Author Interviews, Genetic Research, Race/Ethnic Diversity, Science / 15.02.2016

MedicalResearch.com Interview with: Michael Yudell, PhD, MPH Chair & Associate Professor Drexel University School of Public Health Community Health and Prevention Philadelphia, PA 19104 Medical Research: What is the background for this study? Dr. Yudell: We came together as a group of scholars from the natural sciences, social sciences, and humanities to address what we believe is a long-standing challenge: how to improve the study of human genetic diversity without recapitulating the controversial and problematic concept of race. We believe that the cross-disciplinary focus of our work—an examination of the historical, biological, and sociological aspects of the race concept—can shed new light on the long-standing debate about the use of the race concept in genetics research. We believe modern genetics remains stuck in a paradox: that on the one hand race is a tool to elucidate human genetic diversity, and on the other hand race is believedthree main concerns to be a poorly defined marker of that diversity and an imprecise proxy for the relationship between ancestry and genetics. This paradox is rooted in the nature of the field: it dates back to the evolutionary geneticist Theodosius Dozhansky, who in the 1930s redefined race in his work on what was known as biology’s evolutionary synthesis (the synthesis of population genetics with Darwinian thought). For much of his career, Dobzhansky believed race to be a useful tool to elucidate human genetic diversity. But by the end of his career he became worried that the study of human diversity had “floundered in confusion and misunderstanding” and was concerned over the nonscientific misuse of the term. He, like we and many others in genetics, anthropology, and the social sciences, have called on the field to devise better methods to improve the study of human genetic diversity. Can the race concept in genetics elucidate the relationship between humans and their evolutionary history, between humans and their health? In the wake of the human genome project the answer seemed to be a pretty resounding “no.” In 2004, for example, Francis Collins, then head of the National Human Genome Research Institute and now Director of the National Institutes of Health called race a “flawed” and “weak” concept and argued that science needed to move beyond race. Yet, as our paper highlights, the use of race persist in genetics, despite voices like Collins, like Craig Venter—leaders in the field of genomics-who have called on the field to move beyond it. They, of course, were not the first to do, but we hope they are among the last. We believe it is time to revisit this century-long debate and bring biologists, social scientists, and scholars from the humanities together in a to find better ways to study the ever-important subject of human diversity. (more…)
Author Interviews, Infections, PLoS / 14.02.2016

MedicalResearch.com Interview with: Tamar Kleinberger, Ph.D. Dept. of Molecular Microbiology Faculty of Medicine Technion – Israel Institute of Technology Haifa ISRAEL Medical Research: What is the background for this study? What are the main findings? Dr. Kleinberger: The cellular DNA damage response (DDR) is a conglomerate of pathways designed to detect DNA damage and signal its presence to cell cycle checkpoints and to the repair machinery, allowing the cell to pause and mend the damage, or if the damage is too severe, to trigger cell death or senescence. Replication intermediates and linear double-stranded genomes of DNA viruses are recognized by the cell as DNA damage and activate the DDR. If allowed to operate, the DDR will stimulate ligation of viral genomes and will inhibit virus replication. To prevent this outcome, many DNA viruses evolved ways to limit the DDR. For example, adenoviruses, a family of viruses that cause respiratory illnesses or gastrointestinal disease or eye infections, have been reported to inhibit the DDR by degrading DNA damage sensor proteins or by removing them from virus replication centers. Our present work reveals that adenovirus evolved an additional mechanism to inhibit the DDR, using its E4orf4 protein. The viral E4orf4 protein, together with its cellular partner, the PP2A phosphatase, inhibits damage signaling by reducing phosphorylation of proteins belonging to different DDR branches. As a result E4orf4 causes accumulation of DNA damage in the cells. Inhibition of the DDR regulators ATM and ATR as well as expression of E4orf4 enhance infection efficiency. We found that, at least in the cells we studied, ATM inhibition was important to the early stage of the virus life cycle, whereas ATR inhibition impacted mostly late protein expression and progeny virus production. Furthermore, we previously reported that E4orf4 induces cancer-specific cell death when expressed alone, and in the present report we found that E4orf4 sensitized cells to killing by sub-lethal concentrations of DNA damaging drugs, likely because it inhibited DNA damage repair. These findings provide one explanation for the cancer-specificity of E4orf4-induced cell death because many cancers have DDR deficiencies leading to increased reliance on the remaining intact DDR pathways and to enhanced susceptibility to DDR inhibitors such as E4orf4. Thus DDR inhibition by E4orf4 contributes both to the efficiency of adenovirus replication and to the ability of E4orf4 to kill cancer cells. (more…)
Author Interviews, Heart Disease, JACC, Surgical Research / 14.02.2016

MedicalResearch.com Interview with: Josep Rodés-Cabau, MD Director, Catheterization and Interventional Laboratories Quebec Heart and Lung Institute Professor, Faculty of Medicine, Laval University Quebec City, Quebec, Canada Medical Research: What is the background for this study? What are the main findings? Response: Several concerns have recently emerged regarding valve thrombosis post-TAVR. It has been also proposed that rapid changes in transvalvular gradients may be the hallmark of valve thrombosis despite of the absence of clinical symptoms. However, no data exist on the incidence of and factors associated with valve hemodynamic deterioration (VHD) following TAVR. We included 1,521 patients who underwent TAVR in 10 centers worldwide. VHD was defined as an absolute change in mean transvalvular gradient during follow-up ≥10 mm Hg compared with discharge assessment. Incidence of  valve hemodynamic deterioration was 4.5% during a mean echocardiographic FU of 20 months (2.8% within the first year). We found that the lack of anticoagulation therapy, a valve-in-valve procedure (TAVR in a surgical valve), a greater BMI, and the use of a 23mm transcatheter valve were the factors associated with higher rates of VHD post-TAVR. Also, the absence of anticoagulant therapy remained as an independent predictor of VHD in a sub-analysis excluding patients with small valves, valve-in-valve procedure, and aortic regurgitation at discharge ≥moderate. We think these results suggest a thrombotic mechanism as one of the factors underlying VHD. (more…)
Author Interviews, Gender Differences, Heart Disease, JACC, McGill / 13.02.2016

