MedicalResearch.com Interview with: Carl "Chip" Lavie MD, FACC FACP, FCCP
Medical Director, Cardiac Rehabilitation and Prevention
Director, Exercise Laboratories
John Ochsner Heart and Vascular Institute
Professor of Medicine
Ochsner Clinical School-UQ School of Medicine
Editor-in-Chief, Progress in Cardiovascular Diseases
Medical Research: What is the background for this study? What are the main findings?
Dr. Lavie: This was a review of the literature on this topic.The main findings are that various lifestyle choices, including obesity, hypertension, metabolic syndrome/diabetes, obstructive sleep apnea , moderate and high alcohol intakes, and sedentary lifestyle but also very high exercise doses are all associated with increased risk of atrial fibrillation (AF).
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MedicalResearch.com Interview with: John A. Elefteriades, MD
William W.L. Glenn Professor of Surgery
Chief of Cardiothoracic Surgery
Director, Aortic Institute at Yale-New Haven
Yale University School of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Elefteriades: The race to map the human genome was declared completed in 2003, at a cost of 3 billion dollars for the international collaborative university group and 300 million dollars for Craig Venter at Celera. Whole exome sequencing can now be performed at a cost of only several thousand dollars per individual. So, whole exome sequencing (also called Next Generation Sequencing) can now be applied to understand and treat diseases of many organ systems.
In this study, we applied whole exome sequencing to study over 100 patients with thoracic aneurysm.
In the late 1990s, both Dr. Diana Milewicz in Texas and our group at Yale had determined that many thoracic aortic aneurysms were genetically transmitted. Dr. Milewicz went on to identify many of the causative mutations. In this study, we were able to look, by whole exome sequencing performed on saliva, for all 21 mutations known to cause thoracic aortic aneurysm--all at one time in one comprehensive genetic test. We were able to protect patients with the most serious discovered mutations by early surgery, the need for which could not otherwise have been apparent. (more…)
MedicalResearch.com Interview with:
Sunil Sharma, M.DAssociate professor of pulmonary medicine
Sidney Kimmel Medical College at Thomas Jefferson University
Medical Research: What is the background for this study? What are the main findings?
Dr. Sharma: Obstructive sleep apnea (OSA) is a highly prevalent disorder with significant cardiovascular implications. In this condition the patient may repeatedly quit breathing during sleep, sometimes hundreds of times, leading to loss of oxygen and frequent arousals throughout the night. OSA has been associated with high blood pressure, congestive heart failure, coronary artery disease, arrhythmias and stroke, among other conditions. While overall awareness is improving, the condition is under-recognized in hospitalized patients. Due to multiple co-morbid conditions these patients may be at higher risk for complications. Recent studies have also shown that early recognition of OSA in hospitalized patients may reduce readmission rates. In our study, we used a simple and cost-effective clinical pathway to determine high-risk patients. Of the 149 patient's determined to be high risk by our protocol, 128 (87%) were confirmed with the diagnosis by a polysomnography (gold standard test). Furthermore, data derived from a simple and cost-effective oxygen measuring device (pulse-oximeter) was found to co-relate well with the polysomnography. (more…)
MedicalResearch.com Interview with:
Adam Friedman, MD, FAAD
Associate Professor of Dermatology
Residency Program Director
Director of Translational Research
Department of Dermatology
George Washington School of Medicine and Health Sciences
Medical Research: What is the background for this study? What are the main findings?
Dr. Friedman: Acne vulgaris is one of the most common skin disease that affects approximately 40-50 million people in the United States. Acne’s multifactorial etiology, resulting from a mix of androgen-induced elevations in sebum production, abnormal follicular epithelial desquamation and proliferation, hypercolonization of Propionibacterium acnes and host inflammatory reactions, make treatment often times challenging. In looking at the topical therapeutic armament for Acne Vulgaris, which includes benzoyl peroxide, salicyclic acid, topical antibiotics such as clindamycin, and retinoids, all suffer from various related side effects including irritation, erythema, dryness, peeling and scaling, bacterial resistance, and resulting dyschromia from the associated irritation in patients of darker skin types. These adverse events often serve as major limiting factors influencing patient compliance and ultimately impacting efficacy. Therefore new treatments which target all of the complexities of acne are needed, especially given we have not had anything really new brought to market in years. Here, we looked to biology for the answer. Our bodies generate Nitric Oxide, a diatomic lipid loving gaseous molecule, to perform a broad range of biological activities, including but not limited to killing bacteria/fungi/viruses and inhibiting inflammation - key elements in Acne. Its action however is very short lived and therefore using Nitric Oxide as a treatment is difficult as one would need a delivery system that would allow for continued and controlled release. Enter nanotechnology. We designed exceedingly small particles (of note, 1 nanometer = 1 billionth of a meter) which allow for the generation of nitric oxide gas from nitrite salt, and will only release the gas when exposed to moisture over time. The size of the particles also enables them to better interact with their environment, i.e. cells, pathogens, improving their activity as compared to large sized treatments
In this study, we showed that the nitric oxide generating/releasing nano particles effectively killed the organism, P. acnes but was not toxic to both human skin cells and a live vertebrae model (embryonic zebra fish). More importantly, we found that the nano particles inhibits the activation of a newly recognized but exceedingly important inflammatory pathway that is directly tied to the formation of an acne lesion, called the NLRP3 inflammasome. Research has shown that our bodies already regulate this pathway with nitric oxide, and therefore once again, we are looking to biology for answers. As opposed to a drug that may only have one target, the nanoparticles inhibited multiple components/elements of the inflammasome pathway, giving some insight into its potential as a treatment for acne as well as other inflammatory diseases.(more…)
MedicalResearch.com Interview with:
Patrick O’Neill
CASIS Communications Manager and
Tara Ruttley Ph.D. NASA
Staff Scientist
NASA Office of the Chief Scientist
Editor’s note: CASIS, the four year old Center for the Advancement of Science in Space, presented an informative update and display at the Biotech Conference 2015, in Philadelphia June 2015.
