Author Interviews, Diabetes, Neurological Disorders / 06.03.2015

Dr. John A Kessler MD The Ken and Ruth Davee Professor of Stem Cell Biology Department of Neurology Professor, Department of Pharmacology Northwestern University Feinberg School of MedicineMedicalResearch.com Interview with: Dr. John A Kessler MD The Ken and Ruth Davee Professor of Stem Cell Biology Department of Neurology Professor, Department of Pharmacology Northwestern University Feinberg School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Kessler: Painful diabetic neuropathy afflicts millions of patients. It interferes with sleep and many daily activities of living, and predisposes to depression. There is a loss of sensation in the legs which predisposes to foot/leg ulcers which may lead to amputation. The only currently available treatments, other than controlling glucose levels, are drugs including gabapentin, pregabalin, or antidepressants which have major side effects and which help only some patients. These are medications which must be taken daily or several times daily and are often poorly tolerated by patients. This study examined the effects of a nonviral gene therapy approach for using hepatocyte growth factor (HGF) to treat patients with painful diabetic neuropathy. HGF helps to support the health of neurons and it also helps to grow new blood vessels to support nerve function. Patients received two sets of treatments (injections) and were then followed for 9 months.  The treatment was exceptionally well tolerated -  literally without significant side effects. The patients had highly significant reductions in pain and improvement in the quality of life, and their ability to sense gentle pressure (touch) was improved. The benefits lasted months without additional treatment.
AHA Journals, Author Interviews, Exercise - Fitness, Weight Research / 05.03.2015

MedicalResearch.com Interview with Christopher C. Imes, PhD, RN Assistant Professor, Acute and Tertiary Care University of Pittsburgh, School of Nursing MedicalResearch: What is the background for this study? Dr. Imes: Increased physical activity (PA) with reduced energy intake is the key strategy to achieve weight loss. However, in research, there are challenges to obtaining accurate PA data. Many studies rely on self-report, which is easily accessible and inexpensive but is known to have numerous limitations. Pedometers are a relatively inexpensive and accessible method to objectively measure certain aspects of physical activity. The purpose of this analysis was to examine the associations between self-reported physical activity, pedometer step count data and weight loss during the first 6-months of the Self-Efficacy Lifestyle Focus (SELF) trial. All participants in this trial were instructed to reduce their calorie and fat intake, were encouraged to engage in at least 150 minutes of moderately intense PA/week or 7500 steps/day, and to self-monitor their diet and physical activity. MedicalResearch: What are the main findings? Dr. Imes: Change in self-reported physical activity from baseline to 6 months was not associated with weight change. However, average daily step count, derived from pedometers given to participants during the same time period, was associated with weight loss. More daily steps results in more weight loss. The participants who averaged over 7500 steps/day lost about 9.5% of their initial body weight; whereas, the participants who averaged less than 5000 steps/day only lost about 5.0%.
Author Interviews, Prostate Cancer / 05.03.2015

M. Minhaj Siddiqui, MD Director of Urologic Robotic Surgery Assistant Professor of Surgery - Urology University of Maryland School of Medicine Baltimore MD 21201MedicalResearch.com Interview with: M. Minhaj Siddiqui, MD Director of Urologic Robotic Surgery Assistant Professor of Surgery - Urology University of Maryland School of Medicine Baltimore MD 21201 Medical Research: What is the background for this study? Response: A history of testicular cancer has been suggested to have an association with an increased risk of developing prostate cancer (PCa) in epidemiologic studies. We hypothesized that there may be an increased risk of developing intermediate to high-risk prostate cancer as well. Medical Research: What are the main findings? Response: 147,044 men with melanoma and 32,435 men with testicular cancer were identified. Prostate cancer was diagnosed in 3,205 men in total. The cumulative incidence of all prostate cancer by age 80 was 2.8% in the control melanoma cohort and 12.6% in the case cohort of men with history of testicular cancer (p<0.0001 for KM survival curves, Figure 1). For intermediate/high-risk disease, the incidence was 1.1% versus 5.8% for each cohort respectively (p<0.0001 for KM survival curves, Figure 2). No association with prostate cancer was seen with non-seminomatous versus seminomatous germ cell tumors. Upon multivariate analysis, testis cancer was associated with an increased risk of all prostate cancer (HR 4.7, p<0.0001) and intermediate/high-risk PCa (HR 5.2, p<0.0001) when controlling for race and radiation history.
Author Interviews, Exercise - Fitness, Heart Disease / 05.03.2015

