Author Interviews
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.
10 Jan Banishing Eggs From Diet May Lead To Worse Food Choices
MedicalResearch.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.
09 Jan Brain Location Of Attention And Focusing Ability Identified
MedicalResearch.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.
09 Jan HIV Remains Threat To Urban Heterosexuals
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.08 Jan Salt Intake Reduced By Warnings on Salt Containers
MedicalResearch.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).
08 Jan Telemedicine Convenient and Cost-Effective For Diabetic Retinopathy Screening
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.08 Jan Coronary Heart Disease: Bypass Surgery Has Better Outcomes But At Higher Costs Than Stents
MedicalResearch.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.
07 Jan Healthy Lifestyle In Women Markedly Reduces Cardiovascular Risk
MedicalResearch.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.
07 Jan Proton Pump Inhibitors Not Helpful For Irritable Babies
MedicalResearch.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.
07 Jan Cardiac Defect of Hypertrophic Cardiomyopathy Aggravated By Life Stresses
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.
07 Jan Dual-Hormone Artificial Pancreas Reduces Hypoglycemia Risk
MedicalResearch.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.
07 Jan Night-Shift Work Linked To Increased Mortality In Nurses
MedicalResearch.com Interview with:
Eva Schernhammer, MD, DrPH
Associate Professor of Medicine
Brigham and Women's Hospital and Harvard Medical School
Associate Professor of Epidemiology
Harvard School of Public Health
Channing Division of Network Medicine
Medical Research: What is the background for this study? What are the main findings?
Prof. Schernhammer: The study is an observational cohort study of over 70,000 registered nurses from within the US who reported the total number of years they had worked rotating night work and were followed for several decades. We examined overall mortality in these women, and observed significantly higher overall mortality, as well as higher mortality from cardiovascular disease in women with several years of rotating night shift work, compared to nurses who had never worked night shifts. There was also some suggestion for modest and non-significant increases in mortality from a few cancers. The study is unique due to its size, the fact that all participants were nurses (eliminating potential biases arising from differing occupational exposures), the long follow-up, and the possibility to take into account most known risk factors for chronic diseases that we currently know of (all of this information has been collected regularly and repeatedly).
07 Jan Calcium Score and Coronary CT Offer Additive Prognostic Values in Coronary Artery Disease
MedicalResearch.com Interview with:
Dr. Kongkiat Chaikriangkrai MD
Department of Medicine, Houston Methodist Hospital
Houston, TX 77030
Medical Research: What is the background for this study?
Dr. Chaikriangkrai: Coronary computed tomography angiography (CCTA) and coronary artery calcium score are well known to be useful tools for patients suspected for coronary artery disease. Although both imaging studies are similar in many ways (e.g. CT-based studies, anatomical evaluation of coronary artery disease, etc.), they are completely independent tests that measure different aspects of coronary artery. Furthermore, each test also requires its own separate scan.
In earlier times, calcium score testing was routinely performed prior to CCTA since high calcium score can affect diagnostic accuracy of CCTA. Therefore, CCTA may not be the best option for patients who are known to have high calcium score and other tests along the line can be further considered. However; there have been debates over the need for calcium score scan in this setting alone without enough evidence of additive prognostic benefit of measuring calcium score on top of CCTA due to concerns of extra radiation exposure from performing CT scanning twice.
From this very clinical question, our study was designed to examine whether there was any additional benefit of measuring calcium score over CCTA alone (i.e. Does a patient with high calcium score have worse prognosis than a patient with lower calcium score given that both have similar CCTA results?)
Medical Research: What are the main findings?
Dr. Chaikriangkrai: Our study found that both CCTA and calcium score testing carried its own prognostic value which was independent from each other. Furthermore, measuring calcium score also gave extra ability to predict bad clinical outcomes on top of the information obtained from CCTA alone in patients suspected for coronary artery disease (i.e. A patient with high calcium score did have worse prognosis than a patient with lower calcium score given that both have similar CCTA results).
07 Jan Combination Services Have Higher Smoking Cessation Rates
MedicalResearch.com Interview with:
Mary Puckett, PhD
CDC
Division of Cancer Prevention and Control.
Medical Research: What is the background for this study? What are the main findings?
Dr. Puckett: Smoking causes 480,000 deaths per year in the United States. Quitline services are offered by all 50 states. In addition to telephone quitlines, 96% of states also offer some form of web-based cessation service. Seven months after enrollment in the study, participants from four state quitlines were asked if they had smoked in the past 30 days as a measure of their smoking cessation success. Participants who used quitlines and web-based services in combination had higher rates of smoking cessation than participants who used only one of these services.
