. Rhee MSc, ScD Department of Medicine, Stanford University School of Medicine Palo Alto, CA Medical Research: What is the background for this study? What are the main findings? Response: The goal of this study was to see if the dietary determinants of type 2 diabetes observed in predominantly white populations were similar to those in other racial and ethnic groups.  We created a dietary diabetes risk reduction score using eight different dietary factors found to be associated with risk of type 2 diabetes, where a higher score indicates a healthier overall diet (A higher score included low intakes trans fat, sugar-sweetened beverages, and red and processed meats; lower glycemic index; and higher intakes of cereal fiber, nuts, and coffee; and higher polyunsaturated to saturated fat ratio).  We found a protective association of similar magnitude between a healthy overall diet and type 2 diabetes risk in all racial and ethnic groups.  However, in terms of the actual number of preventable cases, a healthier diet conferred even greater benefit for minority women because they were initially at higher risk than white women. This study is significant because diabetes is a rapidly growing epidemic in most parts of the world, but most previous studies of diet and diabetes have been conducted in populations of European origin.  This analysis was very powerful because it combined two large populations with a total of 156,030 women who were followed for up to 28 years with many repeated assessments of diet.  This allowed us to conduct detailed analyses within specific racial and ethnic groups.
Author Interviews, Breast Cancer, Nutrition / 19.01.2015

Cecilia Cesa Schiavon Department of Nutrition, Federal University of Santa Catarina Florianópolis, Santa Catarina, BrazilMedicalResearch.com Interview with: Cecilia Cesa Schiavon Department of Nutrition, Federal University of Santa Catarina Florianópolis, Santa Catarina, Brazil Medical Research: What is the background for this study? What are the main findings? Response: The study was based on a nutritional intervention for patients undergoing treatment for breast cancer. The intervention took place right after the surgical procedure and lasted about a year, until the end of chemotherapy. The patients were submitted to a special methodology of intervention, aimed at increasing fruit and vegetable intake and reducing red and processed meat, following the World Cancer Research Fund and the American Institute for Cancer Research in the document entitled Food, Nutrition, Physical Activity and the prevention of Cancer: A Global Perspective”. The main findings show that women undergoing breast cancer treatment may benefit from immediate, individualized, and detailed nutrition monitoring through appropriate nutrition education.
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Science / 19.01.2015

Lee Zou, Ph.D. Professor of Pathology, Harvard Medical School The Jim & Ann Orr MGH Research Scholar Associate Scientific Director, MGH Cancer CenterMedicalResearch.com Interview with: Lee Zou, Ph.D. Professor of Pathology, Harvard Medical School The Jim & Ann Orr MGH Research Scholar Associate Scientific Director, MGH Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Lee Zou: Cancer cells must rely on telomerase or the alternative lengthening of telomere (ALT) pathway to maintain telomeres and bypass replicative senescence. The ALT pathway is active in about 10-15% of human cancers, and it is particularly prevalent in specific cancer types, such as osteosarcoma, glioblastoma, and neuroendocrine pancreatic tumors. ALT is a recombination-mediated process. Whether the reliance of cancer cells on  alternative lengthening of telomere can be exploited therapeutically was not known. In our study, we discovered that the ATR kinase is a key regulator of alternative lengthening of telomere. We found that ATR inhibitors disrupt ALT effectively. Furthermore, we found that ATR inhibitors selectively kill ALT-positive cancer cells in a panel of caner cell lines. These findings have suggested the first rational therapeutic strategy for the treatment of ALT-positive cancer.
Author Interviews, Kidney Disease, NEJM / 19.01.2015

MedicalResearch.com Interview with: David K. Packham, M.B., B.S., M.D Royal Melbourne Hospital Melbourne Renal Research Group VIC 3073, Australia, Medical Research: What is the background for this study? What are the main findings? Dr. Packham:  ZS-9 represents a new mechanism of action for addressing hyperkalemia. Unlike traditional nonspecific organic polymer cationexchangers, ZS-9 is a non-absorbed, inorganic crystalline potassium-selective cation exchanger that traps excess potassium in the gastrointestinal tract. It has been evaluated in three prospective, randomized, double-blind, placebo-controlled studies with over 1100 patients to date, representing the largest ever clinical development program for hyperkalemia. ZS-003 was the first of two pivotal Phase 3 studies that evaluated the safety and efficacy of ZS-9 in patients with hyperkalemia. In ZS-003, treatment of patients with an oral suspension of ZS-9 (2.5, 5, or 10 grams, three times a day) resulted in statistically significant and clinically meaningful reductions in serum potassium, compared with placebo, during the “acute phase” (first 48 hours), with 99 percent of patients achieving normal potassium levels with the highest 10 gram dose. During the next 12 days of the trial (the “maintenance phase”), ZS-9 (5 or 10 grams) given once daily could maintain the corrected potassium levels achieved during the acute phase. In contrast, patients who were randomized back to placebo after achieving normal potassium reverted back to hyperkalemia. The tolerability profile has been favorable, with adverse event rates from ZS-9 similar to that of placebo.
Author Interviews, Dental Research, Heart Disease / 19.01.2015

