Author Interviews, Cancer Research, Endocrinology, Journal Clinical Oncology, Menopause, NIH / 07.11.2015

MedicalResearch.com Interview with: Elizabeth K. Cahoon, PhD Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics, National Cancer Institute National Institutes of Health Department of Health and Human Services Bethesda, MD Medical Research: What is the background for this study? What are the main findings? Dr. Cahoon: Although basal cell carcinoma (BCC) is the most common cancer in the United States, there is relatively little research on risk factors since few population-based cancer registries do not capture information on this malignancy. Sun exposure (in particular ultraviolet radiation) is the primary risk factor for basal cell carcinoma, but less is known about other factors that may affect this risk. A previous study found a relationship between menopausal hormone therapy (MHT) use and increased risk of BCC in a population of Danish women. In our study we looked to see if factors related to estrogen exposure from multiple sources was associated with basal cell carcinoma risk in a large, nationwide, prospective study. These included use of oral contraceptives or menopausal hormone therapy, but also reproductive factors (like age at menarche and menopause). We observed that women who experienced natural menopause later in life were more likely to develop basal cell carcinoma compared to women who had natural menopause at a younger age. In addition, women who reported using menopausal hormone therapy for one year or longer were more likely to develop basal cell carcinoma compared to women who did not report MHT use. Women who reported natural menopause and menopausal hormone therapy use for 10 or more years had the highest risk of basal cell carcinoma, compared to women with no menopausal hormone therapy use. (more…)
Author Interviews, Genetic Research, Race/Ethnic Diversity, Weight Research / 06.11.2015

MedicalResearch.com Interview with: Joan C. Han, MD Director, Pediatric Obesity Program, Le Bonheur Children’s Hospital Associate Professor, Division of Pediatric Endocrinology Department of Pediatrics, University of Tennessee Health Science Center Memphis, TN 38103 Medical Research: What is the background for this study? What are the main findings? Dr. Han: Obesity has become a world-wide epidemic. Our research group studies the genetic factors that contribute to the development of obesity. Brain-derived neurotrophic factor (BDNF) is a protein that plays a key role in regulating appetite. We found that a common genetic variant of the BDNF gene is associated with lower expression of this gene in the hypothalamus, a region of the brain that controls energy balance. The mechanism of this reduced gene expression appears to be due to diminished binding of the transcription factor hnRNPD0B. We also observed that this genetic variant is associated with higher body mass index and higher body fat in children and adults. The obesity-predisposing variant of the BDNF gene occurs more commonly in people of African-American or Hispanic backgrounds, which could have important clinical implications given the higher rates of obesity in these populations. (more…)
Author Interviews, Infections, Pediatrics, Respiratory / 06.11.2015

MedicalResearch.com Interview with: Dominik Mertz, MD, MSc, FMH (CH) Assistant Professor, McMaster University Department of Medicine, Division of Infectious Diseases Associate Membership Department of Clinical Epidemiology and Biostatistics / Pathology and Molecular Medicine Medical Director Infection Prevention & Control, Hamilton Health Sciences Juravinski Hospital and Cancer Center Hamilton, ON, Canada  Medical Research: What is the background for this study? What are the main findings? Dr. Mertz: There was a perception that there was an increase in ICU admissions and deaths, initially in Kansas City and Chicago, which was found to be related to the enterovirus strain EV-D68, which had previously not resulted in any major outbreaks in North America. We have one of the first laboratories that was able to provide a specific EV-D68 PCR routine testing allowing us identify EV-D68 cases and to compare the outcomes in patients infected with this strain to children infected by other rhino/enteroviruses. We found a substantial overlap in how the patients presented between patients with EV-D68 and non-EV-D68 infection. It seems that children infected with EV-D68 were in deed at higher risk for having respiratory distress and needing hospital admission, with children with allergies being at a higher risk. We did not find an increase in more severe outcomes, though, i.e. no higher risk for ICU admission (23 vs 15%) and 0 deaths in the EV-D68 group. We also did not find any evidence of in-hospital transmission of EV-D68. (more…)
Author Interviews, Breast Cancer, Education, NYU, Radiology / 06.11.2015