CASIS, the manager of the International Space Station U.S. National Laboratory, facilitates space-based research for the good of mankind. To accomplish it’s goal of ‘driving scientific inquiry toward developing groundbreaking new technologies and products’, CASIS has at its disposal Seed Money, Expertise, Access to Launch, Administrative Support and Educational Outreach.
Mr. O’Neill and Dr. Ruttley spoke with MedicalResearch.com about the work CASIS is doing and the opportunities CASIS is creating for entrepreneurs, educators and scientists.
MedicalResearch: Why don’t you tell us a little about the background for CASIS?Response: The mission of NASA is space exploration, while the complementary mission of CASIS is to use ISS (the International Space Station) to better life on earth. CASIS is the non-profit arm of NASA that recruits, selects and manages the scientific research projects conducted on the space station.
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MedicalResearch.com Interview with:
Dr. Vincent L. Cryns MD
Chief of the Division of Endocrinology, Diabetes and Metabolism
Department of Medicine
University of Wisconsin Carbone Cancer Center
University of Wisconsin School of Medicine and Public Health Madison, Wisconsin
Medical Research: What is the background for this study? What are the main findings?Dr. Cryns: It’s been known for quite some time that many tumors are highly vulnerable to deficiencies in certain amino acids such as methionine, causing tumor cells to stop growing or die. What’s been missing is a molecular explanation for these effects that would allow us incorporate this approach into a rationally designed clinical trial. In our work, we have demonstrated that “starving” triple-negative breast cancer cells of methionine uncovers a “fatal flaw” by increasing the expression of a cell death receptor (TRAIL-R2) that we can activate with a therapeutic antibody to efficiently kill the tumor cells. What’s especially exciting is that we can use a specific diet to metabolically prime cancer cells to respond to a targeted cancer therapy. (more…)
MedicalResearch.com Interview with:
Hubert W. Vesper, PhD
Director, Clinical Standardization Programs in the National Center for Environmental Health, Centers for Disease Control and Prevention
Co-author, “Measuring Estrogen Exposure and Metabolism: Workshop Recommendations on Clinical Issues”
Co-chair of the PATH Steering Committee
Medical Research: What is the background for this study? What are the main findings?
Dr. Vesper: Accurate data on estrogen levels are needed to ensure appropriate and effective patient care. Research studies found high inaccuracies among different estrogen tests, especially at low estrogen levels commonly observed in postmenopausal women, men and children.
Accurate estrogen measurements can be achieved through standardization. Stakeholders should support standardization efforts of the Centers for Disease Control and Prevention (CDC) or alternative strategies to arrive at estrogen measurement methods that are accuracy-based and reliable.
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MedicalResearch.com Interview with:
Haining Yang MD Ph.DAssociate ProfessorThoracic Oncology Program
University of Hawaii Cancer Center
University of Hawaii, Honolulu, HI
Medical Research: What is the background for this study?
Dr. Yang: Mesothelioma is often caused by asbestos and other carcinogenic mineral fibers. When these fibers lodge in the pleura, mesothelial cells and macrophages try to phagocytize and eliminate them. However, asbestos is very bio-persistent and cannot be eliminated, which caused cells undergoing programmed necrosis that leads to the release of HMGB1 into the extracellular space. HMGB1 is a damage-associated molecular pattern molecule (DAMP) that causes inflammation. Asbestos exposure induces HMGB1 release and chronic inflammatory process that overtime may lead to malignancy. Mesothelioma cells develop out of an environment that is rich in HMGB1 and are often dependent on HMGB1 for their own growth. In fact, most mesothelioma cells actively secrete HMGB1 extra-cellularly to promote their own tumor growth. Accordingly HMGB1 levels are high in the serum of mesothelioma patients (reviewed in Yang and Carbone, Clinical Cancer Res 2013). We tested several anti-inflammatory agents to see if we were able to reduce HMGB1-induced mesothelioma cell growth, and none of them worked except for aspirin, that led us to conduct a series of experiments in vitro and in vivo to test the hypothesis that aspirin inhibits HMGB1 activities, and that by doing so, inhibits mesothelioma growth.Medical Research: What are the main findings?