Dr. Francisco Mesa Department of Periodontics, School of Dentistry, University of Granada, Spain MedicalResearch.com Interview with: Dr. Francisco Mesa Department of Periodontics, School of Dentistry, University of Granada, Spain Medical Research: What is the background for this study? What are the main findings? Dr. Mesa: The size of an acute myocardial infarct (AMI) is one of the determinants of its severity, i.e., the degree of myocardial necrosis. This necrosis is indicated by peak troponin I levels in the blood. Among the acute myocardial infarct patients in our study, mediated regression analysis demonstrated that troponin I levels were higher, i.e., the infarct size was larger, in those with chronic periodontitis.
Author Interviews, Brigham & Women's - Harvard, JAMA, Surgical Research / 18.01.2015

Soko Setoguchi, MD DrPH Assistant Professor of Medicine Harvard Medical School and Harvard School of Public Health Director of Safety and Outcome Research in Cardiology Associate Physician in the Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s HospitalMedicalResearch.com Interview with: Soko Setoguchi, MD DrPH Assistant Professor of Medicine Harvard Medical School and Harvard School of Public Health Director of Safety and Outcome Research in Cardiology Associate Physician in the Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Setoguchi: Medicare made a decision to cover Carotid Artery Stenting (CAS) in 2005 after publication of SAPPHIRE, which demonstrated the efficacy of Carotid Artery Stenting (CAS) vs Carotid endarterectomy (CEA) in high risk patients for CEA. Despite the data showing increased carotid artery stenting dissemination following the 2005 National Coverage Determination, peri-procedural and long-term outcomes have not been described among Medicare beneficiaries, who are quite different from trial patients, older and with more comorbidities in general population. Understanding the outcomes in these population is particularly important in the light of more recent study, the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), which established CAS as a safe and efficacious alternative to CEA among non-high-surgical risk patients that also expanded the clinical indication of carotid artery stenting. Another motivation to study ‘real world outcomes in the general population is expected differences in the proficiency of physicians peforming stenting in trial setting vs. real world practice setting. SAPPHIRE and CREST physicians were enrolled only after having demonstrated CAS proficiency with low complication rates whereas hands-on experience and patient outcomes among real-world physicians and hospitals is likely to be more diverse. We found that unadjusted mortality risks over study period of 5 years with a mean of 2 years of follow-up in our population was 32%.  Much higher mortality risks observed among certain subgroups with older age, symptomatic patients and non-elective hospitalizations.
Author Interviews, PLoS, Sexual Health / 18.01.2015

MedicalResearch.com Interview with: Matthew Golden MD, MPH Director, PHSKC HIV/STD Program Professor of Medicine, University of Washington Harborview Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Golden: Gonorrhea and chlamydial infection are the most common reportable infections in the United States and, in women, are associated with pelvic inflammatory disease, ectopic pregnancy, infertility and chronic pelvic pain. One way to decrease the number of cases of gonorrhea and chlamydia is to increase our success in treating the sex partners of persons diagnosed with these infections. Expedited partner therapy (EPT) - treating partners without requiring them to first undergo a medical evaluation - is one way to increase partner treatment. This usually involves giving people medication to give to their partners. Prior randomized trials have found that EPT decreases patients' risk of becoming reinfected. We conducted a community-level randomized trial to evaluate whether making free Expedited partner therapy available to medical providers would increase the use of Expedited Partner Therapy and decrease gonorrhea and chlamydial infections at the population level. We found that a public health program that made Expedited partner therapy widely available could dramatically increase medical providers use of EPT. Although our final result was not statistically significant, our findings suggest that the program likely decreased both gonorrhea and chlamydial infection by about 10% at the population-level.
Author Interviews, Dermatology, Heart Disease / 18.01.2015

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: There is a growing body of literature supporting an association between psoriasis and increased cardiovascular risk. We hypothesized that these associations are not specific to psoriasis. Rather, they likely occur in other chronic inflammatory skin disorders, namely eczema. We studied two large-scale US population-based studies and found that adults with eczema were more likely to smoke cigarettes, drink alcohol and were less physically active. In turn, they also have higher rates of obesity, high blood pressure, prediabetes and type 2 diabetes and high cholesterol. Of note, eczema was associated with these disorders even after controlling for smoking, alcohol consumption and physical activity. This suggests that chronic inflammation and/or other factors related to eczema may also drive increased cardiovascular risk.
Author Interviews, Weight Research / 17.01.2015

Sue Shapses, PhD Professor, Department of Nutritional Sciences Acting Chair, Department of Exercise Sciences and Sports Studies Rutgers, The State University New Brunswick, NJ 08901-8525MedicalResearch.com Interview with: Sue Shapses, PhD Professor, Department of Nutritional Sciences Acting Chair, Department of Exercise Sciences and Sports Studies Rutgers, The State University New Brunswick, NJ 08901-8525 MedicalResearch: What is the background for this study? Dr. Shapses: Improving health outcomes through dieting and weight loss is encouraged for the majority of Americans who are either overweight or obese. However, while most studies show that a moderate reduction in body weight decreases obesity related comorbidities, there may also be loss of bone and muscle in older individuals. Specifically in postmenopausal women, intentional moderate weight loss results in a 1-2.5% bone loss when compared to a weight stable group. Studies in men, designed to address the effect of weight reduction at multiple bone sites, compartments and geometry, are currently lacking. In addition, while a higher body weight is associated with higher bone mass, evidence indicates that bone quality, a predictor of fracture risk, is compromised in the obese. It is possible that frequent dieting or weight cycling in these obese individuals may have deleterious effects on bone. Therefore, understanding whether bone quality changes with weight loss, is important to better predict osteoporosis risk in this population. In this controlled trial, the effect of dietary restriction on bone mineral density (BMD), geometry and strength were examined in middle aged and older obese/overweight men. In addition, we addressed whether endocrine changes associated with weight loss explain bone changes.
Aging, Author Interviews, Frailty / 17.01.2015