MedicalResearch.com Interview with: Roxanne Pelletier, PhD Divisions of General Internal Medicine and of Clinical Epidemiology Department of Medicine The Research Institute of the McGill University Health Centre Montreal, Quebec, Canada Medical Research: What is the background for this study? Dr. Pelletier: The increased risk of mortality in young females compared with males after acute coronary syndrome (ACS) remain difficult to understand. As gender-related characteristics has evolved considerably in the last decades (e.g. hours of paid work have increased significantly among women), we hypothesized that these sex differences in adverse outcomes following  acute coronary syndrome are partly explained by gender, rather than by biological sex itself. As explained in our paper, "Gender reflects social norms and expectations ascribed to women and men, in contrast to biological characteristics that are captured by sex. Gender can be referred to as the nonbiological aspects of being male or female (e.g., social roles, personality traits).Our team had previously shown that sex differences in access to care for ACS were partly explained by these gender-related characteristics, such that both men and women presenting with acute coronary syndrome and with personality traits and social roles traditionally ascribed to women (e.g. sensitive to the needs of others, shy, household  responsibility, child care) were waiting longer before diagnostic tests and were less likely to receive invasive treatment procedures such as percutaneous coronary intervention, when compared to men and women with masculine gender-related characteristics. We then aimed to assess whether gender was also playing a role in sex differences in adverse outcomes following acute coronary syndrome. (more…)
Alcohol, Author Interviews, Nutrition, Weight Research / 13.02.2016

MedicalResearch.com Interview with: Francis Tayie, PhD, MPhil, MS. BSc(HONS) Food, Nutrition and Dietetics Department of Human Environmental Studies Southeast Missouri State University Medical Research: What is the background for this study? Dr. Tayie: This article which is the first report to show a positive link between alcoholic beverage consumption and increased moisture intake, also reports increases in calorie intake above what is supplied by alcohol, as well as increased body weight status. The general view is that alcoholic beverages do not contribute to moisture intake. This view is generally due to the diuretic effect of the ethanol in alcoholic beverages, specifically depression of vasopressin resulting in increased loss of moisture via the kidneys. Nevertheless, much of the water in alcoholic beverages, especially in light drinks such as beer and wine may be retained, as indicated in this study. Alcoholic calories count!! The view that alcoholic beverages do not contribute calories to the intake of drinkers is largely debatable. Most of the confusion results from the complex metabolism of the ethanol in alcoholic beverages. Metabolism of ethanol utilizes specific metabolic pathways different from the metabolism of macronutrients. Notably, the
  • 1) alcohol dehydrogenase system,
  • 2) MEOS (microsomal ethanol oxidizing system),
  • and 3) the catalase system.These metabolic systems variably yield some calories but some calories are lost as body heat. It is likely that all of these pathways are not activated simultaneously, and their activities depends on drinking experience. Some calories become available via the alcohol dehydrogenase system, and to a lesser extent via the MEOS. In addition, alcoholic beverage consumption associates with decreased self-restraint, one consequence of which is increased food intake. The promoting effects of alcohol on food intake is multipronged, from social components, to alterations in the effects of appetite regulating neuropeptides.
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Author Interviews, Exercise - Fitness, Heart Disease, JACC / 13.02.2016

MedicalResearch.com Interview with: Daniel Kim-Shapiro, PhD Professor and Associate Chair of Physics Harbert Family Distinguished Chair Director, Translational Science Center Wake Forest University Medical Research: What is the background for this study? What are the main findings? Dr. Kim-Shapiro: Heart failure with preserved ejection fraction (HDPEF) is the most common form of heart failure.  It is characterized by poor perfusion to active muscles which results in poor exercise capacity and a poor quality of life.  Currently, the only effective treatment for this condition is aerobic exercise. Several studies have shown that dietary nitrate, usually in the form of beet root juice, increases nitric oxide bioavaiability in a way that targets areas of low oxygen so that perfusion increases where it is needed.  This action relies on conversion of nitrate to nitrite by oral bacteria with subsequent conversion of nitrite to nitric oxide.  Nitrite from the blood is taken up by salivary glands so that dosing with dietary nitrate can be long-lasting. The main finding of this study was that daily intake of high nitrate containing beet root juice improved exercise endurance in patients with HFPEF. (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Pancreatic, Weight Research / 13.02.2016

MedicalResearch.com Interview with: Joao Incio, MD Edwin L. Steele Laboratory for Tumor Biology Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A Department of Internal Medicine | Hospital S. Joao | Porto, Portugal  Medical Research: What is the background for this study? What are the main findings? Dr. Incio:  The study focused on the effects of obesity on pancreatic and breast cancer, since more than half of those diagnosed with such tumors are overweight or obese. In addition, a number of large-scale studies have found that obesity leads to an increased risk of death in pancreatic, breast and other types of cancer. But prior to the current study the mechanism of obesity-induced pancreatic and breast cancer progression was unclear. We have uncovered a novel mechanism behind the ability of obesity to promote cancer progression.  We found an association between obesity and an overabundance of a factor called PlGF (placental growth factor) and that PlGF’s binding to its receptor VEGFR-1, which is expressed on immune cells within tumors, promotes tumor progression. We found that obesity increased infiltration of tumor-promoting immune cells and the growth and metastasis of pancreatic cancers. Blocking VEGFR-1 signaling shifted the immune environment towards prevention of tumor progression in obese but not in lean mice in both pancreatic and breast cancer models. We also found that PlGF was present in excess in obesity and that reduction of PlGF produced similar results to VEGFR-1 inhibition in the tumors of obese mice. We also discovered that targeting the PlGF/VEGFR-1 interaction prevents weight gain in a genetically obese mouse model but worsens a diabetes-like condition, a worsening that was alleviated by use of the common diabetes drug metformin, which also had beneficial anti-tumor effects. Our findings in cellular and animal models, as well as in patient tumor samples, indicate that targeting the PlGF/ VEGFR-1 pathway may be particularly effective in obese patients. (more…)
Author Interviews, Hospital Acquired, Outcomes & Safety / 12.02.2016

