Asthma, Author Interviews, Compliance, Lancet, Technology / 30.01.2015

Amy Chan BPharm(Hons) RegPharmNZ MPS ANZCP Pharmacist / PhD candidate Department of Paediatrics Auckland Hospital Faculty of Medical & Health Sciences University of Auckland Auckland, New ZealandMedicalResearch.com Interview with: Amy Chan   BPharm(Hons) RegPharmNZ  MPS  ANZCP Pharmacist / PhD candidate Department of Paediatrics Auckland Hospital Faculty of Medical & Health Sciences University of Auckland  Auckland, New Zealand Medical Research: What is the background for this study? What are the main findings? Response: Asthma is one of the most common childhood conditions, affecting 1 in 4 children in New Zealand.  Although there are many effective medications available for asthma, of which the most important are inhaled corticosteroids, asthma control remains suboptimal due to poor adherence.  In children, adherence to regular preventive asthma therapy is about 50%, and can be as low as 30%.  Our randomised controlled trial looked at use of an electronic monitoring device with an in-built audiovisual reminder to see if it improved adherence and asthma control.  We recruited 220 children aged between 6-15yrs, who presented to the emergency department with asthma and randomised them to receive the device either with the audiovisual function enabled or disabled.  It found that those who received the audiovisual reminder (the intervention arm) took a median of 84% of their inhaled corticosteroids compared to just 30% in those who did not receive the reminder (control arm).  This equates to a 180% improvement in adherence.  We found significant improvements also in asthma control (including reduced asthma symptoms and increased participation in daily activities) and a reduction in reliever use from 17.4% to 9.5% in those who received the reminder. (more…)
Author Interviews, Diabetes, Sugar / 30.01.2015

MedicalResearch.com Interview with: James J. DiNicolantonio, PharmD Associate Editor BMJ Open Heart Cardiovascular Research Scientist Saint Luke's Mid America Heart InstituteJames J. DiNicolantonio, PharmD Associate Editor BMJ Open Heart Cardiovascular Research Scientist Saint Luke's Mid America Heart Institute Medical Research: What is the background for this study? What are the main findings? Dr. DiNicolantonio: We performed a comprehensive literature review comparing the isocaloric exchange of added sugars (sucrose, also known as table sugar, or high fructose corn syrup) versus other types of carbohydrates (such as lactose found in milk, glucose, starch, or dextrose).  Our main findings were that "a calorie isn't a calorie," i.e., that added sugars are more harmful than other carbohydrates even when matched for calories for promoting pre-diabetes and diabetes and the related morbidity and mortality associated with these diseases (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, Mayo Clinic / 30.01.2015

MedicalResearch.com Interview with: Dr. Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester.Dr.  Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Approximately 1 million women in the US every year have a breast biopsy that shows benign findings. We have found that the specific features of the breast tissue seen under the microscope can help to predict the risk of breast cancer in the future.  We developed a mathematical formula to calculate breast cancer risk based on the features seen in the biopsy tissue (named the BBD-BC model).  We found that using these microscopic features provides more accurate predictions of risk than the previous standard- the Breast Cancer Risk Assessment Tool (BCRAT). (more…)
Author Interviews, CDC, Cost of Health Care / 30.01.2015

MedicalResearch.com Interview with: Robin A. Cohen, Ph.D Medical Research: What is the background for this study? Dr. Cohen: Estimates are based on data collected from the 2013 National Health Interview Survey (NHIS). The NHIS is a survey conducted by the Centers for Disease Control and Prevention’s (CDC) National Center for Health Statistics. NHIS collects information about health and health care of the civilian noninstitutionalized population of the United States. In 2013, questions about strategies used to reduce prescription drug cost were asked of more than 34,000 adults aged 18 and over. Medical Research: What are the main findings? Dr. Cohen: To save money, almost 8% of U.S. adults (7.8%) did not take their medication as prescribed, 15.1% asked a doctor for a lower-cost medication, 1.6% bought prescription drugs from another country, and 4.2% used alternative therapies. Adults aged 18–64 (8.5%) were nearly twice as likely as adults aged 65 and over (4.4%) to have not taken their medication as prescribed to save money. Among adults aged 18–64, uninsured adults (14.0%) were more likely than those with Medicaid (10.4%) or private coverage (6.1%) to have not taken their medication as prescribed to save money. The poorest adults—those with incomes below 139% of the federal poverty level—were the most likely to not take medication as prescribed to save money. Among adults aged 65 and over, those living with incomes in the 139-400% FPL range were more likely than adults living in lower or higher income thresholds to have asked their provider for a lower cost prescription to save money. (more…)
Author Interviews, Blood Pressure - Hypertension, Cost of Health Care, NEJM / 29.01.2015

Andrew Moran, MD, MPH Herbert Irving Assistant Professor of Medicine Columbia University Division of General Medicine Presbyterian Hospital 9th floor East room 105 New York, NY 10032MedicalResearch.com Interview with: Andrew Moran, MD, MPH Herbert Irving Assistant Professor of Medicine Columbia University Division of General Medicine Presbyterian Hospital  New York, NY 10032 Medical Research: What is the background for this study? What are the main findings? Response: In 2014, a panel appointed by the Eighth Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure (JNC 8) recommended new guidelines for high blood pressure (hypertension ) treatment in U.S. adults.  The guidelines made sweeping changes to the prior guidelines and stirred up controversy among hypertension and public health experts.  Essentially, the panel recommended more conservative treatment targets that narrowed the population eligible for treatment with blood pressure-lowering medications.  Nonetheless, about 28 million U.S. adults have uncontrolled hypertension even under the new more conservative guidelines.  We asked the question:  are the new guidelines cost-effective? That is, does treating this common condition with the available medicines add more health and reduce medical costs?  It is surprising that this question has rarely been answered before. (more…)
Author Interviews, Brain Injury / 29.01.2015