Prof. Scott Montgomery Prof. Montgomery is a clinical epidemiologist, conducting research in life-course influences on chronic disease risk Örebro UniveristyMedicalResearch.com Interview with: Prof. Scott Montgomery Prof. Montgomery is a clinical epidemiologist, conducting research in life-course influences on chronic disease risk Örebro Univeristy Medical Research: What is the background for this study? What are the main findings? Prof. Montgomery: Stress is thought to increase the risk of heart disease. However, an experience that is stressful for one person may not be so for another, as stress resilience varies. As we believe that stress resilience is influenced by childhood experiences, we examined whether teenagers with low stress resilience were more likely to have coronary heart disease in subsequent adulthood (they were followed to a maximum age of 58 years). In this study of 237,980 men, we found that low stress resilience in adolescence was associated with a raised risk of heart disease. A surprising result was that although higher levels of fitness in adolescence were associated with lower heart disease risk, the benefit of such fitness, in terms of heart disease risk, was not present in the men with low stress resilience.
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA, Personalized Medicine / 05.03.2015

Dr. Michaela A. Dinan Ph.D Department of Medicine Duke UniversityMedicalResearch.com Interview with: Dr. Michaela A. Dinan Ph.D Department of Medicine Duke University Medical Research: What is the background for this study? What are the main findings? Dr. Dinan: We wanted to examine how  Oncotype DX® Breast Cancer Test (ODX) was being used in real-world practice at the population level. ODX has been examined in clinical trials and limited academic settings but we know that these patients are often younger, have fewer medical comorbidities, and do not necessarily accurately reflect the majority patients with cancer.  In our study, we observed that Oncotype DX® Breast Cancer Test was being used predominately in accordance with guidelines which recommend the test for women with estrogen-receptor positive, disease. We also looked just at women under the age of 70 who met guideline criteria for testing, because this population would include those women who were more likely to be chemotherapy candidates, and we saw a rapid uptake of the test between 2005 and 2009, with use of the test increasing from 8% to 39%.
AHA Journals, Author Interviews, Brigham & Women's - Harvard, Heart Disease, Nutrition / 05.03.2015

Luc Djousse, MD, ScD, FAHA Associate Professor of Medicine, Harvard Medical School Editor-in-Chief, Current Nutrition Reports Director of Research, Division of Aging Brigham and Women's Hospital Boston, MA 02120MedicalResearch.com Interview with: Luc Djousse, MD, ScD, FAHA Associate Professor of Medicine, Harvard Medical School Editor-in-Chief, Current Nutrition Reports Director of Research, Division of Aging Brigham and Women's Hospital Boston, MA 02120 MedicalResearch: What is the background for this study? What are the main findings? Dr. Djousse: While some studies have reported a higher risk of coronary heart disease, diabetes, or high blood pressure with frequent consumption of fried foods, other investigators did not confirm those results. To date, only few studies have evaluated whether frequent consumption of fried foods can raise the risk of developing heart failure. Frying foods not only increases the energy density of foods, but also increase the amount of trans fats. Trans fats can lead to development of heart disease and diabetes and consumption of energy-dense foods in large quantity can lead to weight gain and resulting cardiovascular consequences. We followed about 15000 US male physicians who were free of heart failure for an average of 10 years and found that frequent consumption of fried foods was related to a higher risk of developing heart failure. For example, people that consumed fried foods daily or more were twice more likely to develop heart failure than individuals who consumed fried foods less than once per week.
Author Interviews, Endocrinology, JAMA, Thyroid Disease / 05.03.2015

Sebastiano Filetti MD Dipartimento di Medicina Interna Università di Roma RomaMedicalResearch.com Interview with; Sebastiano Filetti MD Dipartimento di Medicina Interna Università di Roma Roma MedicalResearch: What is the background for this study? What are the main findings? Dr. Filetti: Thyroid nodule diagnosis is becoming more and more frequent in clinical practice. This trend stems largely from the incidental discovery of small nodules due to the increased use of diagnostic imaging for purposes unrelated to the thyroid. Ultrasound studies, for example, are widely used for evaluating other structures in the neck, such as the carotid arteries, parathyroid glands, lymph nodes, and salivary glands. Over 90% of detected thyroid nodules are clinically insignificant, in that they have been cytologically proven to be benign or they have no ultrasound features that raise the suspicion of malignancy. However, consensus is lacking regarding the best way to follow these nodules, mainly because little is known about the actual frequency and magnitude of their growth. The results of our study suggest that most benign nodules exhibit no significant size changes over time, and some actually decrease in size. Only a small subgroup of nodules can be expected to grow, about 15% in our series. However, the growth is slow and limited in magnitude. Most important, the occurrence of cancer is very rare in nodules like this, that appear to be benign.
AHA Journals, Author Interviews, Heart Disease, Wake Forest / 05.03.2015