MedicalResearch.com Interview with: Christine Greene, Ph.D. and Chuanwu Xi, Ph.D. School of Public Health, Department of Environmental Health Sciences University of Michigan Medical Research: What is the background for this study? Response: Healthcare-associated infections (HAIs) are a serious problem globally.  Acinetobacter baumannii, a gram-negative opportunistic pathogen, was mostly unheard of 10-15 years ago, but is now a clinically significant pathogen in hospitals.  A. baumannii causes a variety of infections ranging from urinary tract infections to bacteremia and patients who are at high risk of A. baumannii infection are those who are critically ill, who have indwelling catheters or patients with long hospital says.  Once infected, the risk of mortality is high – up to 26% for in-hospital patients and as much as 43% for those in the ICU.  The mortality rate is high largely due to the rapid ability for this pathogen to develop antibiotic resistance.  Despite patient isolation, we still see hospital outbreaks because A. baumannii survives very well in the environment and it is resistant to most biocides, detergents, dehydration, and UV radiation.  A. baumannii is also a known biofilm former.  Biofilms serve to protect the microorganism.  In the open environment, biofilms protect from desiccation and other harsh environmental insults such as biocides, thereby promoting persistence in the open environment.  In the human body, biofilms protect against the immune system, provide an additional layer of protection from antibiotics and contribute to reoccurring infections in the patient. This research characterizes the fitness (desiccation tolerance) trade-offs imposed on A. baumannii isolated from clinical and environmental settings.  This investigation compares isolates of A. baumannii from both environments on the basis of multidrug resistance, biofilms and desiccation tolerance.  We looked to see if either MDR or biofilm formation increased fitness (ability to tolerate desiccation) or impose a fitness cost depending on environmental conditions. Medical Research: What are the main findings? Response: We provide evidence of variation in desiccation tolerance between clinical and environmental isolates of similar phenotypes and show a trend of increased desiccation tolerance for high biofilm forming clinical isolates with additional tolerance when the ability to form biofilms is coupled with the multidrug resistance.  By contrast, biofilm formation had a significant impact on desiccation tolerance for environmental isolates.

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Author Interviews, Cancer Research, Geriatrics, Lung Cancer, Nature / 12.02.2016

MedicalResearch.com Interview with: Chiara Ambrogio, PhD Experimental Oncology Group CNIO-Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre) Melchor Fernández Almagro nº3 Madrid Spain  Medical Research: What is the background for this study? Dr. Ambrogio: The majority of preclinical studies aimed at discovering new therapeutic strategies for lung adenocarcinoma have been conducted so far in full-blown tumors. We wanted to try a new approach by studying early lung lesions in a KRasG12V mouse model in order to bypass the problems imposed by tumor heterogeneity in later stages of the disease. We reasoned that the analysis of the first steps of lung adenocarcinoma development would help us in identifying valuable targets for therapeutic intervention.  Medical Research: What are the main findings? Dr. Ambrogio: 1) We performed gene expression analysis of KRasG12V-driven mouse lung hyperplasias (≤ 500 cells) and we compared it to the gene expression profile of full-blown lung adenocarcinoma. We found that the aggressive nature of this tumor type is determined earlier than what predicted by histopathological criteria. 2) The analysis of transcriptional changes in early lesions allowed us to identify DDR1 as a drugable target in KRasG12V-driven lung adenocarcinoma. We validated its potential as a therapeutic target both genetically and pharmacologically by means of a selective DDR1 inhibitor. We demonstrated that the co-inhibition of DDR1 and NOTCH pathway, a key player in DDR1-mediated survival, exerted additive therapeutic effect. 3) We confirmed these results in human lung adenocarcinoma by reporting, for the first time, the development of an orthotopic Patient-Derived Xenograft (PDX) model as the ideal platform for the preclinical evaluation of new therapeutic strategies. (more…)
Author Interviews, Sexual Health, Social Issues / 12.02.2016

MedicalResearch.com Interview with: Andrea K. Knittel, MD, PhD PGY-3, Department of Obstetrics, Gynecology, and Reproductive Sciences University of California, San Francisco Medical Research: What is the background for this study? Dr. Knittel: The United States has the highest rate of incarceration in the world, and many studies have shown that involvement in the criminal justice system may be a risk factor for HIV/AIDS or other STDs. For example, some studies have found that in areas with high rates of incarceration, rates of STDs are higher, and others have shown that incarcerated individuals are more likely to have higher rates of concurrent sexual partnerships and a greater number of sexual partners. This may happen because of increased rates of partnership dissolution due to physical and emotional distance, as well as a desire on the part of formerly incarcerated men for an increased number of sexual partners to “make up for lost time,” which some studies have suggested. In addition, the female partners of incarcerated men may rely on other relationships, including new sexual partners, for emotional and financial support while their partners are incarcerated, whether their relationships end permanently or temporarily or they maintain their relationships through visits and calls. Very few studies have been able to look at community level effects of incarceration, however, because it is difficult to gather data at this level. This study uses an agent-based model, a computational approach that provide a closed system in which to test hypotheses. An agent-based model is a computer simulation that creates a small community (250 “agents” or simulated people) in which the agents can date and have sexual relationships. The model used in this paper has been shown previously to be similar to young people in the US. The experiment in this study was to run the model without incarceration and see how many partners men and women in the community had, and then add incarceration into the model and see what happened. Based on data from other studies, when men in the model were incarcerated they had a slightly higher risk of ending a relationship and became slightly less desirable as partners. (more…)
Author Interviews, Heart Disease, Pharmacology / 12.02.2016