MedicalResearch.com Interview with: Jiyon Lee, M.D. Assistant Professor of Radiology, NYU School of Medicine NYU Cancer Institute, Breast Imaging Center New York, New York 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Lee:   Even before the USPSTF changed their breast screening guidelines in 2009, I conducted community outreach to help educate others on my area of expertise, breast imaging and breast screening. I presented lay friendly, illustrated, and practical explanations in a structured talk, about the big picture and the salient details, in a way that I would want if I were not a breast radiologist. As is customary for such community outreach, we solicited feedback from attendees. It was gratifying to hear the positive responses. That they wished for such education for others served as a clarion call that is understandable. Education should be objective and noncoercive.  “Knowledge is power,” but only if complete and accurate. Breast cancer is still a common disease, we are all at least at average risk, and screening is still standard of care.  Much of the debate surrounding screening mammography centers on the age of onset of screening and the optimal screening interval. The USPSTF states that shared-decision making between women and their providers may occur, especially for women in 40-49 year group.  But the TF does not stipulate when or how or by whom this talk will ensue, and notice that their guidelines refer to film mammography, and “biennial” mammography. Since the time of this manuscript, the American Cancer Society issued new guidelines on 10/20/2015 that among its bullet points emphasized annual mammography for women 45-54 years and deemphasized clinical breast exam, while supporting option to start annually at age 40 with shared decision making to weigh what are referred to as “risks” and benefits. Although the fine print does reaffirm that annually starting at age 40 is the screening model that saves the most lives, the ACS is encouraging deliberate value judgment regarding “risks” and “harms.” Their fine print is also intimating that women 55 and over have nondense tissue and that their cancers are indolent. The ensued publicity and mixed messaging have caused another cycle of confusion regarding breast cancer screening. As the experts in this field of image-based screening, radiologists have opportunity to clarify and contextualize the issues and details of the screening discussion, and can do so with objectivity, respect for all sides of the debate, and compassion. All responsible ways to continually educate both women and all providers will enable both sides to engage in the discussion fairly. Because as we discourage paternalistic medicine and promote shared decision making, it’s not fair play if all responsible sides do not get fair say. Do realize that not all women see providers regularly, and depending on the medical subspeciality, not all providers are mentioning screening til women reach a certain age and may not relay importance of the physical exam components that complement imaging. This article specifically highlights how such direct and interactive public education can effect potential benefit in two ways.
  • First, directly reduce one of the core criticisms about screening: the “anxiety” that women may experience, which is heavily weighed as a “harm” of screening.  Most women do not experience high anxiety, and are glad to have a test that may help them. And education can help demystify much of the process and protocol, and explain up to what may be that patient’s next test results if she engages in screening at all. No one can tell that.
  • Two, education can directly increase one of the necessary components of shared decision making that is presumed in implementing breast screening: informing women. The pre- and post-lecture questionnaire, along with fact-based quiz questions, provided insight and enabled learning opportunity for the audience that are not usual for community outreach.  Education that keeps on going—and is shareable!-- after the lecture is done.
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Author Interviews, Melanoma, OBGYNE / 06.11.2015

MedicalResearch.com Interview with: Pedram Gerami, MD Department of Dermatology Northwestern University Chicago, IL Medical Research: What is the background for this study? What are the main findings?   Dr. Gerami: The influence of pregnancy on the prognosis of melanoma has been debated for decades. Even in the last ten years, population-based and cohort studies have given us mixed results, with some suggesting no adverse influence of pregnancy, and others reporting poorer outcomes and increased cause-specific mortality. The conflicting data leave many clinicians uncertain of how to advise patients to proceed with family planning after a diagnosis of melanoma. Since one-third of all new cases of melanoma diagnosed in women will occur during childbearing age, this represents a fairly common clinical dilemma for physicians and their patients. We suspected that the different results from different investigators maybe related to the melanoma stage of the patients being studied. We investigated the impact of pregnancy on tumor proliferation in women with primarily early stage melanoma. In comparing melanomas from a group of women with pregnancy-associated melanoma (PAM) and a non-PAM group, we found that women with pregnancy-associated melanoma  actually had a significantly greater proportion of in situ disease, and for cases of invasive melanoma there was no significant difference in proliferative activity, as assessed by mitotic count or two immunohistochemical markers of cell proliferation. In a comparison of additional prognostic features such as Breslow depth and ulceration, we found no significant differences between groups to suggest more aggressive tumor behavior in association with pregnancy. (more…)
Author Interviews, Nutrition, Sleep Disorders / 05.11.2015

MedicalResearch.com Interview with: Mike C Parent, Ph.D. Assistant Professor, Counseling Psychology Texas Tech University Medical Research: What is the background for this study? What are the main findings? Dr. Parent: There is some research out there on energy drinks, and we know a few things about them. For instance, although the drinks are marketed as though they are for extreme sports athletes, most people who drink them are not athletes. It seems as though drinking them makes some men feel as though they are a part of that extreme sports culture, without even needing to participate in the sports, though. The other part was that, clinically, you would be amazed at how many young men present at student counseling centers and university medical centers with "sleep problems." Then, when you ask them about what they eat and drink during a day, it turns out that some of them are guzzling half a dozen of these drinks a day, or drinking them at night, totally unaware of the extremely high caffeine content. It's true that energy drinks can help people focus a but better or work out a bit harder--but that's because the active ingredient is caffeine. In this research, we aimed to marry together those two lines of work--how does wanting to be more masculine impact energy drink use, and what consequences might energy drink use have for something as basic as sleep hygiene? (more…)
Author Interviews, Lifestyle & Health, NIH / 05.11.2015

MedicalResearch.com Interview with: Sarah K. Keadle, PhD, MPH Cancer Prevention Fellow Nutritional Epidemiology Branch Division of Cancer Epidemiology and Genetics National Cancer Institute   Medical Research: What is the background for this study? What are the main findings? Dr. Keadle: Television viewing is extremely prevalent in the U.S. Ninety-two percent of Americans have a television at home and watching TV consumes more than half of their available leisure time, potentially displacing more physical activities. Previous studies have reported a relationship between TV viewing and increased risk of death from the two most common causes of death in the U.S., cancer and heart disease. In our study, we followed more than 221,000 healthy Americans aged 50-71 years old for 14 years to look at this relationship. We confirmed the association with increased risk of death from cancer and heart disease. In addition, we found that TV viewing was associated with an increased risk of six other causes of death, including diabetes, influenza/pneumonia, Parkinson’s disease, and liver disease. Also, compared to individuals who watched less than one hour per day, those who watched 3-4 hours of TV per day were 15% more likely to die from any cause, and individuals who watched seven or more hours of TV per day were 47% more likely to die over the study period. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Immunotherapy, NEJM / 05.11.2015