Simon A. Mahler MD, MS, FACEP Associate Professor Department of Emergency Medicine Wake Forest School of Medicine Winston-Salem NC 27157MedicalResearch.com Interview with: Simon A. Mahler MD, MS, FACEP Associate Professor Department of Emergency Medicine Wake Forest School of Medicine Winston-Salem NC 27157 Medical Research: What is the background for this study? Dr. Mahler: Care patterns for patients with acute chest pain are inefficient. Most patients presenting to US Emergency Departments (ED) with chest pain, including those at low-risk for acute coronary syndrome (ACS), are hospitalized for comprehensive cardiac testing. These evaluations cost the US health system $10-13 billion annually, but have a diagnostic yield for ACS of <10%. American College of Cardiology/ American Heart Association (ACC/AHA) guidelines recommend that low-risk patients with acute chest pain should receive serial cardiac markers followed by objective cardiac testing (stress testing or cardiac imaging). However, guideline adherent care among low-risk patients fails to accurately focus health system resources on those likely to benefit. Among low-risk patients, who have acute coronary syndrome rates less than 2%, objective cardiac testing  is associated with a substantial number of false positive and non-diagnostic tests, which often lead to invasive testing. Consensus is building within the US health care system regarding the need to more efficiently evaluate patients with acute chest pain. Medical Research: What are the main findings? Dr. Mahler: Patients randomized to the HEART Pathway were less likely to receive stress testing or angiography within 30 days than patients in the usual care arm (an absolute reduction of 12%. P=0.048). Early discharge (discharges from the ED without stress testing or angiography) occurred in 39.7% of patients in the HEART Pathway arm compared to 18.4%: an absolute increase of 21.3% (p<0.001). Patients in the HEART Pathway group had a median LOS of 9.9 hours compared to 21.9 hours in the usual care group: a median reduction in LOS of 12 hours (p=0.013). These reductions in utilization outcomes were accomplished without missing adverse cardiac events or increasing cardiac-related ED visits or non-index hospitalizations. The HEART Pathway, which combines the HEART score, with 0- and 3-hour cardiac troponin tests, is an accelerated diagnostic protocol (ADP), which may improve the value of chest pain care by identify patients who can safely be discharged from the ED without stress testing or angiography. Observational studies have demonstrated that the HEART Pathway can classify >20% of patients with acute chest pain for early discharge while maintaining a negative predictive value (NPV) for major adverse cardiac event (MACE) rate of greater than 99% at 30 days. However, prior to this study the real-time use of the HEART Pathway had never been compared with usual care. Therefore, we designed a randomized controlled trial to evaluate the efficacy of the HEART Pathway to guide providers’ testing and disposition decisions for patients with acute chest pain. The hypothesis was that the HEART Pathway would meaningfully reduce objective cardiac testing, increase early discharges, and reduce index hospital length of stay compared to usual care while maintaining high sensitivity and NPV (>99%) for MACE.
Author Interviews, Compliance, Technology / 05.03.2015

MedicalResearch.com Interview with: Avinash Pandey, the study author, is a high school student who conducted this study under the guidance of his mentor, Niteesh K. Choudhry., M.D., Ph.D., executive director of the Center for Healthcare Delivery Sciences, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. Medical Research: What is the background for this study? What are the main findings? Response: Numerous studies have demonstrated that there is poor adherence to medications in cardiac patients (coronary artery disease patients, CAD). Despite the fact that non-adherence to these medications can have serious consequences on long-term health like disease progression, increased risk of cardiac events and premature mortality, many patients consistently miss their medications and many stop their medications only months after they are prescribed. This non-compliance leads to high costs for the health care system and more potentially preventable cardiac events. Studies suggest, that for the vast majority of patients, non-adherence to medications is not intentional. A significant portion simply forget to take their medications. Although many systems are available today to reduce medication non-adherence, like pill boxes and blisterpacks, these have demonstrated limited effect on medication adherence. Other systems may be expensive to purchase and cumbersome to use or of limited availability. With the proliferation of cellphones, text message reminders could represent a simple, cost-effective method to improve adherence to medications. This research began as a high school science fair project 4 years ago and has evolved into a large ongoing assessment of the impact of mobile technologies on adherence to evidence based therapies and lifestyle interventions in a broad cross-section of cardiovascular patients and those at risk for cardiovascular disease. The current report examines the impact of an automated computer program which sends free, personalized text messages to remind patients to adhere to their medications. 30 CAD patients were recruited from a single centre cardiac practice, in this 2 month cross-over study. Patients were randomized to either receive text message reminders in the first month or the second month. Adherence of each patient was compared between months. Text message reminders were shown to significantly impact medication adherence. Patients missed on average 60% less doses when receiving text message reminders. These numbers were even greater when looking at pre-specified groups identified in previous studies to be at high risk of medication non-adherence, including depression patients, dementia patients, elderly patients, and patients with less than 12 years of education. All patients improved with text message reminders but those with the lowest adherence improved the most. Although this study did not examine clinical outcomes, the text message reminder system appears to be a simple and widely applicable method to improve adherence to medications. The system is free to operate and represents no cost for patients receiving messages. Thus it could be implemented at an individual level or by physicians and clinics to improve patient adherence to medications.
Author Interviews, Outcomes & Safety, Surgical Research / 05.03.2015