MedicalResearch.com Interview with: Giuseppe Biondi-Zoccai MD Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of Rome Corso della Repubblica Latina, Italy  Medical Research: What is the background for this study? Dr. Biondi-Zoccai: The main premise of our work is the historically established benefit of aspirin to reduce the risk of cardiovascular events in apparently healthy people, which is however substantially offset by the risk of bleeding. More recently, several pieces of evidence have highlighed the cancer benefits of aspirin, namely its capability of reducing the risk of cancer, in particular cancer in the colon and rectum, as well as deaths due to such cancer. Despite these potentially momentous benefits, there is uncertainty on which dose and preparation of aspirin is best suited to reduce cardiovascular and cancer events, while minimizing bleeding. Indeed, several dosages of aspirin have been tested and are commercially available (for instance from as little as 50 mg per day to more than 300 mg per day). In addition, aspirin is available in different pharmacologic preparations, for instance with specific gastro-protective coatings or controlled-release features, which may have impact on safety and efficacy.     Medical Research: What are the main findings? Dr. Biondi-Zoccai: Our results, building upon the recent research work of the US Government sanctioned Preventive Services Task Force (USPSTF), suggest that a dosage of aspirin of 100 mg per day, combined with enteric-coating, is most likely to be beneficial to reduce the risk of cancer and minimize stomach bleeding. The results, as often in biomedical research, are not however 100% certain, and thus this increased likelihood of benefit must be viewed in the context of our study design, as well as other procedural and patient factors. (more…)
Author Interviews, CDC, HIV, Sexual Health / 12.02.2016

MedicalResearch.com Interview with: Laura Kann, PhD Chief of the School-Based Surveillance Branch (SBSB) Division of Adolescent and School Health (DASH). CDC  Medical Research: What is the background for this study? Dr. Kann:  Young persons aged 13–24 years accounted for an estimated 22% of all new diagnoses of human immunodeficiency virus (HIV) infection in the United States in 2014. Most new HIV diagnoses among youths occur among males who have sex with males (MSM). Among all MSM, young black MSM accounted for the largest number of new HIV diagnoses in 2014 (4,398 among blacks, 1,834 among Hispanics, and 1,366 among whites).  Although other studies have examined HIV-related risk behaviors among MSM, less is known about MSM aged <18 years. Medical Research: What are the main findings? Dr. Kann:  Among male students who had sexual contact with males, black students had a significantly lower prevalence than white students of drinking five or more drinks of alcohol in a row; ever using inhalants, heroin, ecstasy, or prescription drugs without a doctor’s prescription; and drinking alcohol or using drugs before last sexual intercourse. Black students also had a significantly lower prevalence than Hispanic students of drinking five or more drinks of alcohol in a row and ever using cocaine, inhalants, methamphetamines, ecstasy, or steroids without a doctor’s prescription.  However, among male students who had sexual contact with males, black students had a significantly higher prevalence than white students of ever having had sexual intercourse and using a condom during last sexual intercourse; black students also had a higher prevalence than Hispanic students of ever having sexual intercourse. (more…)
Asthma, Author Interviews, OBGYNE, Pediatrics / 12.02.2016

MedicalResearch.com Interview with: Maria C. Magnus Norwegian Institute of Public Health Oslo Norway  Medical Research: What is the background for this study? What are the main findings? Response:  Researchers have found that developing asthma can be linked to pregnant women and infants being exposed to paracetamol, (acetaminophen) by testing that the association was not simply linked to the complaint for which the person is taking paracetamol. The findings were published in the International Journal of Epidemiology Using data from the Norwegian Mother and Child Cohort Study, researchers in Norway compared associations between several conditions during pregnancy (with and without the use of paracetamol) and asthma developing in the 114,500 children in the study. They examined asthma outcomes at ages three and seven and evaluated the likelihood of the association being as a result of the three most common uses of paracetamol in pregnancy: pain, fever, and influenza. The results showed that 5.7 per cent of the children had current asthma at age three, and 5.1 per cent had asthma at age seven. The research found that there was a strong link between children who had asthma at age three who had been exposed to paracetamol as during pregnancy or infancy. The strongest association was seen if the mother used paracetamol during pregnancy for more than one complaint with a child having asthma at three years old. (more…)
Author Interviews, Microbiome, Nutrition, Pediatrics, Weight Research / 12.02.2016

MedicalResearch.com Interview with Tine Rask Licht, Professor Head of Research Group on Gut Microbiology and Immunology Technical University of Denmark National Food Institute Søborg Medical Research: What is the background for this study? What are the main findings? Response:  During childhood, the intestinal microbiota is under establishment. This period thus represents a ’window’, where the microbiota is likely to be more susceptible to be affected by external factors such as diet. Currently, it is well known that breast feeding has a major impact on the microbiota of young infants, but only very few studies have addressed the effect of the ‘next step’ in diet exposure, represented by complementary feeding. We studied two cohorts of children, born to normal-weight and obese mothers, respectively, and mapped the composition of bacteria in their fecal microbiota at age 9 months and 18 months.  We found that at 9 months, the microbiota was clearly affected by the composition of the complementary diet, but not by maternal obesity. (more…)
Author Interviews, Compliance, Electronic Records, Kaiser Permanente, Technology / 12.02.2016

