Author Interviews, Hepatitis - Liver Disease, Lancet, NIH / 13.01.2015

MedicalResearch.com Interview with: Anita Kohli MD Critical Care Medicine Department NIH Clinical Center, National Institutes of Health, Bethesda, MD Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research,  National Laboratory for Cancer Research, Frederick, MD, Medical Research: What is the background for this study? What are the main findings? Dr. Kohli: While therapy using for 8-12 weeks of all oral directly acting antivirals (DAAs) has been shown to result in high SVR "cure" rates for hepatitis C, the optimal combination and minimum duration required for treatment of hepatitis C has not been defined. The development of the simplest, short duration regimen for hepatitis C possible with high cure rates is important given the ~180 million people infected globally. Medical Research: What should clinicians and patients take away from your report? Dr. Kohli: Combination therapy with  directly acting antivirals may allow for the further shortening of treatment duration for hepatitis C. Using the right combination of DAA's therapy for as short as six-weeks may results in high rates of SVR. (more…)
Author Interviews, Cancer Research, Dermatology / 13.01.2015

MedicalResearch.com Interview with : Cédric Blanpain, MD, PhD Professor of Stem Cell and Developmental Biology WELBIO, Interdisciplinary Research Institute (IRIBHM) Université Libre de Bruxelles Belgium MedicalResearch.com : What is the background for this study? What are the main findings? Dr. Blanpain: Squamous cell carcinoma (SCC) represents the second most frequent skin cancer with more than half million new patients affected every year in the world. Cancer stem cells (CSCs) are a population of cancer cells that have been described in many different cancers including skin SCCs and that feed tumor growth. These cells could be resistant to therapy thus being responsible for tumor relapse after therapy. However, still very little is known about the mechanisms that regulate Cancer stem cells functions. In a new study published and making the cover of Cell Stem Cell, researchers led by Pr. Cédric Blanpain, MD/PhD, professor and WELBIO investigator at the IRIBHM, Université libre de Bruxelles, Belgium, report the mechanisms regulating the different functions of Twist1 controlling skin tumour initiation, cancer stem cell function and tumor progression. Benjamin Beck and colleagues used state of the art genetic mouse models to dissect, the functional role and molecular mechanisms by which Twist1 controls tumor initiation, cancer stem cell function and tumor progression. In collaboration with Dr Sandrine Rorive and Pr Isabelle Salmon from the department of Pathology at the Erasme Hospital, ULB and the group of Jean-Christophe Marine (VIB, KUL Leuven), they demonstrated that while Twist1 is not expressed in the normal skin, Twist1 deletion prevents skin cancer formation demonstrating the essential role of Twist1 during tumorigenesis. The authors demonstrate that different levels of Twist1 are necessary for tumor initiation and progression. Low level of Twist1 is required for the initiation of benign tumors, while higher level of Twist1 is necessary for tumor progression. They also demonstrate that Twist1 is essential for tumor maintenance and the regulation of cancer stem cell function. The researchers also uncovered that the different functions of Twist1 are regulated by different molecular mechanisms, and identified a p53 independent role of Twist1 in regulating cancer stem cell functions. (more…)
Author Interviews, Hospital Acquired, JAMA / 13.01.2015

Teresa Waters PhD Professor and Chair, Preventive Medicine University of Tennessee Health Science Center Memphis TNMedicalResearch.com Interview with: Teresa Waters PhD Professor and Chair, Preventive Medicine University of Tennessee Health Science Center Memphis TN Medical Research: What is the background for this study? What are the main findings? Dr. Waters: On October 1, 2008, Medicare implemented the Hospital-Acquired Conditions (HACs) Initiative, a policy penalizing hospitals for eight complications of hospital care, also known as never events. Under the HACs Initiative, hospitals could no longer justify a higher level Medicare MS-DRG when caring for a patient who developed 1 of the 8 never events. This Initiative was one in a series of CMS payment reforms intended to increase emphasis on value-based purchasing. We found that Medicare's nonpayment policy was associated with significant improvements in the time trends for central line associated blood stream infections (CLABSIs) and catheter associated urinary tract infections(CAUTIs). For these outcomes, our data from the National Database of Nursing Quality Indicators showed that introduction of the Medicare policy was associated with an 11% reduction in the rate of change in central line associated blood stream infections and a 10% reduction in the rate of change in CAUTIs. We did not find any relationship between introduction of the policy and significant changes in injurious falls or hospital acquired pressure ulcers (two other important never events covered by the policy). We hypothesized that the Hospital-Acquired Conditions Initiative may have a great effect for conditions where there is strong evidence that better hospital processes yield better outcomes or where processes are more conducive to standardization. (more…)
Author Interviews, Baylor College of Medicine Houston, Radiology / 13.01.2015

MedicalResearch.com Interview with: Aymer Al-Mutairi, MD Primary Care Research fellow Dept. Family and Community Medicine Baylor College of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Al-Mutairi: Previous studies indicate that 8% of abnormal imaging results did not receive follow-up actions by referring providers within 4 weeks. In addition, abnormal imaging results often state recommendations for further testing and radiology reports occasionally contain language that conveys doubt regarding the results. We hypothesized that recommendations for further imaging, and expressions of doubt or uncertainty in the radiology report, are more likely to be associated with lack of timely follow-up. We found that patients with abnormal imaging results where radiologists recommended further imaging were less likely to be followed-up by a treating clinician within 4 weeks compared with patients without such recommendations. Expression of “doubt” in the radiology reports did not affect follow-up actions. (more…)
Author Interviews, Cancer Research, Technology / 12.01.2015