MedicalResearch.com Interview with: Alexander Voukelatos BSc, BA, MA(psych), PhD Healthy Populations Program Manager Health Promotion Sydney Local Health District and Conjoint Lecturer School of Public Health and Community Medicine University of NSW Medical Research: What is the background for this study? Response:Falls in older people has been a significant public health issue in high income countries for several decades now. We know that if current trends continue, given that more people will be living for longer, falls will be an even bigger issue in the not too distant. Falls are not an inevitable part of ageing, and in fact many falls can be prevented relatively simply by increasing physical activity. For over 15 years we've known that physical activity is one of the most effective ways of reducing the risk of falls in older people living in the community; since the publication of the first Cochrane review on Interventions for preventing falls in the elderly by Gillespie and colleagues. [1]  I know that Health Departments here, in Australia, and in New Zealand - as I suspect has been the case in many high income countries - have invested a lot of resources over the past few decades into reducing falls-related hospital admissions in older people. Much of this going into promoting and funding physical activity programs for older people. However, this investment has had very little if any impact on falls-related hospital admissions in older people. There may be several reasons we haven't seen any difference in these rates. In New South Wales - Australia's most populous state -  we know that physical activity rates amongst older people have actually risen by about 15% between 1998 and 2005,[2] the most popular activity by far being walking,[3] yet we haven't see any corresponding change in falls-related hospitalization rates. Perhaps there has not been enough time for these programs to have made an impact on hospitalization rates, or perhaps the change in physical activity levels is insufficient to make an impact on these rates. Another possibility could be that while we've seen an increase in physical activity in older people perhaps its not the kind of physical activity that results in a reduction in falls. Sherrington and colleagues [4] reviewed effective physical activity interventions for preventing falls in older people and found they had several elements in common: a) the physical activity included balance challenging exercise i.e. exercises taking participants to the limits of their stability, b) at least 50 hours of accumulated activity was needed, and c) no walking was included in the exercises. So we know not all types of physical activity will be equally effective in reducing the risk of falling. There is some disagreement in the literature about walking. There are several studies that included walking as part of the intervention and showed a reduction in falls in older people. Other studies supported the conclusions made by Sherrington that walking is not associated with a reduction in falls. All of these studies included walking as a component of an intervention which makes it difficult to figure out what effect walking specifically has on falls rates. This is were our study comes in. We wanted to investigate the effectiveness of a walking program on falls in older people, specifically sedentary older people, who we presumed would get the most benefit from becoming more physically active. We developed a walking program specifically for sedentary older people, that they could do themselves in their own time, at their preferred locale. The aim of the program was to get participants walking for at least 150 minutes per week at a brisk pace. The program comprised of four parts: the first part focused on increasing the frequency of walks, the second part focused on getting participants to walk for at least 150 minutes per week, followed by walking for 150 minutes at a brisk pace, while the final part focused on supporting participants in maintaining their walking levels and incorporating walking as part of their daily activities.
AHA Journals, Author Interviews, Heart Disease, Stroke / 17.01.2015

Jonathan Thigpen, PharmD Assistant Professor Clinical and Administrative Sciences Notre Dame of Maryland University School of PharmacyMedicalResearch.com Interview with: Jonathan Thigpen, PharmD Assistant Professor Clinical and Administrative Sciences Notre Dame of Maryland University School of Pharmacy Medical Research: What is the background for this study? What are the main findings? Dr. Thigpen: This effort assessed the accuracy of International Classification of Disease 9th Edition (ICD-9) stroke codes in identifying valid stroke events in a cohort of atrial fibrillation (AF) patients. The initial electronic search yielded 1,812 events across three stroke centers (Boston Medical Center, Geisinger Health System, and University of Alabama). All ICD-9 identified stroke events were vetted through manual chart review with final adjudication by a stroke neurologist. Atrial fibrillation was verified by evidence via electrocardiogram at stroke admission, 6 months prior to, or 90 days after stroke admission. In addition to assessing the accuracy of the stroke codes alone, we also assessed the accuracy of stroke and Atrial fibrillation codes combined as well as the accuracy of stroke codes when seeking for stroke associated with Atrial fibrillation. These additional steps give readers insight as to the accuracy and reliability of using ICD-9 codes alone to create a stroke plus AF cohort. We feel that this effort is extremely important given the increasing reliance on ICD-9 codes as a means of identifying stroke events and covariates in research, especially research using administrative data. The positive predictive value (PPV) of stroke codes alone was 94.2%. PPVs did not differ across clinical site or by type of event (ischemic vs. intracranial hemorrhage). PPV of stroke codes did differ by event coding position (primary vs. other; 97.2% vs. 83.7%) and by ischemic stroke code (433 vs. 434; 85.2% vs. 94.4%). When combined with validation of Atrial fibrillation codes, the PPV of stroke codes decreased to 82.2%. After excluding ischemic stroke due to a different mechanism (eg, vascular procedure, tumor, sepsis) the PPV dropped further to 72.8%. As a separate exercise, manual review confirmed 33 (7.2%) ischemic strokes in 458 events coded as "without infarction".
Author Interviews, Endocrinology, Weight Research / 16.01.2015