Dr. Yang: We found that aspirin inhibits the growth of human mesothelioma cells in a xenograft model, moreover in vitro experiments demonstrated that this effects was specifically mediated via inhibition of HMGB1 and not via COX2 inhibition. We propose that the so far enigmatic anticancer activity of aspirin is mediated, at least partially, via inhibition of HMGB1, and that aspirin may help delay the onset of mesothelioma and may help inhibit the growth of mesothelioma.(more…)
MedicalResearch.com Interview with:
Latetia V. Moore Ph.D. MSPH
Epidemiologist, Centers for Disease Control
Medical Research: What is the background for this study?
Dr. Moore: For this study, CDC researchers analyzed the average daily fruit and vegetable intake from the 2013 Behavioral Risk Factor Surveillance System (BRFSS) for the 50 states and the District of Columbia (DC) and the percent of each state’s population meeting fruit and vegetable intake recommendations. BRFSS is the sole source of dietary information (systematic surveillance) for most states.
Medical Research: What are the main findings?Dr. Moore: Researchers found that in every state less than 1 in 5 adults in the U.S. are consuming enough fruits and about 1 in 10 are consuming enough vegetables. Estimates ranged from 8% meeting fruit recommendations in Tennessee up to 18% in California, and for vegetables from 6% in Mississippi to 13% in California. (more…)
MedicalResearch.com Interview with:
Nadereh Pourat, PhD
Professor, Department of Health Policy and Management, UCLA Fielding School of Public Health
Adjunct Professor, UCLA School of Dentistry
Director of Research, UCLA Center for Health Policy Research
Medical Research: What is the background for this study? What are the main findings?
Dr. Pourat: We have succeeded to insure most of the uninsured population in the U.S., but now have to figure out how to reduce costs while improving health. We had the opportunity to examine the role of continuity with a primary care provider, which is one of the pathways that looked promising in improving health and reducing costs. We were evaluating a major demonstration program in California called the Health Care Coverage Initiative (HCCI) and one of the participating counties implemented a policy to increase adherence by only paying for visits if patients went to their assigned providers. We examined what happened to patients who always or sometimes adhered to their provider versus those who never adhered. We found that adherence or continuity reduced emergency department use and hospitalizations. This would lead to savings because of the high costs of these services.
Medical Research: What should clinicians and patients take away from your report?Dr. Pourat: The study shows that both patients and clinicians would benefit from continuity with the primary care provider. Clinicians can actually make a difference in helping patients: they can teach patients about self-care and help them manage their conditions better. Patients would benefit from following through with treatment plans and experience less medical error and duplication of services which are potentially harmful. Continuity fosters rapport and trust between patients and providers and can be beneficial to both.
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MedicalResearch.com Interview with:
Christopher M. Jones, Pharm D., M.P.H
Senior advisor, Office of Public Health Strategy and Analysis
Office of the Commissioner, Food and Drug Administration
Medical Research: What is the background for this study?
Dr. Jones: Opioid analgesics and benzodiazepines are the two most common drug classes involved in prescription drug overdose deaths. In 2010, 75% of prescription drug overdose deaths involved opioid analgesics and 29% involved benzodiazepines. Opioid analgesics and benzodiazepines are also the most common drugs associated with emergency department visits due to nonmedical use of prescription drugs.
Combined opioid and benzodiazepine use has been suggested as a risk factor for overdose death.
Opioids and benzodiazepines have complex drug interactions and in combination can result in synergistic respiratory depression, but the exact mechanisms by which benzodiazepines worsen opioid-related respiratory depression are not fully understood.
Widespread co-use of benzodiazepines and opioids has been documented in both chronic pain and addiction treatment settings. Studies suggest that among patients who receive long-term opioids for chronic non-cancer pain, 40% or more also use benzodiazepines. Among patients who abuse opioids, benzodiazepine abuse also is prevalent, and co-users report using benzodiazepines to enhance opioid intoxication.
This study builds on the prior literature by analyzing trends on how the combined use of opioids and benzodiazepines in the U.S. contributes to the serious adverse outcomes of nonmedical use–related ED visits and drug overdose deaths. A better understanding of the consequences of co-use of these medications will help identify at-risk populations, inform prevention efforts, and improve the risk–benefit balance of these medications.
Medical Research: What are the main findings?
Dr. Jones: From 2004 to 2011, the rate of nonmedical use–related Emergency Department visits involving both opioid analgesics and benzodiazepines increased from 11.0 to 34.2 per 100,000 population. During the same period, drug overdose deaths involving both drugs increased from 0.6 to 1.7 per 100,000. Statistically significant increases in Emergency Department visits occurred among males and females, non-Hispanic whites, non-Hispanic blacks, and Hispanics, and all age groups except 12–17-year-olds. For overdose deaths, statistically significant increases were seen in males and female, all three race/ethnicity groups, and all age groups except 12–17-year-olds. Benzodiazepine involvement in opioid analgesic overdose deaths increased each year, increasing from 18% of opioid analgesic overdose deaths in 2004 to 31% in 2011.
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MedicalResearch.com Interview with:
Dr. Ankur Pandya Ph.D.
Assistant Professor of Health Decision Science
Department of Health Policy and Management
Harvard T.H. Chan School of Public Health
Boston, MAMedical Research: What is the background for this study? What are the main findings?
