MedicalResearch.com Interview with:
Jonathan Cedernaes M.D., Ph.D.Department of Neuroscience
Uppsala University Sweden
Medical Research: What is the background for this study? What are the main findings?
Dr. Cedernaes: Previous studies have demonstrated that experimental sleep loss and simulated shift work (i.e. misalignment of circadian rhythms) reduces energy expenditure and insulin sensitivity, providing links to why sleep loss may increase the risk of e.g. type-2 diabetes and obesity. Such phenotypes have also been observed in animals in which clock genes are ablated. Clock genes regulate the circadian rhythms of all cells and variants in these have also been associated with increased risk of obesity, insulin resistance and type-2 diabetes in humans. Almost no study has however investigated whether overnight wakefulness - mimicking a situation which recurrently occurs in shift work - can affect the expression of such clock genes in metabolically important tissues, i.e. adipose tissue and skeletal muscle, in humans. Such gene expression changes may both acutely and more long-term be regulated by changes in methylation, i.e. an epigenetic change, which have been found in blood of e.g. shift workers and in e.g. adipose tissue of type-2 diabetic subjects. However, whether sleep loss can lead to epigenetic changes has been unknown, and therefore also whether this could affect genes important for metabolism, such as the core clock genes which are essential for orchestrating and synchronizing downstream metabolic processes according to our circadian rhythms.
With this background in mind, I and associate professor Christian Benedict set out to conduct a study to investigate how one night of sleep loss altered gene transcription and methylation of core clock genes in adipose tissue and skeletal muscle, and whether this would be reflected at the systemic level by an impaired glucose tolerance test in healthy young individuals.
For the study, we had 15 participants undergo two almost 2-day long sessions in our lab, with the first night of each session serving as a baseline or habituation night, with a normal sleep period. On the second night, in random order, participants slept a full night (8.5 hours) in one session, and were kept awake the entire night while being bed-restricted in the other of two sessions. After each of these conditions, we took biopsies in the fasting condition from the subcutaneous adipose tissue and the skeletal muscle.
In collaboration with researchers from the Karolinska Institute, Gothenburg University and the German Institute of Human Nutrition, we were able to observe transcriptional repression of clock genes in the muscle, but not in the adipose tissue following sleep loss compared with normal sleep. Instead, we found methylation of regulatory elements of clock genes to be increased in the adipose tissue but not the skeletal muscle following sleep loss compared with normal sleep. Finally, we observed that participants had an impaired glucose tolerance test when they had been kept awake as compared with their response after sleep. (more…)
MedicalResearch.com Interview with:
Seema Jain, MD
Medical Epidemiologist
Epidemiology and Prevention Branch, Influenza Division
Centers for Disease Control and Prevention
Atlanta, GA 30329
Medical Research: What...
MedicalResearch.com Interview with:
Quan-Yang Duh MD
Chief, Section of Endocrine Surgery
UCSF Medical Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Quan-Yang Duh: At UCSF we have a monthly Adrenal Conference (involving surgeons, endocrinologists and radiologists) to discuss patients we are consulted for adrenal tumors. About 30% of these are for incidentally discovered adrenal tumors (versus those found because of specific indications such as clinical suspicion or genetic screening). Of these 15-20% has bilateral adrenal tumors.
The evaluation of unilateral incidentaloma has been very well studied and many national guidelines have been published with specific management recommendations. So during our monthly adrenal conference, we have a routine "script" for evaluation and recommendations (rule out metastasis by looking for primary cancer elsewhere, rule out pheochromocytoma and Cushing, resect secreting tumors or large tumors, and if no operation recommended repeat scan in 6 months, etc.). This “script” has worked very well for patients with unilateral incidentaloma.
However, we were less certain when we made recommendations about bilateral incidentalomas because there was very little literature or guidelines written about it. We had some gut feelings, but we were not sure that we were recommending the right things. We needed more data. That was the main reason for the study.
What we found in our study was that although the possible subclinical diseases were the same – hypercortisolism and pheochromocytoma, the probabilities were different. The patients with bilateral incidentalomas were more likely to have subclinical Cushing’s and less likely to have pheochromocytomas than those with unilateral incidentalomas.
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MedicalResearch.com Interview with:
Benjamin D. Sommers, MD, PhD
Assistant Professor of Health Policy & Economics
Harvard T. H. Chan School of Public Health / Brigham & Women's Hospital
Boston, MA 02115Medical Research: What is the background for this study? What are the main findings?