Caroline M. Apovian, MD Chair of the Endocrine Society task force that developed “Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline” Boston University School of Medicine Boston Medical CenterMedicalResearch.com interview with: Caroline M. Apovian, MD Chair of the Endocrine Society task force that developed “Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline” Boston University School of Medicine Boston Medical Center MedicalResearch: What is the background for this report? Dr. Apovian: The Food and Drug Administration has approved four new anti-obesity drugs – lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide – in the past two years. To help clinicians navigate this changing landscape, the Endocrine Society developed its Clinical Practice Guideline to provide strategies for prescribing drugs to manage obesity and promote weight loss. MedicalResearch: What are the main findings? Dr. Apovian: In the Clinical Practice Guideline, the Endocrine Society recommends that diet, exercise and behavioral modifications be part of all obesity management approaches. Other tools such as weight loss medications and bariatric surgery can be combined with behavioral changes to reduce food intake and increase physical activity, in appropriate patients. Patients who have been unable to successfully lose weight and maintain a goal weight may be candidates for prescription medication if they meet the criteria on the drug’s label as well as BMI criteria (BMI greater than or equal to 30 or greater than or equal to 27 with at least one comorbidity). Other recommendations from the CPG include:
  • If a patient responds well to a weight loss medication and loses 5 percent or more of their body weight after three months, the medication can be continued. If the medication is ineffective or the patient experiences side effects, the prescription should be stopped and an alternative medication or approach considered.
  • Since some diabetes medications are associated with weight gain, people with diabetes who are obese or overweight should be given medications that promote weight loss or have no effect on weight as first- and second-line treatments. Doctors should discuss medications’ potential effects on weight with patients.
  • Certain types of medication – angiotensin converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers – should be used as a first-line treatment for high blood pressure in obese people. These are effective blood pressure treatments that are less likely to contribute to weight gain than an alternative medication, beta-adrenergic blockers.
  • When patients need medications that can have an impact on weight such as antidepressants, antipsychotic drugs and medications for treating epilepsy, they should be fully informed and provided with estimates of each option’s anticipated effect on weight. Doctors and patients should engage in a shared-decision making process to evaluate the options.
  • In patients with uncontrolled high blood pressure or a history of heart disease, the medications phentermine and diethylpropion should not be used.
Author Interviews, Technology / 16.01.2015

Moe Alsumidaie MBA MSF President & Chief Scientific Officer Annex ClinicalMedicalResearch.com Interview with: Moe Alsumidaie MBA MSF President & Chief Scientific Officer Annex Clinical   MedicalResearch: What is the background for this study? Response: SUMMARY: A real-world case study measuring the impact of Short Messaging System (SMS) or “Text Messaging” on clinical trial patient recruitment using an interactive two-way patient engagement platform by Mosio, Inc., which provides clinical research services designed to increase patient recruitment, engagement and retention, found that use of text messaging alone can be an effective means of patient engagement that results in clinical trial patient enrollment. Patient recruitment, retention and medication adherence continue to be challenges in conducting effective clinical trials. While clinical trials often rely on email recruitment, recent studies suggest that only 22% of emails are read.1 Alternatively, 98% of text messages are read1 and 90% of text messages are read within the first three minutes of receipt.2 Recent research has evaluated the impact of Short Messaging System (SMS) or “Text Messaging” in healthcare settings, such as appointment reminders and medication adherence. Results have demonstrated that SMS intervention significantly improved patient behavioral outcomes: patients who received SMS reminders were more likely to show up to appointments on time,3 and patients who received SMS reminders were more adherent to medications.4 However, only limited research is available on the effect of SMS on clinical trial subject enrollment. Johnson County Clin-Trials (JCCT), a clinical research facility that specializes in executing 10-15 vaccine clinical trials per year, was facing issues with enrolling patients rapidly in a tight time frame using email. To access a more effective strategy to better engage patients, JCCT employed two-way SMS/text messaging solutions, and this study assessed the impact of SMS/text messaging on patient recruitment and enrollment.
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, JAMA, Medicare, Mental Health Research, Pharmacology / 16.01.2015

Dr. Jeanne Madden PhD Instructor, Department of Population Medicine Harvard Medical SchoolMedicalResearch.com Interview with: Dr. Jeanne Madden PhD Instructor, Department of Population Medicine Harvard Medical School   Medical Research: What is the background for this study? What are the main findings? Dr. Madden: When Medicare Prescription Drug Coverage started in 2006, many experts voiced concerns about disabled patients with serious mental illness making the transition from state Medicaid coverage to Medicare.  Our study is one of the first to examine the impact of the transition in mentally ill populations.  People living with schizophrenia and bipolar disorder are at high risk of relapse and hospitalization and are especially vulnerable to disruptions in access to their treatments. We found that the effects of transitioning from Medicaid to Medicare Part D depended on where patients lived.  Transition to Part D in states that put limits on Medicaid drug coverage resulted in fewer patients going without treatment. By contrast, in states with more generous drug coverage, we saw reductions in use, of antipsychotics in particular, after patients shifted to Medicare Part D.  This may have been due to new cost controls used within many private Medicare drug plans.  Given that most states in the US are in this latter category, with the relatively generous Medicaid drug coverage, we also found reductions in antipsychotic use nation-wide. Although a very large group of people made that transition from Medicaid to Medicare in 2006, thousands more still transition every year because when disabled people qualify for Medicare, they must wait 2 years for their benefits kick in.  Also, many other disabled patients are on Medicaid only and don’t qualify for Medicare.  They are of course affected by restrictions on Medicaid coverage, which vary from state to state.
Author Interviews, Dengue, Infections, PLoS / 16.01.2015