Oleh Taratula, Ph. D. Assistant Professor of Pharmaceutics Department of Pharmaceutical Sciences College of Pharmacy Oregon State University Corvallis, OR 97331-3507MedicalResearch.com Interview with: Oleh Taratula, Ph. D. Assistant Professor of Pharmaceutics Department of Pharmaceutical Sciences College of Pharmacy Oregon State University Corvallis, OR 97331-3507 Medical Research: What is the background for this study? What are the main findings? Dr. Taratula: Our research group is focused on the development of novel nanotechnology-based approaches to treat different cancers, including ovarian cancer. For many cancers, surgery is a first choice of treatment. For example, only optimal surgical resection of most abdominal metastases can significantly reduce ovarian cancer recurrence and, therefore, improve patient survival. However, it is challenging to remove most of the cancer tumors and residual cancer cells eventually may lead to cancer relapse. Therefore, our aim is to develop a nanomedicine platform, which could help surgeons achieve maximal tumor resection, using the intraoperative guidance with real-time near infrared (NIR) fluorescence signal. Moreover, we expect that the same nanoplatform could further enhance surgical outcomes by combinatorial phototherapy to be performed intraoperatively after tumor resection to eradicate unresected cancer cells. Our data published in Nanoscale is the first step towards our main goal. At this point, by utilizing naphthalocyanine, we have developed a single-agent-based nanomedicine platform capable of both NIR fluorescence imaging and combinatorial phototherapy. Naphthalocyanine is a commercially available compound, but its potential clinical application is limited by low water solubility and aggregation. Especially, aggregation diminishes the imaging ability and phototherapeutic efficacy of this compound. To address these shortcomings, we discovered that the loading of naphthalocyanine into the dendrimers significantly enhances water solubility, prevents aggregation and preserves imaging and therapeutic abilities. Our data demonstrated that naphthalocyanine-based nanoplatform can generate a NIR fluorescence signal in the cancer tumors, required for elimination of autofluorescence from healthy tissue and body fluids. Furthermore, our results also indicated that the developed nanoplatform is an efficient therapeutic agent which, upon exposure to NIR light, destroys chemotherapy-resistant ovarian cancer tumors by producing both heat and toxic reactive oxygen species. Finally, many organic fluorophores, including naphthalocyanine, can undergo photobleaching under exposure to light, which could be misinterpreted as a lack of fluorescence signal during the surgery. We demonstrated that the dendrimer encapsulated naphthalocyanine exhibits extremely high photostability and could overcome the above mentioned issue. (more…)
Author Interviews, Education, Technology / 12.01.2015

MedicalResearch.com Interview with: Živa Cotič Research Assistant & PhD Student,Global eHealth Unit Imperial College London and A/Prof Josip Car Director of Health Services and Outcomes Research Programme Lee Kong Chian School of Medicine, Director of Global eHealth Unit School of Public Health, Imperial College London Medical Research: What is the background for this study? What are the main findings? Response: The Department of Health Workforce in collaboration with the Department of Knowledge, Ethics and Research at the World Health Organization commissioned the report to provide countries with evidence to inform and guide the adoption of innovative, technology enabled models into health professional education. The report aims to address complex challenges of 21st century global workforce development through eLearning, which has been recognised as key to building more effective health education and a stronger, better qualified workforce. Global workforce development is one of the most pressing global health issues. The World Health Organization estimates the shortage of the health workforce at approximately 7.2 million health workers, with an expected increase to 12.9 million by 2035. The magnitude of the health workforce challenges the health care systems are facing require both greater investment and more effective and strategic use of available resources. The findings of the report suggest that eLearning could be equivalent to traditional forms of learning in regard to knowledge and skill acquisition in health education. This information is crucial for policy makers and educators who are forming future education. (more…)
Author Interviews, JAMA, Kidney Disease / 12.01.2015

MedicalResearch.com Interview with: James Flory MD, MSCE Division of Endocrinology and Department of Healthcare Policy and Research Weill Cornell Medical College, NY NY Medical Research: What is the background for this study? What are the main findings? Dr. Flory: Metformin is the first-line drug for type 2 diabetes, with much better evidence for safety and improved clinical outcomes than any alternative. The one major safety concern about metformin is the fear that it can cause lactic acidosis, which led to a Food and Drug Administration black box warning against using metformin in patients with even a modest degree of renal impairment. These fears and warnings were based on serious problems with an older drug in the same class, not on experiences with metformin itself, and over the past 20 years it has become clear that the risk of lactic acidosis with metformin is extremely low, and that this warning against the use of the drug in mild renal failure is overly strict. (Dr. Lipska and colleagues published a superb review of this issue a few years back: Diabetes Care June 2011 vol. 34 no. 6 1431-1437) This is important from a public health perspective because so many patients with diabetes have mild to moderate kidney disease, and we were concerned that the FDA warning was preventing the use of metformin in these patients. Our study was intended to estimate how many patients who would benefit from metformin are not taking it because they have mild kidney disease. We found that rates of metformin use are much lower in patients with mild kidney disease – just the population where the FDA warning discourages use, but modern data show that metformin is safe. In all, at least 1 million patients with type 2 diabetes who would benefit from metformin appear not to be taking it because clinicians are following the FDA warning and being too conservative. (more…)
Author Interviews, Diabetes, Geriatrics, JAMA / 12.01.2015