07 Jan Screening Mammography Drops After Age 70 But Invasive Breast Cancer Does Not
MedicalResearch.com Interview with: Pamela Vacek, PhD Research Assistant Professor Department of Pathology Medical Biostatistics Unit, College of Medicine University of Vermont, Burlingon, Vermont Medical Research: What is the background for this study? What are the main findings? Dr. Vacek: Clinical trials to evaluate the effectiveness of screening mammography have focused primarily on women under age 70 and, consequently, its benefit for older women is uncertain. However, many believe that the benefit of screening mammography diminishes as women age and acquire other health problems, because they are less likely to live long enough for any detected breast cancer to have a clinical impact. To gain insight into this, we followed approximately 20,000 women aged 70 and older for an average of 10 years to examine their mammography use, cancer detection and survival. We found that screening mammography use declined steadily (9% per year) after age 70, but this was not accompanied by decline in the incidence of invasive breast cancer. Hence, as the women aged breast cancer was more likely to be detected clinically than by screening. The clinically detected tumors were significantly larger and of more advance stage and were associated with poorer overall survival, for all but the oldest and most infirm women. We also found that the use of breast conserving surgery as the only treatment for early stage cancer increased markedly with age and was associated with shorter survival compared to women receiving radiation or mastectomy.07 Jan Study Aims To Determine Why Patients Drop Out of Colon Cancer Screening
MedicalResearch.com Interview with:
Dr Siu Hing Lo
Research Associate in Health Psychology UCL
Research Department of Epidemiology and Public
Medical Research: What is the background for this study? What are the main findings?
Dr. Lo: Most types of population-based cancer screening – such as the Faecal Occult Blood (FOB) test – require repeat participation to be effective. The Faecal Occult Blood test is a stool test that typically needs to be self-completed every two years. This study investigated predictors of repeat participation in the NHS Bowel Cancer Screening Programme (BCSP). Late kit return, a definitive abnormal [FOB test] result and failure to comply with a follow-up colonoscopy in a previous screening episode were consistently and independently associated with lower repeat uptake.
07 Jan Dabigatran Carries Risk of GI Bleeding; Risk Greater in Kidney Disease, Black Patients
MedicalResearch.com Interview with:
Inmaculada Hernandez, PharmD
PhD Student, Health Services Research and Policy
Deparment of Health Policy and Management
Graduate School of Public Health
University of Pittsburgh Pittsburgh, PA 15261
Medical Research: What is the background for this study? What are the main findings?
Response: The approval of dabigatran was considered a major contribution to the therapeutic arsenal of anticoagulants since warfarin, whose therapeutic management is complicated, was the only oral anticoagulant approved before 2011. Clinicians therefore considered dabigatran a very promising drug; however, the safety warnings released by the regulatory agencies and the reports of bleeding published in 2011 raised concerns about the safety profile of dabigatran. By the time we initiated our study, the FDA had concluded that dabigatran was associated with similar rates of bleeding than warfarin. However, the results of this observational study were not adjusted by patient characteristics. We therefore compared the risks of bleeding with dabigatran and warfarin adjusting for patient characteristics and using propensity score methods to mitigate selection biases, which observational studies are sensitive to.
We found that dabigatran was associated with a higher risk of major bleeding and gastrointestinal bleeding than warfarin. However, the risk of intracranial bleeding was lower with dabigatran. In addition, we found that the increased risk of bleeding with dabigatran was specially higher for African Americans and for patients with chronic kidney disease.
06 Jan Spiders Are Rarely The Source Of Bacterial Infections
MedicalResearch.com Interview with:
Rick Vetter (retired)
Department of Entomology
Univ. Calif. Riverside
Riverside, CA 92521
Medical Research: What is the background for this study? What are the main findings?
Response: Regarding the spider toxinology field, many misconceptions have been voiced over the years with statements being made in the medical literature which are tenable sounding explanations offered by well-meaning physicians, however, when given further scrutiny, are not supported by the data. An example of this is the platitude from years ago (and sometimes still today) that brown recluse spider bites are feasible diagnoses anywhere in North America because the spiders CAN get transported around. However, these authors never actually show that brown recluse spiders ARE frequently transported around in sufficient numbers such that they are tenable culprits in necrotic skin lesions.
The evidence developed in the last decade regarding this situation shows that brown recluses DO NOT get transported often, DO NOT establish extra-indigenous populations often and they are not likely etiologies for necrotic skin lesions outside of their indigenous range. Similarly, a commonly heard statement over the decades is that spiders are likely vectors of bacterial skin lesions. Several studies have swabbed the fangs and mouthparts of spiders, found bacteria and proudly proclaim the association between spider bites and bacterial infections. However, these same authors never actually prove that verified spider bites result in bacterial transfer to humans.