[caption id="attachment_10699" align="alignleft" width="220"]'Tiger Mosquito' Aedes albopictus female mosquito 'Tiger Mosquito'
Aedes albopictus female mosquito[/caption] MedicalResearch.com Interview with: Jose R. Loaiza Smithsonian Tropical Research Institute, Panama City, Panama, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología,  Universidad de Panamá, Ciudad de Panamá, Panamá   Medical Research: What is the background for this study? Response: The mosquito Aedes albopictus is a worldwide vector of both Dengue and Chikungunya viruses. This species invaded Panama in 2002, and it expanded across much of the country since that time. Our main goal was to determine the factors (e.g., ecological and non-ecological) associated with its expansion, and to comment on the implications for vector and disease control programs elsewhere in the American tropics. Medical Research: What are the main findings? Response: We found that road networks alone best predicted the distribution of Ae. albopictus in Panama over other variables such as population density and climate. Our data explain the invasion mode of this mosquito species on a local level and demonstrate a remarkable population expansion velocity across the country. Ae. albopictus is likely moving across the landscape as immature stages (i.e., larvae and pupae) in open water, such as used tires.
Author Interviews, Breast Cancer, Inflammation / 16.01.2015

Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City MéxicoMedicalResearch.com Interview with: Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City México MedicalResearch: What is the background for this study? Dr. Morales-Montor: Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped in several protein families referred as tumour necrosis factors, interleukins, interferons and colony stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis and metastasis, all phenomena in which cytokines are prominent players. The data we have hitherto let us suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer related disorders.
Author Interviews, CDC, Infections, JAMA, Pediatrics / 16.01.2015

MedicalResearch.com Interview with: Dr. Stefan Goldberg MD Medical Officer in CDC’s Division of Tuberculosis Elimination Clinical Research Branch Medical Research: What is the background for this study? What are the main findings? Dr. Goldberg: A shorter, simpler treatment regimen for children with latent TB infection can help prevent TB disease and reduce future transmission. The results from our study, a multinational, clinical trial, found that a once-weekly regimen of the anti-TB drugs rifapentine and isoniazid taken as directly observed therapy over a period of three months was safe and as effective for children (age 2-17) in preventing TB disease as the standard self-administered nine-month daily regimen of isoniazid alone. The study also showed that children are more likely to complete the shorter course of treatment, which is important given that treatment completion can be difficult. Specifically, we found that 88 percent of the trial participants on the combination regimen completed therapy while 81 percent completed the standard regimen. The CDC’s Tuberculosis Trials Consortium (TBTC), which conducted this study, works to include children in research when their inclusion is scientifically supportable and when children also might benefit from important new tools, such as alternative treatment regimens. This study is an extension of a large, international trial among persons age 12 and older, published by TBTC in 2011, which showed the shorter, simpler regimen to be as safe and effective as standard treatment.
Author Interviews, Ebola, PLoS / 16.01.2015

John M. Drake, Ph.D. Associate Professor, Odum School of Ecology, University of Georgia Director, Population Biology of Infectious Diseases REU SiteMedicalResearch.com Interview with: John M. Drake, Ph.D. Associate Professor, Odum School of Ecology University of Georgia Director, Population Biology of Infectious Diseases REU Site Medical Research: What is the background for this study? What are the main findings? Dr. Drake: Ebola virus disease is a deadly illness caused by infection with the zoonotic Ebola virus. The world's largest epidemic of Ebola virus disease is currently ongoing in West Africa, concentrated in the countries of Liberia, Sierra Leone, and Guinea. Ebola emerges in a human population after contact with an infected animal host and persists through human-to-human transmission. Persons with late stage illness are especially infectious. Ebola outbreaks are typically contained by outbreak investigation and patient isolation. But, as the current epidemic shows, containment may be very difficult to achieve in areas of high population density or where there is little health infrastructure. During the second half of 2014, the West African nation of Liberia suffered the greatest rates of Ebola transmission. Slowing the spread of Ebola was found to be especially difficult after the virus reached the urban areas around Monrovia, particularly the township of West Point. The United States, other nations, and non-governmental organizations promised aid and developed a plan to improve Liberia's health infrastructure, but many aspects of urban Ebola transmission were then unknown, including the relative importance of hospital- and community-acquired infection, how much hospital capacity must be increased to provide care for the anticipated patient burden, and what level patient of isolation would be required to contain the outbreak. To address these issues, we developed a model for Ebola transmission that accounted for the separate sites at which infection could occur, for instance in the home, in public places (particularly at funerals), or in health facilities. Based on information available by mid-October, it was not clear whether enough was being done to contain the epidemic in Liberia. But, through public vigilance and community participation, particularly the willingness of infected persons to be treated in health facilities and to allow safe handling of the bodies of the deceased, transmission dropped dramatically in the last quarter of the year. An updated version of our model developed in early December suggests that if these gains can be maintained then the epidemic may be over by the middle of 2015.
Author Interviews, Prostate, Prostate Cancer, Urology / 16.01.2015