MedicalResearch.com Interview with: Toni Choueiri, MD Clinical Director, Lank Center for Genitourinary Oncology Director, Kidney Cancer Center Senior Physician Dana Farber Cancer Institute Associate Professor of Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Choueiri: In the METEOR trial, we aimed to compare cabozantinib, a novel VEGFR, MET, AXL inhibitor to everolimus, a standard 2nd line option in advanced RCC. There is an unmet in this setting. Cabozantinib resulted in a median PFS of 7.4 months compared to 3.8 months with everolimus. Responses also were 4-times higher with cabozantinib-treated patients. At the interim OS analysis, there was a strong trend favoring cabozantinib.  (more…)
Author Interviews, Cancer Research, JAMA, MD Anderson / 05.11.2015

MedicalResearch.com Interview with: William N. William Jr., MD Associate Professor Chief, Head and Neck Section Department of Thoracic / Head and Neck Medical Oncology The University of Texas M. D. Anderson Cancer Center Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. William: Oral pre-malignant lesions are often characterized as white and/or red patches in the mouth and are considered risk factors for oral cancer. This is why it might be best for people to go get oral cancer screening done if they suspect that there might be a problem. However, not all oral pre-malignant lesions will turn into cancer, but when this happens, surgery is usually recommended, many times leading to serious speech and swallowing dysfunction. Chemoprevention is the use of compounds to prevent cancers from happening before they occur. One of the greatest challenges in developing chemopreventive agents is to identify the population at highest cancer risk. The Erlotinib Prevention of Oral Cancer (EPOC) trial involved 379 patients at five sites across the country. All had premalignant lesions in their mouths. Following study enrollment, participants were evaluated for LOH, a chromosomal abnormality characterized by the loss of chromosomal regions, which include tumor suppressor genes. Patients who tested positive for LOH were considered to be at high risk for oral cancer and were randomized to receive either erlotinib (an EGFR inhibitor drug) or a placebo for one year. The study’s primary endpoint was to determine if fewer patients treated with erlotinib would develop oral cancer, compared to those that received placebo. The EPOC study demonstrated that LOH predicted a higher oral cancer risk. LOH-negative patients had a three-year cancer-free survival rate of 87 percent compared to 74 percent for the LOH-positive group. However, patients who took erlotinib showed no statistical difference in terms of cancer-free survival rates after three years: 74 percent for participants given erlotinib compared to 70 percent for those taking placebo. Patients with both LOH and EGFR copy number gains had the highest incidence of cancer, but still did not benefit from erlotinib. (more…)
Author Interviews, CDC, Infections / 05.11.2015

MedicalResearch.com Interview with: Sam Crowe, PhD, MPH Epidemic Intelligence Service Officer Enteric Diseases Epidemiology Branch Division of Foodborne, Waterborne, and Environmental Diseases Centers for Disease Control and Prevention Medical Research: What were the leading causes of multistate foodborne outbreaks and the most common contaminated foods during the study period? Dr. Crowe: Salmonella, Shiga toxin-producing Escherichia coli, and Listeria monocytogenes were the leading pathogens causing multistate foodborne outbreaks. In order of frequency, fruits, vegetable row crops, beef, sprouts, and seeded vegetables were the leading contaminated foods. Medical Research: How severe are multistate foodborne outbreaks? Dr. Crowe: From 2010 through 2014, multistate foodborne outbreaks accounted for only 3% of all U.S. foodborne outbreaks detected, but caused over one third of the hospitalizations and more than half of the deaths. Medical Research: Are these outbreaks occurring more frequently? Dr. Crowe: Multistate foodborne outbreaks are being identified more often in the United States because of better surveillance. Greater centralization of food processing and distribution practices also could be increasing the frequency and size of multistate foodborne outbreaks. This is why your business should Look for Ruggedised Industrial Pointing Devices Today, to ensure your business is staying up with the industry standards. (more…)
Author Interviews, NYU, Technology / 05.11.2015

MedicalResearch.com Interview with: Dustin T. Duncan, ScD Assistant Professor Department of Population Health and Dr. Paul Krebs PhD Assistant Professor in the Department of Population Health New York University School of Medicine  Medical Research: What is the background for this study? What are the main findings? Dr.  Krebs: Everyone seems to be talking about health apps, but there was no quality research on what was actually happening in the US with regard to these apps. Knowing why people use and don’t use health-related apps is critical for advancing this area of healthcare. In terms of main findings, we found that a little over half of Americans are using a health-related app, primarily in the domains of fitness and nutrition. We also found greater use among minority populations, younger persons, among people who were obese, and those with higher incomes. Surprisingly we found that about 40% of people would not pay anything for a health app. Hidden costs and difficulty of data entry were main reasons people stopped using them. Dr. Duncan: Little is know about health app use, which was surprising to us—especially because many people have smartphones so downloading a health app can easy. We wanted to understand the landscape of health app use and patterns in the US to ultimately improve the population’s health. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA / 05.11.2015