Kasia Joanna Lipska MD, MHS Assistant Professor of Medicine (Endocrinology) Yale School of Medicine New Haven, CT 06520-8020MedicalResearch.com Interview with: Kasia Joanna Lipska MD, MHS Assistant Professor of Medicine (Endocrinology) Yale School of Medicine New Haven, CT 06520-8020 Medical Research: What is the background for this study? What are the main findings? Dr. Lipska: Diabetes is common and affects about 1 in 4 older adults (65 years or more). For younger adults with diabetes, most guidelines suggest lowering blood sugar levels to a hemoglobin A1c below 7%. However, in older patients, especially those with complex medical problems, the benefits of this strategy are unclear. What’s more, this strategy can cause harm. Aiming for a hemoglobin A1c below seven increases the risk for hypoglycemia. And older adults are especially susceptible to this risk. As a result, many guidelines suggest that treatment should be more cautious for these vulnerable elders and that aiming for “tight” blood sugar control may not be worth the risk. Medical Research: What are the main findings? Dr. Lipska: We looked at diabetes treatment of older adults using nationally representative data from 2001 to 2010. We found that 62% of older adults with diabetes had a hemoglobin A1c below 7%. But what’s really striking is that this proportion was similar for patients who were relatively healthy, for those with intermediate health, and for those with poor health. What’s more, the use of insulin or sulfonylureas (drugs that increase the risk for hypoglycemia) was common and similar across these groups. (more…)
Author Interviews, End of Life Care, JAMA / 12.01.2015

MedicalResearch.com Interview with: Younsuck Koh Professor of Medicine Professor of Medical Humanities and Social Sciences Chairman, the Organizing Committee of the 12th World Federation of Societies of Intensive and Critical Care Medicine Congress in Seoul Department of Pulmonary and Critical Care Medicine Asan Medical Center, Univ. of Ulsan College of Medicine Seoul, Korea and Jason Phua MBBS, FRCP National University Hospital, Singapore AVF Chairperson. Senior Consultant & Head Division of Respiratory & Critical Care Medicine Medical Research: What is the background for this study? What are the main findings? Response: Provision of humane end-of-life and palliative care for dying patients and their families must remain a focus in today’s intensive care units, which continue to see technological advancements in the forms of life-sustaining measures available. End-of-life care decisions are heavily dependent on the medical, ethical, social, and cultural context. Asia, which accounts for at least half of all patients with critical illness, mechanical ventilation, and intensive care unit deaths internationally, has diverse socioeconomic conditions, cultures, and religions. Therefore, it is likely that substantial difference in the way physicians approach end-of-life care exist between Asia and the West, and among Asian countries and regions themselves. However, prior to our study, little data existed on the end-of-life care practices in this region. We found that even as end-of-life care practices in intensive care units vary significantly across Asian countries and regions, physicians in Asia generally seem less likely to limit life-sustaining treatments than their Western counterparts. Implementation of do-not-resuscitate orders are affected by multiple factors related to country or region, including economic, cultural, religious, and legal differences, as well as personal attitudes. (more…)
Author Interviews, Pediatrics / 12.01.2015

MedicalResearch.com Interview with: Tomi  Ajetunmobi MSc and Bruce Whyte MSc Bespoke Specialist Services Information Services Division NHS National Services Scotland Edinburgh Medical Research: What is the background for this study? What are the main findings? Response: In developing countries, breast milk is considered the best source of nutrition for human infants, vital for child health and development. In developed counties, however, the message that ‘breast is best’ though widely accepted, is not practiced, particularly in the UK; debate continues on the role played by infant feeding in ensuring child health. The benefits of breastfeeding in terms of child health have been difficult to prove methodologically for ethical reasons. Moreover, most studies that have shown an association are often limited by the sample size, scope of the data and adjustment for a wide range of confounders particularly socioeconomic factors, which influence both infant feeding and child health outcomes. Using a range of linked administrative records comprising 502,948 singletons born in Scotland between 1997 and 2013 (representing approximately 70% of all Scottish births) , the study aimed to quantify the association between infant feeding patterns reported at a routine check-up 6 to 8 weeks after birth and hospital admission for childhood common illnesses. These included gastrointestinal, respiratory and urinary tract infections, otitis media, fever, asthma, eczema, diabetes and dental caries. The linkage made it possible to adjust for a wide range of confounders. Our findings were consistent with other studies and showed a greater risk of hospital admission amongst infants who were not breastfed particularly within six months of birth, even after adjustment for parental, delivery and infant health factors and features of the health care system. At least one in five hospitalisations for gastrointestinal and lower respiratory tract infections within six months of birth may have been averted (all other factors remaining constant) had all children in the cohort been exclusively breastfed 6 to 8 weeks after birth. The association was also evident beyond six months of birth. (more…)
Author Interviews, Blood Pressure - Hypertension, Ophthalmology / 12.01.2015

MedicalResearch.com Interview with: Zheng He and Bang V. Bui Department of Optometry & Vision Sciences University of Melbourne, Parkville, Australia Medical Research: What is the background for this study? What are the main findings? Response: Glaucoma, the second leading cause of blindness in the world, is a condition that occurs when too much pressure builds up inside the eye. This excess pressure injures the optic nerve (the wire that transmits visual information to the brain) resulting in vision loss. Many risk factors for glaucoma are not well understood. High blood pressure (> 140/90 mmHg) is probably the most common comorbidity in patients presenting to optometry clinics. The overall prevalence of hypertension worldwide is over 26%, and increases dramatically with advancing age. Long-term hypertension leads to remodeling of the heart and blood vessels, promoting the risk of multiple end organ damage. Whilst chronic hypertension is a well-documented risk factor for stroke, the link between hypertension and glaucoma remains unclear. Previously, it was thought that high blood pressure could counteract high intraocular pressure, which is a clear risk factor for glaucoma. However, this issue may be more complicated than first thought. The Baltimore Eye Survey compared the prevalence of glaucoma in young and older patients with hypertension. They found that young patients with high blood pressure were at lower risk of glaucoma compared to the entire cohort. This outcome is consistent with the idea that higher blood pressure provides better perfusion pressure to the eye. Paradoxically systemic hypertension in older subjects actually increased the risk of glaucoma. Its seems that longer durations of systemic hypertension impact glaucoma risk negatively. One explanation for this is that any benefit from high blood pressure counteracting high eye pressure is lost as damage to blood vessels — a consequence of hypertension — becomes more dominant. This hypothesis was tested by comparing the effect of acute (one hour) and chronic (four weeks) hypertension in lab rats with elevated eye pressure. When blood pressure was raised for four weeks, there was less functional protection against eye pressure elevation compared with the one-hour case. This shows that having high blood pressure for a longer time compromises the eye's capacity to cope with high eye pressure. This impairment was associated with thicker and narrower blood vessels and a reduced capacity for the eye to maintain blood flow at normal levels in response to eye pressure elevation (this process is known as autoregulation). Thus in chronic hypertension, smaller reduction in ocular perfusion pressure can result in blood flow deficiency. (more…)
Author Interviews, BMC, Genetic Research, Heart Disease, Pharmacology / 12.01.2015