MedicalResearch.com Interview with: Mufaddal Mamawala, MBBS, MPH, CPH Biostatistician Johns Hopkins School of Medicine Brady Urological Institute Medical Research: What is the background for this study? What are the main findings? Dr. Mamawala: Twenty years after prostate-specific antigen (PSA) was FDA approved for the diagnosis of prostate cancer, its use remains highly controversial. There has been an ‘over- diagnosis’ and ‘over-treatment’ of low-risk prostate cancers that would have never progressed to a more lethal form of the disease during one’s life. Active surveillance (AS) is an alternative to immediate treatment, which allows for monitoring of favorable risk patients with selective delayed intervention among those with disease progression. However  ‘misclassification’ is a cause of concern for patients in the initial years of been in AS. The initial biopsy may have missed an area of prostate with an aggressive cancer, due to under-sampling of cores or due to randomness, such that this patient could get misclassified as having a low-risk disease and by the time the follow-up biopsy shows an aggressive cancer the window of curability is lost. However with more sampling of the prostate there is more likelihood to find an aggressive cancer. As such if the patient is compliant with their biopsies, and more prostate is sampled under the microscope, better are the chances of finding a higher risk cancer. Conversely if the patient has more biopsies that show no high-risk cancer then they are less likely to have a high-risk cancer on future biopsies. Thus we wanted to evaluate the risk of reclassification, from a low-risk disease to a high-risk disease (higher Gleason score, or increase in extent of the disease), over a period of time in compliant active surveillance patients.  The length of time under Active surveillance without reclassification has not been evaluated as a predictor of future reclassification. Biopsies are invasive procedures, and the fact that patient has to undergo this invasive procedure regularly is a deterrent from been in Active surveillance. This study would help to make informed decisions about the need for doing frequent biopsies in light with other clinical factors especially in older patients who had many non-reclassifying biopsies before. We found that the risk of reclassification was not equally distributed across time. As a result of ‘under sampling’ of prostate at diagnostic biopsy we had highest rates of reclassification in the first two years of been in Active surveillance with more than 50% of total reclassifications happening during those two years. The ‘low-risk’ and the ‘very-low-risk’ groups, determined by the Epstein criteria, had similar rates of reclassification in the first two years. After first two years the ‘low-risk’ group were 2.4 times as likely to have a higher risk of reclassification than the ‘very-low-risk’ group. In both the groups the risk of reclassification declined over time significantly by at least 30% with each biopsy that did not show reclassification.
AHA Journals, Author Interviews, Heart Disease, Hospital Readmissions, NYU / 16.01.2015

Leora Horwitz, MD, MHS Director, Center for Healthcare Innovation and Delivery Science New York University Langone Medical Center Director, Division of Healthcare Delivery Science Department of Population Health, NYU School of Medicine New York, NY 10016MedicalResearch.com Interview with: Leora Horwitz, MD, MHS Director, Center for Healthcare Innovation and Delivery Science New York University Langone Medical Center Director, Division of Healthcare Delivery Science Department of Population Health, NYU School of Medicine New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Horwitz: We reviewed over 1500 discharge summaries from 46 hospitals around the nation that had been collected as part of a large randomized controlled trial (Telemonitoring to Improve Heart Failure Outcomes). All summaries were of patients who were admitted with heart failure and survived to discharge. We found that not one of them met all three criteria of being timely, transmitted to the right physician and fully comprehensive in content. We also found that hospitals varied very widely in their average quality. For instance, in some hospitals, 98% of summaries were completed on the day of discharge; in others, none were. In the accompanying Data Report, we show that summaries transmitted to outside clinicians and including more key content elements are associated with lower risk of rehospitalization within 30 days of discharge. This is the first study to demonstrate an association of discharge summary quality with readmission.
Author Interviews, CDC, OBGYNE, Supplements / 15.01.2015

Jennifer Williams MSN, MPH, FNP-BC National Center on Birth Defects and Developmental Disabilities CDC, Atlanta, Georgia MedicalResearch.com Interview with: Jennifer Williams MSN, MPH, FNP-BC National Center on Birth Defects and Developmental Disabilities CDC, Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Response: Neural tube defects are serious birth defects of the brain and spine that can cause significant disability and death. Studies have shown that taking 400 mcg of folic acid daily before and during pregnancy can reduce the prevalence of neural tube defects. Therefore, in 1992, the US Public Health Service (USPHS) recommended that all women of childbearing age in the United States who are capable of becoming pregnant consume 400mcg of folic acid per day to reduce the risk of neural tube defects. To help women meet this requirement, in 1998 the US Food and Drug Administration (FDA) mandated that folic acid be added to enriched grain products for the prevention of neural tube defects. This study looks at how many neural tube defects have been prevented annually since folic acid fortification. Using data from birth defects tracking systems, researchers found that since folic acid fortification, the birth prevalence of neural tube defects has decreased by 35% in the United States, which translates to about 1,300 babies that are born each year without a neural tube defect who might otherwise have been affected.  This study also reports that the number of babies born with a neural tube defect annually differs by the mother’s race/ethnicity. Hispanic mothers continue to be at the highest risk for having a baby with a neural tube defect.
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids / 15.01.2015