MedicalResearch.com Interview with: Shayna L. Henry, PhD Postdoctoral Research Fellow Department of Research & Evaluation Kaiser Permanente Southern California Medical Research: What is the background for this study? What are the main findings? Dr. Henry: In this study, we analyzed the electronic health records of 838,638 Kaiser Permanente members in Southern California. We decided to conduct this study because Kaiser Permanente always strives to advance standards of excellence for care, and even with all the outreach resources available to health care providers and staff, gaps in preventive care still arise. It can be hard to get patients engaged in managing their preventive care, because there are so many tasks for them to keep track of – many of which don’t happen on a very regular basis. Online patient portals have been very useful at helping patients get more engaged in their care, but patients still have to make the first move, and put all the pieces together. Our tool, the Online Personal Action Plan (oPAP), puts our members’ health status and preventive and chronic care tasks in a single dashboard, and alerts them via email to their upcoming care needs, prompting them to log in, view their upcoming health care tasks such as annual vaccinations, tests and blood draws for chronic conditions, and routine cancer screenings, and make the necessary medical appointments to close those gaps in care. We wanted to better understand if having access to the oPAP tools was associated with a higher likelihood of taking care of those outstanding health care tasks in a timely manner. We found that members who used oPAP were more likely to get a mammogram, Pap smear, receive colorectal cancer screenings, and more likely to complete HbA1c testing for diabetes within 90 days of their coming due compared to members who were not registered on our patient portal.   (more…)
Anesthesiology, Author Interviews, Breast Cancer, Duke, Radiology / 11.02.2016

MedicalResearch.com Interview with: Mary Scott Soo, M.D. FACR Associate professor of Radiology Duke Cancer Institute Medical Research: What is the background for this study? Dr. Soo: Imaging-guided needle breast biopsies for diagnosing suspicious breast lesions have been performed for many years and have definite advantages as a diagnostic tool over surgical biopsies. These biopsies are performed in outpatient settings, which decrease costs and reduce delays, and are highly accurate and less invasive than surgical procedures, requiring only local anesthesia. However, performing biopsies in this outpatient setting limits the use of intravenous sedation and pain medication that could address commonly experienced patient anxiety and occasional associated pain. Anxiety and pain can negatively impact the patient's experience and could possibly affect the biopsy outcome due to patient movement, and could potentially even alter patients' adherence to follow-up recommendations. Prior studies have explored methods to reduce anxiety, using interventions such as music, hypnosis and anxiolytics. Although hypnosis and anxiolytics are effective, these are a little more complicated to implement due to training costs for administering hypnotherapy, and costs, potential side effects, and need for an adult driver to take the patients home when anxiolytics are used. Other research has shown that meditation-based interventions can lead to positive psychological and physical outcomes, and may be helpful for decreasing anxiety, pain and fatigue. Loving-kindness mediation is a type of mediation that focuses on relaxation and developing positive emotions, by silently repeating phrases encouraging compassion and goodwill towards oneself and others, while also reducing negative emotions. Previous studies have shown that even a 7-minute loving-kindness meditation can be effective for increasing positive emotions, so my co-authors Rebecca Shelby PhD, a clinical psychologist at Duke’s Pain Prevention and Treatment Research Program,clinical psychologist Anava Wrenn PhD, who has used loving-kindness meditation in a different practice setting, and breast imaging radiologist Jennifer Jarosz MD and I put together a team to study whether an audio-recorded, lovingkindness meditation could reduce anxiety, fatigue and pain during the imaging-guided breast biopsy time frame.  We consulted with Mary Brantley, MA, LMFT, who teaches loving-kindness meditation at Duke's Integrative Medicine, to develop an audio-recorded loving-kindness mediation used specifically in the breast biopsy setting, and compared this to using music during biopsies or standard care (supportive dialogue) from the technologist and radiologist performing the biopsy. (more…)
Author Interviews, Sleep Disorders / 11.02.2016

MedicalResearch.com Interview with: Helen J. Burgess, Ph.D. Professor, Departments of Behavioral Sciences & Internal Medicine Director, Biological Rhythms Research Laboratory Director, Center for Clinical Chronobiology Rush University Medical Center Chicago IL 60612  Medical Research: What is the background for this study? What are the main findings? Dr. Burgess: The 24 hour circadian clock in the brain has a profound influence on mental and physical health.  Circadian rhythm sleep disorders occur when the internal circadian clock’s timing is out of synch with the external social world, which often dictates when we should eat, work and sleep.  One such disorder, delayed sleep phase disorder, occurs when the circadian clock runs too late relative to social time. Patients with delayed sleep phase disorder can appear to simply have insomnia, but careful measurement of their circadian timing can reveal the underlying circadian cause. Also, the treatment of delayed sleep phase disorder with either bright light and/or melatonin can be optimized by knowing a patient’s circadian timing, because the effect of these treatments can vary widely depending on when they are administered. A problem in the sleep and circadian field is that the gold standard marker of circadian timing in humans, the dim light melatonin onset (DLMO), is typically only measured in the clinic or laboratory.  Many clinics do not even measure the DLMO. Our group recently developed a home saliva collection kit to assist people in measuring their DLMO at home.  Previously, we found the home DLMOs compared very well to laboratory DLMOs in healthy controls.  In this paper, we extended this work to show the kit also works well in patients with delayed sleep phase disorder. (more…)
AHRQ, Author Interviews, Electronic Records, Outcomes & Safety / 11.02.2016

