Author Interviews, Herpes Viruses / 23.12.2014

MedicalResearch.com Interview with: Professors Lynda A. Morrison, Ph.D. and John E. Tavis, Ph.D. Dept. of Molecular Microbiology and Immunology Saint Louis University School of Medicine St. Louis, MO 63104 Medical Research: What is the background for this study? What are the main findings? Response: A number of viruses use enzymes in the nucleotidyl transferase superfamily (NTS) to carry out their genome replication. These enzymes include the RNaseH and integrase of HIV and the RNaseH of hepatitis B virus (HBV). Herpesviruses also encode proteins with functions that are consistent with NTS enzymes. We therefore tested compounds known or suspected to inhibit the HBV RNaseH for their capacity to reduce herpes simplex virus (HSV)-1 and HSV-2 in cell culture assays. We found that certain compounds from several different chemical families could inhibit HSV replication up to 1 million-fold, and were effective down to concentrations that are already in the same range as existing anti-herpesvirus drugs. Many of the same compounds that inhibited HSV-1 and HSV-2 also inhibited another human herpesvirus, cytomegalovirus. Importantly, we showed that these new inhibitory compounds have a different mechanism of action than acyclovir, a nucleoside analog that is the standard of care. In addition, the new compounds we identified could inhibit the replication of acyclovir-resistant HSV-1 and HSV-2. (more…)
Author Interviews, Autism, Toxin Research / 23.12.2014

MedicalResearch.com Interview with: Raanan Raz, PhD Visiting Scientist Harvard School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Raz: Air pollution contains various toxicants that have been found to be associated with neurotoxicity and adverse effects on the fetus in utero. Several studies have explored associations of air pollution with autism spectrum disorders (ASD). These studies suggest increased chances of having a child with autism spectrum disorders with higher exposures to diesel particulate matter (PM), criteria pollutants and some organic materials as well as closer proximity to a freeway. (more…)
Author Interviews, CDC, HPV, OBGYNE, Vaccine Studies / 22.12.2014

dr-pedro-moroMedicalResearch.com Interview with: Pedro Moro MD MPH Immunization Safety Office, Division of Healthcare Quality Promotion National Center for Emerging and Zoonotic Infectious Diseases Centers for Disease Control and Prevention Medical Research: What is the background for this study? What are the main findings? Dr. Moro: Gardasil® is a human papillomavirus (HPV) vaccine recommended for all girls and boys at age 11 or 12, and teens and young adults who did not get the vaccine when they were younger. Because there is limited safety data available on use of the vaccine during pregnancy, it is not currently recommended for pregnant women. However, some pregnant women will inadvertently receive Gardasil® because they do not yet know that they are pregnant at the time of vaccination. The study reviewed non-manufacturer reports to the Vaccine Adverse Event Reporting System (VAERS) about pregnant women who received Gardasil®. VAERS is a national vaccine safety surveillance program co-administered by the Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA). VAERS accepts reports of health problems that occur after any US-licensed vaccine (these are called adverse events). VAERS may also accept reports not describing any health problem but vaccination errors (for example, administration of a vaccine not recommended to a particular group of people like pregnant women). VAERS is an early-warning system and cannot generally assess if a vaccine caused an adverse event. After reviewing all non-manufacturer reports of Gardasil vaccination during pregnancy, this study found no unexpected patterns of safety issues for pregnant woman who received Gardasil®, or for their babies. This finding is reassuring and reconfirms the safety of this vaccine for pregnant women, as was previously reported by the pregnancy registry maintained by Gardasil®’s manufacturer. (more…)
Author Interviews / 22.12.2014

Turhan Canli, Ph.D. Associate Professor, Psychology and Radiology Director, SCAN (Social, Cognitive, and Affective Neuroscience) Center Senior Fellow, Center for Medical Humanities, Compassionate Care, and Bioethics Stony Brook University Stony Brook, NY 11794MedicalResearch.com Interview with: Turhan Canli, Ph.D. Associate Professor, Psychology and Radiology Director, SCAN (Social, Cognitive, and Affective Neuroscience) Center Senior Fellow, Center for Medical Humanities, Compassionate Care, and Bioethics Stony Brook University Stony Brook, NY 11794 Medical Research: What is the background for this study? What are the main findings? Response: I was struck by two aspects of major depression treatment. First, that today's drug treatments are not much different from those used decades ago, with no real progress in treatment effectiveness. In severe cases of major depression, antidepressants may give some symptom relief, but for less severe cases, the effectiveness of antidepressants is not clinically relevant. Second, recurrence rates remain stubbornly high: patients with diagnosed MDD have a lifetime recurrency rate of 50%. We are not treating depression; at best, we reduce symptoms. (more…)
Author Interviews, PLoS, Weight Research / 22.12.2014

Elina Helander, PhD Personal Health Informatics Department of Signal Processing Tampere University of Technology, Tampere, FinlandMedicalResearch.com Interview with: Elina Helander, PhD Personal Health Informatics Department of Signal Processing Tampere University of Technology, Tampere, Finland Medical Research: What is the background for this study? What are the main findings? Dr. Helander: Frequent or at least regular self-weighing is a part of behavioral therapy in many weight programs. However, self-weighing frequency typically varies over time. We analyzed almost 3,000 weight observations from 40 overweight individuals that participated in a 1-year health promotion program. These individuals were instructed to weigh themselves daily but eventually had varying self-weighing frequencies. We examined how different self-weighing frequencies of the same individual were linked with weight changes. We found that weight loss generally occurred during daily weighing. When there were longer breaks in self-weighing such as one month or more, there was a risk of weight gain.  We also computed a theoretical minimum self-weighing frequency for having no weight gain that was 5.8 days in our study. That corresponds approximately weekly weighing. (more…)
Author Interviews, HIV, Nature, UCLA / 22.12.2014