Response: The Affordable Care Act (ACA) expanded insurance options for millions of adults, via an expansion of Medicaid and the new health insurance Marketplaces, which had their first open enrollment period beginning in October 2013. We used a large national survey to assess the changes in health insurance, access to care, and self-reported health since these expansions began. What we found is that the beginning of the ACA’s open enrollment period in 2013 was associated with significant improvements in the trends of insurance coverage, access to primary care and medications, affordability of care, and self-reported health. Among low-income adults in Medicaid expansion states, the ACA was associated with improvements in coverage and access to care, compared to non-expansion states. Gains in coverage and access to medicines were largest among racial and ethnic minorities.
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MedicalResearch.com Interview with:Junfeng Jiao, PhD
Assistant Professor, The University of Texas at Austin School of Architecture
Director, Urban Information Lab
Austin, Texas
Medical Research: What is the background for this study? Dr. Jiao: The increase in obesity rates has been explained by dietary changes including the consumption of high-energy, low-nutrient foods. Over the past thirty years, trends reveal increases of eating away from home. Public Health professionals have hypothesized that the heightened exposure to the ubiquitous fast food establishments may be an avenue through which health and diets are impacted. Medical Research: What are the main findings?Dr. Jiao: This study examined whether the reported health impacts of eating at a fast food or quick service establishment on a frequent basis were associated with having such a restaurant near home. Results indicated that eating at a fast food or quick service restaurant two times or more per week was related with perceived poor health status, overweight, and obese. Simply living close to such establishments was not related to negative health outcomes such as being overweight or obese, having cardiovascular disease (CVD) or diabetes.
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MedicalResearch.com Interview with:
Christina Y. Lee BADepartment of Dermatology
Pedram Gerami, MD
Robert H. Lurie Cancer Center
Feinberg School of Medicine
Northwestern University
Chicago, Illinois
Medical Research: What is the background for this study? What are the main findings?Response: Melanoma is responsible for the majority of skin cancer-related mortality. While AJCC staging of melanoma provides highly valuable information that helps predict the behavior of cutaneous melanoma, there are likely a number of other variables not included that may help predict which melanomas may result in metastasis. Some of these data points are not be easily assessed or available in large databases. In this study, we sought to assess a broad range of specific clinical factors directly obtained from clinic notes that may help predict melanoma behavior. The study consisted of a large cohort of patients with clinical follow up from our melanoma center at Northwestern University. Some examples of evaluated characteristics include a documented history of tanning bed use, blistering sunburns, or outdoor activity. In our study, patients who were older or immunosuppressed at the time of diagnosis were associated with aggressive tumor behavior in multivariate statistical analysis, when controlled for traditional AJCC factors such as tumor depth, ulceration, and mitotic figures.
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MedicalResearch.com Interview with:
Wade Harrison, MPH
The Dartmouth Institute for Health Policy & Clinical Practice
Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
Medical Research: What is the background for this study? What are the main findings?
Dr. Harrison: This study used national birth certificate data to examine time trends in Neonatal Intensive Care Unit (NICU) admission rates for all U.S. newborns and the composition of the cohort of admitted newborns. Most of the existing studies of neonatal intensive care are limited in examining specific groups of newborns (e.g. those <1500 g, those with a specific complication, within limited geographies, etc.) or only looking at how care is delivered after a baby is admitted, leaving aside the question of whether to admit them in the first place. This is an important area to study because the newborn period is a critical time for babies and their families to establish good feeding practices and increase bonding among other important needs; also, neonatal intensive care is very expensive and like all medical interventions can carry certain risks. We found that NICU admission rates increased for all newborns across the birth weight spectrum. Additionally, although NICUs were initially developed to care for very small and premature newborns, just under half of current NICU admissions are for normal birth weight and full term infants, who are likely to be less ill.
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MedicalResearch.com Interview with:
Dr. Pinar Karaca-Mandic Ph.D
Associate Professor, Health Policy & Management
School of Public HealthDivision of Health Policy & Management Minneapolis MN
University of Minnesota
Medical Research: What is the background for this study? What are the main findings?
Dr. Karaca-Mandic: Drug safety has received a lot of attention recently, and FDA's post-marketing drug surveillance program (FAERS) offers and important opportunity to monitor drug safety and update drug warnings. There has been an increasing trend in reports to FAERS of serious adverse drug events and earlier studies suggested that these trends were primarily driven by increased manufacturer reports of serious and unexpected adverse events. While these studies highlighted the overall increase in adverse event rates, manufacturer timeliness in reporting and compliance with the 15 calendar day regulation for expedited reports was unknown, though some recent media coverage has offered anecdotal examples of delay. My co-authors and I were interested in studying not only the reporting of these events, by manufacturers to FDA, but also their timely reporting as required by the Federal regulation. Delays in reporting can have important public health consequences because the FDA uses this information to update drug warnings.
