Author: Marie Benz MD FAAD
14 Jan Melanoma: BRAF Inhibition May Switch Cancer Cells To Become More Metastatic
MedicalResearch.com Interview with:
Keiran Smalley, PhD.
Scientific Director, The Comprehensive Melanoma Research Center
Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FL
Medical Research: What is the background for this study? What are the main findings?
Dr. Smalley: Although many patients with BRAF mutant melanoma respond very well to BRAF inhibitors and the BRAF/MEK inhibitor combination, resistance is commonplace and the majority of those treated ultimately fail therapy. Most studies to date have focused upon the genetic changes that are associated with acquired BRAF and BRAF/MEK inhibitor resistance. We decided to take a different approach and to use proteomics to comprehensively map all of the signaling changes associated with resistance. Our study showed that melanoma cells with resistance to BRAF and BRAF/MEK inhibition were highly invasive and aggressive. This aggressive phenotype was driven through a cell surface receptor called EphA2, and this became upregulated in both melanoma cell cultures and in patient tumors following BRAF inhibitor treatment. As this suggested that the resistant cells would be more metastatic, we then performed animal experiments and analyzed tumors from melanoma patients receiving BRAF inhibitor. These studies showed an increase in EphA2 expression in the metastatic tumors that was lacking in the primary tumors. When we looked at cohorts of melanoma patients who received either a BRAF inhibitor or an older chemotherapy drug, we found that more of the BRAF inhibitor treated patients seemed to develop disease at new sites. Together this suggested that BRAF inhibition may switch the cancer cells to being more metastatic.
14 Jan Yoga Has Potential To Improve Cardiovascular Risk Factors
MedicalResearch.com Interview with: Paula Chu Doctoral candidate Harvard University's Health Policy Program Boston MA Medical Research: What is the background for this study? What are the main findings? Response: This study was borne out of a mutual interest in the effects of yoga and wellness in general between myself and my coauthors. We had heard and read about yoga's effects on certain conditions like anxiety and pain, and we wanted to see if there was scientific evidence on yoga's impact on measurable physiological cardiovascular outcomes.14 Jan Researchers Coax Engineered Muscle Cells To Contract in 3D Matrices
MedicalResearch.com Interview with:
Nenad Bursac PhD
Rooney Family Associate Professor of Biomedical Engineering
Associate Professor of Medicine Duke University
Medical Research: What is the background for this study? What are the main findings?
Dr. Bursac: Researchers have tried for a long time to coax human muscle cells (obtained from needle biopsies) into contracting muscle fibers in a dish in order to be able to study human muscle physiology ex vivo. We are the first group that succeeded by carefully optimizing culture conditions including methods to expand and then culture cells in three-dimensional hydrogel matrices under passive tension. By doing so, we made first human muscle model that in response to electrical stimulation generates classical muscle contractile responses (twitch and tetanus). We have also shown that these engineered muscles (that we call "myobundles") contract in response to acetylcholine as it naturally happens when neurons in our body activate muscle. We demonstrated reproducibility and robustness of the approach by generating functional myobundles with similar properties from 10 independent donor muscle samples. We further went to show that myobundles have intact signaling characteristic of native muscle and respond to diverse set of drugs as human muscles do in clinics.
14 Jan Bilingualism Can Preserve White Matter in Brain
MedicalResearch.com Interview with:
Dr Christos Pliatsikas PhD
Lecturer in Cognitive Psychology School of Psychology
University of Kent Canterbury Kent
Medical Research: What is the background for this study? What are the main findings?
Response: It has been proposed that lifelong bilingualism preserves the white matter structure of older bilinguals because of the increased cognitive demands that come with handling two languages for their entire life. We wanted to extend this by investigating whether active (or "immersive") bilingualism in younger late bilinguals would give similar results.
We showed increased white matter integrity (or myelination) in several white matter tracts that have also been shown to be better preserved in older lifelong bilinguals, compared to monolinguals. Based on our findings, we propose that any benefit of bilingualism to the brain structure is simply an effect of actively handling two languages without presupposing lifelong usage- our participants were only about 30 years old and had been active bilinguals for only about 7-8 years. In other words, immersive bilingualism, even in late bilinguals, leads to structural changes that can bring about benefits in older age, by assisting in the preservation of the white matter structure in the brain.