This current study was instigated in part due to statements made in the 1990s by the late Dr. Philip Anderson, Missouri dermatologist and brown recluse spider bite expert, that recluse spider bites are never infected even in non-medicated patients. So if spiders actually can vector bacteria, then a data-mining of the vast literature on spider bites worldwide should show significant bacteria association in the form of infected skin lesions as signs of envenomation. In contrast, there is almost a complete absence of reports of infection when one examines the thousands of spider bites that include a vast array of medically important spiders including the widows, recluses, armed or wandering spiders of South America, Sydney funnel web spiders, wolf spiders, yellow sac spiders, as well as studies involving a random conglomeration of species. A mechanism to explain this lack of bacterial vectoring may lie in the fact that the venom of spiders (as well as other venomous animals) has antibacterial and antimicrobial capabilities which may function evolutionarily to prevent bacterial transfer from prey to spider in bites.
06 Jan Your Mother Was Right! Cold Viruses Thrive At Cooler Temperatures
MedicalResearch.com Interview with:
Akiko Iwasaki PhD
Departments of Immunobiology and
Laboratory Medicine, Yale University School of Medicine
New Haven, CT 06520
Medical Research: What is the background for this study? What are the main findings?
Dr. Iwasaki: Since the 1960's, scientists have known that the rhinovirus, the common cold virus, replicates preferably at the cooler temperature found in the nose (33C) but not at the core body temperature found in the lungs (37C). However, the underlying mechanisms were not known. We focused on the host immune response as a possible factor that enables rhinovirus to replicate in the cooler temperature. Indeed, we found that by incubating airway cells isolated from mice at the cooler temperature, immune response to the virus was impaired. By using airway cells from knockout mice from which key innate sensor pathway or interferon receptor is deleted, we found that the virus now replicates even at the core body temperature of 37C. These experiments showed us that the rhinovirus replication is blocked at the higher temperature because of a more efficient immune defense at the core body temperature.
06 Jan Study Highlights Need To Minimize Familial Suicide Tendency
MedicalResearch.com Interview with:
Dr. Brent David MD
Academic Chief, Child and Adolescent Psychiatry at Western Psychiatric Institute and Clinic Professor of Psychiatry, Pediatrics & Epidemiology
University of Pittsburgh School of Medicine
Medical Research: What is the background for this study?
Dr. David: There are now many studies that show that suicide and suicidal behavior run in families. A family history of suicide increases the risk for suicide attempt and vice versa, so that we believe that the trait that is being passed from parent to child is a tendency to act on suicidal thoughts, resulting in either an attempt or an actual suicide. However, what was not not known was the mechanism by which parents transmitted the risk of suicidal behavior to their children, and what the precursors of suicidal behavior looked like in individuals who were at risk for suicidal behavior, but had not yet engaged in a suicide attempt. Therefore, we conducted a high-risk family study, in which studied the children of parents with mood disorders, about half of whom also had a history of a suicide attempt.
Medical Research: What are the main findings?
Dr. David: We followed 701 offspring for an average of 5.6 years, and found that those offspring whose parents had made a suicide attempt were almost 5 times more likely to make a suicide attempt themselves, even after accounting for mood disorder in parent and child and past suicidal behavior in the offspring. We found three main pathways by which suicidal behavior was passed from parent to child:
- Parental mood disorder was transmitted to children, and that was a precursor of a suicide attempt.
- Parent attempt was related to offspring impulsive aggression, which in turn increased the risk for mood disorder, which then increased the likelihood of a suicide attempt. (We define impulsive aggression as a tendency to response with hostility or aggression to provocation or frustration.
- Finally, there is a direct path from parent attempt to child attempt, with no precursors or intervening variables.
- First, these findings highlight that a parental history of a suicide attempt increases the risk of an attempt in the parent's children. Clinicians who take care of adults who have attempted suicide should make sure that children are assessed as they are at increased risk and that parents know what to look for in the future in order to get their children into needed treatment.
- Second, the transmission of suicidal behavior from parent to child can be attenuated by preventing the transmission of mood disorder, and of impulsive aggression. There are now evidence based interventions that reduce the likelihood of a child of a depressed parent from developing depression; these treatment involve cognitive behavioral principles and may also involve family interventions. There are now good family-based interventions for impulsive aggression that can attenuate the risk that the child or adolescent will go on to develop a mood disorder, which in turn greatly increases the risk for suicidal behavior.