David Gerberry PhD Center for Biomedical Modeling, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CaliforniaMedicalResearch.com Interview with: David Gerberry PhD Assistant Professor Department of Mathematics and Computer Science Xavier University, Cincinnati, Ohio   Medical Research: What is the background for this study? What are the main findings? Response: In an attempt to control the spread of HIV, governments in sub-Saharan Africa are considering providing antiretroviral drugs to people who do not have the virus but are at risk for becoming infected. Such drugs are known as pre-exposure prophylaxis, or PrEP.  Given the cost of PrEP, an important question is how to maximize the impact of interventions given a fixed level of prevention resources. A common strategy is to target resources to the individuals that are at the highest risk for infection.  This group of people is often referred to as the "core group" and can be thought of as sex workers, clients of sex workers and other individuals that are at very high risk for infection.  While targeting this core group is ideal and would result in the most cost-effectiveness interventions, being able to identify these individuals is difficult in practice and they are often unwilling to participate in the intervention; take pre-exposure prophylaxis or change their behavior for example.  From a mathematical perspective it is also very difficult to quantify their increased level of risk.  For example, is a sex worker at 5 times, 25 times, 100 times or 1000 times the risk for HIV infection?  Without this quantification, it is impossible to estimate the cost-effectiveness of a targeted strategy. In our work, we build an intervention strategy based on geographical targeting.  This takes advantage of the fact that HIV incidence is much higher in certain geographical locations than others.  Therefore, individuals in these areas are at increased risk for HIV infection.  Most importantly, such an intervention is feasible because reliable data exists across much of sub-Saharan Africa for the severity of the HIV epidemic in different regions.  To illustrate our ideas we used mathematical modeling to consider resource allocation in South Africa and found that targeting the provinces with highest HIV incidence would prevent 40% more infections than a plan that ignored geographic variation while using the same amount of resources. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Kidney Disease, University of Pittsburgh / 22.12.2014

MedicalResearch.com Interview with: Florentina E. Sileanu BS Center for Critical Care Nephrology and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center Departments of Critical Care Medicine and Department of Biostatistics, University of Pittsburgh Graduate School of Public Health and Dr. John A. Kellum, MD, MCCM Professor of Medicine, Bioengineering and Clinical & Translational Science Vice Chair for Research Center for Critical Care Nephrology, University of Pittsburgh School of Medicine Pittsburgh, PA Medical Research: What is the background for this study? What are the main findings? Response: Acute Kidney Injury (AKI) affects millions of Americans each year resulting in increased short and long-term complications including need for dialysis and death. Many trials recruiting subjects at risk for AKI have focused on those with other (e.g. cardiovascular and respiratory) organ failures because these patients are at highest for AKI. However, patients without these conditions might not be at low-risk for AKI. We explored whether Acute Kidney Injury occurring as a single organ failure or occurring before other organ failures would be associated with the same outcomes as in sicker patients. Using a large, academic medical center database, with records from July 2000 through October 2008, we identified a "low-risk" cohort as patients without cardiovascular and respiratory organ failures defined as not receiving vasopressor support or mechanical ventilation within the first 24 hours of ICU admission. We were able to show that low-risk patients have a substantial likelihood of developing AKI and that the relative impact on mortality of AKI is actually greater for low-risk patients (OR, 2.99; 95% 2.62-3.41) than for high-risk patients (OR, 1.19; 95% 1.09-1.3). (more…)
Author Interviews, Infections, PLoS / 22.12.2014

Leonard A. Mermel DO FACP, FIDSA, FSHEA Professor of Medicine, Warren Alpert Medical School of Brown University and Division of Infectious Diseases, Rhode Island Hospital Providence, Rhode IslandMedicalResearch.com Interview with: Leonard A. Mermel DO FACP, FIDSA, FSHEA Professor of Medicine, Warren Alpert Medical School of Brown University and Division of Infectious Diseases, Rhode Island Hospital Providence, Rhode Island Medical Research: What is the background for this study? What are the main findings? Dr. Mermel: While talking to infectious diseases physicians some years ago in Israel, Greece, and Thailand, I learned that unlike my experiene here in the US, most of the bloodstream infections they see are far and away due to Gram-negative bacteria.  So, a hypothesis was generated, namely that the likelihood of Gram-negative bacteremia compared to Gram-positive bacteremia was greater the closer to the equator.  A writing group was formed, colleagues around the world graciously shared their data.  The main finding is that in fact, we unequivocally found that the likelihood of Gram-negative, compared to Gram-positive bacteremia is more common closer to the equator.  This difference was greatest during the warmer months of the year.  We also found that the % GDP spent on healthcare in a given country is also associated with more Gram-negative than Gram-positive bacteremia.  These findings may reflect differences in the human microbiome as one gets closer or farther from the equator as has been recently demonstrated, differences in survival of Gram-negative compared to Gram-positive bacteria under certain environmental conditions, and likely reflects differences in public health and other factors. (more…)
Author Interviews, Infections, Vaccine Studies / 22.12.2014