MedicalResearch.com Interview with: Mr. Noel Eldridge Center for Quality Improvement and Patient Safety Agency for Healthcare Research and Quality Medical Research: What is the background for this study? What are the main findings? Mr. Eldridge: We used existing data on adverse events from the Medicare Patient Safety Monitoring System, which AHRQ, CMS, and Qualidigm have been analyzing for years, and focused on the question as to whether rates of the adverse event measures were higher or lower in patients whose charts indicated that they had been treated with a full electronic health record (EHR) or a partial EHR during their inpatient stay. The main finding was that the adverse event rates were lower in the full EHR patients. We saw three different diagnosis groups of patients (cardiovascular, pneumonia, and major surgery), and looked at combined rates for all adverse event types, as well as for four combined subtypes separately: hospital-acquired infections, adverse drug events, post-procedural events, and falls and pressure ulcers combined. Not all of our findings were what people unfamiliar with our measures would have expected. (more…)
Author Interviews, Biomarkers, Genetic Research, Ophthalmology / 11.02.2016

MedicalResearch.com Interview with: Dr Shi Song Rong PhD and Guy Li-Jia CHEN MBBS, MMed, MRCSEd (Ophth), PhD Assistant Professor Department of Ophthalmology & Visual SciencesPrince of Wales Hospital Faculty of Medicine The Chinese University of Hong Kong Medical Research: What is the background for this study? What are the main findings? Response: Glaucoma is a leading cause of irreversible blindness worldwide. Primary angle-closure glaucoma (PACG) as a major form of glaucoma accounts for about half of the cases blinded from the disease. So far, more than 50 genes/loci have been assessed for their associations with PACG and a wider spectrum of relevant conditions, primary angle-closure disease (PACD).  In the article, we summarize the statistical associations of individual genes varying across different study cohorts and conducted meta-analysis to evaluate the associations of 28 polymorphisms in 11 genes/loci with PACD and its subtypes, including PACG, primary angle-closure (PAC) and/or primary angle-closure suspect (PACS). Thus, we affirmed the association of PACG and combined PACS/PAC/PACG with 10 polymorphisms in 8 genes/loci as potential biomarkers. Among them 3 were identified in the genome-wide association study (COL11A1,PLEKHA7 and PCMTD1-ST18), and 5 (HGF, HSP70, MFRP, MMP9 and NOS3) in candidate gene studies. (more…)
Author Interviews, Cognitive Issues, NEJM / 11.02.2016

MedicalResearch.com Interview with: Claudia L. Satizabal, PhD Instructor in Neurology Boston University School of Medicine The Framingham Heart Study Boston, MA 02118-2526 MedicalResearch: What is the background for this study? What are the main findings?   Dr. Satizabal: Our societies are expected to face an increasing burden of dementia in the next decades due to increasing life expectancies and the aging of a big proportion of the population, the so called “baby boomers”. However, some studies conducted in high-income countries have suggested a decline in the total number of cases (prevalence) as well as new cases (incidence) of dementia at any given age. Yet the findings of these studies were not seen as definitive, either because results were of borderline significance or because they were based on survey data, and stronger evidence was lacking. We used information collected since 1975 in the Framingham Heart Study to estimate the trends in dementia incidence. One of the strengths of this study is that investigators have been careful to use the same diagnostic criteria for over the past 30 decades, which allows us to provide more robust evidence of dementia trends over time. We found that there has been a progressive decline in the incidence of dementia at any given age over the past 30 decades. Compared to the late 1970s, we observed a decline of 22% in the late 1980s, 38% in the 1990s and 44% in the 2000s. This beneficial trend was only seen among persons with at least a high school diploma. We also explored trends in vascular risk factors such as blood pressure, smoking, diabetes, and others; however, these trends did not completely explain the decline in dementia incidence. One interesting finding was that the risk of dementia associated with cardiovascular diseases, such as stroke or atrial fibrillation, decreased dramatically over the course of time from the late 1970s to the 2000s. (more…)
Author Interviews, End of Life Care, JAMA / 11.02.2016

MedicalResearch.com Interview with: Joan M Teno, MD, MS Professor of Medicine Division of Gerontology and Geriatrics Cambia Palliative Care Center of Excellence University of Washington Medical Research: What is the background for this study? What are the main findings? Dr. Teno: Hospices in the US are paid a daily rate, regardless of the service delivered. Key to hospice patients dying comfortably is that the caregiver and dying person received the needed visits by hospice professional staff, such as a nurse or social worker. These staff are trained to assess the patient and make appropriate changes to care plan to ensure the comfort and safety of the hospice patient. Multiple studies attest to the finding that pain and other symptoms exacerbate in the last days of life - key is the primary caregiver, usually a close family member receives the need training in administering of medicine to ensure the dying person is comfortable in the last hours of life. We studied visits pattern by professional staff in the last 2 days of life finding that one in eight hospice patients were not visited. While we would not expect every patient to have visits, there was several key finding that raised concern.
  • First, blacks were 30% less likely to receive visits compared to whites
  • Second, 16% persons dying in a nursing home were not visited - historically, bereaved family members identify concerns with the quality of end of life care in NH, even when the person is on hospice services.
  • Third, one in five persons who died on Sunday were not visited in the last 2 days of life - which raises a concern with how hospices are staffing weekend coverage. There is nothing that would suggest biologically that persons don’t experience pain while dying on sturdy.
Additionally, the provision of these visits varied by geographic region in the country and by hospice program which suggest this is the practice of organization and not patient preferences. (more…)
Annals Internal Medicine, Author Interviews, Orthopedics / 11.02.2016