We found that about 10% of serious and unexpected adverse events that are subject to the 15-day regulation were not reported by 15 days. We also found that events that involved a patient death were more likely to be delayed. For example, we found that after adjusting for other characteristics of the report and the patient, about 12% of events that involved patient death, and 9% of those that did not involve patient death were delayed beyond 15 days.
(more…)
MedicalResearch.com Interview with:
Yigal Abramowitz, MD
Cedars-Sinai Heart Institute
Medical Research: What is the background for this study? Dr. Abramowitz: The number of elderly patients with severe symptomatic aortic stenosis (AS) that require aortic valve replacement has been significantly increasing in recent years. However, a decade ago, third of the patients were not referred to surgery, in particular because of advanced age, and /or multiple comorbidities. TAVR has emerged as a treatment option for elderly inoperable or high-risk surgical patients with severe aortic stenosis. There is scarce evidence on the feasibility and safety of TAVR in very old patients.
Medical Research: What are the main findings?Dr. Abramowitz: We compared 136 patients that were at least 90 years old at the time of TAVR (mean age: 92.4years) to 598 younger patients (mean age: 79.7years). Device success was excellent in both groups (96% for both). All-cause mortality at 30-days and 1-year was 2.9% and 12.5% vs. 2.8% and 12.3% in patients aged ≥ 90 and ˂ 90, respectively. All major complication rates were similar between groups.
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MedicalResearch.com Interview with:
Andrew T. Patterson, MD
The Ohio State University College of Medicine
The Ohio State University Wexner Medical Center
Columbus, Ohio
Medical Research: What is the background for this study? What are the main findings?
Dr. Patterson: The utilization of Agent Orange (AO) and other herbicides by the United States during the Vietnam War was controversial at the time and remains a prominent topic of scrutiny even today due to the potential long-term health effects facing exposed military and civilian personnel. The Institute of Medicine (IOM) in accordance with the National Academy of Sciences publishes a semi-annual review of the scientific and medical data regarding the resultant medical effects of Agent Orange and other organochlorine chemical exposures, however, skin diseases are no longer comprehensively assessed.
This represents an important practice gap, as in our experience, we had encountered a significant number of patients inquiring whether their cutaneous ailment could be the result of Agent Orange exposure. Our goal was to perform a systematic review of the literature and produce a practical summary of the current evidence regarding cutaneous manifestations of organochlorine exposures that could be utilized by military and non-military dermatologists alike when responding to questions related to prior Agent Orange contact.
After examining the literature, there appears to be an increased risk for chloracne, porphyria cutanea tarda, cutaneous lymphoma, and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas in organochlorine-exposed patients. Some evidence exists for a possible increased incidence of melanomas, non-melanoma skin cancers, milia, eczema, dyschromias, dysesthesias, and rashes not otherwise specified, but the data is not conclusive. Even less support exists for an association with psoriasis, seborrheic dermatitis, neurodermatitis, and hypertrichosis (more…)
MedicalResearch.com Interview with:
Patricia Kim Phuong Nguyen MD and
Joseph C. Wu, MD, PhD
Stanford Cardiovascular Institute
Stanford University School of Medicine, Stanford, California
Medical Research: What is the background for this study? What are the main findings?Response: The application of CT imaging has greatly increased in the last two decades, raising concern over the effects of low dose radiation exposure from medical imaging.
In this study, we recruited 67 patients who underwent CT imaging for various cardiovascular indications including:
1) Pre atrial fibrillation ablation
2) Pre Trans-catheter valve replacement
3) Aortic dissection, and
4) coronary artery disease.
A wide range of doses were sampled. We detected damage to DNA and a small percentage of death of T lymphocytes isolated from patients who were exposed to greater than 7.5 mSv of radiation.
No damage was detected in patients exposed to very low doses (less than or equal 7.5 mSv).
This study did not look at the relationship between radiation and cancer.
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MedicalResearch.com Interview with:
Philippe Bouillet, PhD
Walter and Eliza Hall Institute
Parkville, Vic Australia
Medical Research: What is the background for this study? What are the main findings?