Caroline Attardo Genco, PhD Professor Department of Medicine, Section of Infectious Diseases Department of Microbiology Boston University School of Medicine Boston MA 02118MedicalResearch.com Interview with: Caroline Attardo Genco, PhD Professor Department of Medicine, Section of Infectious Diseases Department of Microbiology Boston University School of Medicine Boston MA MedicalResearch: What is the background for this study? What are the main findings? Dr. Genco: Atherosclerosis is a common cardiovascular disease associated with heart attack and stroke. Although it has been shown that a diet high in fat as well as exposure to certain bacteria can cause atherosclerosis (the buildup of fats, cholesterol, and other substances on artery walls which can restrict blood flow), we have for the first time identified distinct gene pathways that are altered by these different stimuli. One of these bacteria, Porphyromonas gingivalis, is found in the mouth of humans with periodontal disease. Another is the bacteria Chlamydia pneumoniae, which causes pneumonia. We found that even though these three different stimuli all cause atherosclerosis, the gene pathways are distinct depending upon stimulus. This is the first study that has performed side-by-side comparison of genome-wide gene expression changes to address this issue. In this study, we used four experimental groups to compare genome-wide expression changes in vascular tissue. The first group was subjected to Porphyromonas gingivalis, while the second group received Chlamydia pneumoniae. The third group was placed on a high-fat Western style diet, while the fourth group was the control group. In collaboration with the Clinical and Translational Science Institute (CTSI) at Boston University, we performed genome-wide microarray profiling and analysis of vascular tissue from all groups to reveal gene pathways altered in vascular tissue by each treatment group. These findings may explain how specific infections or high-fat diet may cause atherosclerotic plaques to undergo changes that affect their size and stability and may ultimately lead to a heart attack. (more…)
Author Interviews, Leukemia, Social Issues / 12.01.2015

Professor Eleni Petridou Preventive Medicine & Epidemiology, Department of Hygiene Epidemiology and Medical Statistics, Athens University Medical School Athens GreeceMedicalResearch.com Interview with: Professor Eleni Petridou Preventive Medicine & Epidemiology, Department of Hygiene Epidemiology and Medical Statistics, Athens University Medical School Athens Greece Medical Research: What is the background for this study? What are the main findings? Prof. Petridou: Impressive gains in survival from childhood leukemia have been achieved during the last decades mainly on account of advancements in treatment of the disease. Yet, these big improvements do not seem to be equally shared by all sick children. Disparities in the survival of children suffering leukemia who live in high versus low-income countries, as well as among different racial groups pointed to socio-economic status (SES) of the family as a factor that might adversely affect the outcome. SES, however, is a multifaceted variable comprising economic, social and professional components, which cannot be easily assessed. Therefore, an array of area of residence- and individual family- based proxy indices have been used in order to investigate the association between SES and overall or event-free survival from childhood leukemia. We have intensively searched for published articles around the globe and also analyzed primary data kindly provided by the US National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) for the period 1973-2010 as well as the Nationwide Registry for Childhood Hematological Malignancies (NARECHEM) in Greece for the period 1996-2011. This study is the first meta-analysis summing up the findings of 29 individual studies and quantifying the adverse effect in the survival due to SES differentials among 60 000 afflicted children. According to the findings, lower socio-economic status children suffering, at least, the more common Acute Lymphoblastic Leukemia (ALL) type have nearly two fold higher death rates compared to those of high socio-economic status. Of note, the SEER data show that the survival gap was wider in the USA with increased risk of death from ALL in the lower SES children (by 20-82%) and widening during the last 40 years time period. (more…)
Author Interviews, Rheumatology, Statins / 12.01.2015

Dr Geeske Peeters Postdoctoral Research Fellow School of Public Health The University of Queensland AustraliaMedicalResearch.com Interview with: Dr Geeske Peeters Postdoctoral Research Fellow School of Public Health The University of Queensland Australia Medical Research: What is the background for this study? What are the main findings? Dr. Peeters: The hypothesis we set out to investigate was that statin use is associated with reduced joint pain/stiffness and consequently improved physical functioning and quality of life. This hypothesis was based on findings from previous studies suggesting that statin use may prevent the development of radiographic osteoarthritis. However, in contrast with this hypothesis, results from this large study did not demonstrate an association between statin use and reduced onset of joint pain or stiffness. Moreover, statin use did seem to be associated with an increased risk of functional limitations and poorer self-reported health, especially in the middle-aged women. (more…)
Author Interviews, Breast Cancer, Genetic Research, Nature / 11.01.2015