E. Patchen Dellinger, M.D. Professor of Surgery University of Washington, Box 356410 Seattle, Washington MedicalResearch.com Interview with: E. Patchen Dellinger, M.D. Professor of Surgery University of Washington Seattle, Washington Medical Research: What is the background for this study? What are the main findings? Dr. Dellinger: We know from previous large studies that use of checklists is associated with improvements in patient morbidity and mortality. However, recent large studies have also shown that mandating teams to use the checklist without providing the support required for adequate implementation does not result in better outcomes. This report reviews findings from studies examining checklist compliance and use. We found that when compliance with the checklist is poor it is not as effective as when the checklist is carried out as it is intended. Checklist use appears to be a marker for institutional culture of safety, and organizations with a more robust safety culture may be more likely to use the checklist in an effective manner with resulting improvements in patient safety.
Author Interviews, CDC, HIV, Race/Ethnic Diversity, Sexual Health / 05.03.2015

MedicalResearch.com Interview with: Cyprian Wejnert Center For Disease Control MedicalResearch: What is the background for this study? What are the main findings? Cyprian Wejnert: Men who have sex with men (MSM) remain the risk group most severely affected by HIV in the United States, accounting for approximately two-thirds of new infections each year.  Understanding racial and age disparities among MSM is critical to tailor effective prevention efforts. Our study examined data from CDC’s National HIV Behavioral Surveillance system (NHBS) from 20 U.S. cities. We assessed changes in HIV prevalence, awareness of infection, and risk behavior among MSM, by age and race, from 2008 to 2011, finding that: o   Among black Men who have sex with men, 30 percent were HIV-infected overall, and 1 in 5 black MSM aged 18-24 were infected with HIV. Compared to 14 percent and 4 percent among white MSM. o   In all age groups younger than 40 years, black Men who have sex with men were significantly more likely to be HIV-positive compared to all other racial/ethnic groups. o   Disparities in HIV prevalence between black and white MSM were greatest among the youngest MSM, and increased between 2008 and 2011. o   Black MSM were less likely to be aware of their infection than their white counterparts (54 vs. 86 percent). o   Black Men who have sex with men did not report higher levels of condomless sex overall or condomless sex with partners of discordant or unknown HIV status.
Author Interviews, CDC, Gender Differences, HIV, Race/Ethnic Diversity / 05.03.2015

MedicalResearch.com Interview with: Dr. Ndidi Nwangwu-Ike Center Disease Control MedicalResearch: What is the background for this study? What are the main findings? Response: CDC data has shown encouraging signs of a decrease in new HIV infections among black women in recent years.  However, African American women continue to be far more affected by HIV than women of any other race or ethnicity, with a rate of new infection 20 times that of white women and nearly five times that of Hispanic women.  Ensuring people with HIV are diagnosed and remain in care is key to controlling HIV in the nation. When used consistently, antiretroviral medication can keep HIV controlled at very low levels in the body (known as viral suppression), allowing people with HIV to live longer, healthier lives and reducing the likelihood they will transmit HIV to others. Our study finds that viral suppression among women diagnosed with HIV is low, with young women and black women the least likely to achieve viral suppression. Specifically, we found that: o   Of women newly diagnosed with HIV in 2012, 83 percent were linked to care within three months of diagnosis. o   Retention in care varied by age and race/ethnicity; overall, just over half of women (52 percent) diagnosed and living with HIV in 2011 received ongoing HIV care. o   Overall, only 44 percent of women diagnosed and living with HIV in 2011 had a suppressed viral load.
Author Interviews, BMJ / 05.03.2015

Minna Johansson, PhD student Department of Public Health and Community Medicine, Institute of Medicine The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Research Unit and Section for General Practice, Vänersborg, Sweden MedicalResearch.com Interview with: Minna Johansson, PhD student Department of Public Health and Community Medicine, Institute of Medicine The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Research Unit and Section for General Practice, Vänersborg, Sweden Medical Research: What is the background for this study? What are the main findings? Response: The decision to introduce screening for abdominal aortic aneurysms (AAA) was based on four randomised controlled trials from the 1980s and 1990s that showed a 50% relative risk reduction in aneurysm-related mortality. Over the last 15 years Sweden, the UK and the USA have introduced AAA screening programmes. However, abdominal aortic aneurysms screening does not only have intended benefits but also unintended harms. The most important harm is overdiganosis; i.e. the overdetection of aneurysms that would not have caused symptoms in that man´s remaining life, nor been the cause of his death. In this study, we estimate that 176 of every 10,000 men invited to screening are overdiagnosed as a consequence of screening. These men are unnecessarily turned into patients and may experience appreciable anxiety throughout their remaining lives. Moreover, 37 of these men unnecessarily have preventive surgery and 1.6 of them die as a consequence. Furthermore, a recent drop in abdominal aortic aneurysms prevalence by over 70% reduces the potential benefits of AAA screening. Unfortunately, the harms are not likely to be reduced by the same rate, thus leading to a worsened benefit:harm ratio. This means that the benefit:harm ratio is likely to be worse in current screening programmes than in the trials on which they were based. Additionally, it has been proposed to lower the cut-off for the abdominal aortic aneurysms-diagnosis from 30 to 25 mm. Our estimates show that such a change of definition would increase the rate of overdiganosis substantially and further worsen the benefit:harm ratio of abdominal aortic aneurysms screening.
Author Interviews, HPV, Lancet, Vaccine Studies / 05.03.2015