MedicalResearch.com Interview with: Dr. Brad A. Bryan Ph.D Assistant Professor Biomedical Sciences Texas A&M University Health Science Center, Houston, TX Department of Biomedical Sciences Texas Tech University Health Sciences Center Medical Research: What is the background for this study? What are the main findings? Dr. Bryan: In 2008 it was serendipitously discovered that the beta blocker propranolol was effective in treating a common benign pediatric vascular tumor called infantile hemangioma.  Over the past few years, my lab has been working on elucidating the molecular mechanisms underlying this pediatric tumor and part of this research involved uncovering how propranolol selectively inhibited these tumors.  At the same time these studies were taking place, other members of my lab were working on pre-clinical drug development for a malignant vascular tumor called angiosarcoma.  Patients with angiosarcoma are faced with very few effective treatment options and abysmal survival rates, so we decided to see if the efficacy of beta blockade observed in infantile hemangiomas transferred to angiosarcomas.  Using preclinical in vitro and in vivo assays, we demonstrated that propranolol was very effective at inducing cell death, blocking migration, and inhibiting tumor growth in our angiosarcoma models.  This work was subsequently published in Plos One (Stiles et al., 2013).  I then collaborated with Dr. William Chow from San Francisco to test propranolol off-label (propranolol is FDA approved to treat high blood pressure, heart dysrhythmias, thyrotoxicosis, and essential tremors) in a patient suffering from a rapidly expanding angiosarcoma covering a large portion of his face.  In the window between diagnosis of the tumor and the start of chemotherapy, we placed the patient on oral propranolol.  The redness of the tumor very rapidly lessened and remarkably by only one week of treatment the tumor margins appeared to significantly shrink.  We examined biospies of the tumor before and after only one week of propranolol and found that the proliferation of the tumor cells was markedly decreased following beta blockade.  After a combination of propranolol, chemotherapy, and radiation that lasted several months, the patient had no detectable metabolically active tumor or distant metastases. We published these findings in JAMA Dermatology (Chow et al., 2015). (more…)
Author Interviews, Breast Cancer / 05.11.2015

MedicalResearch.com Interview with: Shirley Mertz President of the US Metastatic Breast Cancer Network (Ms. Mertz has been living with metastatic breast cancer since 2003) Medical Research: What do you mean by the term, "Long Term Responders"? How is this different than "Survivor"? Shirley Mertz: For many years, especially in the month of October in the U.S., the media and breast cancer organizations have written stories and celebrated women who have received an early stage breast cancer diagnosis, gone through treatment and now see breast cancer in their "rear view mirror." For these women (Stage I, II or III disease), treatment has an end and they can get on with their lives. In contrast, for patients diagnosed with Stage IV disease, also called metastatic breast cancer, treatment never ends and they will ultimately succumb to the disease. Long term responders are those metastatic breast cancer patients who have responded well to a treatment--experiencing perhaps a complete remission (not a cure) or stable disease. While that treatment may continue to keep their disease under control for 5 or more years, such patients must continue with treatment. Ultimately, their disease will progress and they will die of the disease. This can be immensely traumatic for the patient and the family if they were failed to be diagnosed by a doctor. If the cancer was found sooner then there would be a better chance of survival. If this has ever happened to you then you may want to contact a failure to diagnose attorney. (more…)
Author Interviews, Breast Cancer, Diabetes / 05.11.2015

MedicalResearch.com Interview with: Dr Nicoletta Provinciali, MD Oncologist from the E.O. Ospedali Galliera Genoa, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Provinciali: We know that higher insulin levels have been associated with a worse prognosis in early breast cancer patients. In this study we wanted to evaluate the impact of insulin resistance on metastatic breast cancer patients receiving first line chemotherapy. We found that insulin resistance status together with the endocrine status had an adverse prognostic effect. (more…)
Author Interviews, Chemotherapy, Lymphoma, NEJM / 04.11.2015

Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021MedicalResearch.com Interview with: Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021   Medical Research: What is the background for this study? What are the main findings? Dr. Ruan: Mantle cell lymphoma is an uncommon subtype of non-Hodgkin lymphoma that primarily affects elderly populations. Conventional chemotherapy regimens are generally not curative, and may not be tolerated by many patients, underscoring the need for treatment alternatives.  Previous experience with immunomodulatory compound lenalidomide has shown favorable activity and was well tolerated in patients with relapsedMantle cell lymphoma.  We evaluated the efficacy and safety of the biologic combination with lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma (MCL). The main findings of the study showed that the combination was effective and generally well tolerated when given as induction and maintenance treatment. The overall response rate was 92%, with complete response rate of 64% in the 36 evaluable patients. Median duration of response has not been reached at a median follow up of 30 months.   Treatment was outpatient-based and quality-of-life was preserved for most patients. (more…)
Author Interviews, Fertility, OBGYNE / 04.11.2015

MedicalResearch.com Interview with Dr. Norbert Gleicher, MD, FACOG, FACS Founder, Center for Human Reproduction Background: What’s My Fertility and the Center for Human Reproduction in New York, have announced the first screening for Premature Ovarian Aging (POA) in young women, based on new research that the FMR1 gene can be predictive of POA. Medical Research:   What is Premature Ovarian Aging (POA)? How does POA differ from Premature Ovarian Failure? Dr. Gleicher: Premature Ovarian Aging (POA) is a condition that causes a young woman’s ovaries to age faster than normal. It affects roughly 10% of all women, regardless of race or ethnic background. POA typically causes no symptoms until the ovarian reserve is already very low. Women are born with all their egg cells (called oocytes). Scientists refer to this as a woman’s original “ovarian reserve.” From birth on, significant numbers of these eggs are constantly lost until menopause. As women age, their ovarian reserve, therefore, depletes and fertility declines. In most women, fertility begins to decline around age 35 – but for women at risk for POA, fertility declines can begin as early as in their teens or 20s. POA in early stages typically has no symptoms. Most women until now, therefore, are usually only diagnosed after troubles conceiving become apparent, which brings them to a fertility specialist. At that point, most require stressful and costly infertility treatment to have children. Premature Ovarian Failure (POF), sometimes also called premature menopause of primary ovarian insufficiency (POI) is the end stage of POA, when women reach menopause under age 40. Fortunately, this happens only to 10% of the 10% of women with Premature Ovarian Aging, - which means to 1% of the total female population. In those unfortunate few, even routine IVF can usually no longer help, and most of these women will only conceive with use of young donor eggs.  (more…)
Accidents & Violence, Author Interviews, Pediatrics, Race/Ethnic Diversity / 04.11.2015