Jean-Claude Tardif MD Professor of Medicine Director of the Research Centre Montreal Heart Institute Montreal, Quebec CanadaMedicalResearch.com Interview with: Jean-Claude Tardif MD Professor of Medicine Director of the Research Centre Montreal Heart Institute Montreal, Quebec Canada MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Tardif: Epidemiological and mechanistic studies have suggested that high-density lipoproteins (HDL) could have beneficial cardiovascular properties. However, several medications targeting HDL have failed in recent clinical trials, including the CETP inhibitor dalcetrapib in the dal-Outcomes trial. We hypothesized that dalcetrapib would be beneficial in the subset of patients with the appropriate genetic profile. We conducted the pharmacogenomic analysis of approximately 6000 patients from the dal-Outcomes study which showed that patients with the AA genotype at a specific genetic location (rs1967309) of the adenylate cyclase (ADCY9) gene benefited from a 39% reduction in cardiovascular events including cardiovascular death, myocardial infarction, stroke, unstable angina and the need for coronary revascularization when treated with dalcetrapib compared to placebo. In contrast, patients with the GG genotype had a 27% increase in cardiovascular events. We then obtained confirmatory evidence from the dal-Plaque-2 imaging study which revealed that patients with the protective genotype (AA) had a reduction in their carotid artery wall thickness and that those with the genotype associated with clinical harm (GG) had an increase in their wall thickness.
Author Interviews, Heart Disease / 15.01.2015

MedicalResearch.com Interview with: Lauren Petrick Ph.D. The Lipid Research Laboratory Rappaport Faculty of Medicine and Research Institute The Technion Center of Excellence in Exposure Science and Environmental Health (TCEEH), Technion, Haifa, Israel MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Petrick: Nanoparticles are becoming ubiquitous in our environment, leading to higher chances of exposure. This exposure may be especially chronic for those employed in research laboratories and in high tech industry where workers handle, manufacture, use and dispose of nanoparticles. Furthermore, nanoparticle exposure to the general population occurs in the form of ultrafine particles (UFP) primarily from transportation exhaust. While nanoparticle toxicity has been investigated in general terms, its atherogenic effects and mechanisms of nanoparticle atherogenicity are not yet clear. Therefore, we decided to expose engineered silica nanoparticles to macrophages in order to investigate cell atherogenicity and cytotoxicity. What we found is that the nanoparticles were cytotoxic and increased oxidative stress and triglyceride (TG) accumulation in the cells.  Triglyceride accumulation in macrophages was not due to a decrease in triglyceride cell secretion or to an increased triglyceride biosynthesis rate, but was the result of attenuated triglyceride hydrolysis secondary to decreased lipase activity and both adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein expression. This supports a possible role for ultrafine particles in exacerbating atherosclerosis development, and shows increased cardiovascular risk associated with nanoparticle exposure.
Author Interviews, Genetic Research, PTSD, UCLA / 15.01.2015

Armen K. Goenjian, M.D., L.D.F.A.P.A., F.A.C.G.S. Research Professor of Psychiatry Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLAMedicalResearch.com Interview with: Armen K. Goenjian, M.D., L.D.F.A.P.A., F.A.C.G.S. Research Professor of Psychiatry Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA Medical Research: What is the background for this study? Response: Post-traumatic stress disorder (PTSD) is a psychiatric disorder that develops after exposure to a traumatic event such as rape, war, natural disaster, and accident. Symptoms include recurrent intrusive traumatic memories, flashbacks, nightmares, hyper-vigilance, jumpiness, and anxiety. Dopaminergic and serotonergic systems have been implicated in PTSD. Catechol-O-methyltransferase (COMT) is an enzyme that degrades dopamine, an important brain neuro-hormone that regulates human behavior, thoughts and emotions.  Tryptophan hydroxylase is the rate limiting step in the synthesis of serotonin, another important neuro-hormone that regulates arousal, sleep, anxiety, and mood. This study evaluated the association of four COMT gene loci, and the joint effect of COMT and tryptophan hydroxylase 2 (TPH-2) genes on PTSD symptoms.
Annals Thoracic Surgery, Author Interviews, Biomarkers, Kidney Disease / 15.01.2015