MedicalResearch.com Interview with: Dr. Pentao Liu PhD and Dr. Walid Khaled PhD Wellcome Trust Sanger Institute Cambridgeshire United Kingdom Medical Research: What is the background for this study? What are the main findings? Dr. Pentao Liu: The significance of this research is that it aims to tackle the worst type of breast cancer. Triple Negative Breast Cancer (TNBC) has the poorest patient survival rate compared to other forms of breast cancer.  At present there are no targeted therapies available for TNBC, leaving the non-specific chemotherapy as the only treatment option. In this study we identify a new key gene in  Triple Negative Breast Cancer which could potentially be inhibited for the targeted treatment of TNBC. In this study we report the identification of a novel gene for Triple Negative Breast Cancer. By analyzing genomics data from 3,000 patients we find BCL11A to be highly expressed in TNBC. We then demonstrate experimentally that upregulation of BCL11A drives tumour development while its downregulation leads to reduction in tumour size. In the experimental mouse model, inactivation of this gene completely abolishes breast tumour development. (more…)
Author Interviews, Breast Cancer, JNCI / 11.01.2015

https://medicalresearch.com/category/hepatitis-liver-disease/page/2/MedicalResearch.com Interview with: Hazel B. Nichols, PhD Assistant Professor, Department of Epidemiology University of North Carolina Gillings School of Global Public Health MedicalResearch:What is the background for this study? Dr. Nichols: Tamoxifen, a drug that is often used to treat breast cancer, has also been approved to prevent breast cancer in women who may be at high risk for developing the disease. Taking tamoxifen for 5 years can lower breast cancer risk by up to 48%. The United States Federal Drug Administration (FDA) approved tamoxifen for breast cancer prevention more than 15 years ago (in 1998) for women ages 35 and older who are at high risk of breast cancer and who are at low risk for serious side effects. National estimates show that <1% of women who are eligible to use tamoxifen actually use it for breast cancer prevention. While tamoxifen lowers breast cancer risk it does cause hot flashes and may lead to serious side effects such as cataract, stroke, and uterine cancer. Women who start taking may also stop taking it before the recommended 5-years due to side effects. We used a tool developed by scientists at the National Cancer Institute (NCI) to calculate whether the benefits of tamoxifen outweighed the risks for women in the Sister Study, a study of more than 50,000 U.S. and Puerto Rican women with a family history of breast cancer. The tool uses information on a woman’s age, race, breast cancer risk, menopausal status, and whether she had a hysterectomy (surgical removal of the uterus) to estimate whether there is no, moderate or strong evidence that the benefits of tamoxifen will outweigh the risks. (more…)
Author Interviews, Brigham & Women's - Harvard, Pain Research / 11.01.2015

John N. Mafi, M.D. Fellow, Harvard Combined Program in General Medicine Beth Israel Deaconess Medical Center Brookline, MA 02446MedicalResearch.com Interview with: John N. Mafi, M.D. Fellow, Harvard Combined Program in General Medicine Beth Israel Deaconess Medical Center Brookline, MA 02446 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Mafi: Headache costs our healthcare system over 30 billion dollars annually. Clinical guidelines recommend conservative treatments for uncomplicated headache, such as counseling on dietary trigger avoidance. The Choosing Wisely Campaign of the American Board of Internal Medicine has in turn identified advanced imaging (e.g. CT or MRI) and opioid or barbiturate medications as low value treatments in the management of headache. In this context we used a nationally representative database to evaluate trends in physician practice patterns on headache management. We found a doubling in use of advanced imaging, referrals to other physicians and no change in opioid/barbiturate medications, although these continued to be used at high rates (18%). We also found a decline in life-style modification counseling, meant to prevent headaches from starting. (more…)
Author Interviews, Breast Cancer, Genetic Research / 10.01.2015

Dr. Chao Cheng PhD Department of Genetics Geisel School of Medicine at Dartmouth Hanover 03755, NHMedicalResearch.com Interview with: Dr. Chao Cheng PhD Department of Genetics Geisel School of Medicine at Dartmouth Hanover 03755, NH   MedicalResearch: What is the background for this study? What are the main findings? Dr. Chao Cheng: Cancer survival prognosis—“How long do I have, Dr.?” is a topic of great importance to cancer patients and their families. While clinical and pathological variables, such as cancer type, stage, grade, and patient demographics, have long been used to predict survival outcomes, only recently have molecular signatures become incorporated into survival prediction. A molecular approach holds great promise for improving prediction accuracy and additionally elucidating mechanisms of disease, however it is fraught with difficulty due to assay “noise” and “big data” statistical issues, such as the multiple comparisons problem In this study, we began by analyzing transcription factor binding profiles across available cell lines. By restricting our analysis to transcription factors, DNA expression regulators known to be involved in tumor genesis, we reasoned that we could avoid many of the “big data” issues and achieve results that would make mechanistic and biological sense. We first employed a statistical method we described previously to calculate which genes were the major downstream targets of our transcription factors. With these targets identified, we then analyzed gene expression data using a bioinformatics method to infer the relative activity of each transcription factor based upon the overall expression levels of their gene targets. From here, we incorporated cancer survival data and examined how each transcription factor’s regulatory activity did, or did not, correlate with survival. The most prognostic transcription factor was E2F4, a member of the E2F family and a known regulator of the cell cycle. We therefore restricted our analysis to E2F4 and examined how its activity level impacted survival in breast cancer patients. We found that tumors with high E2F4 regulatory activity as compared to low E2F4 regulatory activity had much worse survival outcomes. These results were stable even after controlling for tumor stage, grade, patient age, and treatment, and were based on data from over 1900 patients across eight independent datasets. These results demonstrate that E2F4 is an independent and enhancing predictor of survival above the currently examined variables. (more…)
Author Interviews, Prostate Cancer, Vaccine Studies / 10.01.2015