Dennis Kim, MD Los Angeles Biomedical Research Institute (LA BioMed) Researcher MedicalResearch.com Interview with: Dennis Kim, MD Los Angeles Biomedical Research Institute                                                                                                                 MedicalResearch: What is the background for this study? What are the main findings? Dr. Kim: More than 1.7 million people in the U.S. alone suffer a traumatic brain injury (TBI) every year, often resulting in permanent disabilities or death. Up to half of these patients will experience progression of bleeding inside or around the brain, the occurrence of which is associated with an increased risk of death. A common treatment to prevent progression of “traumatic intracranial hemorrhage” is the transfusion of platelets, which are irregular shaped cells that cause blood to clot, and the administration of desmopressin (DDAVP), a naturally occurring hormone used to treat bleeding and a number of other medical conditions. Researchers at LA BioMed conducted a three-year retrospective study of the records of patients admitted to a Level 1 trauma center with traumatic brain injury between Jan. 1, 2010 and Dec. 31, 2012. Of the 408 patients who fit the criteria, 126 received platelet transfusions and DDAVP and 282 did not. Overall, 37% of the patients demonstrated progression of traumatic intracranial hemorrhage within four hours of admission. We compared outcomes for patients who received platelet transfusions and DDAVP and patients who did not receive this therapy. Our comparison found no significant differences in mortality or hemorrhage progression between the two groups. We reported our findings in a study that was recently published online ahead of print in the Journal of Neurotrauma. (more…)
Author Interviews, Nature, Ovarian Cancer / 29.01.2015

Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599MedicalResearch.com Interview with: Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599 Medical Research: What is the background for this study? What are the main findings? Response: Ovarian clear-cell carcinoma is a lethal form of ovarian cancer with limited therapeutic options. Recent patient-derived tumor sequencing studies support a strong genetic basis for the disease, but the roles of gene mutations in cancer causation are still unclear. We observed rapid induction of ovarian clear-cell carcinoma in mice that were genetically engineered to carry mutations in ARID1A and PIK3CA−the two most frequently mutated genes. Comparisons between human and mouse tumors uncovered a downstream role for the Interleukin-6 (IL-6) cytokine-signaling pathway in tumor progression. Thus, ARID1A and PIK3CA mutations cause ovarian clear-cell carcinoma and promote tumor cell growth by acting upon the IL-6 signaling pathway. (more…)
Author Interviews, Dermatology, PLoS, Stem Cells / 29.01.2015

Alexey Terskikh, Ph.D. Associate Professor Department of Developmental and Stem Cell Biology Sanford-Burnham Medical Research Institute La Jolla, CAMedicalResearch.com Interview with: Alexey Terskikh, Ph.D. Associate Professor Department of Developmental and Stem Cell Biology Sanford-Burnham Medical Research Institute La Jolla, CA Medical Research: What is the background for this study? What are the main findings? Dr. Terskikh: Hair loss is a wide spread human condition with an unmet need for hair replacement. In the United States alone, over 40 million men and 21 million women are affected by hair loss. I have been interested in the differentiation of human pluripotent stem cells into various cell including neural crest cells. In-vivo neural crest cells give rise to a multitude of cell types, including dermal papilla cells, which populate the bulb of hair follicles and regulate hair growth. We have established new method to differentiate human pluripotent stem cells into dermal papilla-like (DP-like) cells, with a goal of inducing hair growth. To find out whether DP-like cells induce hair growth we transplanted these cells under the skin of mice (which have a small amounts of white hair) along with the skin cells from dark-haired mice. We observed the growth of new black hairs suggesting the induction of hair growth by transplanted human DP-like cells. (more…)
Author Interviews, Breast Cancer / 29.01.2015

William J. Brackenbury, Ph.D. MRC Fellow Department of Biology University of York, Heslington, York UKMedicalResearch.com Interview with: William J. Brackenbury, Ph.D. MRC Fellow Department of Biology University of York, Heslington, York UK Medical Research: What is the background for this study? Dr. Brackenbury: Metastasis, the spread of cancer cells from the primary tumour to secondary sites, e.g. the lungs or bones, is the main cause of deaths from cancer. However, there are no effective treatments available to slow or stop this devastating aspect of the disease. We and others have found that sodium channels, normally present in neurons and muscle cells, are up-regulated in metastatic breast cancer cells. Sodium channels appear to regulate the behaviour of these cancer cells, helping them to move and squeeze their way out of the primary tumour as they invade and metastasise on their way to distant sites. This suggests that sodium channels might be useful new therapeutic targets for drugs that could slow metastasis. Medical Research: What are the main findings? Dr. Brackenbury: Sodium channels are important drug targets for treating epilepsy. We have found that the antiepileptic drug phenytoin, which is a sodium channel blocker, reduces tumour growth and metastasis in a preclinical model of breast cancer. We found that phenytoin reduces proliferation of cancer cells within the primary tumour. It also reduces local invasion of cancer cells into the surrounding fat and muscle, and reduces the number of cells metastasising to distant sites in the liver, lungs and spleen. (more…)
Author Interviews, General Medicine, Journal Clinical Oncology, Leukemia, Pediatrics / 29.01.2015