Dr. Pandya: The American College of Cardiology and the American Heart Association (ACC-AHA) cholesterol treatment guidelines were controversial when first released in November 2013, with some concerns that healthy adults would be over-treated with statins.
We found that the current 10-year ASCVD risk threshold (≥7.5%) used in the ACC-AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (incremental cost-effectiveness ratio of $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0%) or $150,000/QALY (≥3.0%). (more…)
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: Sleep is known to facilitate the formation of long-term memory in humans, by transferring newly learned memories from short-term to long-term memory stores. Studies however indicate that even shorter periods of sleep - including naps - can ensure access to different types of memories under normal restful conditions. Furthermore, while some studies have shown that acute sleep loss can exacerbate e.g. physiological responses to acute stress, it it has not been studied whether shortened sleep in combination with acute cognitive stress can have a negative impact on the retrieval of newly learned memories.
With this background in mind, we conducted a study where we aimed to investigate how nocturnal sleep duration impacts this memory transfer, and to what extent long-term memories formed by sleep remain accessible after acute cognitive stress.
We recruited 15 participants who in each of two sessions first underwent a learning session in the evening, during which they learned 15 card pair locations on a computer screen. Then, in one of the two experimental session, subjects slept for half a night (4-hr), instead being able to sleep for a full night (8-hr) in the other session. On the morning after each sleep condition, we had the subjects try to recall as many card pair locations as possible. We found that following half a night of sleep (4-hr), participants were equally able to recall memories for the learned card pair locations, as after a full night of sleep (8-hr). However, we also showed that the ability to retrieve memories following 30 minutes of acute stress, in the morning after these two sleep conditions, was different depending on whether the participants had slept for 8 or 4 hours. Following short sleep, the 30-min long stress exposure reduced the participants' ability to recall the card pair locations that the participants had learned the previous night by around 10%. In contrast, no such stress-induced memory impairment was observed when the same men were allowed to sleep for a full night.
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MedicalResearch.com interview with
Dr. Ella James, Post-Doctoral Investigator Scientist
Medical Research Council Cognition and Brain Sciences Unit
Cambridge, UK.
MedicalResearch: What is the background for this study? Dr. James: Post-traumatic stress disorder (PTSD) is experienced by some people after a traumatic event. While many people who’ve been involved in traumatic events don’t experience PTSD, those who do typically have repeated visual intrusive memories of certain moments in vivid detail that pop back into mind, seemingly out of the blue. For example, with PTSD after a car crash might repeatedly ‘see’ the moment the other car crashed into them.
The recommended treatment for PTSD is cognitive behaviour therapy, a talking therapy that has been demonstrated to work well. But it is only delivered once intrusive memories have become established and PTSD is diagnosable – i.e. at least one month after the traumatic event occurred. At present, there is nothing readily available for use soon after trauma that has been shown to prevent symptoms building up and PTSD becoming established.
In previous laboratory work our research team showed that playing Tetris shortly after viewing events with traumatic content (e.g. film footage of road safety campaigns – what we call an experimental trauma) could reduce intrusive memories of those events in healthy volunteers over the following week [2, 3] when played in a 4-hour time window after viewing. We reasoned that this was because having to follow and track the shapes, colour and movement of the coloured blocks in Tetris soon after seeing the experimental trauma (the film) disrupted aspects of the visual memory of that event from being ‘laid down’ in the sensory part of the brain, whilst leaving memory for the narrative and meaning of the events unaffected.
However, it is hard to reach people so soon after a traumatic event in the real world and memories for events become ‘fixed’ in mind within hours after an event making them difficult to change. Therefore it was important to show whether we can change older, established memories of trauma.
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MedicalResearch.com Interview with:
Nora V. Becker MD/PhD candidate
Department of Health Care Management and Economics
Wharton School, University of Pennsylvania, in Philadelphia.
Medical Research: What is the background for this study? What are the main findings?
Response: The Affordable Care Act mandates that private health insurance plans cover prescription contraceptives with no consumer cost sharing. The positive financial impact of this new provision on consumers who purchase contraceptives could be substantial, but it has not yet been estimated. Using a large administrative claims data set from a national insurer, we estimated out-of-pocket spending before and after the mandate. We found that mean and median per prescription out-of-pocket expenses have decreased for almost all reversible contraceptive methods on the market. The average percentages of out-of-pocket spending for oral contraceptive pill prescriptions and intrauterine device (IUD) insertions by women using those methods both dropped by 20 percentage points after implementation of the ACA mandate. We estimated average out-of-pocket savings per contraceptive user to be $248 for the IUD and $255 annually for the oral contraceptive pill.
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MedicalResearch.com Interview with:
Diana W. Bianchi, M.D.
Executive Director, Mother Infant Research Institute
Vice Chair for Research and Academic Affairs
Department of Pediatrics
Tufts Medical Center
Medical Research: What is the background for this study? What are the main findings?