Dr. Robert S. DiPaola Director, Rutgers Cancer Institute of New Jersey New Brunswick, NJ 08901MedicalResearch.com Interview with: Dr. Robert S. DiPaola Director, Rutgers Cancer Institute of New Jersey New Brunswick, NJ 08901   Medical Research: What is the background for this study? What are the main findings? Dr. DiPaola: Despite significant recent improvements in the treatment of advanced castration-resistant prostate cancer, there remains a need for a standard therapy for those patients who have an early relapse with PSA progression after local therapy.  Immune therapy with poxvirus vaccines are optimal, because they can induce potent immune responses by mimicking natural infection, have great flexibility regarding antigen composition and are easily administered. ECOG-ACRIN Cancer Research Group investigators conducted a Phase II clinical trial examining adult patients from member institutions with advanced prostate cancer (as evidenced by two rising prostate-specific antigen or PSA values and no visible metastasis) who had prior surgery or radiation. We explored two different experimental treatment options. In step one, patients were treated with PROSTVAC-V/TRICOM and PROSTVAC-F/TRICOM. PROSTVAC-V is derived from a vaccinia virus that was used for many years to vaccinate against smallpox. This virus is modified to produce a PSA protein that helps focus the body’s immune response to the PSA in the prostate tumor. In addition, it is modified to produce three other proteins that help increase an immune cell’s ability to destroy its target (TRICOM). PROSTVAC-F is made from the fowlpox virus, which is found in birds and not known to cause any human disease.  It contains the same genetic material as PROSTAC-V, but is given multiple times to further boost the body’s immune system. Patients in the study were given one cycle of PROSTVAC-V/TRICOM followed by PROSTVAC-F/TRICOM for subsequent cycles in combination with a drug known as GM-CSF. GM-CSF is a protein normally made by the body to increase the amount of certain white blood cells and make them more active. When in drug form, it is used to boost the body’s immune system to fight off disease.  After six months from first treatment, 25 of 40 eligible patients (63 percent) were found to have no disease progression and experienced minimal toxicity.  The rate of rise of PSA also decreased.  The second part of the study included the addition of hormone therapy (androgen ablation) to the PROSTVAC-VF/TRICOM combination. In the 27 patients eligible for this step, 20 patients (74 percent) experienced a significant response at seven months. (more…)
Author Interviews, Heart Disease, Yale / 10.01.2015

David L. Katz, MD MPH FACPM FACP President of the American College of Lifestyle Medicine Yale University Prevention Research Center Derby, CT; Griffin Hospital, Derby, CTMedicalResearch.com Interview with: David L. Katz, MD MPH FACPM FACP President of the American College of Lifestyle Medicine Yale University Prevention Research Center Derby, CT; Griffin Hospital, Derby, CT Medical Research: What is the background for this study? What are the main findings? Dr. Katz: We have long advised patients at risk for heart disease to avoid eggs- but have thought relatively little about what they might wind up eating instead.  While coronary care units banish eggs, they routinely serve white bread, bagels, pancakes, etc.  In general, the exclusion of eggs from the diet may result in more sugary, starchy foods- and if so, might do net harm.  We have previously studied egg intake in healthy and dyslipidemic adults, and seen no adverse effects on blood flow or biomarkers in the short term (6 wks).  This study examined this issue in adults with coronary artery disease- and again, no adverse effects were seen. (more…)
Author Interviews, Neurological Disorders / 09.01.2015

Julio C. Martinez-Trujillo, MD, PhD Canada Research Chair in Neuroscience Associate Professor, Department of Physiology McGill University Montreal, Quebec, CanadaMedicalResearch.com Interview with: Julio C. Martinez-Trujillo, MD, PhD Canada Research Chair in Neuroscience Associate Professor, Department of Physiology McGill University Montreal, Quebec, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Martinez-Trujillo: Humans and other primates have an extraordinary ability to voluntarily and efficiently focus attention on important information while ignoring distraction. For decades it has been hypothesized that this ability relies on the evolutionary expansion of the lateral prefrontal cortex, a part of the brain located in the lateral convexity of the frontal lobe, that reaches its highest level of complexity in primates. Several studies have demonstrated that the activity of single neurons in the lateral prefrontal cortex of behaving primates is strongly modulated by allocating attention to different objects or locations. However, one fundamental outstanding question in this field of research is whether assemblies of simultaneously active lateral prefrontal cortex neurons (neuronal assembly) can generate sufficient information to implement the cognitive operation of attention. This is not trivial since when multiple neurons are simultaneously active the amount of information they generate depends on processes such as correlated noise and trial-to-trial response variability, which can substantially impair the information carried by a neuronal population. In order to investigate this issue we recorded the activity of hundreds of lateral prefrontal neurons in non-human primates while they allocated attention to one of several objects across the visual field. We input the recorded signals into a machine-learning algorithm running on a personal computer that mimicked the computations performed by a brain network of interconnected neurons. We tested the hypothesis that the computer will reliably signal where the subjects allocated attention on a computer display. Indeed, the machine could predict with 100 milliseconds resolution where the subjects directed attention on the display. This prediction was made well in advance the subjects executed any action towards the attended object. Thus, assemblies of prefrontal neurons can reliably signal the allocation of attention across the visual field within realistic timeframes. (more…)
Author Interviews, CDC, Sexual Health / 09.01.2015

MedicalResearch.com Interview with: Dr. Catlainn Sionean Epidemiologist, CDC’s Division of HIV/AID Medical Research: What is the background for this study? Dr. Sionean: Previous research has shown that heterosexuals in low socio-economic communities are disproportionately affected by HIV, so we analyzed data on low-SES heterosexuals in 21 metropolitan areas with a high AIDS burden from CDC’s National HIV Behavioral Surveillance system to better understand individual risk and HIV testing behaviors within this population. Medical Research: What are the main findings? Dr. Sionean: This analysis makes it clear that we must do a better job reaching heterosexuals in urban areas with prevention services. CDC recommends that everyone be tested at least once for HIV. However, we found that overall, 1 in 4 (25%) participants had never been tested for HIV.  HIV testing rates were notably low among Latinos, who, with African Americans, share a disproportionate burden of HIV in the U.S. Additionally, 1 in 3 participants (34%) received free condoms in the last year and only 11 percent of participants participated in a prevention intervention. (more…)
Author Interviews, Blood Pressure - Hypertension, Nutrition, Salt-Sodium / 08.01.2015