MedicalResearch.com Interview with: Jun J. Yang  Ph.D. Assistant Member Dept. of Pharm. Sci. St. Jude Children's Research Hospital Memphis, TN 38105 Medical Research: What is the background for this study? What are the main findings? Dr. Yang: Mercaptopurine is highly effective in acute lymphoblastic leukemia (ALL) and essential for the cure of this aggressive cancer. However, it also has a narrow therapeutic index with common toxicities. Identifying genetic risk factors for mercaptopurine toxicity will help us better understand how this drug works and also potentially enable clinicians to individualize therapy based on patients’ genetic make-up (precision medicine). In addition to confirming the role of TPMT, we have identified another important genetic risk factor (a genetic variation in a gene called NUDT15) for mercaptopurine intolerance. Patients carrying the variant version of NUDT15 are exquisitely sensitive and required up to 90% reduction of the normal dose of this drug. TPMT variants are more common in individuals of African and European ancestry, whereas NUDT15 variants are important in East Asians and Hispanics. (more…)
Author Interviews, JAMA, Prostate Cancer, Radiology / 29.01.2015

MedicalResearch.com Interview with: Mohummad Minhaj Siddiqui, MD AssiMohummad Minhaj Siddiqui, MD Assistant Professor of Surgery - Urology Director of Urologic Robotic Surgery University of Maryland School of Medicine andstant Professor of Surgery - Urology Director of Urologic Robotic Surgery University of Maryland School of Medicine and Peter A. Pinto, M.D Head, Prostate Cancer Section Director, Fellowship Program Urologic Oncology Branch National Cancer Institute National Institutes of Health Bethesda, Maryland 20892-1210 Peter A. Pinto, M.D Head, Prostate Cancer Section  Director, Fellowship Program Urologic Oncology Branch National Cancer Institute  National Institutes of Health  Bethesda, Maryland Medical Research: What is the background for this study? What are the main findings? Response: For men suspected of having prostate cancer due to an elevated PSA or abnormal digital rectal exam, the next step in their diagnostic workup has traditionally been a standard 12-core biopsy to evenly sample the entire gland.  Unlike most other cancers, prostate cancer is one of the few solid tumors left which is diagnosed by randomly sampling the gland with the hope of biopsying the tumor, if it is present.  This paradigm has been largely due to the fact that imaging to date has been limited in its ability to identify prostate cancer.  Recent advancements in multiparametric MRI of the prostate however has significantly improved clinician's ability to identify regions in the prostate suspicious for cancer.  This has led to the emergence of MR/Ultrasound fusion technology which allows for targeted biopsy of the prostate into regions suspicious for cancer. Although conceptually, it makes sense that a targeted biopsy has the potential to perform better than the standard random sampling of the prostate in the diagnosis of prostate cancer, studies were needed to understand if this is true, and if so, if the improvement was substantial enough to justify the extra expense and effort needed to obtain a MRI guided biopsy.  This study performed at the National Cancer Institute's Clinical Center sought to address this clinical question of interest.  From 2007-2014, a total of 1003 men suspected to have prostate cancer underwent an MRI of the prostate.  If an area of suspicion was seen in the prostate, these men underwent both the targeted biopsy of the suspicious region in the prostate as well as the standard 12-core needle biopsy during the same session.  The results from the targeted biopsy were compared to the results of the standard biopsy. The key findings in this study was that targeted biopsy improved the rate at which high-risk clinically significant cancer was diagnosed by 30%.  Of interest, the study also found that low-risk, clinically insignificant disease (the type of prostate cancer that is unlikely to cause any harm to the patient over the course of his natural life) was decreased in diagnosis by 17%.  Decrease of diagnosis of such disease has the potential benefit that it could lead to less over-treatment of cancer that never needed to be treated.  In a subset of 170 men that ultimately underwent surgery to remove the prostate to treat their cancer, we were further able to examine how well the prostate biopsy reflected the actual cancer burden in the whole gland.   It is well known that standard biopsy can actually underestimate the total cancer grade in the whole prostate in upwards of 30-40% of cases.  We found that the targeted biopsy was significantly better at predicting whether the patient had intermediate to high-risk cancer compared to standard biopsy.  Through further analysis using a statistical method called decision curve analysis, we further found that for men who wish to undergo surgery for intermediate to high-risk cancer, but wish to go on active surveillance for low-risk cancer, targeted biopsy led to better decision making compared to standard biopsy, or even the two techniques combined. (more…)
Author Interviews / 29.01.2015