MedicalResearch.com Interview with: Marc Brisson Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease Associate Professor, Université LavalMedicalResearch.com Interview with: Marc Brisson Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease Associate Professor, Université Laval Medical Research: What is the background for this study? What are the main findings? Response: Since 2007, 52 countries have implemented human papillomavirus vaccination (HPV) programmes. Two HPV vaccines are currently available worldwide: the bivalent vaccine, which targets HPV types 16 and 18, causing 70-80% of cervical cancer, and the quadrivalent vaccine, which also targets HPV types 6 and 11, associated with 85-95% of anogenital wart cases. Large international randomised controlled clinical trials have shown both vaccines to be safe, well tolerated and highly efficacious against vaccine-type persistent infections and precancerous cervical lesions.  Furthermore, both vaccines have shown some level of cross-protection against 3 HPV types (HPV 31, 33 and 45) not included in the vaccine and associated with a supplementary 10-15% of cervical cancers worldwide. Now that 7 years have elapsed since the implementation of the first HPV vaccination program, we verified whether the promising results from clinical trials are materialising at the population level. We conducted a meta-analysis to examine the population-level impact in countries that have introduced HPV vaccination programs. In countries with high female vaccination coverage (<50%), our main findings indicate:
  • sharp declines in HPV-related outcomes among females targeted for vaccination (e.g., HPV-16/18 infection and anogenital warts declined by more than 60% in females younger than 20 years), and
  • evidence of cross-protection with significant reductions in HPV-31/33/45 infection among females younger than 20 years
  • evidence of herd effects (indirect benefit of vaccination among unvaccinated individuals) with significant reductions in anogenital warts among males and older females.
In countries with low coverage (<50%), we report:
  • significant reductions in HPV-16/18 infection and anogenital warts among young females, with no indication of herd effects or cross-protection.
Allergies, Author Interviews, Microbiome, Pediatrics / 04.03.2015

Anita Kozyrskyj Ph.D Professor, Department of Pediatrics University of AlbertaMedicalResearch.com Interview with: Anita Kozyrskyj Ph.D Professor, Department of Pediatrics University of Alberta Medical Research: What is the background for this study? What are the main findings? Prof. Kozyrskyj: Our study determined what "good" gut bacteria were present in 166 full-term infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Funded by CIHR and AllerGen NCE, this landmark study involves more than 3,500 families and their newborn infants across Canada. Gut bacteria were identified by DNA sequences extracted from infant poop. Infants with a fewer number of different bacteria in their gut at 3 months of age were more likely to become sensitized to foods such as milk, egg or peanut, by the time they were 1 years old. Infants who developed food sensitization also had altered levels of two specific types of bacteria, Enterobacteriaceae and Bacteroidaceae, compared to infants who didn’t.
Author Interviews, Breast Cancer, Chemotherapy, Cleveland Clinic, NEJM / 04.03.2015

Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195MedicalResearch.com Interview with: Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195 Medical Research: What is the background for this study? What are the main findings? Dr. Moore: Ovarian failure is a common long-term side effect of chemotherapy. Previous studies investigating whether suppressing ovarian function during chemotherapy treatment will preserve ovarian function following chemotherapy have had mixed results. Our study found that suppressing the ovaries with the GnRH analog goserelin during chemotherapy treatment for early stage ER-negative breast cancer resulted in a reduced risk of ovarian failure two years after initiation of treatment. Also, more women who received the goserelin with chemotherapy became pregnant than women who received chemotherapy without goserelin. In addition, there was an apparent improvement in survival among the goserelin group, confirming the safety of this approach in this patient population.
Author Interviews, Heart Disease / 04.03.2015