MedicalResearch.com Interview with: Zvonko Rumboldt, MD, PhD Professor emeritus Split University School of Medicine; Split, CroatiaMedicalResearch.com Interview with: Zvonko Rumboldt, MD, PhD Professor emeritus Split University School of Medicine; Split, Croatia Medical Research: What is the background for this study? What are the main findings? Dr. Rumboldt: Arterial hypertension is the major common denominator of a number of cardiovascular diseases and untoward outcomes including stroke, myocardial infarction, terminal renal insufficiency, heart failure and death. Excessive salt intake is the leading causative factor of blood pressure elevation across the world. It has been shown beyond any reasonable doubt that reduction in salt consumption decreases the prevalence of arterial hypertension and eases its management. Therefore many endeavors and campaigns aimed at moderation in salt ingestion have been launched with fair but less than expected results. The main source of ingested salt in developed countries is processed food, while in transitional and developing countries it is addition during food preparation (cooking), serving and salting at the table. This study, executed in Mostar, Bosnia and Herzegovina, and Split, Croatia, was designed to evaluate the effects of emphasized warning, consisting in self-adhesive stickers with clear, short message, put on household salt containers. Analyzed were 150 treated hypertensives, randomized in two groups, both receiving oral information and written leaflet concerning salt-hypertension relationship; the intervention group received in addition warning labels to be put on salt containers. In both groups measured were 24-hour urinary sodium excretion (natriuria), blood pressure, and several other parameters at inception of the trial, and one and two months later. In the intervention group observed was a marked decrease in sodium excretion (e.g. from 211 mmol/l at the beginning to 176 mmol/l at two months), much less (from some 207 to 200 mmol/l) in the control group. At the same time, the  mean blood pressure (already fairly well controlled) was reduced by additional 4 mm Hg in the intervention group (from 104 to 100 mm Hg), which was not the case in the control group (from 104 to 103 mm Hg). (more…)
Author Interviews, Diabetes, Ophthalmology, Telemedicine / 08.01.2015

MedicalResearch.com Interview with: Shi Lili Department of Medical informatics and Nantong University Library Nantong University, Nantong, China Medical Research: What is the background for this study? What are the main findings? Response: Diabetic retinopathy (DR) is the most frequently occurring complication of diabetes and one of the major causes of acquired blindness in the working-age population around the world. DR can be detected using various methods. Telemedicine based on digital photographs of the fundus is being used with increasing frequency to detect DR, and especially for Diabetic retinopathy screening. The purpose of our study was to assess the diagnostic accuracy of telemedicine in the full range of DR and DME severity compared with the current gold standard. We found that the diagnostic accuracy of telemedicine using digital imaging in DR was overall high. It can be used widely for Diabetic retinopathy screening. (more…)
Author Interviews, Heart Disease, JACC / 08.01.2015

Zugui Zhang PhDMedicalResearch.com Interview with: Zugui Zhang PhD Value Institute, Christiana Care Health System Newark, Delaware MedicalResearch: What is the background for this study? Dr. Zhang: The strategies of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for revascularization have been compared in randomized clinical trials. Questions still remain concerning the comparative effectiveness of PCI and CABG. The best way to control for treatment-selection bias is to conduct a randomized trial, but such trials often have limited power to evaluate subgroups. More importantly, the results may not be generalizable, since patients are often highly selected. Nonrandomized, observational data from clinical databases can complement data from clinical trials, because observational data, if they are from a larger and more representative population, may better reflect real-world practice. ASCERT (American College of Cardiology Foundation and the Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies) was a large observational study designed to compare the long-term effectiveness of CABG and PCI to treat coronary artery disease (CAD) over 4 to 5 years. This study examined the cost-effectiveness of CABG versus PCI for stable ischemic heart disease. MedicalResearch: What are the main findings? Dr. Zhang: This study examined the cost-effectiveness of CABG versus PCI for stable ischemic heart disease.   Adjusted costs were higher for CABG for the index hospitalization, study period, and lifetime by $10,670, $8,145, and $11,575, respectively. Patients undergoing CABG gained an adjusted average of 0.2525 and 0.3801 life-years relative to PCI over the observation period and lifetime, respectively. The life-time incremental cost-effectiveness ratio of CABG compared to PCI was $30,454/QALY gained. This study shows that over a period of 4 years or longer, CABG is associated with better outcomes but at higher cost than PCI among older patients with 2- or 3-vessel CAD. Under the assumption that our analysis has fully accounted for both measured and unmeasured confounding, in patients with stable ischemic heart disease, CABG will often be considered cost-effective at thresholds of $30,000 or $50,000/QALY. (more…)
Author Interviews, Gender Differences, Heart Disease, JACC, Lifestyle & Health / 07.01.2015

Andrea Kaye Chomistek ScD Assistant Professor Epidemiology and Biostatistics Indiana University BloomingtonMedicalResearch.com Interview with: Andrea Kaye Chomistek ScD Assistant Professor Epidemiology and Biostatistics Indiana University Bloomington   Medical Research: What is the background for this study? What are the main findings? Dr. Chomistek:  Although mortality rates from coronary heart disease in the U.S. have been in steady decline for the last four decades, women aged 35-44 have not experienced the same reduction. This disparity may be explained by unhealthy lifestyle choices. Thus, the purpose of our study was to determine what proportion of heart disease cases and cardiovascular risk factors (diabetes, hypertension, and high cholesterol) could be attributed to unhealthy habits. We defined healthy habits as not smoking, a normal body mass index, physical activity of at least 2.5 hours per week, watching seven or fewer hours of television a week, consumption of a maximum of one alcoholic drink per day on average, and a diet in the top 40 percent of a measure of diet quality based on the Alternative Healthy Eating Index. We found that women who adhered to all six healthy lifestyle practices had a 92 percent lower risk of heart attack and a 66 percent lower risk of developing a risk factor for heart disease. This lower risk would mean three quarters of heart attacks and nearly half of all risk factors in younger women may have been prevented if all of the women had adhered to all six healthy lifestyle factors. (more…)
Author Interviews, Pediatrics, Pharmacology / 07.01.2015