Dr Maddy Greville-Harris Research Fellow University of SouthamptoMedicalResearch.com Interview with: Dr Maddy Greville-Harris Research Fellow University of Southampton   Medical Research: What is the background for this study? What are the main findings? Dr. Greville-Harris: Our research looks at the effects of non-understanding feedback ('invalidation') and discusses its implications in the medical consultation in eliciting the nocebo response. We carried out interviews with five patients and four healthcare providers to explore their experiences of receiving non-understanding feedback during their chronic pain consultations. Patients reported feeling dismissed and disbelieved by healthcare providers. As a result of these encounters, patients reported feeling angry or hopeless after invalidating consultations, describing an increased need to justify their condition or to avoid treatment altogether. Our earlier work too, suggests that receiving non-understanding feedback can have very powerful effects. Participants who received such feedback were more physiologically aroused, reported more negative mood and were less willing to participate in the research again. These effects were much more powerful than the positive effects of receiving understanding feedback. Our research suggests that the power of negative communication is stronger than that of positive communication, and that invalidating feedback may be a nocebo effect that has largely been overlooked. (more…)
Author Interviews, NEJM, Opiods, Pharmacology / 29.01.2015

Richard C. Dart, M.D., Ph.D Denver Health & Hospital Authority Professor, University of Colorado School of MedicineMedicalResearch.com Interview with: Richard C. Dart, M.D., Ph.D Denver Health & Hospital Authority Professor, University of Colorado School of Medicine   Medical Research: What is the background for this study? What are the main findings? Dr. Dart: For the past two decades, prescription opioid medication abuse has increased significantly in the US. An estimated 25 million people initiated nonmedical use of pain relievers between 2002 and 2011.  In 2010 the number of death attributed to prescription opioid medications reached 16,651. The  RADARS® System (Researched Abuse, Diversion and Addiction Related Surveillance) has been monitoring prescription drug abuse and diversion for over 13 years. We use a “mosaic” approach, measuring abuse and diversion from multiple perspectives, to describe this hidden phenomenon as comprehensively as possible. For the current publication we used 5 separate RADARS® System programs to collect data and the study period was from January 2002 through December 2013. We noticed a substantial increase  of prescription drug abuse from 2002 through 2010, followed by a flattening or decrease in 2010 and, lastly, a decline in 2011 through 2013. We also noticed a similar pattern in opioid-related deaths. Nonmedical use did not change significantly among college students. (more…)
Author Interviews, Geriatrics, Hearing Loss, JAMA / 28.01.2015

Margaret T. Dillon, AuD University of North Carolina School of MedicineMedicalResearch.com Interview with: Margaret T. Dillon, AuD University of North Carolina School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Dillon: The goal of this study was to evaluate whether age at revision cochlear implantation influences post-revision speech perception performance. A cochlear implant is an implantable auditory prosthesis that aims to provide sound to patients with certain degrees of hearing loss, by converting and transmitting the acoustic sound into electric stimulation. Research has shown cochlear implant recipients experience improved speech perception in quiet and noise as compared to preoperative performance with conventional amplification (ie, hearing aids). There is variability in postoperative performance. Understanding the cause or causes of this variability is the primary goal of a number of research studies. One suspected indicator for this variability is advanced age at the time of surgery. Though the incidence of revision cochlear implantation is low, it may be warranted when the internal device is no longer functional or not functioning optimally. We reviewed the pre-revision and post-revision speech perception performance of younger (< 65 years of age) and older (> 65 years of age) adult cochlear implant recipients. There was no difference between the post-revision speech perception performance between the two groups. (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Cancer / 28.01.2015

Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, MassachusettsMedicalResearch.com Interview with: Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Freedman: Studies have previously looked at how general cancer knowledge may impact health conditions and rates of screening but none (to my knowledge) have focused on one’s knowledge about his/her own breast cancer. We surveyed 500 women who were diagnosed with early-stage breast cancer within the Northern California Cancer Registry and asked questions about their breast cancer subtype (I.e. Hormone receptor status and HER2 status), tumor grade, and stage. We then matched women’s answers to those collected by the registry to examine the correctness of the answers given. We found low overall rates of having knowledge about one’s disease and this was even more apparent for black and Hispanic patients. When education and health literacy were accounted for, disparities in knowledge remains for black women but were narrowed for Hispanic women in some cases. (more…)
Author Interviews, Brigham & Women's - Harvard, Infections, PNAS / 28.01.2015

Rakesh K. Jain, Ph.D. A.W.Cook Professor of Tumor Biology Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA 02114MedicalResearch.com Interview with: Rakesh K. Jain, Ph.D. A.W.Cook Professor of Tumor Biology Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114 Medical Research: What are the primary findings of this study and why are they important? Dr. Jain: Pulmonary granulomas are the hallmark of the Tuberculosis (TB) infection, yet it is not fully understood how these structures contribute to disease progression and treatment resistance. In this study, we applied our insight in tumor biology – gained over three decades – to explore and exploit the similarities between vasculature (blood vessel network) in solid cancerous tumors and TB pulmonary granulomas. We demonstrate for the first time that TB granulomas have abnormal vasculature. This abnormality provides a mechanism for the observation that TB granulomas are often hypoxic (have low oxygen conditions) and have differential distribution of anti-TB drugs. We showed that bevacizumab, a widely prescribed anti-VEGF antibody for cancer and eye diseases, is able to create more structurally and functionally normal granuloma vasculature and improve small molecule delivery. This study suggests that vasculature normalization in combination with anti-TB drugs has the potential to enhance treatment in patients with TB. Tuberculosis (TB) is a global scourge that is responsible for nearly 2 million deaths annually. Due to the inability of currently available treatment regimens to eradicate this devastating disease, it is clear that new treatment strategies are urgently needed. Unlike many researchers in the TB field, we do not seek to discover new therapeutics that target bacterial resistance; instead, we strive to overcome physiological resistance to treatment resulting from abnormalities in the granuloma vasculature that impair drug delivery and create hypoxia that impairs efficacy of drugs and immune system. By using an FDA-approved drug, our study has the potential to be rapidly translated into the clinic. Medical Research: Has any association previously been made between the vascular structure of TB granulomas and the challenges of treating TB – both the fact that treatment takes so long and the development of multidrug resistance? Dr. Jain: Our study is the first to implicate a specific facet of the granuloma – the abnormal vasculature – as a potential contributor to disease progression and treatment resistance. Granuloma hypoxia is known to negatively affect the local immune system while conferring resistance to some of the TB drugs. Our collaborators have shown that different anti-TB drugs have differential abilities to penetrate the granuloma structure, especially to the interior granuloma regions where the TB bacteria are found in greatest numbers. Our study is the first to provide evidence that by modulating the granuloma vasculature, hypoxia can be alleviated and drug delivery can be improved. (more…)
Author Interviews, Infections, PNAS, University Texas / 28.01.2015