Bindu Kalesan PhD MPH Director Evan’s Center for Translational Epidemiology and Comparative Effectiveness Research Assistant Professor of Medicine Preventive Medicine & Epidemiology Department of Medicine Boston University School of Medicine Boston, MA 02118MedicalResearch.com Interview with: Bindu Kalesan PhD MPH Director Evan’s Center for Translational Epidemiology and Comparative Effectiveness Research Assistant Professor of Medicine Preventive Medicine & Epidemiology Department of Medicine Boston University School of Medicine Boston, MA 02118  Medical Research: What is the background for this study? What are the main findings? Dr. Kalesan: Firearm injuries are one of the 3 major causes of death in children in the US. for every 7 pediatric firearm deaths there are 8 children non-fatally injured by a gun. Those that survive will live with disability and severe morbidity. From our earlier studies, we found that this burden of survivorship and injury is different according to race/ethnicity. There is also evidence that Injury related hospitalizations are also associated low-income households and neighborhoods. In the background of gun (violence) control, frequently comparisons are drawn between firearm injuries and motor vehicle accidents. In this study we use nationally representative hospitalization data and compared pediatric firearm-related hospitalization and pedestrian motor vehicle accident hospitalizations to assess whether the risk of firearm related hospitalizations among minorities varies depending on the neighborhood they live. We found that black children were at substantially greater risk of firearm hospitalization as compared to pedestrian motor vehicle hospitalization. This greater risk of firearm hospitalization among black children persisted across neighborhoods. Simply put, the risk of firearm hospitalization versus pedestrian motor vehicle hospitalization among black children was high, regardless of whether they lived in low income or high income neighborhoods.We also found that all minority race children (black, Hispanic and other race) as compared to white children were at a greater likelihood of homicide-firearm hospitalization than of pedestrian motor vehicle hospitalization and all minority race children were significantly less likely to be hospitalized for unintentional firearm than pedestrian injuries in comparison to white children. Therefore, overall we found a minority race disadvantage regardless of whether they lived in high and low-income neighborhoods. (more…)
Author Interviews, Cancer Research, Personalized Medicine / 04.11.2015

Timothy Humphrey DPhil. CRUK/MRC Oxford institute for Radiation Oncology University of Oxford, UKMedicalResearch.com Interview with Timothy Humphrey DPhil. CRUK/MRC Oxford institute for Radiation Oncology University of Oxford, UK Medical Research: What is the background for this study? What are the main findings? Response: Multiple mutations resulting in loss of a particular histone mark (H3K36me3) are frequently found in a number of cancer types. These include mutations resulting in loss of the tumour suppressor SETD2 (which trimethylates H3K36) and over-expression of the oncogene KDM4A (which demethylates H3K36me3), which together are observed in more than 10% of a number of cancer types. Notably, loss of H3K36me3 has been reported in more than 50% of pediatric high-grade gliomas. While loss of this histone mark is associated with poor prognosis, there is no targeted therapy yet. Following observations made in fission yeast, we have found a new way to selectively target H3K36me3-deficient cancers using the WEE1 inhibitor, AZD1775. Surprisingly, treatment of H3K36me3-deficient cancer cells with the WEE1 inhibitor resulted in S-phase arrest. Further analysis revealed ribonucleotide reductase to be the target of this synthetic lethal interaction, thereby leading to dNTP starvation, replication fork collapse and cell death. (more…)
Author Interviews, Brigham & Women's - Harvard, Nutrition, Race/Ethnic Diversity / 04.11.2015

MedicalResearch.com Interview with: Daniel (Dong) Wang  Doctoral Student Departments of Nutrition and Epidemiology Harvard T. H. Chan School of Public Health Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Response: Over the past more than one decade, many changes related to nutrition and food supply have happened and therefore influence individuals' dietary behaviors and ultmately dietary quality. Also, the changes in dietary quality may impact the disease burden, measured by avoided major chronic disease cases and premature deaths. Therefore, in this study, we were trying to understand 1) how the dietary quality in US population changed from 1999 to 2012, and 2) how changes in dietary quality over time impacted disease and premature death. The quality of the US diet, measured by the Alternate Healthy Eating Index, improved modestly from 39.9 to 48.2 from 1999 through 2012, but the dietary quality of US population remains far from optimal (the optimal score is 110). There is huge room existing for further improvements. We also found that even the modest improvements in dietary quality that we observed contributed to substantial reductions in disease burden, which is measured by avoided disease cases and premature deaths. We estimated that healthier eating habits cumulatively prevented 1.1 million premature deaths over the 14 years, and the difference in dietary quality between 1999 and 2012 resulted in 12.6% fewer type 2 diabetes cases, 8.6% fewer cardiovascular disease cases, and 1.3% fewer cancer cases. Among different key components of healthy diets, despite a large reduction in consumption of trans fat, as well as a relatively large reduction in sugary beverages, most key components of healthy diets showed only modest or no improvements. The improvement in dietary quality was greater among persons with higher socioeconomic status and healthier body weight. African Americans had the poorest dietary quality, which was accounted for by lower incomes and education. The gaps in dietary quality persisted or even widened from 1999 to 2012. (more…)
AHA Journals, Author Interviews, Duke, Outcomes & Safety, Stroke, Surgical Research / 04.11.2015