MedicalResearch.com Interview with: Joo-Yong Hahn, MD, PhD Associate Professor Heart Vascular Stroke Institute, Samsung Medical Center Sungkyunkwan University School of Medicine Medical Research: What is the background for this study? What are the main findings? Response: In the Effects of Postconditioning on Myocardial Reperfusion in Patients with ST-segment Elevation Myocardial Infarction (POST) trial, ischemic postconditioning failed to improve myocardial reperfusion (Hahn JY et al. Circulation 2013;128:1889-96) . However, long-term effects of ischemic postconditioning on clinical outcomes are not known in patients with ST-segment elevation myocardial infarction (STEMI). Therefore, the aim of this study was to investigate the long-term effects of ischemic postconditioning on clinical outcomes. In this prospective, randomized trial, ischemic postconditioning with primary percutaneous coronary intervention  (PCI) did not improve clinical outcomes compared with conventional primary PCI in patients with STEMI. There was no significant difference in a composite of death, myocardial infarction, severe heart failure, or stent thrombosis between the 2 groups. Beneficial effects of ischemic postconditioning were not found in any of various subgroups.
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 04.03.2015

MedicalResearch.com Interview with: Dr. Lucia Del Mastro MD Department of Medical Oncology Istituto Nazionale per la Ricerca sul Cancro Genova, Italy Medical Research: What is the background for this study? What are the main findings? Response: Adjuvant chemotherapy regimens with anthracyclines and taxanes improve the outcome of patients with early breast cancer. Among the most widely used anthracycline-based chemotherapy in sequential combinations with the taxane paclitaxel (P) there are epirubicin and cyclophosphamide (EC) and fluorouracil, epirubicin, and cyclophosphamide (FEC). The contribution of fluorouracil to the anthracycline-cyclophosphamide regimen (EC) was unclear until now. Various randomized trials attempted to assess the role of a more intense schedule of chemotherapy (i.e. dose-dense chemotherapy with cycles administered every 2 weeks instead of every 3 weeks) in patients with early breast cancer. However, most of these trials compared dose-dense chemotherapy with regimens that use standard intervals but with different drugs or dose in the treatment groups, thus making difficult to extrapolate the true role of the dose-dense strategy. The results of GIM2 study show that the addition of fluorouracil to  a sequential regimen with epirubicin, cyclophosphamide and paclitaxel increases the toxicity, in terms of neutropenia, fever, nausea, and vomiting, and is not associated with an improved outcome compared with the same treatment without fluorouracil.
Author Interviews, Mental Health Research, Pediatrics, University of Pennsylvania / 04.03.2015

Courtney Benjamin Wolk, Ph.D. Postdoctoral Researcher Center for Mental Health Policy and Services Research Perelman School of Medicine Department of Psychiatry University of Pennsylvania Philadelphia, PA 19104MedicalResearch.com Interview with: Courtney Benjamin Wolk, Ph.D. Postdoctoral Researcher Center for Mental Health Policy and Services Research Perelman School of Medicine Department of Psychiatry University of Pennsylvania Philadelphia, PA 19104 Medical Research: What is the background for this study? What are the main findings? Response: Previous research investigating the relationship between anxiety and suicidality has been mixed. An ongoing question in the field has been whether anxiety disorders independently increase risk for suicidal ideation and behavior or if the high co-occurrence of anxiety and mood symptoms or other shared demographic factors are driving relationships that have been observed between anxiety and suicidality. We examined the relationship between response to treatment for an anxiety disorder in childhood and suicidal ideation, plans, and attempts 7 to 19 years after treatment with cognitive-behavioral therapy, more commonly referred to as CBT. Our results indicated that participants who responded favorably to cognitive-behavioral therapy during childhood had lower rates of lifetime, past month, and past two-week suicidal ideation endorsement than treatment non-responders. This was the case across both self-report and interview-report of suicidal ideation. Treatment response was not significantly associated with suicide plans or attempts, though plans and attempts were infrequently endorsed in our sample, limiting the ability to detect findings.
Author Interviews, Genetic Research, Nature / 04.03.2015

Fernando Pardo-Manuel De Villena, PhD Professor and Associate Chair for Research Department of Genetics School of Medicine University of North Carolina at Chapel HMedicalResearch.com Interview with: Fernando Pardo-Manuel De Villena, PhD Professor and Associate Chair for Research Department of Genetics School of Medicine University of North Carolina at Chapel Hill Medical Research: What is the background for this study? What are the main findings? Response: We set out to identify mutations that affect diseases through changes in gene expression. Our first major finding is that some mouse populations such as the Collabaorative Cross are exceptionally good models to achieve this goal. We also wanted to sort out an ongoing controversy about the number, location and type of genes that are differentially expressed when you inherit them from your mom or your dad (so called imprinted genes).  We conclude that to some extent both sides were right; there are only a limited number of imprinted genes in the classical sense but there are also hundreds or thousands of genes that are preferentially expressed from the father.
Author Interviews, Cancer Research, MD Anderson, PNAS / 04.03.2015

