Author Interviews, CDC, Endocrinology, JCEM / 16.07.2015

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.
Author Interviews, Cancer Research / 16.07.2015

Dr-Haining-Yang MedicalResearch.com Interview with: Haining Yang MD Ph.D Associate Professor Thoracic 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.
CDC, Nutrition / 15.07.2015

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.
Author Interviews, Compliance, Cost of Health Care, Emergency Care, Primary Care, UCSD / 15.07.2015

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 ResearchMedicalResearch.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.
Author Interviews, Emergency Care, FDA, Opiods, Pharmacology / 15.07.2015

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.
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Statins / 14.07.2015

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, MA 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, MA Medical 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%).
Author Interviews, Memory, Occupational Health, Sleep Disorders / 14.07.2015

MedicalResearch.com Interview with: Jonathan Cedernaes M.D., Ph.D. Department of Neuroscience Uppsala University SwedenJonathan 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.
Author Interviews, PTSD / 14.07.2015

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.
Author Interviews, Cost of Health Care, OBGYNE, Pharmacology / 14.07.2015

Nora V. Becker MD/PhD candidate Department of Health Care Management and Economics Wharton School, University of Pennsylvania, in Philadelphia. 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.
Author Interviews, JAMA, OBGYNE / 13.07.2015

Diana W. Bianchi, M.D. Executive Director, Mother Infant Research Institute Vice Chair for Research and Academic Affairs, Department of Pediatrics Tufts Medical CenterMedicalResearch.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.
Author Interviews, Cost of Health Care, Heart Disease / 13.07.2015

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.
AHA Journals, Author Interviews, Stroke / 13.07.2015

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.
Author Interviews, Cancer Research, Cognitive Issues, Radiation Therapy / 13.07.2015

MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UKMedicalResearch.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.
Author Interviews, CHEST, Clots - Coagulation / 13.07.2015

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.
Author Interviews, Genetic Research / 13.07.2015

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.
Author Interviews, Orthopedics, Surgical Research / 13.07.2015

Brett D. Owens, MD Professor of Orthopaedic Surgery Brown University Alpert Medical School Providence, RIMedicalResearch.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
Author Interviews, Infections / 11.07.2015

Prof. Urs Greber, PhD Professor of Molecular Cell Biology Institute of Molecular Life Sciences University of Zurich Zurich, SwitzerlandMedicalResearch.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.
Author Interviews, Cognitive Issues, Diabetes, JCEM / 11.07.2015

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.
Author Interviews, Beth Israel Deaconess, Cognitive Issues, Diabetes, Neurology / 11.07.2015

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, MAMedicalResearch.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.
Author Interviews, JCEM, Sexual Health, Testosterone / 11.07.2015

Darius A. Paduch, MD, PhDAssociate 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 10065MedicalResearch.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.
Author Interviews, Heart Disease, Psychological Science, Sexual Health, University Texas / 11.07.2015

Amelia Stanton, Graduate Student Department of Psychology The University of Texas at Austin Austin, TXMedicalResearch.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.
Author Interviews, Colon Cancer, Duke, Weight Research / 10.07.2015

S. Yousuf Zafar, MD, MHS Associate Professor of Medicine Duke Cancer Institute Duke Clinical Research InstituteMedicalResearch.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.
Author Interviews, Blood Pressure - Hypertension, NYU/NYMC, Pediatrics, Toxin Research / 10.07.2015

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.
Author Interviews, Gastrointestinal Disease, Microbiome, PLoS / 10.07.2015

MedicalResearch.com Interview with: Mashkoor A.  Choudhry, PhD Professor of Surgery, Microbiology & Immunology Burn & Shock Trauma Research Institute Stritch School of Medicine Loyola University Chicago Health Sciences Division Maywood, IL 60153 Medical Research: What is the background for this study? What are the main findings? Dr. Choudhry: Intestine is the major reservoir of bacteria in the body. We observed that gut bacterial composition is altered after burn injury. We found that burn causes a significant increase in Enterobacteriaceae, a group of bacteria that has the potential to be harmful for the host. Dysbiosis of the healthy intestinal microbiome is associated with a number of inflammatory conditions.
Author Interviews, Infections / 10.07.2015