Thomas Wisniewski MD Lulu P. and David J. Levidow Professor of Neurology Professor; Director Aging and Dementia New York University School of Medicine Dept. of Neurology, Psychiatry and Pathology New York, NY  10016MedicalResearch.com Interview with: Thomas Wisniewski MD Lulu P. and David J. Levidow Professor of Neurology Professor; Director Aging and Dementia New York University School of Medicine Dept. of Neurology, Psychiatry and Pathology New York, NY  10016 Medical Research: What is the background for this study? What are the main findings? Dr. Wisniewski: Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment.  This is a relatively new prion disease that has many similarities to bovine spongiform encephalopathy which spread to humans to produce new variant Creutzfeldt-Jakob disease. Chronic wasting disease is the most infectious prion disease to date; having the potential to spread by aerosol. Previously, we have demonstrated we could prevent transmission of prions in a proportion of susceptible mice with a mucosal vaccine. In the current study, white-tailed deer were orally inoculated with attenuated Salmonella expressing PrP, while control deer were orally inoculated with vehicle attenuated Salmonella. Once a mucosal response was established, the vaccinated animals were boosted orally and locally by application of polymerized recombinant PrP onto the tonsils and rectal mucosa. The vaccinated and control animals were then challenged orally with CWD-infected brain homogenate. Three years post CWD oral challenge all control deer developed clinical CWD (median survival 602 days), while among the vaccinated there was a significant prolongation of the incubation period (median survival 909 days; p=0.012 by Weibull regression analysis) and one deer has remained CWD free both clinically and by RAMALT and tonsil biopsies. This negative vaccinate has the highest titers of IgA in saliva and systemic IgG against PrP. Western blots showed that immunoglobulins from this vaccinate react to PrPCWD. We document the first partially successful vaccination for a prion disease in a species naturally at risk. (more…)
Author Interviews, Cognitive Issues, Metabolic Syndrome / 22.12.2014

Prof. Giovambattista Desideri Università degli Studi dell'Aquila Direttore  UOC Geriatria e Lungodegenza Geriatrica Scuola di Specializzazione in Geriatria Scuola di Specializzazione in Medicina d'Emergenza-UrgenzaMedicalResearch.com Interview with: Prof. Giovambattista Desideri Università degli Studi dell'Aquila Direttore  UOC Geriatria e Lungodegenza Geriatrica Scuola di Specializzazione in Geriatria Scuola di Specializzazione in Medicina d'Emergenza-Urgenza Medical Research: What is the background for this study? What are the main findings? Dr. Desideri: Over the past decade, there has been an accumulating body of evidence that indicates that the consumption of cocoa flavanol-containing products can improve vascular function. Though much research has focused on the cardiovascular system, there is reason to believe that some of the benefits of cocoa flavanol consumption could extend also to the brain which is a heavily vascularized tissue that depends on regular blood flow to meet its metabolic demands. Thus, the current study tested the hypothesis that the regular inclusion of cocoa flavanols for 8 weeks could positively affect cognitive function in cognitively-intact older adults. The effects of cocoa flavanol ingestion on various cardiometabolic endpoints, including blood pressure and insulin sensitivity, were also evaluated given consistent evidence of positive effects of flavanols on these outcomes and the potentially influential role of these outcomes on cognitive function. Medical Research: What are the main findings? Dr. Desideri:The study enrolled 90 men and women aged 61-85 years with no evidence of cognitive dysfunction who were assigned to one of three flavanol groups, consuming a drink containing high (993 mg), intermediate ( 520 mg) or low (48 mg) amounts of cocoa flavanols every day for 8 weeks. Among those individuals who regularly consumed either the high-or intermediate-flavanol drinks, there were significant improvements in some measures of age-related cognitive dysfunction.  In the high- and intermediate-flavanol groups, both systolic and diastolic blood pressures were reduced and insulin resistance was significantly improved.   It is not yet fully understood how cocoa flavanols bring about improvements in cognitive function, but the study results suggest that the improvements in insulin resistance and blood pressure could be revealing. (more…)
Author Interviews, Breast Cancer, JNCI / 21.12.2014