MedicalResearch.com Interview with: Teppo L N Järvinen MD PhD Sports Medicine, Orthopedic Surgery, Clinical Trials University of Helsinki, Helsinki MedicalResearch: What is the background for this study? What are the main findings? Dr. Järvinen: When the primary analysis of the FIDELITY trial was published in the New England Journal of Medicine (http://www.nejm.org/doi/full/10.1056/NEJMoa1305189), showing that arthroscopic partial meniscectomy (APM) is no better than sham/placebo surgery in relieving knee pain and improving knee function in patients with a degenerative meniscus tear and no knee OA, the study was met with unprecedented criticism, even hostility. The advocates of APM (which was at the time and probably still is the most common orthopedic procedure in the US and most other “western” countries) argued – despite the fact that our study only confirmed what several other high-quality RCTs had suggested – that  arthroscopic partial meniscectomy is a highly beneficial procedure in the “right” patients. Among the subgroups of patients allegedly having a favourable response to APM, those experiencing “mechanical symptoms” — sensations of knee catching or locking — represented the most obvious group who would benefit from  arthroscopic partial meniscectomy surgery. This assertion is plausible because knee catching or locking is believed to result from a mechanical blocking mechanism in the knee - a piece of the joint structure lodging between the articular surfaces. Because degenerative meniscal tears are very common pathologic alterations found by arthroscopy in the knee joints of patients with degenerative knee disease, trimming the torn meniscus should, in theory at least, improve the apparent mechanical derangement. Against this background, it is somewhat unusual that no study has yet specifically tested whether  arthroscopic partial meniscectomy is effective in alleviating these symptoms. Mechanical symptoms are usually thought to be a solid indication for arthroscopic knee surgery. This is what we set out to examine in our secondary analysis of our sham-surgery controlled FIDELITY trial.

Our key finding: arthroscopic partial meniscectomy (partial resection of a torn meniscus) does not reduce or alleviate mechanical symptoms any better than a sham surgical procedure.

(more…)
Author Interviews, Hematology, NEJM / 11.02.2016

MedicalResearch.com Interview with: Dr. Filip Callewaert PhD Senior Clinical Scientist Clinical Development, Ablynx Zwijnaarde, Belgium Medical Research: What is the background for this study? What are the main findings? Dr. Callewaert: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening coagulation disorder, in which accumulation of ultra-large von Willebrand factor (ULvWF) multimers is implicated, leading to an increased risk of thrombus formation in small blood vessels due to excessive platelet aggregation. There are no approved pharmacological therapies for acquired TTP. Despite treatment with the current standard of care (plasma exchange and immunosuppressive therapy), mortality remains at 10-20% and there is significant neurological, cardiac, and renal morbidity. Caplacizumab is a bivalent Nanobody that binds to the A1 domain of vWF thereby preventing vWF-mediated platelet aggregation. The clinical effects of caplacizumab were demonstrated in the phase II randomised, placebo-controlled TITAN study in 75 patients with acquired TTP. Compared to placebo, there was a nearly 40% reduction in median time to platelet count normalisation in the caplacizumab group (p = 0.005). Treatment with caplacizumab reduced the use of daily plasma exchange and prevented further consumption of platelets in microthrombi and small blood vessel occlusion. In addition, there were fewer recurrences of TTP requiring re-initiation of daily plasma exchange during treatment with caplacizumab (N=3) vs. placebo (N=11). The safety profile of caplacizumab was favorable, with a slightly higher tendency of mostly mild bleeding events.  (more…)
Author Interviews, End of Life Care, JAMA, Mental Health Research, NIH / 11.02.2016

MedicalResearch.com Interview with: Scott Y. H. Kim, MD, PhD Department of Bioethics, National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? Dr. Kim: Euthanasia and/or physician assisted suicide (EAS) of persons suffering from psychiatric disorders is increasingly practiced in some jurisdictions such as Belgium and the Netherlands but very little is known about the practice.  There is an active debate over whether to legalize such a practice in Canada, after a Supreme Court ruling last year that struck down laws banning physician assisted death.  Medical Research: What are the main findings? Dr. Kim: The main findings are that:
  1. Most patients who receive psychiatric euthanasia and/or physician assisted suicide are women, of diverse ages, with a variety of chronic psychiatric conditions accompanied by personality disorders, significant physical problems, and social isolation/loneliness, often in the context of refusals of treatment.  A minority who are initially refused EAS ultimately receive euthanasia and/or physician assisted suicide through a mobile euthanasia clinic.
  2. Given that the patients have chronic, complicated histories requiring considerable physician judgment, extensive consultations are common. But independent psychiatric input does not always occur; disagreement among physicians occurred in one in four cases; and the euthanasia review committees generally defer to the judgments of the physicians performing euthanasia and/or physician assisted suicide.
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Accidents & Violence, Author Interviews, JAMA / 11.02.2016

MedicalResearch.com Interview with: Dr. Andrew Fenelon PhD NIH Postdoctoral Fellow Brown University Medical Research: What is the background for this study? What are the main findings? Dr. Fenelon: The life expectancy of the US population is about 2 years less than that of other high-income nations, which is an important problem in public health. Although much previous work looks at differences in death rates among older adults, some recent work has shown that deaths at younger ages (below age 50) account for a significant fraction of the life expectancy gap. Our study examines the contribution of major injuries, Motor Vehicle Crashes, Firearm-related deaths, and drug poisonings, which often occur at younger ages and account for many years of lost life. Our findings indicate that US men and women experience significantly higher death rates from these three causes of injury death than each of the 12 comparison high-income countries. Overall, these three causes of death explained 48% of the 2.2 year life expectancy gap between the United States and other high-income countries among men, with firearm injuries alone explaining 21%. Among women, these causes explained 19%. (more…)
Author Interviews, Cancer Research, Radiation Therapy, Stem Cells / 11.02.2016