Christopher S. Sullivan, Ph.D. Associate Professor Dept. Molecular Biosciences The University of Texas at Austin anMedicalResearch.com Interview with: Christopher S. Sullivan, Ph.D. Associate Professor Dept. Molecular Biosciences The University of Texas at Austin and Jennifer Cox, lead author Graduate student in Dr. Sullivan’s laboratory. Jennifer Cox, lead author Graduate student in Dr. Sullivan’s laboratory. Jennifer Cox's Replies: MedicalResearch: What is the background for this study? What are the main findings? Jennifer Cox: In the last decade, researchers have identified that many viruses encode small regulatory molecules known as microRNAs. Some viral microRNAs are able to manipulate host processes including stress responses, proliferation, and cell death. However, there are many viral microRNAs with unknown functions. Many of the viruses that encode microRNAs are associated with severe pathologies including various cancers so understanding the role of viral microRNAs can shed light on virus biology. For this study, we focused on identifying viral microRNAs that can regulate innate immune signaling for several reasons. First, all viruses have proteins to combat interferon signaling. Second, we have identified microRNAs from two diverse viruses (retro and annello) that can inhibit interferon signaling so we hypothesized that additional viral microRNAs will perform this same function. We screened ~70 viral microRNAs for the ability to regulate innate immune signaling and identified three herpesviruses, Epstein-Barr Virus, Kaposi’s Sarcoma Associated Virus, and Human Cytomegalovirus, that inhibit the interferon response. Epstein-Barr Virus, causes an estimated 200,000 cancers every year, including lymphomas, nasopharyngeal cancers and some stomach cancers. Interestingly, most of these cancers harbor latent EBV – a state of limited gene expression that produces no virus. microRNAs are one of the few viral gene product expressed during latency. Our further work identified that Epstein-Barr Virus, KSHV, and Human Cytomegalovirus have converged to inhibit interferon signaling in the same manner – through decreasing expression of a central hub of innate immune signaling, CREB binding protein (CBP). We show that this regulation conveys partial resistance to the negative effects of interferon treatment on an EBV+ lymphoma cell line. Additionally, removing the microRNA from a similar cell line increases the sensitivity to interferon. Interferon can be used in combination with other chemotherapies to treat lymphomas but varies in success. Our results may partially explain the variability seen in patients with EBV-associated cancers. (more…)
Author Interviews, Heart Disease, Ophthalmology / 28.01.2015

MedicalResearch.com Interview with: Ren-Long Jan Department of Pediatrics, Chi Mei Medical Center, Liouying, Tainan, Taiwan Graduate Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan. Medical Research: What is the background for this study? What are the main findings? Response: The pathologenic factors underlying retinal artery occlusion (RAO) are also associated with acute coronary syndrome (ACS). Previous studies showed the relation but was limited by sample sizes. We used Taiwan Longitudinal Health Insurance Database and found the increased risk of ACS following Retinal artery occlusion. (more…)
Author Interviews, Heart Disease, JACC, Lipids / 28.01.2015