MedicalResearch.com Interview with: Dr Ranjit Manchanda Consultant Gynaecological Oncologist, St Bartholomew’s Hospital, London, UK Honorary Sr Lecturer, Women’s Cancer, EGA Institute for Women's Health, University College London, UK  and Professor Ian Jacobs Vice President, The University of Manchester Dean & Head School of Medicine Faculty of Medical & Human Sciences, Director MAHSC (Manchester Academic Health Science Centre) Medical Research: What is the background for this study? What are the main findings? Dr. Jacobs:  Background- Women carrying a BRCA1/2 gene alteration have a very high risk of developing breast and ovarian cancer and men carrying this alteration have an increased risk of prostate and breast cancer. Approximately 45-65% women who have this inherited genetic change will develop breast cancer and 15-35% ovarian cancer. They also have a 50% chance of passing these genes on to their children. At risk individuals can access available options of screening and prevention through the National Health Service (NHS). Some population groups across the world are known to have a higher frequency of BRCA 1/2 gene alterations than others. One example is Ashkenazi Jews who have a 1 in 40 likelihood of having a BRCA1/2 gene alteration. This is 10-20 times higher than in the general non-Jewish population. At present in the UK, genetic testing is available within the NHS to individuals who have a strong family history of cancer. However, many people are not aware of their family history or its significance and do not seek advice. Many other individuals with BRCA1/2 gene alterations do not have a family history at all. The current approach misses a large number of people at risk who could benefit from knowing about their BRCA 1/2 mutation status and the ability to access opportunities for prevention or screening. In order to address this the GCaPPS study has investigated the best method of screening for risk of inherited (familial) cancer by exploring the alternative approach of offering the genetic test to all men and women >18 years in the Ashkenazi Jewish population. It does so by comparing the benefits and disadvantages of: (i) The current system of testing only those with a family history and (ii) The new option of testing everyone in the population. Main Findings: Over half of the BRCA1/BRCA2 carriers detected did not give a strong family history of cancer and would not have been identified by current family history based testing criteria used in the NHS (National Health Service) in the UK and most health systems internationally. Reassuringly population-based genetic testing in Ashkenazi Jews did not adversely affect short term psychological health or quality-of-life. A health economic analysis indicated that population-based screening for BRCA-mutations in Ashkenazi Jewish women ≥30years would be highly cost-effective compared to the traditional family history based approach. Such an approach if implemented could reduce the incidence of and deaths from breast and ovarian cancer as well as reducing cost and save the NHS funds. (more…)
Author Interviews, Pediatrics, Toxin Research, University Texas / 21.12.2014

Ying Xu Assistant Professor, Ph.D. Department of Civil, Architectural and Environmental Engineering University of Texas, AustinMedicalResearch.com Interview with: Ying Xu Assistant Professor, Ph.D. Department of Civil, Architectural and Environmental Engineering University of Texas, Austin Medical Research: What is the background for this study? What are the main findings? Response: Phthalates have been widely used as plasticizers to enhance the flexibility of polyvinyl chloride (PVC) products.  They are ubiquitous and persistent indoor pollutants and may result in profound and irreversible changes in the development of human reproductive tract. In this study, we found that the emissions of phthalates and phthalate alternatives increase significantly with increasing temperature.  We developed an emission model and validated the model via chamber experiments.  Further analysis showed that, in infant sleep microenvironments, an increase in the temperature of mattress can cause a significant increase in emission of phthalates from the mattress cover and make the concentration in breathing zone about four times higher than that in the room, resulting in potentially high exposure.  In residential homes, an increase in the temperature from 25 to 35 ºC can elevate the gas-phase concentration of phthalates by more than a factor of 10, but the total airborne concentration may not increase that much for less volatile compounds. (more…)
Opiods / 21.12.2014

Erik Gunderson, M.D., FASAM Assistant Professor Department of Psychiatry and Neurobehavioral Sciences and Department of Medicine University of Virginia Principal Investigator of the studyMedicalResearch.com Interview with: Erik Gunderson, M.D., FASAM Assistant Professor Department of Psychiatry and Neurobehavioral Sciences and Department of Medicine University of Virginia Principal Investigator of the study Medical Research: What is the background for this study? What are the main findings? Response: The ISTART/006 study was a randomized, multicenter, non-inferiority Phase 3 clinical trial designed to evaluate the efficacy of ZUBSOLV® (buprenorphine and naloxone) sublingual tablet (CIII) compared with generic buprenorphine tablets during induction and with Suboxone® film during stabilization of patients with opioid dependence. The co-primary endpoint was retention in treatment at day 3 (when patients began maintenance therapy with either ZUBSOLV or Suboxone film) and retention in treatment at day 15. Secondary endpoints included assessment of treatment effects on opioid withdrawal symptoms for ZUBSOLV versus Suboxone film via both the Clinical Opiate Withdrawal Scale (COWS) score and Subjective Opiate Withdrawal Scale (SOWS), and opioid cravings via the visual analogue scale (VAS). 758 patients participated in a two-day blinded induction phase randomized to ZUBSOLV or generic buprenorphine tablets, and on day 3 those taking the generic tablets were switched to Suboxone film for a 20-day open-label stabilization and early maintenance phase. At day 15, ZUBSOLV patients switched to Suboxone film and those taking Suboxone film switched to ZUBSOLV. Please note ZUBSOLV currently is not indicated for induction treatment. In October 2014, Orexo submitted a sNDA to the FDA for that indication. We found ZUBSOLV demonstrated comparable patient retention in treatment at days 3 and 15 versus generic buprenorphine and Suboxone film respectively, as well as no increased rate of withdrawal symptoms or opioid cravings versus Suboxone film. The safety profile of ZUBSOLV was similar to that of Suboxone film. (more…)
Author Interviews, Endocrinology, JCEM, Menopause, UCLA / 20.12.2014

Carolyn J. Crandall, MD, MS Professor of Medicine David Geffen School of Medicine at University of California, Los Angeles UCLA Medicine/GIM Los Angeles, CA 90024MedicalResearch.com Interview with: Carolyn J. Crandall, MD, MS Professor of Medicine David Geffen School of Medicine UCLA Medicine/GIM Los Angeles, California 90024 Medical Research: What is the background for this study? What are the main findings? Dr. Crandall: In a large group of postmenopausal women aged 50-79, we found that women who reporting having hot flashes at baseline had increased risk of hip fracture during the subsequent 8 years of observation, nearly double the risk compared with women who did not have hot flashes at baseline. (more…)
Author Interviews, Brigham & Women's - Harvard, Psychological Science, Surgical Research / 20.12.2014