Dr. Bouillet: This study was initiated when we discovered mice that developed rheumatoid arthritis as a result of what was obviously a spontaneous dominant genetic mutation. Using several approaches, we identified the mutation as the insertion of a mobile genetic element called retrotransposon into the regulatory sequences of the gene encoding tumor necrosis factor (TNF). The mutation caused excessive amounts of TNF to be produced, a known cause of rheumatoid arthritis. The surprise came when some mice with the mutation died prematurely and suddenly with from heart disease. We showed that excess TNF also led to inflammation of the aortic and mitral valves, causing aortic regurgitation. Depending on the genetic background of the mice, the disease could also culminate in aortic aneurysm and death.
We also investigated the regulatory region of the TNF gene and identified novel regulators and a new genetic element that normally make sure that levels of serum TNF are kept within reasonable limits, high enough to ensure its numerous physiological functions, low enough to prevent its harmful effects such as those described here.
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MedicalResearch.com Interview with:
Mara Meyer Epstein, ScD
Assistant Professor
Meyers Primary Care Institute
University of Massachusetts Medical School
MedicalResearch: What is the background for this study? What are the main findings?Dr. Epstein: Hodgkin lymphoma is a relatively rare cancer, with about 9,000 new cases diagnosed in the US each year. Hodgkin lymphoma is most commonly diagnosed in earlier (aged 15-34 years) or later adulthood (aged ≥50 years). The causes of the disease are not well understood, and most identified risk factors are not modifiable (for example, age, sex, family history, and infection with Epstein-Barr virus [EBV]). Previous studies have suggested that chronic inflammation may play a role in the development of Hodgkin lymphoma. Therefore, it is possible that a factor that can influence inflammation, such as diet, may be associated with risk of Hodgkin lymphoma. Discovering modifiable risk factors for Hodgkin lymphoma could offer a means for preventing this disease. The few existing studies of diet and Hodgkin lymphoma risk have focused on individual nutrients or foods; this is the first study to examine dietary pattern and risk of Hodgkin lymphoma. By examining dietary patterns instead of individual foods, we sought to assess Hodgkin lymphoma risk from the food combinations that may more closely reflect typical dietary habits.
The current study includes 435 cases of Hodgkin lymphoma and 563 controls with no history of cancer from Massachusetts and Connecticut who were enrolled in the study between 1997 and 2000. Cases and controls provided information about their average intake of 61 food and beverage items over the year prior to the study. By evaluating foods commonly consumed by the study participants, we identified four major dietary patterns; high vegetable intake, high meat intake, high intake of fruit and low-fat dairy, and high intake of desserts and sweets. We looked for associations between each dietary pattern and risk of Hodgkin lymphoma overall, and also separately by age group (<50 years or ≥50 years old), tumor EBV status (positive or negative), and by tumor cell pattern (nodular sclerosis or mixed cellularity). The dietary pattern characterized by high intake of desserts and sweets was associated with a statistically significant increased risk of Hodgkin lymphoma among younger adults, and in particular, a 2-fold increased risk among younger adults with EBV-negative tumors. The dietary pattern featuring high meat intake was associated with a 3-fold increased risk of Hodgkin lymphoma among older adults, and again, we saw a stronger association among older adults with EBV-negative tumors, although the number of such cases in this group was small. We did not observe a clear association between the high vegetable dietary pattern, or the dietary pattern high in fruit and low-fat dairy intake, with Hodgkin lymphoma risk, and we also did not find any clear associations with EBV-positive tumors, which were relatively infrequent in the study population. The findings described above were obtained from statistical calculations that also took into account known Hodgkin lymphoma risk factors, other lifestyle factors, total caloric intake, and body mass index.(more…)
MedicalResearch.com Interview with:
Nisha C. Hazra MSc
Department of Primary Care and Public Health Sciences,
King's College London, London, UK
Medical Research: What is the background for this study? What are the main findings?
Response: Our study was motivated by limited evidence about the health status of very old people, the fastest growing group of the UK population with significant implications for future NHS health-care costs. Our findings indicated an increasing number of people reaching the age of 100 years, with the increase being higher among women comparing to men (a ratio of 4 to 1). Another interesting finding was that men reaching 100 years tended to be healthier than their female counterparts. In particular, women were more likely to present multiple chronic diseases compared to men and tended to be more frail, experiencing more falls, fractures, incontinence and hearing/visual impairments.
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MedicalResearch.com Interview with:
Laura Rosella, PhD MHSc
Assistant Professor, Dalla Lana School of Public Health, University of Toronto
Scientist, Public Health Ontario
Adjunct Scientist, Institute for Clinical Evaluative Sciences
Toronto, Ontario
Medical Research: What is the background for this study? What are the main findings?