MedicalResearch.com Interview with: Dong Zhao MD.PhD Deputy Director & Professor andDong Zhao MD.PhD Deputy Director & Professor and Dr. Que Qi, MD.PhD Assistant Professor Beijing Institute of Heart,Lung & Blood Vessel Diseases Capital Medical University Beijing Anzhen HospitalDr. Que Qi, MD.PhD Assistant Professor Beijing Institute of Heart,Lung & Blood Vessel Diseases Capital Medical University Beijing Anzhen Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Dong Zhao: Lower serum HDL-C level used to be considered as a key risk factor of atherosclerotic cardiovascular diseases. This knowledge was based on very consistent findings from researcher of basic science and observational studies of epidemiology. HDL-C has been also introduced as "good cholesterol" to the public. However, this well accepted knowledge was challenged when two large RCTs demonstrated that increased serum HDL-C by CETP inhibitor (ILLUMINATE and dal-OUTCOMES) failed to show benefits on reducing the risk of atherosclerotic cardiovascular disease. Therefore, many researchers questioned whether serum HDL-C can fully represent the capacity of cholesterol reverse transport of HDL particle, an underpinning of the anti-atherogenic function of HDL. And HDL particle number was considered to be better than HDL-C as a proper parameter to assess the function of HDL. In fact, RCTs that increased serum HDL-C substantially by CETP inhibitor had little effect on HDL particle number, thus resulting in increased cholesterol-overloaded HDL particle. Previous experimental studies observed that cholesterol-overloaded HDL particle exerted a negative impact on cholesterol reverse transport. However, it remains unclear whether cholesterol-overloaded HDL is involved in the development of atherosclerosis in humans. In our study, we measured HDL particle number using nuclear magnetic resonance spectroscopy, and calculated the ratio of HDL-C to HDL particles number to estimate the cholesterol content per HDL particle (HDL-C/P ratio). We found that cholesterol-overloaded HDL particles, indicated by high HDL-C/P ratio, are independently associated with the progression of carotid atherosclerosis in asymptomatic individuals from a community-based cohort study of the Chinese Multi-provincial Cohort Study-Beijing Project. (more…)
Alcohol, Author Interviews, Gastrointestinal Disease / 28.01.2015

Gro Askgaard MD Department of Hepatology, Copenhagen University Hospital, Rigshospitalet National Institute of Public Health, University of Southern Denmark Copenhagen DenmarkMedicalResearch.com Interview with Gro Askgaard MD Department of Hepatology, Copenhagen University Hospital, Rigshospitalet National Institute of Public Health, University of Southern Denmark Copenhagen Denmark Medical Research: What is the background for this study? Dr. Askgaard: Alcohol is the main risk factor of cirrhosis in Europe, where 1.8% of all deaths are attributable to liver disease. Alcohol amount is known to be a significant factor of development of cirrhosis - the greater alcohol amount, the greater risk. Less is known about drinking pattern - how the way you drink alcohol affects your risk. In this study we evaluated the influence of drinking frequency (drinking days/week), of lifetime alcohol consumption versus recent alcohol consumption, and alcohol type (wine, beer, liquor). (more…)
Author Interviews, Cost of Health Care, Heart Disease / 28.01.2015

Andre Lamy MD MHSc COMPASS (CABG sub-group PI) CORONARY Principal Investigator Professor, Dept Surgery, Division Cardiac Surgery Associate Member, Dept Clinical Epidemiology & Biostatistics McMaster University Hamilton General Hospital Hamilton, ON, CanadaMedicalResearch.com Interview with: Andre Lamy MD MHSc COMPASS (CABG sub-group PI) CORONARY Principal Investigator Professor, Dept Surgery, Division Cardiac Surgery Associate Member, Dept Clinical Epidemiology & Biostatistics McMaster University Hamilton General Hospital Hamilton, ON, Canada Medical Research: What is the background for this study? Dr. Lamy: The Canadian healthcare system operates in an environment that must constantly find new ways to make healthcare delivery more efficient. In the TIMACS clinical led by Dr. Shamir Mehta, it was found that the primary outcome was similar for an early invasive procedure within 24 hours and a delayed approach of after 36 hours in outcomes. However, because of the inherent shorter length of stay associated with early invasive procedures within 24 hours there will be definite cost-savings from an early invasive strategy. Dr. Andre Lamy et al looked at the cost implications of this shorter length of stay in the TIMACS trial and explored the impact of the use of a catheterization lab on days when they are normally not in use (i.e. weekends), which may negate the savings of early intervention. Medical Research: What are the main findings? Dr. Lamy: The main findings of our study were that early invasive strategy was cost-saving for Canadian NTSE-ACS patients due to significant savings from the shorter length of stay. These savings were present even if as many as 50% of TIMACS patients were assumed to be weekend cases. Given many high-risk NSTE-ACS patients receive delayed intervention due to weekend catheterization lab status, these findings support operating catheterization labs on weekends to facilitate the use of early invasive intervention. (more…)
Author Interviews, Endocrinology, JCEM, OBGYNE / 28.01.2015

Roger Hart MD FRANZCOG MRCOG CREI Winthrop Professor of Reproductive MedicineSchool of Women's and Infants Health Director of Fertility Specialists of Western Australia The University of Western Australia Perth Western Australia 6008MedicalResearch.com Interview with: Roger Hart MD  FRANZCOG MRCOG CREI Winthrop Professor of Reproductive MedicineSchool of Women's and Infants Health Director of Fertility Specialists of Western Australia The University of Western Australia Perth Western Australia 6008 Medical Research: What is the background for this study? What are the main findings? Dr. Hart: PCOS is a very common condition affecting approximately 1 in 12 women and has an estimated annual impact upon the health system in the USA of up to $4.36 billion per year. PCOS is a condition that often manifests itself early in girls life with menstrual problems in adolescence and may lead to reduced fertility in later life due to problems with ovulation. Previous studies have suggested that women with this condition may have other problems in later life, however they have generally been small studies over a short duration. We studied women from 15 years of age, who were admitted to a hospital in Western Australia where a diagnosis of PCOS was recorded on admission. We compared them to women who did not have a PCOS diagnosis recorded on admission using our state-wide hospital database system data linkage. The medical records of 2,566 women with a PCOS diagnosis were followed from 1980 onwards until an average of almost 36 years, and these women were matched to 25,660 women without PCOS. Women with PCOS on average had twice as many hospital admissions and unfortunately were twice as likely to die during the study period. As expected women with PCOS women had a higher rate of menstrual problems and infertility, and require IVF treatment, have a miscarriage or an ectopic pregnancy, and ultimately require surgical intervention for heavy periods and a hysterectomy. In pregnancy women with PCOS were more likely to deliver preterm or have a stillbirth. In addition women with PCOS were four times more likely to develop late onset diabetes, even after taking into consideration obesity. These women wore more likely to have problems with blood pressure and ischemic heart disease, despite being relatively young. They were more likely to develop a deep vein thrombosis and have a diagnosis of asthma. With regard to mental health women with PCOS were twice as likely to have a diagnosis of stress and anxiety and depression. They were more likely to be a victim of self-harm and be involved with a land transport accidents. With regard to cancer; cervical cancer was diagnosed less frequently in women with PCOS, but they had an increased risk of cancer of the womb. The incidence of breast and skin cancers was no different between the groups. (more…)
AHRQ, Author Interviews, Cost of Health Care / 28.01.2015