Brian I. Labow, MD Director, Adolescent Breast Clinic Assistant in Surgery Assistant Professor of Surgery Harvard Medical School PrimaryMedicalResearch.com Interview with: Brian I. Labow, MD Director, Adolescent Breast Clinic Assistant in Surgery Assistant Professor of Surgery Harvard Medical School Primary   Medical Research: What is the background for this study? What are the main findings? Dr. Labow:  This study is part of our larger Adolescent Breast Disorder Study, in which we examine the impact of several breast disorders on adolescent girls and boys and measure the effect of treatment. In this present study we have found breast asymmetry, defined as having at least 1 cup size difference between breasts, can have a significant impact on the psychological wellbeing of adolescent girls.  Validated surveys were given to adolescent girls with breast asymmetry, macromastia (enlarged breasts), and healthy unaffected girls between the ages of 12-21 to assess a wide array of health domains. Girls with breast asymmetry had noted deficits in psychological wellbeing and self-esteem when compared to healthy girls of the same age.  These impairments were similar to those of girls with macromastia, a condition known to have significant negative mental health effects. Interestingly, these negative psychological outcomes did not vary by patient’s age or severity of breast asymmetry. Older and younger adolescents were negatively impacted similarly, as were those with lesser and greater degrees of breast asymmetry. (more…)
Author Interviews / 20.12.2014

MedicalResearch.com Interview with: Charlotta Ljungman, MD, PhD Sahlgrenska University Hospital/Cardiology Gothenburg, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Ljungman: The background of this study is the known differences between women and men regarding antihypertensive therapy. In studies both in Europe and the United States it has been shown that women are more often treated with diuretics and men with ACE-inhibitors. The reasons for these differences is not known but it has been suggested that differences in comorbidities between women and men can contribute to this finding. In our study we tested if comorbidities could explain the differences but could conclude that the differences persist even after taking comorbidities (mainly diabetes mellitsu and cardiovascular comorbidity) into account. Women were more often treated with thiazide diuretics and beta blockers and men with ACE inhibitors and Ca channel blockers. Further women with diabetes and hypertension were not treated with ACEinhibitors and ARBS as often as their male counterparts. (more…)
Author Interviews, Diabetes, Diabetologia / 20.12.2014

MedicalResearch.com Interview with: Dr Guy Fagherazzi Center for Research in Epidemiology and Population Health INSERM, Villejuif, France, and colleagues. Medical Research: What is the background for this study? What are the main findings? Dr. Fagherazzi: Our work has been based on previous findings regarding the associations between blood type and the risk of stroke or coronary heart disease, where people with the O blood group seamed to have lower risk of developping the disease. The suggested mechanisms could be also be involved with type 2 diabetes. And our results were in agreement with our first hypothesis. We have followed more than 80 000 women from the E3N cohort study, during 18 years and we have found that individuals with the O blood type had lower risk of type 2 diabetes than the others (people with groups A, B and AB). (more…)
AHA Journals, Author Interviews, Stroke / 20.12.2014

Jeff Perry, MD, MSc, CCFP-EM Associate Professor, Department of Emergency Medicine Senior Scientist, Ottawa Hospital Research Institute Research Chair in Emergency Neurological Research, University of Ottawa Emergency Physician, The Ottawa Hospital Epidemiology Program, F6 The Ottawa Hospital, Civic Campus Ottawa, OntarioMedicalResearch.com Interview with: Jeff Perry, MD, MSc, CCFP-EM Associate Professor, Department of Emergency Medicine Senior Scientist, Ottawa Hospital Research Institute Research Chair in Emergency Neurological Research, University of Ottawa Emergency Physician, The Ottawa Hospital Epidemiology Program, The Ottawa Hospital, Ottawa, Ontario Medical Research: What is the background for this study? What are the main findings? Dr. Perry: Currently it is not well known which patients with a TIA or a non-disabling stroke will have a subsequent stroke or die within the days to weeks following their initial event.  This study found that patients with acute ischemia, especially if it is associated with an old infarction or microangiopathy, are at a much higher risk for an early subsequent stroke. (more…)
Heart Disease, Kidney Disease, Stem Cells / 20.12.2014

Madhav Swaminathan, MBBS, MD, FASE, FAHA Associate Professor with Tenure Clinical Director, Division of Cardiothoracic Anesthesiology & Critical Care Medicine Department of Anesthesiology Duke University Health System Durham, NC 27710MedicalResearch.com Interview with: Madhav Swaminathan, MBBS, MD, FASE, FAHA Associate Professor with Tenure Clinical Director, Division of Cardiothoracic Anesthesiology & Critical Care Medicine Department of Anesthesiology Duke University Health System Durham, NC 27710 Medical Research: What is the background for this study? What are the main findings? Dr. Swaminathan: The background is the need for salvage therapies for acute kidney injury (AKI,) which is a common complication in hospitalized patients. It is particularly a problem in the postoperative period after cardiac surgery. Preventive strategies have not worked well for decades. Hence the focus on strategies that target kidney recovery. Mesenchymal stem cells have been shown to be useful in enhancing kidney recovery in pre-clinical trials. We therefore hypothesized that administration of human Mesenchymal stem cells (AC607, Allocure Inc, Burlington, MA) to patients with established post-cardiac surgery AKI would result in a shorter time to kidney recovery. We conducted a phase 2, double blinded, placebo controlled, randomized clinical trial to test our hypothesis. Unfortunately we could not confirm the hypothesis and there were no significant differences in time to kidney recovery among patients that received AC607 versus placebo in 156 randomized cardiac surgery subjects. (more…)
Breast Cancer / 20.12.2014