MedicalResearch.com Interview with: Erina Vlashi, PhD Assistant Professor Department of Radiation Oncology David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1714 Medical Research: What is the background for this study? What are the main findings? Dr. Vlashi: It has been known for quite some time that head and neck squamous cell carcinomas (HNSCC) that test positive for human papilloma virus (HPV) respond to radiation therapy more favorably than HPV-negative HNSCCs. Our team reviewed a cohort of 162 patients with a head and neck squamous carcinoma diagnosis over a two-year period, and confirmed that the outcomes were correlated with the patient's HPV status. The work that followed was prompted by a discovery we had made earlier in breast cancer suggesting that breast cancer cells that manage to survive radiation therapy have the capacity to convert into more de-differentiated, therapy-resistant cells with characteristics of cancer stem cells, and that the degree of this conversion depended on the type of breast cancer: the more aggressive types of breast cancer being more prone to the therapy-induced phenotype conversion. So, we hypothesized that this therapy-induced conversion phenomenon may especially be at play in  head and neck squamous cell carcinomas given the clinical observation that HPV-positive HNSCCs respond to radiation therapy much more favorably than HPV-negative HNSCCs, despite optimum treatment modalities. And indeed, that is what we found: tumor cells derived from a panel of  head and neck squamous cell carcinomas cell lines that do not respond well to radiation therapy have an enhanced ability to convert the cells that survive radiation into more aggressive cells, cancer stem-like cells that will resist the next round of radiation therapy.  (more…)
Author Interviews, JAMA, Surgical Research, Weight Research / 11.02.2016

MedicalResearch.com Interview with: Lance Davidson, PhD Assistant Professor Department of Exercise Sciences Brigham Young University Provo, UT  84602  Medical Research: What is the background for this study? What are the main findings? Dr. Davidson: A growing body of literature indicates that bariatric surgery imparts a mortality benefit in severely obese individuals.  Whether age at surgery affects this relationship is not well established.  One might suppose that a person who has been severely obese for several decades may already have sustained enough metabolic damage that weight loss surgery would have less influence on subsequent mortality.  We conducted an age-specific analysis of a previously-published mortality cohort in gastric bypass patients and severely obese controls, following them for up to 18 years (mean 7.2 years), and examined mortality rates in four age categories: under 35, 35-44, 45-54, and 55-74. The primary finding of this retrospective cohort study was that gastric bypass surgery attenuated the age-related increase in mortality, demonstrating a widening gap in mortality risk when compared to age-matched severely obese controls as age-at-surgery increased, with a 66% reduction in mortality in the oldest group.  Another interesting result, highlighted in our previous publication on this cohort (Adams et al. NEJM 2007), was a higher mortality rate from external causes (accidents, poisonings, suicides, homicides) in surgery patients.  We explored this phenomenon further by age at surgery and found that externally-caused deaths were only increased in women (not men) who had surgery before age 35. (more…)
Accidents & Violence, Alcohol, Author Interviews, CMAJ / 10.02.2016

MedicalResearch.com Interview with: [wysija_form id="5"]Dr. Russ Callaghan, PhD Associate Professor Northern Medical Program University of Northern British Columbia Prince George, British Columbia  Medical Research: What is the background for this study? Dr. Callaghan: In Canada, the minimum legal drinking age (MLDA) is 18 years in Alberta, Manitoba and Québec, and 19 in the rest of the country. Given that public-health organizations not only have recommended increasing the MLDA to 19 years, but also have identified 21 years as ideal, the current study tested whether drivers slightly older than the MLDA had significant and abrupt increases in alcohol-impaired driving (AID) crimes, compared with their counterparts just younger than the MLDA. Data on the effectiveness of Canadian drinking-age laws is lacking, and the current study provides important information for the current national and international MLDA debates. (more…)
Author Interviews, Nursing, Zika / 10.02.2016

MedicalResearch.com Interview with: Nancy Dirubbo, DNP, FNP, FAANP, Certificate in Travel Health, American Association of Nurse Practitioners (AANP) Fellow Cindy Cooke, DNP, FNP-C, FAANP, American Association of Nurse Practitioners (AANP) President of the Board Medical Research: Can you provide some background on what is the Zika virus? Response: Zika virus was first found in monkeys in the Zika Forest of Uganda in 1947 during a research project on mosquito borne viral diseases. From Africa, it spread to India, Indonesia and South East Asia over the next 20-30 years. Not much attention was paid to this illness, as it is often asymptomatic (perhaps as much as 80% of all cases). It causes few symptoms in adults (mild rash, conjunctivitis and headache) and so is often underdiagnosed or misdiagnosed as other self-limiting, viral diseases. Then fast forward to 2015, when a sudden increase in infants born in Brazil with microcephaly occurred and a connection was made with a sharp increase in Zika viral infections, even though the direct mechanism for causing this birth defect is not known. In 2014, there were less than 150 cases of microcephaly in Brazil, and by October 2015, there were 4,700 cases reported. Medical Research: What is the concern regarding pregnant women and their babies? Response: The concern for pregnant women is that there appears to be a link between Zika virus and microcephaly, still birth and miscarriages. Children who do survive have severe intellectual disabilities. The virus is most often transmitted by mosquitos, but may also be sexually transmitted. According to the CDC, “Sexual transmission of Zika virus is possible, and is of particular concern during pregnancy. Current information about possible sexual transmission of Zika is based on reports of three cases.” The CDC also recommends, “Men who reside in or have traveled to an area of active Zika virus transmission who have a pregnant partner should abstain from sexual activity or consistently and correctly use condoms during sex (i.e., vaginal intercourse, anal intercourse or fellatio) for the duration of the pregnancy.” It has yet to be determined if Zika virus can be transmitted in other ways, including blood transfusions. (more…)