MedicalResearch.com Interview with: Dr. J. Todd Kuenstner MD Clinical Laboratories Charleston Area Medical Center, Charleston, Virginia West Virginia School of Medicine, Charleston, West Virginia Medical Research: What is the background for this study? What are the main findings? Dr. Kuenstner: Prior to the advent of recent antiviral therapies with sustained virologic response rates (SVR) of 94%, ultraviolet blood irradiation (UVBI) was proposed as a method to improve the outcome of treatment with interferon and ribavirin which had an virologic response rates of 50%. This therapy was invented by Dr. Emmett Knott in 1928 and used to treat viral and bacterial infectious disease in the 1930s through the 1950s and an estimated 60,000 treatments were conducted in the United States by 1948. The AVIcure hemo-irradiator is a modification of the Knott Hemo-irradiator and meets contemporary safety standards. This study describes the FDA phase II controlled clinical trial that was conducted before the advent of sofosbuvir and ledipasvir with the AVIcure hemo-irradiator using ultraviolet blood irradiation (UVBI) for the treatment of 10 patients infected with the hepatitis C virus (HCV). This study is significant because of the potential of this device for treating other infectious diseases with few treatment options. This therapy was safe and beneficial in the 10 patients that were studied. At the nadir of the viral load, the mean reduction of hepatitis C viral load was 45% (p=0.0048) or 0.35 log viral load (p=0.015). Three of the patients in the group achieved a greater than 0.5 log viral load reduction at some point in the trial. The phase I controlled clinical trial of UVBI in patients with HCV infection on 10 patients (submitted for publication) showed that 7 of 10 patients had a greater than 0.5 log reduction in viral load and a mean viral load reduction of 56% and a mean log viral load reduction of 0.60 (p=0.039). In the phase II clinical trial, 8 of 10 patients also showed a concurrent reduction in their serum transaminase levels, mean reduction in AST of 15% (p=0.0069) and mean reduction in ALT of 19% (p=0.0031). The above phase II trial results were achieved in spite of two therapeutic “holidays” of 7 weeks duration during the trial and during these therapeutic “holidays” the patients did not receive any treatments.
Author Interviews, Cost of Health Care, OBGYNE, Yale / 10.07.2015

Xiao Xu, Ph.D. Assistant Professor Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of MedicineMedicalResearch.com Interview with: Xiao Xu, Ph.D. Assistant Professor Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Xiao Xu: While research has shown hospital variation in costs of care for other conditions, we know little about whether and how hospitals differ in costs of childbirth related care. With nearly 4 million births each year, childbirth is the most common reason for hospital admission in the U.S. Understanding the pattern and causes of variation in resource utilization during childbirth among hospitals can help inform strategies to reduce costs. Our study used data from 463 hospitals across the country and analyzed hospital costs of maternity care for low-risk births. We found that hospital varied widely in average facility costs per maternity stay.
Author Interviews, Mayo Clinic, Opiods, Tobacco Research / 10.07.2015

W. Michael Hooten, M.D Professor of Anesthesiology Mayo ClinicMedicalResearch.com Interview with: W. Michael Hooten, M.D Professor of Anesthesiology Mayo Clinic Medical Research: What is the background for this study? Dr. Hooten: The purpose of the study was to investigate a gap in knowledge related to the progression of short-term opioid use to longer-term use. Medical Research: What are the main findings? Dr. Hooten: The main findings are that a history of substance abuse or tobacco use is associated with the progression from short-term to a longer-term pattern of opioid prescribing.
Author Interviews, Cancer, Cancer Research, Chemotherapy / 10.07.2015

MedicalResearch.com Interview with: Junichi Nishimura MD, PhD Assistant professor Osaka University in Japan Medical Research: What is the background for this study? What are the main findings? Dr. Nishimura: Oxaliplatin is classified as moderately emetogenic chemotherapy and 2-drug combination antiemetic therapy is recommended for Oxaliplatin based chemotherapy including FOLFOX and XELOX in all guidelines for antiemesis. Nausea and vomiting are still frequent adverse events which decrease the patient’s QOL. However, there was no study investigating whether 3-drug combination antiemetic therapy (5HT3 receptor antagonist+dexamethasone+aprepitant) reduce chemotherapy-induced nausea and vomiting. In this study, we conducted a multicentre, randomized phase III study to evaluate the usefulness of the combined use of aprepitant in colorectal cancer patients treated with Oxaliplatin based chemotherapy. In this phase III study, 3-drug combination therapy significantly increased the inhibition rate of vomiting which was the primary endpoint of this study. Moreover, the inhibition rate of nausea, complete response (no vomiting and no rescue medication use), and complete protection (no vomiting , no rescue medication use and no moderate or worsened nausea) was significantly higher in aprepitant group in overall and delayed phase. We, next, compared the inhibition of vomiting and nausea between males and females in delayed phase. When patients were grouped by sex regardless of the assigned treatment group, females were more affected by nausea and vomiting than males. Finally, in female, aprepitant did significantly prevent nausea and vomiting as well as increased chance of complete protection.