Thomas Rogers PhD Candidate- Cancer Biology Graduate Program Laboratory of Jennifer Richer Department of Pathology University of Colorado-Anschutz Medical Campus Laboratory of CU Cancer Center investigator, Jennifer Richer, PhD.MedicalResearch.com Interview with: Thomas Rogers PhD Candidate- Cancer Biology Graduate Program Laboratory of Jennifer Richer Department of Pathology University of Colorado-Anschutz Medical Campus Laboratory of CU Cancer Center investigator, Jennifer Richer, PhD. Medical Research: What is the background for this study? What are the main findings? Response: Background: Survival while detached from a basement membrane is a critical trait of cancer cells progressing through the metastatic cascade. This is particularly important for the triple-negative breast cancer (TNBC) subtype, which lacks estrogen and progesterone receptors and does not have amplification of HER2, and has a peak risk of recurrence within the first three years post-diagnosis. Triple-negative breast cancer also has the highest mortality rate in the first five years as compared to other breast cancer subtypes. We performed global profiling of TNBC cells in adherent versus forced suspension culture conditions after24 hours. These data revealed that triple-negative breast cancer cells surviving in suspension upregulate multiple genes involved in tryptophan catabolism, also known as the kynurenine pathway, including the rate limiting enzyme tryptophan 2,3,-dioxygenase (TDO2) and kynureninase (KYNU). Kynurenine, a key intermediate metabolite of this pathway activates the aryl hydrocarbon receptor (AhR), which was also up-regulated in TNBC cells grown in forced-suspension culture. Main Findings: Critical enzymes of the kynurenine pathway, TDO2 and KYNU, are upregulated in triple-negative breast cancer cells grown in forced-suspension culture. Furthermore, secreted kynurenine doubles in TNBC cells in forced-suspension culture as measured by high performance liquid chromatography (HPLC). Kynurenine activates the aryl hydrocarbon receptor in triple-negative breast cancer cells grown in forced-suspension culture. Targeting TDO2 and AhR with small molecule inhibitors or short hairpin RNAs decreased survival in suspension, migration/invasion, and proliferation of TNBC cells. Lastly, TDO2 gene expression is higher in invasive ductal breast carcinoma as compared to normal breast tissue and is significantly higher in estrogen receptor negative tumors as compared to estrogen receptor positive tumors. In addition, patients with higher (above-median) TDO2 expression in their primary tumor had significantly shorter overall survival than those with low TDO2. Conclusions: The kynurenine pathway is activated in TNBC cells in forced suspension and facilitates the invasive/metastatic phenotype of this aggressive breast cancer subtype. Our findings support further investigations into targeting the enzyme TDO2 in TNBC as a novel therapeutic strategy with potential to reduce TNBC mortality rates. Kynurenine is well-known to suppress immune cell function via activation of AhR. (more…)
Author Interviews, CMAJ, Pharmacology / 19.12.2014

MedicalResearch.com Interview with: Naveen Poonai MSc MD FAAP FRCPC Paediatric Emergency Physician Children's Hospital, London Health Sciences Center Assistant Professor Paediatrics and Internal Medicine Schulich School of Medicine and Dentistry London, Ontario, Medical Research: What is the background for this study? What are the main findings? Dr. Poonai: We found that in children discharged home with a fracture, both ibuprofen and oral morphine were effective at relieving pain. However, there were no significant differences in efficacy between the two agents and oral morphine was associated with more side effects. MedicalResearch.com: What was most surprising about the results? Dr. Poonai: The most surprising findings for us were that over 70% of children experienced pain significant enough to require analgesia once they were discharged home.  Furthermore, we were surprised to find that the anecdotally more potent agent morphine, was equivalent to ibuprofen for post-fracture pain relief in children. (more…)
Author Interviews, NEJM / 19.12.2014