MedicalResearch.com Interview with: Soko Setoguchi-Iwata, M.D MPH Adjunct Associate Professor Department of Medicine Duke Clinical Research Institute 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 vs Carotid Endarterectomy 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 performing stenting in trial setting vs. real world practice setting. SAPPHIRE and CREST physicians were enrolled only after having demonstrated  Carotid Artery Stenting 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 an 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.   (more…)
Author Interviews, JAMA, Stroke, Surgical Research / 04.11.2015

MedicalResearch.com Interview with: Saleh A Almenawer, MD Neurosurgeon, Hamilton Health Sciences McMaster University Hamilton, ON Canada  Medical Research: What is the background for this study? Dr. Almenawer: The current standard therapy for acute ischemic stroke is intravenous tissue plasminogen activator (tPA), which improves survival and functional outcomes when administered as early as possible after stroke. However, the use of intravenous tPA is limited by the narrow therapeutic time window (< 4.5 hours) and by important contraindications, including coagulopathy, recent surgery, or stroke or head injury within the past 3 months. This leaves as few as 10% of patients presenting with ischemic stroke eligible for treatment with tPA. Moreover, intravenous tPA is associated with long recanalization times and poor revascularization rates in proximal large vessel occlusion, and the prognosis of these patients remains poor. The limitations of intravenous tPA have spurred interest in endovascular thrombectomy for acute ischemic stroke, analogous to thrombolysis versus percutaneous coronary intervention for myocardial infarction. Several randomized clinical trials (RCTs) have compared clinical outcomes of mechanical thrombectomy to standard medical treatment with intravenous tPA. The current study was a meta-analysis of RCTs that aimed to answer the question of whether endovascular thrombectomy is associated with better clinical outcomes than intravenous tPA, and accordingly, whether endovascular thrombectomy should replace intravenous tPA as the new standard of care for ischemic stroke. (more…)
Author Interviews, Cancer Research, Microbiome / 04.11.2015

MedicalResearch.com Interview with: Simba Gill Ph.D CEO, Evelo Therapeutics MedicalResearch: Evelo Therapeutics, a new company focuses on leveraging the power of the microbiome to develop novel therapies for cancer. Evelo is pioneering Oncobiotic™ therapeutics, a new modality in cancer therapy based on the cancer microbiome. Dr. Gill, CEO of  Evelo Therapeutics began his career at Celltech, focused on antibody research. Dr. Gill earned his Ph.D. from King’s College, London, and his MBA from INSEAD. Medical Research:  What is a microbiome? How do microbiomes play a role in health and disease? Dr. Gill: The microbiome is the collection of trillions of bacteria, funguses, viruses and other microbes that live on and within the human body. There are different clusters of microbes in different parts of the body, including the skin, mouth, large intestine, and vagina. Recently we have learned that our microbial populations shift depending on changes to an individual’s health and wellness. The makeup of one’s microbiome has a strong influence on one’s health, immune response, and metabolic state. (more…)
Author Interviews, Nutrition, PLoS, University Texas, Weight Research / 04.11.2015

Dr. Marcia C. de Oliveira Otto MD PhD Division of Epidemiology, Human Genetics and Environmental Sciences The University of Texas Health Science Center School of Public Health, Houston, TexasMedicalResearch.com Interview with: Dr.  Marcia C. de Oliveira Otto MD PhD Assistant professor  Division of Epidemiology, Human Genetics and Environmental Sciences The University of Texas Health Science Center School of Public Health, Houston, Texas  Medical Research: What is the background for this study? What are the main findings?  Dr. Otto: Eat a variety of foods, or food diversity, is a long standing public health recommendation because it is thought to ensure adequate intake of essential nutrients, to prevent excessive intakes of less healthy nutrients such as refined sugars and salt, thus promoting good health. However there hasn’t been empiric evidence from populational studies testing this hypothesis. In our study, we characterized three metrics of diet diversity and evaluated their association with metabolic health using data from 6,814 participants in the Multi-Ethnic Study of Atherosclerosis, including whites, blacks, Hispanic-Americans, and Chinese-Americans in the United States, including the total count (number of different foods eaten in a week), evenness (the distribution of calories across different foods consumed), and dissimilarity (the differences in food attributes relevant to metabolic health, such as fiber, sodium or trans-fat content). We then evaluated how diet diversity was associated with change in waist circumference five years after the beginning of the study and with onset of Type 2 diabetes ten years later. We also examined the relationship between diet quality and the same metabolic outcomes. Diet quality was measured using established scores such as the Dietary Approaches to Stop Hypertension (DASH) and the Alterative Healthy Eating (AHEI) score. When evaluating both food count and evenness, we found no associations with either increase in waist circumference or incidence of diabetes. In other words, more diversity in the diet was not linked to better metabolic outcomes. Participants with greater food dissimilarity actually experienced more central weight gain, with a 120 percent greater increase in waist circumference than participants with lower food dissimilarity. Contrary to what we expected, our results showed that participants with greater diversity in their diets, as measured by dissimilarity, had worse diet quality. They were eating less healthy foods, such as fruits and vegetables, and more unhealthy foods, such as processed meats, desserts and soda. When evaluating diet quality, we found about a 25 percent lower risk of developing Type 2 diabetes after 10 years of follow up in participants with higher diet quality. There was no association between diet quality scores and change in waist circumference.  (more…)
Author Interviews, Cost of Health Care, JAMA, Pharmacology, Sloan Kettering / 04.11.2015