Response: High-cost users of health care generally refer to the top five per cent of health care users. They are a small portion of the population who consume a disproportionately high share of health care resources. We undertook a study to explore the social and economic determinants that were associated with future, high cost users. That is, the characteristics of these individuals before they proceed on a trajectory of high health care utilization. By understanding these associations we can better understand the role that socio-economic factors play in future health care utilizations and costs.
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MedicalResearch.com Interview with:
Riyaz Bashir MD, FACC, RVT
Professor of Medicine
Director, Vascular and Endovascular Medicine
Department of Medicine
Division of Cardiovascular Diseases
Temple University Hospital
Philadelphia, PA 19140
Medical Research: What is the background for this study?
Dr. Bashir: Catheter-based thrombus removal also known as Catheter Directed Thrombolysis (CDT) is a minimally invasive therapeutic intervention that has evolved over the past two decades to reduce the incidence of post thrombotic syndrome (PTS), a very frequent and disabling complication of proximal deep vein thrombosis (DVT). Catheter-based thrombus removal has been shown to reduce this lifestyle limiting complication of DVT and as a result we have observed a significant increase in the utilization rates of CDT across United States. Recent nationwide observational data suggests that higher adverse events such as intracranial hemorrhage rates and need for blood transfusions are seen with CDT use. Nonetheless specific reasons for these findings have not been explored prior to this study. Thread veins, also known as spider veins, are small veins which can appear on your face, thighs or calves and are an issue that many patients want help with. However, they are a cosmetic issue rather than a medical problem. People who suffer from the spider veins often feel that they affect their appearance and confidence and question why do we get thread veins?
Medical Research: What are the main findings?Dr. Bashir: This study showed a significant inverse relationship between the institutional Catheter-based thrombus removal volumes and safety outcomes like death and intracranial hemorrhage. The institutions with higher volume of CDT cases annually (greater than or equal to 6 cases) were associated with lower in-hospital mortality rates and lower intracranial hemorrhage rates as compared to institutions, which performed less than 6 cases annually. This study also showed that at high volume institutions there was no difference in terms of death or intracranial bleeding rates between CDT plus anticoagulation versus anticoagulation alone.
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MedicalResearch.com Interview with:
Holly G. Prigerson, Ph.D.
Irving Sherwood Wright Professor in Geriatrics
Professor of Sociology in Medicine
Director, Center for Research on End...
MedicalResearch.com Interview with:Benjamin D. Horne, PhD, MPH, FAHA, FACC
Director, Cardiovascular and Genetic Epidemiology, Intermountain Heart Institute
Adjunct Assistant Professor, Genetic Epidemiology Division, Department of Medicine,
University of Utah
Medical Research: What is the background for this study? What are the main findings?
Dr. Horne: A rapidly expanding set of results from animal studies exists regarding the effects of intermittent fasting among animals. Many pilot studies of intermittent fasting have been performed now, too, but the body of literature regarding the human response to fasting is incomplete. This study sought to determine how preliminary and incomplete the evidence is in humans regarding the health benefits and the harmful side-effects of intermittent fasting. The purpose was to determine how reliable the evidence is that people should be engaging in fasting to improve their health. In particular, one major concern is that diet gurus and even some scientists are marketing intermittent fasting to the public through diet books and other methods that produce additional income for them, but it is unclear whether their claims can be supported.
The main findings of the study are that only three controlled clinical trials of intermittent fasting in humans have been published that were designed rigorously and included a control group in addition to the fasting intervention arm of the study. One of the three had a pre-specified primary outcome (weight loss) and another used the Bonferroni correction to account for inflated false positive results due to multiple hypothesis tests (the third study unfortunately did neither, which is the common approach in human studies of intermittent fasting). These three controlled trials only used surrogate or intermediate endpoints, though, such as weight, cholesterol, or other risk factors for disease. The three trials also have substantial limitations, including small sample sizes (~30 people total), a fasting regimen that was studied for less than three months, and no evaluation of clinical safety outcomes. Only one of the three trials was registered on ClinicalTrials.gov, a site instituted as part of the FDA Modernization Act and a pre-requisite for trials that are published in scientifically sound medical journals and are to be reviewed by the FDA.
Two observational studies of the association of intermittent fasting with clinical events (i.e., coronary artery disease diagnosis and diabetes diagnosis) also have been published. These two studies included 200 patients and 445 patients. They were performed in patients drawn from a general population in which a large proportion of people engage in fasting intermittently over a period of decades. These observational studies provide the only evidence that fasting is associated with a lower risk of disease outcomes. Such studies are limited, though, by adjustment for only known or measured confounders, making it possible that some important factors may be unobserved in the studies that would account for the fasting benefit that was observed. No randomized controlled clinical trial of fasting for clinical events or disease outcomes has been performed, though, thus these five studies are the whole body of reliable evidence that intermittent fasting is beneficial to humans.