14 Jan Excess Working Hours Linked To Higher Alcohol Use
MedicalResearch.com Interview with:
Professor Marianna Virtanen PhD
Unit of Expertise for Work and Organizations
Finnish Institute of Occupational Health
Helsinki, Finland.
Medical Research: What is the background for this study? What are the main findings?
Professor Virtanen: Risky alcohol use is common among working populations but the contribution of work-related factors such as long working hours has rarely been studied. In the present study we performed the first systematic analysis on published studies regarding long working hours and risky alcohol use and added unpublished individual participant data to the analyses. Altogether 61 studies were included in the cross sectional analysis and 20 studies in the prospective analysis. The pooled cross sectional analysis showed 11% higher alcohol use associated with long working hours. In the prospective analysis we found that working 49-54 hours a week was associated with a 13% increase in the probability of new-onset risky alcohol use and working 55 hours or more with a 12% increased risk.
14 Jan Race and Ethnicity Affect Breast Cancer Diagnosis and Survival
MedicalResearch.com Interview with:
Javaid Iqbal, MD, MSC (Candidate)
Institute of Medical Sciences, and
Women’s College Research Institute/Women’s College Hospital
University of Toronto, Toronto Canada
What is the background for this study? What are the main findings?
Dr. Iqbal: A woman’s racial/ethnic background predicts her participation in breast cancer control program (i.e., awareness and screening). The ultimate objective of breast cancer control program is to detect cancer at an optimal stage, which is stage I, because women with stage I breast cancer survive longer. Given the racial/ethnic diversity of North America, this poses questions such as “what predicts stage I breast cancer in the multiethnic North American population?”, “what predicts its survival?”, and “does a woman’s ethnic background plays a role in predicting an early stage, and survival?”
We studied 373,563 women diagnosed with invasive breast cancer in the United States between 2004 and 2011. We followed these women for 7 years and recorded whether or not they died of breast cancer, or whether they are still alive. We then divided all women into different ethnic groups, in particular white, black, Chinese, Japanese, and Indian/Pakistani (South Asian). For each racial/ethnic group, we estimated proportions of women who were diagnosed with stage I breast cancer, and risk of death at 7 years. Our aim was to determine if the racial/ethnic differences in early stage breast cancer, and its survival were better explained by intrinsic biological differences in tumor characteristics, or by differences in early-detection of breast cancer.
We found that a woman’s racial/ethnic background predicted the diagnosis of stage I breast cancer, as well as her risk of dying at 7 years after breast cancer. A black woman was less likely than a white woman to be diagnosed with stage I breast cancer. A black woman was also more likely than a white woman to die of stage I breast cancer 7 years after her diagnosis. The Japanese and Chinese women were more likely than white women to be diagnosed with stage I breast cancer. The risk of death at 7 years was lowest for Indian or Pakistani (South Asian) women. Furthermore, even for small sized (2.0) breast cancers the risk of death at 7 years was higher for black women (9%), compared to white women (5%). Compared to white women, small sized breast cancers in black women were more aggressive at diagnosis, and had spread to lymph nodes and other organs.
13 Jan Melanoma: Study Support 6mm Criteria in ABCD Rule
MedicalResearch.com Interview with: Razieh Soltani-Arabshahi, MD, MSci Department of Dermatology, University of Utah, Salt Lake City, Utah MedicalResearch.com: What is the background for this study? Dr. Soltani-Arabshahi: The incidence of melanoma is rapidly rising. Dermatologists are the leading specialty group to diagnose melanoma. While ABCD cirteria for diagnosis of melanoma have been used by many dermatologists, there are few studies of it's predictive value. MedicalResearch.com: What are the main findings? Dr. Soltani-Arabshahi: We showed that at an academic dermatology center, nearly 16 clinically suspicious lesions need to be biopsied to find one case of melanoma. Biopsies of lesions larger than 6 mm in diameter on older male patients had the highest yield.13 Jan Pediatric Office Visits May Miss Autism Diagnosis
MedicalResearch.com Interview with:
Terisa P. Gabrielsen, PhD, NCSP
Assistant Professor, School Psychology
Dept. of Counseling Psychology and Special Education
Brigham Young University, Provo, UT 84602
Medical Research: What is the background for this study? What are the main findings?