natalie_walkerMedicalResearch.com Interview with: Natalie Walker, Ph.D. National Institute for Health Innovation School of Population Health, University of Auckland Auckland, New Zealand Medical Research: What is the background for this study? What are the main findings? Dr. Walker: Cytisine is a plant-based alkaloid and is structurally similar to nicotine.  It is found in various plants from the Legume Family (Fabaceae), the third largest plant family on earth.  Cytisine is currently manufactured by Sopharma Ltd, Bulgaria (Tabex®) and Aflofarm Pharma, Poland (Desmoxan®) as a smoking cessation treatment, with the cytisine used in the tablets taken from a plant called Golden Rain (Laburnum anagyroides).  Cytisine has been available with and without prescription for smoking cessation since the 1960s, largely in Eastern Europe.   Cytisine is not currently registered for use in any Western countries (although regulatory approval is currently been sought for the USA , UK and Japan).             We know from trial evidence that cytisine is better than a placebo for helping people quit smoking.  Cytisine is also one of the most affordable smoking cessation medicines available. It is much cheaper than nicotine patches, gum and/or lozenges and other smoking cessation medicine such as varenicline. This means smokers and governments are more likely to afford cytisine, especially those from low and middle income countries. However, we don’t know if cytisine is as good as nicotine patches and/or gum or lozenges, one of the most commonly used smoking cessation treatments in many western countries. We therefore undertook a pragmatic non-inferiority trial to answer this question, with recruitment of 1310 adult daily smokers who were motivated to quit, undertaken using the New Zealand national Quitline. Smokers were randomised to receive the standard 25 days of cytisine treatment or 8 weeks of nicotine patches and/or gum or lozenges.  Both groups received standard Quitline behavioural support.  Follow-up occurred at one week and one, two, and six months. At all time points, cytisine was found to be better at helping people quit smoking than nicotine patches and/or gum or lozenges.  This finding was consistent irrespective of ethnicity, age, alcohol consumption, degree of cigarette dependence or whether participants smoked factory-made cigarettes or roll-your-owns. For reasons unknown, cytisine helped more women quit smoking than nicotine patches, gum and/or lozenges.  For men the effectiveness of the two products was similar.  Cytisine use made people less likely to relapse back to smoking. Those who did smoke when using cytisine didn’t enjoy smoking as much, and reduced the number of cigarettes they smoked.  Self-reported, non-medically verified adverse events were more common in those that used cytisine. Three out of every 10 people who used cytisine reported an adverse event, compared to 2 out of every 10 that used nicotine patches, gum and/or lozenges.  However the majority of reported side effects were mild and self-limiting. More people in the cytisine group experienced nausea, vomiting and sleep disturbances (e.g. bad dreams). (more…)
Author Interviews, Herpes Viruses, Pediatrics / 19.12.2014

Ann J. Melvin MD, MPH Division of Pediatric Infectious Disease Department of Pediatrics Seattle Children's Hospital, Seattle, WA 98105.MedicalResearch.com Interview with: Ann J. Melvin MD, MPH Division of Pediatric Infectious Disease Department of Pediatrics Seattle Children's Hospital, Seattle, WA 98105. Medical Research: What is the background for this study? What are the main findings? Dr. Melvin: While relatively uncommon, neonatal Herpes Simplex Virus is a potentially devastating infection with significant morbidity and mortality.  We reviewed all of the neonatal HSV cases treated at our institution between 1993 and 2012 who had HSV DNA PCR results available from the plasma and/or CSF.  Most of the infants had quantitative PCR results available.  The objective of the study was to determine the clinical correlation of HSV PCR levels in the plasma and CSF.  We found a clear association between the plasma HSV level, clinical presentation and mortality.  All of the infants who died had HSV plasma DNA levels of greater than 7 log10 copies/ml.   However, neither plasma nor CSF HSV levels predicted neurologic outcome.   Clinical evidence of CNS disease was more predictive of neurologic outcome than was the CSF PCR level. We also showed the most sensitive test for diagnosis of neonatal HSV to be HSV PCR on the plasma.  However, no single test diagnostic test (plasma PCR, CSF PCR, surface cultures) was positive across all infants, so it is important to obtain samples from plasma, CSF and surface swabs in infants with symptoms consistent with HSV infection. (more…)
Author Interviews, Race/Ethnic Diversity / 19.12.2014

Glenn Firebaugh, Ph.D. Roy C. Buck Professor of American Institutions, Sociology, and Demography College of the Liberal Arts The Pennsylvania State University University Park, PAMedicalResearch.com Interview with: Glenn Firebaugh, Ph.D. Roy C. Buck Professor of American Institutions, Sociology, and Demography College of the Liberal Arts The Pennsylvania State University University Park, PA Medical Research: What is the background for this study? What are the main findings? Dr. Firebaugh: Lifespans are more variable for blacks than for whites in the United States. The objective of this study was to determine why. Is it because blacks are more likely to die of causes, such as homicide, that disproportionately strike the young and middle-aged, or because age at death varies more for blacks than for whites among those who die of the same cause? It is primarily the latter. For almost all causes of death, age at death varies more among black victims than it does among white victims, especially for women. To be sure, some youthful causes of death, such as homicide and AIDS, are more prevalent among blacks, accounting for some of the greater variances in blacks' lifespans. But these causes are largely offset by higher rates of suicide and drug poisoning deaths among whites. As a result, differences in causes of death for blacks versus whites on net account for relatively little of the difference in lifespan variance for blacks and whites. (more…)
Author Interviews, Biomarkers, Brigham & Women's - Harvard, Critical Care - Intensive Care - ICUs, PLoS / 19.12.2014

Daniel Irimia, M.D., Ph.D. Assistant Professor  Division of Surgery, Science & Bioengineering Massachusetts General Hospital and Harvard Medical School Associate Director, BioMEMS Resource Center Boston, MA 02129MedicalResearch.com Interview with: Daniel Irimia, M.D., Ph.D. Assistant Professor Division of Surgery, Science & Bioengineering Massachusetts General Hospital and Harvard Medical School Associate Director, BioMEMS Resource Center Boston, MA 02129 Medical Research: What is the background for this study? What are the main findings? Response: Sepsis is affecting more than half of the patients with major burn injuries (20 percent of body surface) and is the leading cause of death among these patients.  Sepsis is also a significant complication for other critically ill patients. More than one million Americans are affected and it has been estimated that approximately 30% of these people die, despite significant advances in life support and antibiotics.  Early diagnosis is essential, and it has been calculated that every 6 hours of delay in a sepsis diagnosis decreases the chances of survival by 10 percent. We have found that the motility of the white blood cells called neutrophils, inside a microfluidic device, is significantly altered two to three days before sepsis develops. (more…)
Author Interviews, Cancer Research, Nature / 19.12.2014