MedicalResearch.com Interview with: Dr. Elizabeth D. Kantor PhD MPH Assistant Attending Epidemiologist Memorial Sloan Kettering Cancer Center

Medical Research: What is the background for this study? What are the main findings? Dr. Kantor: We know that use of prescription drugs represents a major expenditure in the United States and research suggests that use of prescriptions has increased. However, much of what we know is derived from information on expenditures, is outdated, or is limited to certain populations, such as older adults or those with a given clinical condition. For example, a number of studies have looked at things like use of drugs used to control condition x among persons with condition x, but that doesn't tell us about use of that class of drugs in the population. It’s important that we continue to monitor use of prescription drugs in the population, as practice patterns are continually evolving as the population ages, the health needs of the population change, drugs enter/exit the market, scientific knowledge advances, and policies change. We therefore sought to create an updated comprehensive reference on prescription drug use among US adults using nationally representative data from the National Health And Nutrition Examination Survey, a continuous survey conducted by the Centers for Disease Control and Prevention. We examined trends in use of prescription drugs over 7 cycles, ranging from 1999-2000 to 2011-2012 (the sample size per cycle ranged from 4,861 to 6,212).Participants were asked about use of prescription medications over the prior 30 days, from which we were able to estimate the prevalence of use within each survey cycle. We then looked at trends in prescription drug use, both overall and within drug classes. In our study, we observed that use of any prescription medications increased over the study period, with 51% of adults reporting any prescription medication use in 1999-2000 and 59% reporting any use in 2011-2012. We also observed an increase in polypharmacy (or use of 5 or more prescription drugs) over the study period, with approximately 8% of adults reporting use of 5 or more drugs in 1999-2000, as compared to 15% in 2011-2012. Polypharmacy was much more common among older adults: 24% of adults ages 65 and older reported use of 5 or more drugs in 1999-2000 and 39% reported use of 5 or more drugs in 2011-2012. At first glance, one might take a look at these results and think that this is probably because the US population is aging and people tend to take more drugs as they age. But we found that the increase in overall prescription drug use and polypharmacy persisted even after accounting for the aging of the US population. This means that something else is driving the observed increase in use of prescription drugs. We also found that use of the majority of drug classes increased over the study period. For example, among commonly used drug classes, we observed marked increases in use of drugs taken to control high cholesterol, high blood pressure, and diabetes. We also observed marked increases in some less commonly used drug classes, such as muscle relaxants. Interestingly, if we look at the ten most commonly used drugs in 2011-2012, we can see that most are taken for conditions associated with cardiometabolic disease This raises the question of how much of this increase in prescription drug use may be attributable to overweight/obesity, as we know that the prevalence of obesity has increased among US adults. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, McGill, Pharmacology / 04.11.2015

MedicalResearch.com Interview with: Tewodros Eguale, MD, PhD Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada Research Fellow in Medicine Brigham and Women's Hospital Medical Research: What is the background for this study? Dr. Eguale: Off-label prescribing is common and has been identified as a potentially important contributor to preventable adverse drug events (ADE). Significant deleterious effects were reported with off-label use of some drugs. Moreover, studies in children, where drugs are often used without sufficient scientific investigation, have shown that off-label uses increase the risk of ADE.  In adults, there has been no systematic investigation of the effects of off-label use in real world situation. The lack of knowledge is related to the methodological challenges of measuring off-label use and its effects; specifically the lack of link between prescribed drugs and their indication for use. The Medical Office of the XXI Century (MOXXI) electronic health record (EHR), developed by team of researchers at McGill University, facilitates the documentation of treatment indications, reasons for discontinuation of drug orders and adverse drug event. These new features provided the first opportunity to systematically monitor and evaluate off-label use and the occurrence of adverse drug events.  This study took advantage of the use of this new generation of software in a network of primary care practices to systematicaly evaluate the effect of off-label use on ADEs. (more…)
Author Interviews, Columbia, Compliance, HIV, JAMA, Pediatrics / 04.11.2015