Response:Noninvasive Prenatal Testing (NIPT) is the fastest growing genetic test. It has been available since late 2011. Over 2 million tests have been performed worldwide. Cancer in pregnancy is rare, and only occurs in 1 in 1,000 pregnant women. About 0.2 per cent of noninvasive prenatal tests that use sequencing of maternal plasma DNA have a so-called “false positive” result. In most cases this is not an error, but there is a biological explanation for the discrepancy between the abnormal noninvasive prenatal test result and a normal fetal chromosome result obtained from a diagnostic procedure, such as amniocentesis or chorionic villus sampling (CVS). We are very interested in the underlying biological explanations for the false positive cases, and it turns out that a clinically silent tumor in the mother is one of them. The mother’s tumor is shedding DNA into her blood that is detected by the prenatal test.
In a large clinical dataset of over 125,000 pregnant women who had a DNA sequencing screen for fetal chromosome abnormalities there were 10 women who were subsequently found to have cancer. We retrospectively analyzed the DNA sequencing results in 8 of these women and found that they had abnormalities in multiple areas of the genome, suggesting that it was DNA from the tumor that was shed into the maternal blood and being detected by the prenatal screen.
The noninvasive prenatal sequencing test result that was most suggestive of a cancer risk was the presence of more than one aneuploidy. This finding was present in 7 of the 10 women who had cancer.
In three of the eight women we studied it was the abnormal prenatal test result that triggered a subsequent work-up that led to the diagnosis of cancer.
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MedicalResearch.com Interview with:
Christopher M. Jones, Pharm D., M.P.H.
Senior advisor, Office of Public Health Strategy and Analysis
Office of the Commissioner, Food...
MedicalResearch.com Interview with:
Azfar B. Sheikh, M.D.
Internal Medicine Resident Physician
Staten Island University Hospital
New York
Medical Research: What is the background for this study?Dr. Sheikh: The background of this review article circles around the impact of
atrial fibrillation on epidemiology, trends in hospitalizations, costs
associated with hospitalization and outpatient care, in the United
States. This article also describes the benefits of newer treatment
modalities compared to the standard of care with regards to
symptomatic improvement and prevention of thromboembolism. These
findings are supported by several cost-utility analyses.
Medical Research: What are the main findings?Dr. Sheikh: The main findings of the study are:
The cost of hospitalization is three times higher for patients with
atrial fibrillation than those without atrial fibrillation.
5 million new cases are being reported annually.
The incidence of atrial fibrillation is projected to increase from
1.2 million cases in 2010 to 2.6 million cases by 2030. Due to this
increase in incidence, the prevalence of atrial fibrillation is
projected to increase from 5.2 million cases to 12.1 million cases by
2030.
The most common co-moribidites associated with atrial fibrillation
were hypertension, diabetes mellitus, and chronic obstructive lung
disease.
According to the NIS database, the atrial fibrillation.
hospitalization rate has increased from 1552 to 1812 per one million
US residents per year from 2000 to 2010 (relative increase 14.4%).
According to the NIS database, the mortality associated with atrial
fibrillation hospitalizations has decreased significantly from 1.2% in
2000 to 0.9% in 2010 (relative decrease 29.2%).
The median length of stay in the hospital is 3 days and increases
proportionally with a rise in CHADS2 score.
The largest source of direct healthcare costs associated with
atrial fibrillation is hospitalization. According to the NIS database,
the mean cost of inpatient atrial fibrillation hospitalization
increased significantly from $6401 in 2001 to $8439 in 2010 (relative
increase 24.0%). The mean cost of atrial fibrillation hospitalization
also increases proportionally with a rise in CHADS2 score.
In the outpatient setting, the highest costs were associated with
physician office visits in comparison to emergency room and urgent
care visits.
With regards to prevention of thromboembolism, the new oral
anticoagulant agents (dabigatran, rivaroxaban, and apixaban) have been
found to be more cost-effective compared to warfarin.
Left atrial catheter ablation is more effective than rate control
and rhythm control. It is more cost-effective in younger patients who
are moderate risk for stroke.
MedicalResearch.com Interview with:
Dr. Ángel Chamorro
Director, Comprehensive Stroke Center
Hospital Clinic
Barcelona, Spain
Medical Research: What is the background for this study? What are the main findings?
Dr. Chamorro: There is a great need of new therapies in patients with acute stroke and our study is based on the clinical observation that patients with acute stroke recover better if at the time of the stroke the levels of uric acid are increased in their blood. That first observation led to a long way of research and administrative challenges but we finally came out with a solution of uric acid (a potent antioxidant) manufactured according to the strict rules which apply to drugs aimed for human use. Thus, we performed a pilot study that showed that uric acid could be safely administered to these patients. We then performed a larger clinical trial in 421 patients which provided very encouraging results overall. Now we are reporting in the Stroke journal appearing on July 9, that women obtained a much greater benefit than men because they had lower levels of uric acid than men because estrogens (female hormones) are efficient excretors of uric acid. In consequence, women were in greater need of uric acid replenishment following the stroke than men.