MedicalResearch.com Interview with: Kristen Turner PhD. (first author) and Wei Zhang, Ph.D. Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas 77030 Medical Research: What is the background for this study? What are the main findings? Response: Glioblastoma (GBM) is the most commonly diagnosed type of brain tumor and is among the most aggressive and challenging cancer types to treat. The traditional approaches to combat this pervasive cancer include surgery combined with radiation and chemotherapy (temozolomide); yet, most will succumb to the disease in just over one year. In this study, we investigated the Akt family of proteins that are known to be highly active in the majority of Glioblastoma cases. We compared each Akt family member and its ability to initiate glioma progression. We discovered that activation of the third Akt member (Akt3) led to glioma progression and very aggressive tumors. We then studied these tumors to compare their molecular attributes and found evidence of increased DNA repair. Finally, we discovered that the Akt3-induced DNA repair function led to increased survival of Glioblastoma cells after treatment with the DNA damaging agents, radiation and temozolomide.
Author Interviews, Neurological Disorders / 04.03.2015

MedicalResearch.com Interview with: Dr. Richard H. Myers Ph.D. Department of Neurology and Genome Science Institute Boston University School of Medicine, Boston, MAMedicalResearch.com Interview with: Dr. Richard H. Myers Ph.D. Department of Neurology and Genome Science Institute Boston University School of Medicine, Boston, MA MedicalResearch: What is the background for this study? What are the main findings? Dr. Myers:  Andy Hoss, who is a graduate student in my group is the primary investigator for this project. We are investigating changes that occur in the brain of individuals who had Huntington's disease. We were focused on studying regulatory mechanisms that control the levels of messenger RNAs (mRNAs) in the brain, since that is an area that has been implicated in this disease. MicroRNAs (miRNAs) are known to target mRNAs for degradation or to be sequestered for storage and later use. A few limited studies of microRNAs had been done, but we sought to measure the levels of all of the  miRNAs  present in the brains of persons with Huntington's disease and in controls using next-generation sequencing.
Author Interviews, Cost of Health Care, Health Care Systems / 04.03.2015

MedicalResearch.com Interview with: Sophie Coronini-Cronberg Honorary research Fellow Department of Primary Care and Public Health, Imperial College London Consultant in public health Centre Medical Directorate with Bupa, United Kingdom. Medical Research: What is the background for this study? What are the main findings? Dr. Coronini-Cronberg: From April 2011, England’s National Health Service (NHS) was challenged to find £20 billion of efficiency savings over four years, in part by reducing the use of ineffective, overused or inappropriate procedures. However, there was no clear instruction as to which procedures are of 'limited clinical value' and also under which circumstances they should be reduced. We looked at hospital admissions statistics for six procedures that appear on local and/or unofficial lists to see which had been affected and whether cuts were applied consistently across commissioners in the first year of the savings programme. We found a significant drop in three procedures considered potentially ‘low value’ compared to the underlying time trend: removal of cataracts, hysterectomy for heavy menstrual bleeding, and myringotomy to relieve eardrum pressure. There was no significant change in three other ‘low-value’ procedures: spinal surgery for lower back pain, inguinal hernia repair, and primary hip replacement, or in two ‘benchmark’ procedures (coronary revascularisation, gall bladder removal). Myringotomy, a procedure to relieve pressure in the ear which is considered relatively ineffective, declined by 11.4 per cent overall. Two procedures considered only effective in certain circumstances also fell overall. Hysterectomy for heavy menstrual bleeding declined by 10.7 per cent overall, and cataract removal declined by 4.8 per cent.ý ýWe also found the reductions were inconsistently applied by commissioning groups (so-called Primary Care Trusts).
Author Interviews, HIV, Nature, Scripps / 04.03.2015

Dr. Michael Farzan PhD Vice Chairman Department of Immunology and Microbial Science Florida Campus The Scripps Research InstituteMedicalResearch.com Interview with: Dr. Michael Farzan PhD Vice Chairman Department of Immunology and Microbial Science Florida Campus The Scripps Research Institute Medical Research: What is the background for this study? Dr. Farzan: The key points are that HIV-1 needs two receptors – CD4 and CCR5 – to infect cells.  CD4’s primary job is to initially bind the viral entry protein, which upon CD4 binding, uncloaks its CCR5 binding site.   A number of years ago we observed that CCR5 had an unusual modification that was really important to HIV-1.  We later showed that antibodies – protein your body makes to protect from pathogens – mimics CCR5 by incorporating this modification.  We develop a peptide from one of these antibodies that mimics CCR5. Medical Research: What are the main findings? Dr. Farzan: By combined a soluble form of CD4 with this CCR5-mimicking peptide, we created a protein that neutralizes all HIV-1 isolates tested, including the hardest-to-stop viruses, as well as distantly related viruses found in monkeys.  It does so better than the best HIV-1 antibodies.  We expressed this protein using a commonly used gene-therapy vector, and showed that after a one-time inoculation we could protect from doses much higher than most humans are likely to see, and we did so 34 weeks after the inoculation.
Genetic Research, MD Anderson, Melanoma, Personalized Medicine / 04.03.2015