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MedicalResearch.com Interview with;
Poonamjot Deol, Ph.D.
Asst. Project Scientist,
University of California, Riverside,
Department of Cell Biology & Neuroscience
Riverside, CA
MedicalResearch: What is the background...
MedicalResearch.com Interview with:Charles R. Marmar, MD
The Lucius Littauer Professor and Chair, Department of Psychiatry, NYU Langone Medical Center and
Director of the Steven and Alexandra Cohen Veterans Center at NYU Langone
MedicalResearch: What is the background for this study? What are the main findings?Dr. Marmar: Approximately 2.7 million men and women served in Vietnam, and, for those who returned, many have suffered for decades from a variety of psychological problems resulting from their experiences and other injuries such as traumatic brain injury (TBI).
The 25-year National Vietnam Veterans Longitudinal Study (NVVLS) was a way we could determine at various points in time how veterans were faring emotionally four decades after their service. While the vast majority are resilient, there are still over 270,000 Vietnam veterans who still have some form of post-traumatic stress disorder (PTSD) and one-third of these veterans have depression.
We followed up with veterans who participated in the National Vietnam Veterans Readjustment Study (NVVRS) from 1984 to 1988 who were evaluated for PTSD. The NVVRS group represented a probability sample of those who served in Vietnam. Of the 1,839 participants still alive, 1,409 participated in at least one phase of the NVVLS, which involved a health questionnaire, health interview and clinical interview.
The results showed that between 4.5 percent and 11.2 percent of male Vietnam veterans and 6.1 and 8.7 percent of the female veterans are currently experiencing some level of PTSD.
About 16 percent of veterans in the study reported an increase of more than 20 points on a PTSD symptom scale compared to 7.6 percent who reported a decrease of greater than 20 points.
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MedicalResearch.com Interview with:
Eduardo Vilar-Sanchez, MD, PhD
Assistant Professor, Department of Clinical Cancer Prevention
Division of OVP, Cancer Prevention and Population Science
The University of Texas MD Anderson Cancer Center
Houston, TX 77030
Medical Research: What is the background for this study? What are the main findings?
Dr. Vilar-Sanchez: I am a physician scientist at The University of Texas MD Anderson Cancer Center (MDA), a medical oncologist specializing in cancer genetics, especially colorectal cancer (CRC) syndromes. At MD Anderson, I have medical practice consisting primarily of colorectal cancer, as part of the clinical cancer arm of MD Anderson.
I became interested in this topic because it is now well recognized that colorectal cancer is increasing in prevalence in young individuals. CRC is the third most common cancer in the US with 90% diagnosed in patients older than 50. While most CRC patients develop cancer in their 60s or 70s, the incidence is now rising in individuals younger than 50. Over the next two decades, it is projected that the incidence of CRC in young adults under 35 will double.
Only 5% of all CRC patients have a known hereditary predisposition cancer syndrome. Patients diagnosed at or under age 35 represent an extreme phenotypic presentation, constituting only 1.5% of all CRC cases.
We retrospectively reviewed all patients with CRC patients age 35 or under, who were evaluated by the Genetic Services group at MD Anderson. In this group, a surprising 30% had a recognized hereditary cancer syndrome, a marked increase compared to the general CRC population.
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MedicalResearch.com Interview with:
Adam G Alani, PhD
Assistant Professor of Pharmaceutics
Department of Pharmaceutical Sciences
College of Pharmacy
University Affiliate Assistant Professor
Department of Biomedical Engineering
School of Medicine at Oregon Health & Science University Oregon State University-Portland Campus at OHSU Portland Oregon
Medical Research: What is the background for this study? What are the main findings?
Dr. Alani: Doxorubicin, a potent anticancer agent is being under-utilized in the clinic due to its life threatening cardiotoxicity. This cardiotoxicity has imposed a life dose limit of 450 -550 mg/m2 which restricts clinicians use of this drug for subsequent relapses when a patient has responded to the drug favorably in the past. In our lab, we are looking to pair this drug with natural products that have shown both cardioprotective effects and while enhancing the potency of common chemotherapeutics like doxorubicin. Using this complementary approach with a high dose of doxorubicin known to cause cardiotoxicity, we have fully/ partially mitigated this cardiotoxicity in healthy mice. The goal is not to change the dosing regimen for doxorubicin, but to pair it with our nanoscale drug delivery systems containing these natural products as complementary therapy.