Dr Catherine Olsen  |  Senior Research Officer QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, QLD 4029MedicalResearch.com Interview with: Dr Catherine Olsen  |  Senior Research Officer QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, QLD 4029 Medical Research: What is the background for this study? What are the main findings? Response: Squamous cell carcinomas (SCCs)are the second most common skin cancer occurring in white skinned populations. They cause significant morbidity as they can invade local structures (often the nose or ears) and they also have the potential to metastasize although most are successfully treated before any spread occurs. They are also very expensive cancers to treat because they are so common, posing a significant burden on health care budgets. NSAIDS have been shown to be protective for other cancers (e.g. colorectal and oesophageal cancer). This prompted use to evaluate all of the available evidence on NSAIDs use and SCC by conducting a systematic review and meta-analysis of the association. (more…)
Author Interviews, Dermatology, JAMA, Melanoma, Occupational Health, UCSF / 18.12.2014

Martina Sanlorenzo, MD Department of Dermatology Mount Zion Cancer Research Center University of California, San FranciscoMedicalResearch.com Interview with: Martina Sanlorenzo, MD Department of Dermatology Mount Zion Cancer Research Center University of California, San Francisco Medical Research: What is the background for this study? Dr. Sanlorenzo: We recently performed a meta-analysis and found an increased risk of melanoma in pilots and cabin crew. One of the possible occupational hazards responsible for this risk is UV radiation. Medical Research: What are the main findings? Dr. Sanlorenzo: We performed UV measurements in airplane cockpits during flight and we found that windshields blocked UV-B but allowed UV-A transmission. We compared the UV-A dose in airplanes with the UV-A dose in tanning beds, whose use is a known risk factor for melanoma. Pilots flying for 56.6 minutes at 30,000 feet received the same amount of UV-A carcinogenic effective radiation of a 20-minute tanning beds session. (more…)
Author Interviews, Heart Disease, JACC / 18.12.2014

MedicalResearch.com Interview with: Dexter Canoy, PhD Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, United Kingdom Medical Research: What is the background for this study? What are the main findings? Response: Over a million middle-aged women in the UK who took part in our study between 1996 and 2001 provided information regarding their health and lifestyle, including their reproductive history such as age when they had their first menstruation. We followed them for over 10 years and identified those who developed heart disease (and other vascular diseases) by obtaining information on hospitalizations and death records. Our study demonstrates that on average, women with menarche before age 13 or after this age have slightly increased risks of developing heart disease, stroke and hospital admissions associated with hypertension. The increased risks for these vascular diseases were highest in women with menarche at age 10 years or younger, or age 17 years or older. This U-shaped association was consistently found among lean, overweight and obese women, among never, past or current smokers, or among women in low, middle or high socioeconomic group. (more…)
Author Interviews, Pain Research, Rheumatology / 18.12.2014

Sandra Goldsmith, MA, MS, RD Director of Public and Patient Education at Hospital for Special Surgery New York City.MedicalResearch.com Interview with: Sandra Goldsmith, MA, MS, RD Director of Public and Patient Education at Hospital for Special Surgery New York City. Medical Research: What is the background for this study? What are the main findings? Response: Almost 50 million adults in the United States suffer from some form of musculoskeletal disorder, which can affect their mobility and quality of life. Osteoarthritis (OA) is the leading cause of disability in the U.S. and affects more than 70 percent of adults between the ages of 55 and 78. Research has shown that there is a connection between being physically active and maintaining joint health, pain relief and improved quality of life. This study attempts to support the efficacy of Hospital for Special Surgery’s hospital-based exercise programs in increasing physical activity and improving quality of life through pain relief and improved stiffness, fatigue and balance in the older adult community. This study found that after taking the exercise classes, fewer participants reported experiencing a high level of muscle/joint pain from their condition (56 percent before the program started vs. 47 percent after completing the program). The study also reported improved quality of life, as evidenced by statistically significant reductions in how much their pain interfered with their general activities, ability to walk, mood, sleep and enjoyment of life. In addition, 83 percent of participants indicated a reduction in stiffness; 82 percent said they felt their balance improved; and 67 percent said they experienced less fatigue as a result of taking part in the program. Health outcomes were also related to the type of exercise class participants chose, with the greatest reduction in muscle/joint pain reported by those who took t’ai chi. (more…)
Author Interviews, Blood Pressure - Hypertension, Weight Research / 18.12.2014

Mohammed Elfaramawi , MD PhD MPH MSc Assistant Professor Epidemiology Department College of Public Health University of Arkansas for Medical Sciences Little rock, AR 72205 MedicalResearch.com Interview with: Mohammed Elfaramawi , MD PhD MPH MSc Assistant Professor Epidemiology Department College of Public Health University of Arkansas for Medical Sciences Little rock, AR 72205 Medical Research: What is the background for this study? What are the main findings? Dr. Elfaramawi: A substantial increase in prevalence of obesity has been documented globally. In the USA, overweight and obesity are the second leading cause of preventable death in the USA, affecting ∼97 million adults. Evidence has accumulated showing that visit-to-visit blood pressure variability is associated with adverse cardiovascular outcomes. This study is one of few studies which explored the relationship between obesity and visit-to-visit blood pressure variability. (more…)