MedicalResearch.com Interview with: Dr. Louise Kuhn PhD Professor, Epidemiology Sergievsky Center Columbia University  Medical Research: What is the background for this study? What are the main findings? Dr. Kuhn: Ritonavir-boosted lopinavir-based antiretroviral therapy is recommended as first-line treatment for HIV-infected infants and young children while efavirenz is recommended for adults and older children. There are several advantages of transitioning HIV-infected children to efavirenz-based treatment as they get older.  These advantages include the possibility of once-daily dosing, simplification of co-treatment for tuberculosis, avoidance of some metabolic toxicities, preservation of ritonavir-boosted lopinavir for second-line treatment, and alignment of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz-based treatment in children exposed to nevirapine for prevention of mother-to-child transmission.  This is because efavirenz and nevirapine are in the same drug class and the majority of children who become infected despite exposure to nevirapine used for prevention have mutations in their virus that usually predict resistance to this drug class. In this study, we randomized HIV-infected children to two different treatment strategies: In the control strategy they remained on their initial ritonavir-boosted lopinavir regimen; in the alternative strategy they transitioned to an efavirenz-based regimen.  All children had been exposed to nevirapine used (unsuccessfully) to prevent mother to child HIV transmission and were virologically-suppressed (HIV in blood < 50 copies/ml) at the time of enrollment into the study.  We observed excellent virological control in both groups with fewer than 3% of children having levels of HIV in their blood greater than 1000 copies/ml.  Sustained suppression of virus in blood below 50 copies/ml throughout follow-up was achieved in 82% of the children transitioned to efavirenz-based treatment compared to 72% of children remaining on the control treatment. (more…)
Antibiotic Resistance, Author Interviews, CDC, Infections / 04.11.2015

Dr. Bob Kirkcaldy MD, MPH Epidemiologist, Division of STD Prevention CDCMedicalResearch.com Interview with: Dr. Bob Kirkcaldy MD, MPH Epidemiologist, Division of STD Prevention CDC Medical Research: What is the background for this study? What are the main findings? Dr. Kirkcaldy: Gonorrhea is a common sexually transmitted disease that, if untreated, can cause severe reproductive health complications. While gonorrhea is very common, it is often symptomless and many may not realize they have it. 333,004 cases were diagnosed in 2013, but more than 820,000 are estimated to occur annually. Because antibiotic resistance has jeopardized treatment for gonorrhea, CDC’s Gonoccocal Isolate Surveillance Project (GISP) monitors antimicrobial susceptibility and tracks patterns of resistance among antibiotics currently used to treat gonorrhea. From 2006-2009, susceptibility to the oral cephalosporin antibiotic cefixime declined in GISP, threatening the effectiveness of this drug. Continued use of cefixime in the face of declining susceptibility could theoretically foster broad resistance to the cephalosporin class (including ceftriaxone, the last treatment option). So in 2012,  CDC changed its treatment recommendations to recommend only dual gonorrhea treatment with injectable ceftriaxone plus oral azithromycin. The most recent data from GISP analyzed urethral gonorrhea samples of men from STD clinics in 34 cities from 2006-2014 and found resistance to cefixime increased in 2014 after two years of dramatic decreases. While CDC’s STD Treatment Guidelines suggest cefixime should only be considered as an alternative treatment for gonorrhea when ceftriaxone is not available, trends of cefixime susceptibility have historically been a precursor to trends in ceftriaxone so it’s important to continue monitoring cefixime to be able to anticipate what might happen with other drugs in the future. GISP data also found that resistance remained stable for ceftriaxone and resistance levels remain highest among men who have sex with men (MSM). We’re concerned about the increase in resistance for cefixime; however, more years of data are needed to know if the 2014 increase is the beginning of a new trend. (more…)
Anesthesiology, Author Interviews, Pain Research / 03.11.2015

MedicalResearch.com Interview with: Dr Emmanuel Boselli, MD, PhD Anesthesiology and Intensive Care University Claude Bernard Lyon I University of Lyon Lyon, France Medical Research: What is the background for this study? What are the main findings? Dr. Boselli: We hypothesized that the use of conversational hypnosis in patients undergoing regional anesthesia procedures for ambulatory upper limb surgery might provide better comfort than the use of oral premedication during the regional anesthesia procedure. We assessed the subjective effect of conversational hypnosis on a patient self-reported comfort scale ranging from 0 (no comfort) to 10 (maximal comfort), and the objective effect was assessed using the Analgesia/Nociception Index (ANI), a 0-100 index derived from heart rate variability reflecting the relative parasympathetic tone. In our study of 100 patients undergoing hand surgery in two different centers, 50 had conversational hypnosis while being given regional anesthesia (Saint-Grégoire hospital), and 50 were given of oral hydroxyzine 30 minutes to an hour before the regional anesthesia procedure (Lyon hospital). Patients having hypnosis measured an average ANI of 51 before and 78 after hypnosis, whereas those who had premedication averaged 63 before and 70 after. The average comfort scale of those who had received hypnosis was 6.7 before and 9.3 after, while patients who had medication averaged 7.8 before and 8.3 after. The main finding of this study is that conversational hypnosis induced greater increase in comfort scales and ANI values than oral premedication. Medical Research: What is conversational hypnosis? What does it consist of? Dr. Boselli: Conversational hypnosis consists of matching the patient's behavioral communication patterns, reflective listening, avoiding any negative suggestion (e.g. "Keep calm and quiet" instead of "Please don't move!") and focalizing the patient's attention on something else than the regional anesthesia procedure, such as the ultrasound machine screen. (more…)
Author Interviews, Nutrition, Social Issues / 03.11.2015

MedicalResearch.com Interview with: Meg Bruening, PhD, MPH, RD Assistant Professor Arizona State University School of Nutrition and Health Promotion College of Health Solutions Phoenix, AZ 85004 Medical Research: What is the background for this study? What are the main findings? Dr. Bruening: Food insecurity is understudied in college populations, particularly college freshmen. We saw that over 1/3 of our population of freshmen living in dorms reported inconsistent access to healthy foods. Students who were food insecure reported higher odds of anxiety and depression (by almost 3-fold), and were less likely to eat breakfast and eat home cooked meals. (more…)