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healtMedicalResearch.com Interview with:
Sajal Chattopadhyay, Ph.D.
Economic Advisor, The Community Guide Branch
Division of Public Health Information Dissemination
Center for Surveillance, Epidemiology, and Laboratory Services
Office of Public Health Scientific Services
Centers for Disease Control and Prevention
Medical Research: What is the background for this study? What are the main findings?Dr. Chattopadhyay: Based on an updated review of all of the available scientific studies, the Community Preventive Services Task Force (CPSTF) reiterated its recommendation for tobacco price increases based on strong evidence of their effectiveness in reducing tobacco use and its harmful consequences. This study expands on the conclusions on effectiveness of price increases by systematically reviewing the evidence on the economic impact of policies that raise the unit price of tobacco products in the U.S. and other high-income countries, primarily through taxation.
The findings indicate that tobacco price increases generate substantial healthcare cost savings and can generate additional gains from improved workplace productivity.
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MedicalResearch.com Interview with:
Dr. Pam Marcus PhD
Epidemiology and Genomics Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
National Institutes of Health
Bethesda, MD 20892
MedicalResearch: Why do we need to consider targeted cancer screening?Dr. Marcus: Cancer screening, the routine testing of asymptomatic individuals without a history of the disease of interest, is an important approach to cancer prevention and control. There is compelling evidence that screening for at least four cancers reduces disease-specific mortality, but population-based cancer screening also leads to unfavorable events. Only a minority of those screened will benefit, and many will have false-positive exams. Some screenees will experience undesirable sequelae, ranging from minor inconveniences to serious adverse events due to the exam itself or diagnostic evaluation.
MedicalResearch: What is the goal of targeted cancer screening in average-risk individuals?Dr. Marcus: Targeted cancer screening attempts to segregate those who will benefit from screening from those who will not through use of information on disease risk. Average risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without co-morbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. The goal of targeted cancer screening in average risk individuals is to reduce the number of individuals who need to be screened while preserving the overarching benefit of reduced cancer-specific mortality in the general population. Targeted cancer screening is an example of precision medicine; visit http://www.nih.gov/precisionmedicine/goals.htm to learn more about the National Institute of Health’s Precision Initiative.
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MedicalResearch.com Interview with:
Mitchell H. Gail, M.D., Ph.D.
Senior Investigator
Biostatistics Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute National Institutes of Health
Rockville MD 20850-9780
Medical Research: What is the background for this study?
Dr. Gail: In the United States, breast cancer survival following diagnosis has been improving since the 1970s. We wanted to understand what might explain these shifts, to fully characterize the changes over time, and to explore whether tumor size and estrogen receptor status could help explain the trends in age- and stage-specific breast cancer death rates after diagnosis.
We evaluated survival from breast cancer from the date of diagnosis of all women diagnosed with invasive breast cancer in the US SEER Cancer Registries between 1973 and 2010. We excluded women with ductal or lobular carcinoma in situ. We analyzed separate age groups (<50, 50-69, 70+ years) and SEER stage of disease (local, regional, distant).
Medical Research: What are the main findings?
Dr. Gail: Between 1973 and 2010, breast cancer death rates after diagnosis in the United States have fallen for each age group of women diagnosed with local or regional stage disease, not only in the first five years after diagnosis, but also thereafter. For women under age 70, rates also fell for women with distant disease.
Changes in tumor size or estrogen-receptor status do not explain much of the improvement among women under age 70 years, but do explain roughly half the improvement in 70+ year old women in the first five years after diagnosis. (more…)
MedicalResearch.com Interview with:
Dr. Marc Schermerhorn, MD
Chief of Vascular and Endovascular Surgery
Beth Israel Deaconess Medical
Medical Research: What is the background for...
MedicalResearch.com Interview with:Dr. ParaskeviChristofidou
Department of Cardiovascular Sciences, University of Leicester
NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester UK
MedicalResearch: What is the background for this study? Dr.Christofidou: Homozygosity arises when identical alleles are present on both chromosomes. Runs of homozygosity (ROHs) are very long segments of uninterrupted sequences of homozygous variants across the human genome. Runs of homozygosity represent "re-union" of pieces from DNA from parents in their children. The two DNA copies are identical because have been inherited from a common ancestor somewhere in the distant past.