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MedicalResearch.com Interview with:
MB. Pinkham, Clinical Oncology
Christie NHS Foundation Trust
Manchester UK
Medical Research: What is the background for this study? Response: Brain metastases are a serious complication of advanced malignancy and for most patients the objective is to maximise quality of survival. As treatment decisions become increasingly tailored to the individual, patient-focussed measures of efficacy such as neurocognitive function (NCF) are an important consideration. This is illustrated by the NCCTG N0574 randomised study reported last month at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. 208 patients with 1-3 brain metastases each <3cm were randomised to stereotactic radiosurgery (SRS) or SRS with whole brain radiotherapy (WBRT). The addition of WBRT improved intracranial disease control but did not translate into a survival benefit and was associated with a decline in neurocognitive function at 3 months.
The objective of our study was to describe the types of changes in neurocognitive function that can occur, summarise how they are assessed and review approaches used to mitigate their effects. We wanted to provide busy physicians with a clear and comprehensive overview of the topic that could be used to inform clinical decisions.
Medical Research: What are the main findings?
Response: Using sensitive tests, most patients with brain metastases have deficits in neurocognitive function at diagnosis. Evaluating and understanding changes after treatment is complex because neurocognitive function is a dynamic process that is influenced by a long list of inter-related factors.
For patients treated using whole brain radiotherapy alone, worsening neurocognitive function is observed in about two-thirds within 2-6 months. Deficits in verbal memory and fine motor control are most common. It is unclear what proportion relates to treatment toxicity as opposed to disease progression or pre-terminal decline because both are unfortunately also common events during this interval. By contrast, in other patients, NCF improves after WBRT due to treatment response.
For patients with 1-4 brain metastases treated using SRS, the addition of WBRT improves intracranial disease control at the expense of deficits in verbal memory at 4 months but the impact of recurrence and salvage therapy on neurocognitive function later than this is uncertain. Scant data suggests that some deficits in neurocognitive function after WBRT may improve with time in long term survivors. For patients with ≥5 brain metastases, SRS and/or systemic therapies may be considered in select patients instead of upfront whole brain radiotherapy but high quality evidence is lacking.
Advanced radiotherapy technologies, such as hippocampal-sparing WBRT and post-operative cavity SRS, can limit the dose delivered to unaffected areas of the brain in the hope of reducing toxicity. Randomised studies assessing their efficacy and cost-effectiveness in various clinical situations are underway prior to routine use. Small but statistically significant improvements in certain neurocognitive domains can also be achieved using medications such as memantine and donepezil. Preclinical data suggests that some commonly available drugs (such as ramipril, lithium and indomethacin) may have neuroprotective properties following WBRT; further evaluation is warranted.
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MedicalResearch.com Interview with:
David Jimenez PhD, FCCP
Respiratory Department and Medicine Department
Ramon y Cajal Hospital IRYCIS, and Alcala de Henares University
Madrid Spain
Medical Research: What is the background for this study? What are the main findings?
Dr. Jimenez: Normotensive patients that have an estimated high-risk for pulmonary embolism (PE)-related complications (i.e., intermediate-risk PE) might benefit from surveillance in an intensive care setting or from the administration of specific advanced therapy. The Bova score was developed for identifying these patients. This study confirms the validity and reproducibility of the Bova score.
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MedicalResearch.com Interview with:
Chun Chieh Fan Ph.D student
USCD Cognitive Science and
Professor Anders M. Dale Ph.D
Department of Cognitive Science,
Multimodal Imaging Laboratory, Department of Radiology
University of California, San Diego School of Medicine
La Jolla, CA 92037
Medical Research: What is the background for this study? What are the main findings?
Response: The shape of human skull is closely associated with the ancestral background. Forensics uses it for determining ethnicity. Anthropologists use it to infer neuroanatomical change in human evolution. Yet it is unclear the inner content of skull, human brain, contains how much information about individual’s ancestry.
Our study found that different continental ancestries are associated with unique cortical folding patterns. Even for contemporary populations in modern day USA, a melting pot of ethnicities, cortical folding patterns are highly predictive of the percentage of each continental ancestry, as determined based on the person’s genotype. These shape differences between ancestral heritages are not necessarily related to brain function. It is highly possible that the shape differences are resulting from a random process accumulated along human history, without significant functional consequences.
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MedicalResearch.com Interview with:
Brett D. Owens, MD
Professor of Orthopaedic Surgery
Brown University Alpert Medical School
Providence, RI
Medical Research: What is the background for this study? What are the main findings?
Response: Last year at this meeting we presented the results of a prospective multicenter study of collegiate contact athletes who experienced in-season shoulder instability events. While most were able to return to sport within a week, only roughly one quarter were able to successfully return without recurrent instability. We continued to follow this cohort and 39 athletes with additional eligibility the subsequent season. We found that 90% of the 29 who underwent arthroscopic stabilization successfully returned the next season compared with 40% of the 10 underwent nonoperative treatment (more…)
MedicalResearch.com Interview with:
Prof. Urs Greber, PhD
Professor of Molecular Cell Biology
Institute of Molecular Life Sciences
University of Zurich
Zurich, Switzerland
Medical Research: What is the background for this study? What are the main findings?
Prof. Greber: This study has addressed two fundamental questions in virology - how do non-enveloped viruses which are lipid-free penetrate through cell membranes, and how is this process tuned by host lipids?