Linda Chin, MD Department Chair, Department of Genomic Medicine, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TXMedicalResearch.com Interview with: Linda Chin, MD Department Chair, Department of Genomic Medicine, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Chin: BRAF inhibitors have worked very well against melanoma in the clinic, but when the tumors relapse on treatment, it is not always clear what causes it. Without this information, it can be difficult for doctors to identify specific second-line therapies likely to overcome the drug resistance. In this study, we used both mouse and patient melanoma samples to identify patterns of selected protein levels that can categorize modes of drug resistance when other assays such as DNA sequencing are uninformative. We hope that this information can provide missing clues for clinicians.
Author Interviews, BMJ, End of Life Care, Heart Disease / 04.03.2015

MedicalResearch.com Interview with: Prof. Dr. med. Paul Erne AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute University of Zurich Department of Cardiology Clinic St. Anna, Lucerne and University Hospital Zurich Zurich, SwitzerlandProf. Dr. med. Paul Erne AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute University of Zurich Department of Cardiology Clinic St. Anna, Lucerne and University Hospital Zurich Zurich, Switzerland MedicalResearch: What is the background for this study? What are the main findings? Prof. Erne: Very little is known on this important subgroup of patients with Acute Coronary Syndrome (ACS) at admission who for various reasons receive restricted or palliative treatment only. Reasons for withholding comprehensive and/or invasive therapy may be the very limited life expectancy, advanced age or severe comorbidities. These patients are not represented in prospective trials and often not included in outcome statistics and registries. This study provides evidence that the population which received palliative therapy is older and sicker when compared to patients who underwent conservative or reperfusion treatment. However, this study shows that these decisions are very individually addressed. Acute Coronary Syndrome patients treated palliatively were older, sicker, with more heart failure at admission and very high in-hospital mortality. Changes of treatment decisions over time and the proportion of patients surviving 1 year suggest in part non homogenous and potentially questionable decision criteria. While refraining from more active therapy may be the most humane and appropriate approach in many patients, in others it represents under treatment.
Author Interviews, PNAS, Statins / 04.03.2015

Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester UKMedicalResearch.com Interview with: Professor Andrew W. Munro FRSC FSB Professor of Molecular Enzymology Manchester Institute of Biotechnology Faculty of Life Sciences University of Manchester Manchester UK MedicalResearch: What is the background for this study? What are the main findings? Dr. Munro: Statins are blockbuster drugs that inhibit the key enzyme in cholesterol synthesis: 3-beta-hydroxymethylglutaryl CoA reductase (HMG-CoA reductase), which catalyzes the rate-limiting step in the biosynthesis of cholesterol. As a consequence, statin drugs reduce levels of low-density lipoprotein (LDL-) cholesterol, are effective against hypercholesterolemia and reduce the risk of atherosclerosis and heart attack. One of the major statin drugs is pravastatin, which is derived from a fungal natural product called compactin. The process of conversion of compactin into pravastatin involves the use of an oxygen-inserting enzyme called a cytochrome P450 (or P450), which catalyzes the hydroxylation of compactin to form pravastatin. In order to produce a more cost-efficient and streamlined route to pravastatin production, our teams from the University of Manchester (UK) and DSM (Delft, The Netherlands) developed a single-step process for pravastatin production. This process involved harnessing the productive efficiency of an industrial strain of the beta-lactam (penicillin-type) antibiotic producing fungus Penicillium chrysogenum. The beta-lactam antibiotic genes were deleted from this organism, and replaced by those encoding for compactin biosynthesis (transferred from a different Penicillium species). This led to high level production of compactin, but also to substantial formation of a partially degraded (deacylated) form. To get around this problem and in order to further improve compactin production, the enzyme responsible for the deacylation (an esterase) was identified and the gene encoding this activity was deleted from the production strain. The final stages of development of the novel, one-step pravastatin production process involved the identification of a suitable P450 enzyme that could catalyze the required hydroxylation of compactin. A bacterial P450 was identified that catalyzed hydroxylation at the correct position on the compactin molecule. However, the stereoselectivity of the reaction was in favour of the incorrect isomer – forming predominantly epi-pravastatin over the desired pravastatin. This was addressed by mutagenesis of the P450 – ultimately leading to a variant (named P450Prava) that hydroxylated compactin with the required stereoselectivity to make pravastatin in large amounts. Determination of the structure of P450Prava in both the substrate-free and compactin-bound forms revealed the conformational changes that underpinned the conversion of the P450 enzyme to a pravastatin synthase. The expression of P450Prava in a compactin-producing strain of P. chrysogenum enabled pravastatin production at over 6 g/L in a fed-batch fermentation process, facilitating an efficient, single-step route to high yield generation of pravastatin.