Dr. Gabrielsen: One of the keys to improving outcomes for individuals with outcomes is to begin intervention as early as possible, which means we need to identify autism symptoms as early as possible, preferably during the early toddler years. The current study grew out of a screening feasibility study to see what would happen if pediatricians followed the AAP guidelines for screening every child for autism at ages 18 and 24 months as part of their regular pediatric care appointments. That study was conducted in a large, independent community pediatrics practice. We found that universal screening of 796 patients helped to identify 10 toddlers with autism who had not previously been referred for evaluations. Physicians had previously identified 3 others with autism in the group, and toddlers with other delays, such as language delays, were also identified through the screening process. We wondered what some possible causes were for the low rate of autism referrals and designed the current study to look for what information was available to a pediatrician during the timespan of a typical pediatric exam. We found that even in toddlers with autism, a brief (10-minute) sample contains an overwhelming ratio of typical behaviors (averaging 89%) compared to infrequent atypical behaviors (11%) that would indicate the presence of autism. We had autism experts identifying the behaviors from videos of the evaluations of children in the previous study, so they had many luxuries that a clinician doesn't have during an exam (i.e., ability to focus on one aspect of development, ability to rewind and re-view behaviors). After watching the 10-minute video observations, we asked our experts, "Would you refer this child for an autism evaluation?" We found that even the experts missed referring a child for an autism evaluation 39% of the time when the only data available were the brief observations.
13 Jan New Dengue Vaccine Trial in Latin America Demonstrates Efficacy
MedicalResearch.com Interview with:
Gustavo Dayan, MD
Director, Clinical Development
Sanofi Pasteur Discovery Drive
Swiftwater, PA 18370
Medical Research: What is the background for this study? What are the main findings?
Dr. Dayan: This is the first dengue vaccine efficacy trial conducted in Latin America. The trial met its primary objective showing an efficacy of 60.8% against symptomatic VCD (virologically confirmed dengue) after a 3-dose vaccination schedule. Serotype-specific efficacy was also demonstrated against all four serotypes. Furthermore, the dengue vaccine candidate effectively reduced hospitalization due to dengue by 80.3% and severe dengue disease by 95.5% over the 25-month study period.
13 Jan Combination Medications May Cure Hepatitis C In Six Weeks
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.13 Jan Twist1 Necessary For Squamous Cell Tumor Formation and Progression
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.13 Jan Medicare Initiative Reduced Hospital-Acquired Infections
MedicalResearch.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.
13 Jan Study Examines Follow-up Of Abnormal Radiology Results
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.13 Jan Highly Sensitive Troponins Improve ER Diagnosis of Heart Disease
MedicalResearch.com Interview with: James Louis Januzzi, Jr, MD, FACC, FESC Director, Cardiac Intensive Care Unit Director, Dennis and Marilyn Barry Fellowship in Cardiology Research Massachusetts General Hospital Boston, MA, 02114. Medical Research: What is the background for this study? What are the main findings? Dr. Januzzi: Evaluation for suspected or proven acute coronary syndrome is...
12 Jan Nanomedicine Platform Uses Fluorescence Imaging To Seek and Destroy Cancer Cells
MedicalResearch.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.
12 Jan E-Learning May Facilitate Education of Health Professionals
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.12 Jan Metformin May Be Underutilized In Patients With Modest Kidney Disease
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.12 Jan Diabetes May Be Frequently Overtreated In Older Adults
MedicalResearch.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.
12 Jan End-of-Life Care Practices Vary Across Asia
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.12 Jan Hospitalizations Reduced in Breastfed Infants
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.12 Jan High Blood Pressure Must Be Carefully Managed In Glaucoma Patients
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.12 Jan Genetics and Common Bacteria Affect Atherosclerosis Progression
MedicalResearch.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.
12 Jan Socioeconomic Status Affects Long Term Childhood Leukemia Survival
MedicalResearch.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.
12 Jan Statins Not Helpful For Joint Disease of Osteoarthritis
MedicalResearch.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.
11 Jan Novel Gene Is Potential Therapeutic Target for Triple Negative Breast Cancer
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.11 Jan Risk-Benefits of Tamoxifen for Breast Cancer Prevention
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.
11 Jan Rushed Office Visits May Lead To Poor Headache Management
MedicalResearch.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.
10 Jan Tumor Marker E2F4 Linked to Breast Cancer Survival
MedicalResearch.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.
10 Jan Vaccine Boosts Response To Prostate Cancer Therapy
MedicalResearch.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.