Raynard E. Washington, PhD, MPH Center for Delivery, Organization, and Markets Agency for Healthcare Research and Quality Rockville, MD 20850MedicalResearch.com Interview with: Raynard E. Washington, PhD, MPH Center for Delivery, Organization, and Markets Agency for Healthcare Research and Quality Rockville, MD 20850 Medical Research: What is the background for this study? What are the main findings? Dr. Washington: Many individuals with low income who require a hospital stay are uninsured or covered by Medicaid, a joint Federal-State health insurance program for eligible individuals and families with low income. The difference in hospital utilization among patients covered by Medicaid and those who are uninsured may reflect differences in the characteristics of these populations and their level of access to health care. This HCUP Statistical Brief describes 2012 hospital stays with a primary expected payer of Medicaid and stays that were uninsured. Of the 36.5 million total hospital inpatient stays in 2012, 20.9 percent had an expected primary payer of Medicaid and 5.6 percent were uninsured; 30.6 percent were covered by private insurance. Patients covered by Medicaid were on average younger and more likely to live in low-income areas than were patients with private insurance. Patients who were uninsured were more likely to be male and to live in low-income communities than were patients with private insurance. The majority of the top 10 diagnoses for Medicaid hospitalizations were ambulatory care sensitive conditions. Cholecystectomy (gall bladder removal) was the most common operating room procedure for Medicaid and uninsured stays. (more…)
Author Interviews, Heart Disease, Mayo Clinic, Testosterone / 27.01.2015

Abraham Morgentaler, MD Director and Founder Men’s Health BostonMedicalResearch.com Interview with: Abraham Morgentaler, MD Director and Founder Men’s Health Boston Medical Research: What is the background for this study? What are the main findings? Response: There has been  tremendous media attention over the last 15 months to two retrospective studies that reported increased cardiovascular risks with testosterone. Those reports anchored a variety of stories critical of testosterone therapy for non-scientific reasons, such as alleged dangers of direct-to-consumer advertising.  In this review we investigated the two recent studies in depth, as well as the broader literature regarding testosterone and cardiovascular issues. One primary finding was that the studies alleging risk were remarkably weak and flawed- one reported low rates of MI and had no control group, and the other had such large data errors (nearly 10% of the all-male population turned out to be female!) that 29 medical societies have called for its retraction. In contrast, there is substantial literature suggesting that testosterone therapy, or naturally occurring higher levels of testosterone, is protective against atherosclerosis, and mortality.  Several small randomized controlled trials in men with known heart disease- angina and congestive heart failure- have even shown benefits for men that received testosterone compared with placebo. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, Kidney Disease, Rheumatology / 27.01.2015

Dr Gomez-Puerta MD, PhD, MPH Division of Rheumatology, Immunology, and Allergy; Brigham and Women's Hospital, Harvard Medical School, Boston, MA Medical Research Interview Dr Gomez-Puerta MD, PhD, MPH Division of Rheumatology, Immunology, and Allergy; Brigham and Women's Hospital, Harvard Medical School, Boston, MA MedicalResearch: What is the background for this study? What are the main findings? Dr. Gomez-Puerta: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology which can cause multiorgan system damage and which disproportionately affects women and non- Caucasian minorities. Up to 60% of SLE patients develop renal disease, lupus nephritis (LN), and of these, approximately one fifth progress to end-stage renal disease (ESRD). The risk of cardiovascular (CV) events and mortality is higher in patients with ESRD and in particular in patients suffering SLE. However, information about CV outcomes and mortality is limited in patients with LN associated ESRD. We observed important variation in cardiovascular outcomes and mortality by race and ethnicity among lupus nephritis related ESRD patients. After adjusting for multiple demographic and clinical factors and accounting for the competing risk of kidney transplantation and loss to follow-up, our results illustrate for the first time that Asian (vs. White) and Hispanic (vs. non-Hispanic) lupus nephritis related ESRD patients have lower mortality risks. (more…)
Author Interviews, Autism, Radiology / 27.01.2015