We found that certain neutral lipids, ceramide lipids, were upregulated during the entry process of human adenovirus into cells. The ceramide lipids enhanced the uptake of viruses into cells by endocytosis, and they boosted the disruption of endosomal vesicles which carried the virus,, and thereby enhanced infection.
The ceramide lipids were found to be produced by the enzyme acid sphingomyelinase (ASMase), which was secreted from lysosomes to the plasma membrane upon virus attachment to cells.
ASMase is a clinical target, and can be inhibited by the antidepressant amitriptyline, a small chemical compound, which is widely used to treat mental disorders. (more…)
MedicalResearch.com Interview with:
Wei-Che Chiu, MD, PhD
National Taiwan University College of Public Health,
Cathay General Hospital and Fu Jen Catholic University
Taipei, Taiwan
Medical Research: What is the background for this study?Response: Diabetes mellitus is a common risk factor for dementia and accounts
for 6–8% of all cases of dementia in older populations. Cognitive
impairment is associated with the presence of diabetic complications
and diabetic severity, but the effects of diabetic severity on
dementia are unclear. Our study was to investigate the association
between the severity and progress of diabetes and the risk of
dementia.
Medical Research: What are the main findings?Response: The diabetic severity and progression reflected the risk
of dementia, and the early progress in diabetic severity could predict
the risk of dementia in new-onset diabetic patients.
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MedicalResearch.com Interview with:
Vera Novak, MD PhD
Associate Professor of Neurology
Dept. of Neurology, Stroke Division
Director Syncope and Falls in the Elderly Laboratory
Beth Israel Deaconess Medical Center
Boston, MA
MedicalResearch: What is the background for this study?Dr. Novak: Diabetes mellitus (DM) is a major contributor to morbidity and mortality.
Type 2 diabetes mellitus affects more than 44 million people in the U.S., and its numbers are growing rapidly, affecting up to 27% of older adults. Diabetes mellitus accelerates brain aging by about 5 years1, manifests as a widespread generalized atrophy2, and promotes earlier onset of vascular dementia and Alzheimer’s disease (AD).3,4 Diabetes mellitus -related atrophy manifests as worse cognitive function, memory, and gait, especially during a dual task, 5,6 and even a tight glycemic control did not improve cognitive function in participants of the large clinical trials 7.
MedicalResearch: What are the main findings?Dr. Novak: Sixty-five participants (aged 66± 9.2 years) 35 with T2DM and 30 non-diabetic controls participated in this study. After 2 years of follow-up, participants with T2 Diabetes mellitus had diminished vascular reactivity in the brain (an ability to increase blood flow in responses to a task or metabolic demands) and performed worse on multiple cognitive tasks (in particular verbal learning and memory). In T2DM group, lower cerebral vasoreactivity correlated with worse performance on daily living activities. Specifically, the lower vasodilatation (ability to increase blood flow) was associated with worse mental functions. In addition, those with higher markers of inflammation had greater decline in vascular function in the brain.
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MedicalResearch.com Interview with:
Darius A. Paduch, MD, PhD
Associate Professor of Urology and Reproductive Medicine
Director Sexual Health and Medicine
Research Director of Male Infertility Fellowship
Co-Director Male Infertility Genetics Laboratory
Weill Cornell Medical College
Dept of Urology
New York, NY 10065
Medical Research: What is the background for this study? What are the main findings?
Dr. Paduch: Ejaculatory dysfunction, inability to ejaculate or delayed ejaculation affects 10-8% of men. Inability to ejaculate either intravaginally or at all is independent of erectile function.
Men with normal erection may take very long time to ejaculate (>30 min) or not able to ejaculate at all. The men in our study had either normal erections or minimal erectile dysfunction.
Men of all ages have spontaneous erections but don't ejaculate just from erection, it is progression of arousal and activation of spinal cord motor generator for ejaculation which is necessary for ejaculation.
One of important factors in our ability to ejaculate is testosterone (T), testosterone allows for normal function of CNS centers for ejaculation, it is a modulator and is necessary; preadolescent boys don't ejaculate because their spinal cord centers for ejaculations are not mature – process dependent on testosterone. However testosterone is just one of many neurotransmitters and hormones needed of normal ejaculation.
Actually our study showed that in men who achieved normal levels of testostosterone the ejaculatory function have improved. As this was first double blinded and randomized clinical trial we had to report our results based on radomization to testosterone treatment or placebo. Unfortunately only 70-80% of men treated with topical testosterone preparation will achieve normal testosterone level , we simply didn’t reach statistical significance based on randomization and considering relatively low number of patients in each group. But in men who achieved normal testosterone levels the difference was statistically significant.
Testosterone should not be used to treat any conditions, including ejaculatory dysfunction, in absence of low testosterone level.
EjD is very common but it bares significant embarrassment stigma, it is difficult for the couple to bear fact that male partner can’t ejaculate, it also creates issues within couple and question about attraction and fidelity.
We have previously showed that treatment with tadalafil improves ejaculatory and orgasmic dysfunction and these data has been published.