Runs of homozygosity are recognized signature of recessive inheritance, because they allow unmasking of recessive variants. Recessive variants only show their effect when present on both chromosomes of an individual's genome. Some of these ROHs may potentially harbor variants that exert their pathological effects in the homozygous recessive state. This is important because it helps us better understand the consequences of the recessive model of inheritance in relation to complex diseases.
Coronary artery disease (CAD) is a terminal clinical manifestation of cardiovascular disease and is the leading cause of death worldwide and is the UK's single biggest killer. Nearly one in six men and one in ten women die from CAD. Coronary artery disease is a complex, multifactorial disorder originating from a complicated interplay of multiple genetic and environmental factors.
Contributions of ROHs to the genetic architecture of CAD are not known. The primary goal of this project was a comprehensive analysis of association between genome-wide homozygosity measures and CAD in individuals of white European ancestry. A secondary aim was to explore the association of ROHs and gene expression in human monocytes and macrophages.
MedicalResearch: What are the main findings?Dr.Christofidou: Our analysis of 24,320 individuals from 11 populations of white European ethnicity revealed statistically significant differences in homozygosity levels between individuals with Coronary artery disease and control subjects.
On average, individuals with CAD had 0.63 ROHs more than control subjects. The average total length of ROHs was approximately 1046.92 kb greater in individuals with CAD than control subjects. We were able to qualify a measure of genome-wide homozygosity levels in relation to CAD - an estimated 13% increase in CAD per 1 standard deviation increase in the proportion of the autosomal genome covered by ROHs.
Individual ROHs showed significant associations with monocyte and macrophage expression of genes located nearby. These associations suggest that many ROHs might be signatures of biologically active recessive variants with a potential to regulate transcription.
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MedicalResearch.com Interview with:
Samar R. El Khoudary, Ph.D., M.P.H.
Assistant professor
Graduate School of Public Health Department of Epidemiology
University of Pittsburgh
Medical Research: What is the background for this study?
Dr. El Khoudary: Cardiovascular disease is the leading cause of death in women, and it increases after age 50 - the average age when a woman is going through menopause. Weight gain in women during and after menopause has long been attributed to aging, rather than menopause itself. However, recent research identified changes in body fat composition and distribution due to menopause-related hormonal fluctuations.
No previous study had evaluated whether those changes in fat distribution during menopause affect cardiovascular fat. Increased and excess fat around the heart and vasculature can be more detrimental than abdominal fat, causing local inflammation and leading to heart disease. Doubling certain types of cardiovascular fat can lead to a more than 50 percent increase in coronary events. My team and I investigated whether there may be a link between menopause and cardiovascular fat using data from 456 women from Pittsburgh and Chicago enrolled in the Study of Women's Health Across the Nation (SWAN). The women averaged about 51 years of age and were not on hormone replacement therapy.
Medical Research: What are the main findings?Dr. El Khoudary: Our study is the first to find that late- and post-menopausal women have significantly greater volumes of fat around their hearts than their pre-menopausal counterparts. As concentrations of the sex hormone estradiol - the most potent estrogen - declined during menopause, greater volumes of cardiovascular fat were found. The finding held even after my colleagues and I took into account the effects of age, race, obesity, physical activity, smoking, alcohol consumption, medication use and chronic diseases. (more…)
MedicalResearch.com Interview with: Dr. Stephanie K. Venn-Watson
Doctor of Veterinary Medicine, MS
Director, Translational Medicine and Research Program
National Marine Mammal Foundation
Medical Research: What is the background for this study? What are the main findings?
Dr. Venn-Watson: Bottlenose dolphins, just like people, can develop a condition called metabolic syndrome. In humans, metabolic syndrome is also called prediabetes, which affects 1 in every 3 adults in the U.S.
Some human studies have suggested that eating a diet high in fish may lower the risk of developing metabolic syndrome. Other similar studies, however, have had inconsistent findings. To better understand how fish diets may be associated with dolphin metabolic health, we compared 55 fatty acids among 49 dolphins and their dietary fish.
We were surprised to find that the strongest predictor of lower, healthier insulin levels in dolphins was a saturated fat called, heptadecanoic acid (or C17:0). When we provided a diet higher in C17:0 to six dolphins over six months, their insulin, glucose, and triglycerides normalized. We also saw an immediate decrease in ferritin, a protein which - at high levels - may be a risk factor for metabolic syndrome.
In addition to some fish, C17:0 is present in dairy fat, including whole fat milk and butter. C17:0 was not present in nonfat dairy products. We hypothesize that movement towards nonfat dairy foods may be lowering human C17:0 blood levels, which may be contributing to the global rise in metabolic syndrome and type 2 diabetes.
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