Prof. H. Szajewska The Medical University of Warsaw Department of Paediatrics Warsaw, PolandMedicalResearch.com Interview with: Prof. H. Szajewska The Medical University of Warsaw Department of Paediatrics Warsaw, Poland   Medical Research: What is the background for this study? Dr. Szajewska: Proton pump inhibitors (PPIs) are increasingly being used in the management of irritability and excessive crying in young infants. For example, a 7-fold increase in PPI prescriptions for infants was demonstrated in one US-based study. While differences among countries may occur, over-prescription of PPIs for infants remains a problem. The use of PPIs is mainly based on the assumption that these symptoms are attributable to gastroesophageal reflux or gastroesophageal reflux disease. Indeed, in infants, common symptoms of both conditions include regurgitation or vomiting associated with irritability or crying. However, there is still uncertainty with regard to the role of proton pump inhibitors for the management of excessive crying and irritability. Dr. Szajewska: What are the main findings? We aimed to examine whether proton pump inhibitors are effective in the management of excessive crying and irritability in infants. Only 5 randomized controlled trials fulfilled the inclusion criteria, so the evidence remains limited. There was variability in how crying/irritability outcomes were reported, but all trials used reliable methods. Some trials showed a decrease in crying/irritability from baseline to the end of the intervention; a similar effect was observed in the control group. However, no significant differences between the treatment groups were observed. (more…)
Author Interviews, JAMA / 07.01.2015

Sakthivel Sadayappan, PhD, MBA Associate Professor Department of Cell and Molecular Physiology Loyola University Chicago Health Sciences Division Maywood, IL 60153-5500, USA.MedicalResearch.com Interview with: Sakthivel Sadayappan, PhD, MBA Associate Professor Department of Cell and Molecular Physiology Loyola University Chicago Health Sciences Division Maywood, IL  60153-5500, USA. MedicalResearch: What is the background for this study? What are the main findings? Dr. Sadayappan: Hypertrophic cardiomyopathy (HCM) is the most common form of genetic heart defect, affecting 1 in 500 people in the general population. HCM results in excessive thickening of heart muscle without an obvious cause, such as hypertension or exercise stress. Often, HCM results in sudden cardiac arrest as a result of cardiac arrhythmia. Electrocardiogram, echocardiogram and cardiac magnetic resonance imaging are commonly used to diagnose HCM. However, genetic defects in more than 10 genes could also cause HCM, and standard screening for these genes is readily available. Notwithstanding our ability to diagnose the disease, a major challenge arises from its heterogeneity. That is, individuals with the same genetic defect often present with different symptoms, ranging from no symptoms at all to severe heart enlargement. Therefore, treatment options vary from person to person, and, at present, no permanent cure is available for HCM. Beta-blockers, calcium antagonists and anti-arrhythmic drugs are currently being used to manage the disease. However, scientists must discover the reasons that explain why some people experience more severe symptoms than others. In today’s modern world, people are afflicted with stresses including, for example, diabetes, hypertension, hyperlipidemia (high cholesterol), and alcoholism. Therefore, we have hypothesized that additional cardiac stresses can aggravate the onset of Hypertrophic cardiomyopathy. To prove our hypothesis, we used a mouse model having a genetic defect known to affect cardiac muscle contractility. We subjected these mice to severe cardiac stress over a period of 12 weeks. Compared with normal mice, we found that the mutant mice showed significant cardiac abnormalities, including those associated with HCM. Thus, this demonstrated, for the first time, that additional cardiac stress applied in the presence of known genetic defects exacerbates the onset of HCM. (more…)
Author Interviews, Diabetes, Lancet / 07.01.2015

Ahmad Haidar PhD Institut de Recherches Cliniques de Montreal Montreal, QC, CanadaMedicalResearch.com Interview with: Ahmad Haidar PhD Institut de Recherches Cliniques de Montreal Montreal, QC, Canada Medical Research: What is the background for this study? What are the main findings? Response: We published a study in 2013 (Canadian Medical Association Journal 185.4 (2013): 297-305) where we did the first randomized trial comparing dual-hormone artificial pancreas against conventional pump therapy. We showed spectacular reduction in hypoglycemia (8-fold) with the artificial pancreas, but the first question people asked: Out of the improvement you showed, how much is due to simply closing the loop between the glucose sensor and the insulin pump, and how much is due to adding glucagon? In other words: if you just close the loop with insulin alone and use an advanced dosing algorithm, you may get a very high reduction of hypoglycemia that glucagon may not be needed (glucagon is associated with increased cost and device complexity). We were not able to answer this question with our study design. Since then, there have been other studies by other groups either comparing single-hormone artificial pancreas vs conventional pump therapy, or comparing dual-hormone artificial pancreas vs conventional pump therapy, and most of these studies showed improvement of both artificial pancreas systems compared to conventional pump therapy. However, there has been no study comparing the three interventions to allow us to quantify the relative benefits of simply closing the loop between glucose sensor and insulin pump versus adding glucagon to the system. Quantifying the relative benefits of glucagon is important given the increased cost and device complexity of the dual-hormone artificial pancreas. So our study compared the three interventions, and is the first study to do so. (more…)