Gabriel S. Dichter, PhD Associate Professor UNC Departments of Psychiatry and Psychology Carolina Institute for Developmental Disabilities MedicalResearch.com Interview with: Gabriel S. Dichter, PhD Associate Professor UNC Departments of Psychiatry and Psychology Carolina Institute for Developmental Disabilities Medical Research: What is the background for this study? What are the main findings? Dr. Dichter: The background for this study is that although most brain imaging research in autism spectrum disorders has focused on understanding the brain basis of social communication impairments, we know that autism symptoms are pervasive and may include difficulties with irritability, anxiety, mood, and even in some instances aggression or self injurious behaviors.  Additionally, these types of associated features are among the first that prompt parents to bring their child to a pediatrician for an evaluation for a neurodevelopmental disorder, and so we know these symptoms can be deeply troubling to parents.  All of these associated symptoms of autism suggest difficulty with regulating emotional responses, and so our team set out to investigate the brain basis of these difficulties.  We taught participants with and without autism simple strategies to change their emotion responses and then scanned them using functional MRI to measure brain activity when they actively tried to change their emotional responses to pictures of faces.  Our central finding was that although they reported they were able to change their emotional responses, brain imaging findings told us something quite different.  The dorsolateral prefrontal cortex, a part of the brain that controls emotional responses, was underactive in the participants with autism.  Consequently, they were less able to modulate parts of the brain’s limbic system that produces strong emotional responses.  In other words, they had difficulty “turning on the brakes” to control emotional responses.  Finally, the differences we observed in their brain activity predicted the severity of their overall autism symptoms, suggestion a direct linkage between emotion regulation impairments and autism severity. (more…)
Author Interviews, Circadian Rhythm, CMAJ / 27.01.2015

Scott R. Garrison MD PhD Associate Professor, Department of Family Medicine Director, Pragmatic Trials Collaborative Faculty of Medicine University of Alberta EdmontonMedicalResearch.com Interview with: Scott R. Garrison MD PhD Associate Professor, Department of Family Medicine Director, Pragmatic Trials Collaborative Faculty of Medicine University of Alberta Edmonton MedicalResearch: What is the background for this study? What are the main findings? Dr. Garrison: Nocturnal leg cramps (also called rest cramps) are painful muscle tightenings, most often in the legs or feet, that are brought on by rest and often wake the sufferer from sleep. They are very common in older adults and can also occur during pregnancy. Having read anecdotal mention that the rest cramps of pregnancy appeared to be worse in summer we sought cohort level evidence to determine whether the more common presentation of age-related rest cramps was also seasonal. To do this we primarily looked at new quinine starts in the province of British Columbia over a period of several years. British Columbia has a publicly funded health care system and maintains electronic records on all health services, including prescription drugs, provided to its roughly 4.2 million residents. Quinine is approved for the treatment of acute malaria in Canada but is instead almost exclusively used off-label to prevent rest cramps. As such, new quinine starts are an excellent marker for new or escalating cramp burden. We also looked at Internet searches, geographically limited to the USA, for the term “leg cramps” (reflecting public interest) obtained from the Google Trends Search Volume Index Tool. Seasonality for both of these indicators of cramp burden was assessed by determining how well a least squares minimizing sinusoidal model predicted variability. We found that quinine starts and "leg cramp" related Internet queries were both strikingly sinusoidal with a 365-day periodicity (mid-summer high, mid-winter low) and a peak-to-peak variability that is approximately 2/3 of the mean. Seasonality accounted for 88% of the observed monthly variability (p < 0.0001) in quinine starts, and 70% of the observed variability (p < 0.0001) in “leg cramp” related internet searches. (more…)
Author Interviews, Cognitive Issues, HIV / 27.01.2015

Sophie Cohen MD, PhD Student Department of Pediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands Cairns Base Hospital Australia MedicalResearch.com Interview with: Sophie Cohen MD, PhD Student Department of Pediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands Cairns Base Hospital Australia Medical Research: What is the background for this study? What are the main findings? Response: Since combination antiretroviral therapy (cART) has become widely available for HIV-infected children, the incidence of severe neurological complications has decreased drastically from 30-50% to less than 2%. Unfortunately, even in cART-treated HIV-infected children a range of cognitive problems have been found, such as a lower intelligence quotient (IQ) and poorer visual-motor integration. Importantly, while most HIV-infected children in industrialized countries are immigrants with a relatively low socioeconomic status (SES), cognitive studies comparing HIV-infected children to SES-matched controls are very scarce.  Understanding the prevalence and etiology of cognitive deficits in HIV-infected children is essential because they may result in more pronounced problems, and influence future intellectual performance, job opportunities and community participation. Also, early detection of cognitive impairment might trigger the development of early intervention strategies. In this study we aimed to compare the neuropsychological profile of HIV-infected children to that of healthy controls, matched for age, gender, ethnicity and SES. Also, we aimed to determine the prevalence of cognitive impairment in the HIV-infected group and detect associations between HIV/cART parameters and cognitive performance. We found that the HIV-infected group had a poorer cognitive performance compared with the healthy children on all tested domains (including intelligence, information processing speed, attention, memory, executive- and visual-motor functioning). Using a novel statistical method called Multivariate normative comparison (MNC), we detected a prevalence of 17% with cognitive impairment in the HIV-infected group. Lastly, we found that the center for disease control (CDC) clinical category at HIV diagnosis was inversely associated with verbal IQ (CDC C: coefficient -22.98, P=0.010). (more…)