MedicalResearch.com Interview with: Professeur Sidney Chocron Chef de Service Chirurgie Thoracique et Cardio-Vasculaire CHU de Besançon - Hôpital Jean Minjoz BESANCON Cedex Medical Research: What is the background for this study? What are the main findings? Prof. Chocron: Acute kidney injury (AKI) is one of the most frequent complications after cardiac surgery.There is a time delay between the onset of renal impairment and the resulting telltale increase in blood creatinine levels. Recent studies have underlined the promising properties of Neutrophil Gelatinase-Associated Lipocalin (NGAL). NGAL values early after surgery could predict the duration and severity of Acute Kidney Injury. In addition, NGAL can independently predict deteriorating renal function and could therefore be useful even in the context of pre-existing renal failure. We aimed to assess the predictive ability of plasma NGAL levels to identify deteriorations in renal function after cardiac surgery in patients with pre-existing renal failure. Medical Research: What are the main findings? Prof. Chocron: One hundred sixty six patients with pre-operative renal failure i.e pre-operative creatinine clearance ≤60 mL/min/1.73m2 according to the Cockcroft Gault formula, were included in the study. The threshold NGAL values at 6 hours after operation, as determined by ROC curve analysis was 155 ng/mL with a sensitivity of 79% and a specificity of 58%. By multivariate analysis at 6 hours, a history of hypertension (OR=3.2 [1.2 - 8.9]), occurrence of at least 1 post-operative complication (OR=4.5 [1.3 - 15]), and an NGAL value above 155 ng/mL (OR=7.1 [2.7 - 18]) were shown to be independent predictors of the occurrence of post-operative AKI.
Author Interviews, Melanoma / 14.01.2015

Keiran Smalley, PhD. Scientific Director, The Comprehensive Melanoma Research Center Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FLMedicalResearch.com Interview with: Keiran Smalley, PhD. Scientific Director, The Comprehensive Melanoma Research Center Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FL   Medical Research: What is the background for this study? What are the main findings? Dr. Smalley: Although many patients with BRAF mutant melanoma respond very well to BRAF inhibitors and the BRAF/MEK inhibitor combination, resistance is commonplace and the majority of those treated ultimately fail therapy. Most studies to date have focused upon the genetic changes that are associated with acquired BRAF and BRAF/MEK inhibitor resistance. We decided to take a different approach and to use proteomics to comprehensively map all of the signaling changes associated with resistance. Our study showed that melanoma cells with resistance to BRAF and BRAF/MEK inhibition were highly invasive and aggressive. This aggressive phenotype was driven through a cell surface receptor called EphA2, and this became upregulated in both melanoma cell cultures and in patient tumors following BRAF inhibitor treatment. As this suggested that the resistant cells would be more metastatic, we then performed animal experiments and analyzed tumors from melanoma patients receiving BRAF inhibitor. These studies showed an increase in EphA2 expression in the metastatic tumors that was lacking in the primary tumors. When we looked at cohorts of melanoma patients who received either a BRAF inhibitor or an older chemotherapy drug, we found that more of the BRAF inhibitor treated patients seemed to develop disease at new sites. Together this suggested that BRAF inhibition may switch the cancer cells to being more metastatic.
Author Interviews, Brigham & Women's - Harvard, Heart Disease / 14.01.2015

MedicalResearch.com Interview with: Paula Chu Doctoral candidate Harvard University's Health Policy Program Boston MA Medical Research: What is the background for this study? What are the main findings? Response: This study was borne out of a mutual interest in the effects of yoga and wellness in general between myself and my coauthors. ​We had heard and read about yoga's effects on certain conditions like anxiety and pain, and we wanted to see if there was scientific evidence on yoga's impact on measurable physiological cardiovascular ​outcomes.
Author Interviews, Duke / 14.01.2015

Nenad Bursac PhD Rooney Family Associate Professor of Biomedical Engineering Associate Professor of Medicine Duke UniversityMedicalResearch.com Interview with: Nenad Bursac PhD Rooney Family Associate Professor of Biomedical Engineering Associate Professor of Medicine Duke University     Medical Research: What is the background for this study? What are the main findings? Dr. Bursac: Researchers have tried for a long time to coax human muscle cells (obtained from needle biopsies) into contracting muscle fibers in a dish in order to be able to study human muscle physiology ex vivo. We are the first group that succeeded by carefully optimizing culture conditions including methods to expand and then culture cells in three-dimensional hydrogel matrices under passive tension. By doing so, we made first human muscle model that in response to electrical stimulation generates classical muscle contractile responses (twitch and tetanus). We have also shown that these engineered muscles (that we call "myobundles") contract in response to acetylcholine as it naturally happens when neurons in our body activate muscle. We demonstrated reproducibility and robustness of the approach by generating functional myobundles with similar properties from 10 independent donor muscle samples. We further went to show that myobundles have intact signaling characteristic of native muscle and respond to diverse set of drugs as human muscles do in clinics.
Author Interviews, Cognitive Issues, PNAS / 14.01.2015

Dr Christos Pliatsikas PhD Lecturer in Cognitive Psychology School of Psychology University of Kent Canterbury KentMedicalResearch.com Interview with: Dr Christos Pliatsikas PhD Lecturer in Cognitive Psychology School of Psychology University of Kent Canterbury Kent Medical Research: What is the background for this study? What are the main findings? Response: It has been proposed that lifelong bilingualism preserves the white matter structure of older bilinguals because of the increased cognitive demands that come with handling two languages for their entire life. We wanted to extend this by investigating whether active (or "immersive") bilingualism in younger late bilinguals would give similar results. We showed increased white matter integrity (or myelination) in several white matter tracts that have also been shown to be better preserved in older lifelong bilinguals, compared to monolinguals.  Based on our findings, we propose that any benefit of bilingualism to the brain structure is simply an effect of actively handling two languages without presupposing lifelong usage- our participants were only about 30 years old and had been active bilinguals for only about 7-8 years. In other words, immersive bilingualism, even in late bilinguals, leads to structural changes that can bring about benefits in older age, by assisting in the preservation of the white matter structure in the brain.