This study was focused on effect of testosterone, but its main significance was it’s design: we developed new tools to assess ejaculatory function and learned a lot about when patients or their partners start to be bothered by EjD. If time to ejaclate takes > 30 min
We are now looking into novel and available pharmacotherapy modulating dopaminergic and canabioid signaling and reward mechanisms. I am also very excited about our potential work in direct spinal cord motor generator nano stimulator, this could be very useful for men with spinal cord injuries and diabetic patients. We paved the road for others and I am sure new treatments are just a matter of time.
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MedicalResearch.com Interview with:
Amelia Stanton, Graduate Student
Department of Psychology
The University of Texas at Austin
Austin, TX
Medical Research: What is the background for this study? What are the main findings?
Response: Heart rate variability (HRV) has emerged as a valuable non-invasive test to assess autonomic nervous system (ANS) activity. Several studies have linked low resting Heart rate variability to mental health conditions including depression, anxiety, and alcohol dependence, indicating these disorders may be related to an imbalance in autonomic activity. As Heart rate variability is an index of the balance of sympathetic nervous system (SNS) and parasympathetic nervous system activity (PNS), it has proven a useful tool for examining the relative role of SNS activity in female sexual arousal. Moderate SNS dominance (relative to PNS activity) has been shown to predict women’s genital arousal in the laboratory, while high levels of SNS activation have been shown to inhibit genital arousal. Based on this background evidence and on a growing clinical literature indicating that low HRV (generally indicative of high SNS) is associated with negative health outcomes, we predicted a positive linear relationship between Heart rate variability and sexual arousal function. That is, we predicted that women with autonomic balance indicating moderate or low resting SNS activity (relative to PNS activity) would be less likely than women with autonomic balance indicating high resting SNS to report clinically relevant sexual arousal dysfunction. We also predicted that this relationship would hold for overall sexual function.
To test this hypothesis, sexual arousal function, overall sexual function, and resting HRV were assessed in 72 women, aged 18-39. The main finding of the study is that women with below average Heart rate variability were significantly more likely to report sexual arousal dysfunction (p < .001) and overall sexual dysfunction (p < .001) than both women with average HRV and women with above average HRV. Based on these results, we concluded that low HRV may be a risk factor for female sexual arousal dysfunction and overall sexual dysfunction.
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MedicalResearch.com Interview with:
S. Yousuf Zafar, MD, MHS
Associate Professor of Medicine
Duke Cancer Institute
Duke Clinical Research Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Zafar: Multiple studies have suggested that obesity and colorectal cancer are related. For instance, obesity has been linked with an increased incidence of colon cancer. Obesity has also been associated with a greater risk of colon cancer recurrence. To date, no study has looked at the role of obesity in outcomes for patients with metastatic colorectal cancer. In our study of over 6000 patients receiving treatment for metastatic olcolorectal cancer, we found that patients with the lowest body mass index (BMI) were at greatest risk for worse survival. This does not mean that obesity is good. More likely, it means that those who are very underweight are least able to tolerate the best treatment, or being very underweight is a biologic marker of poor prognosis.
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MedicalResearch.com Interview with:
Teresa M. Attina, MD, PhD, MPH and
Leonardo Trasande, MD, MPP
Department of Pediatrics
NYU Langone Medical Center
Medical Research: What is the background for this study?Response: Phthalates are environmental chemicals widely used in consumer and personal care products, and often found in plastic to increase flexibility. Di-2-ethylhexylphthalate (DEHP) is of particular interest because industrial processes to produce food frequently use plastic products containing DEHP. Because recognition of potential health risks related to DEHP exposure has increased, DEHP is being replaced by di-isononyl phthalate (DINP) and di-isodecyl phthalate (DIDP), two phthalates with similar chemical properties. Specifically, DINP is used in plastic products for food packaging, and DIDP is used in furnishings, cookware, medications, and several other consumer products. These alternatives have not been substantially studied for toxicity in laboratory studies because these studies are not required for regulatory approval: unlike the EU, in the US the current regulatory framework assumes that chemicals are safe until proven toxic.
Medical Research: What are the main findings?Response: We examined DINP and DIDP levels in urine samples from children and adolescents (6 to 19 years old) who participated in the National Health and Nutrition Examination Survey between 2009 and 2012, to assess if these levels were associated with blood pressure measurements. Diet, physical activity, gender, race/ethnicity, income, and other factors that can contribute to increased blood pressure were also included in the analysis. A significant association was found between high blood pressure and DINP/DIDP levels in study participants. This is not a cause-and-effect relationship but it suggests that phthalates may contribute to increased blood pressure.
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MedicalResearch.com Interview with:
Carl "Chip" Lavie MD, FACC FACP, FCCP
Medical Director, Cardiac Rehabilitation and Prevention
Director, Exercise Laboratories
John Ochsner Heart and Vascular Institute
Professor of Medicine
Ochsner Clinical School-UQ School of Medicine
Editor-in-Chief, Progress in Cardiovascular Diseases
Medical Research: What is the background for this study? What are the main findings?
Dr. Lavie: This was a review of the literature on this topic.The main findings are that various lifestyle choices, including obesity, hypertension, metabolic syndrome/diabetes, obstructive sleep apnea , moderate and high alcohol intakes, and sedentary lifestyle but also very high exercise doses are all associated with increased risk of atrial fibrillation (AF).
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