AHA Journals, Author Interviews, Heart Disease, PTSD / 27.03.2016

MedicalResearch.com Interview with: S. Marlene Grenon, MDCM, MMSc, FRCSC Associate Professor of Surgery Division of Vascular and Endovascular Surgery University of California, San Francisco Veterans Affairs Medical Center- Surgical Services San Francisco, CA   MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Grenon: In this study, we investigated the impact of PTSD on endothelial function using flow-mediated brachial artery vasodilation. After adjustments for different risk factors and comorbidities, we found that patients with PTSD had worse endothelial function. (more…)
Author Interviews, Infections, PLoS / 27.03.2016

MedicalResearch.com Interview with: Dr. Cameron Stewart PhD Team Leader within the Emerging Infectious Diseases Program CSIRO Biosecurity Flagship Commonwealth Scientific and Industrial Research Organisation MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Stewart: Hendra and Nipah viruses (referred to jointly as henipaviruses) are deadly cousins of the more common mumps, measles, and respiratory syncytial viruses, all members of the paramyxovirus family. Henipavirus outbreaks are on the rise, but little is known about the viruses, partly because research has to be undertaken under extreme containment conditions.  Our team performs research at the largest high containment facility in the Asia-Pacific region, the CSIRO Australian Animal Health Laboratory in Geelong, Australia. To understand the henipavirus infection cycle and to identify targets for new antiviral therapies, we performed a genome-wide screen to identify the host molecules required by henipaviruses for infection. The host gene with the largest impact, called fibrillarin, codes for a protein present in the nucleolus. Inhibiting fibrillarin impaired henipavirus infection greater than 1,000-fold in human cells.  We examined closely which step of the viral life cycle was blocked by interfering with fibrillarin function, and found it was required for the early synthesis of viral RNA. Results from our study suggest that fibrillarin could be targeted therapeutically to combat henipavirus infections. This research was undertaken by an international team of researchers from CSIRO, the Victorian Centre for Functional Genomics, Duke-NUS, the University of Georgia and the Centers for Disease Control and Prevention. (more…)
Author Interviews, Heart Disease / 26.03.2016

MedicalResearch.com Interview with: Eric Alexander Secemsky, MD, MSc Fellow in Cardiovascular Medicine Massachusetts General Hospital Harvard Medical School Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center MedicalResearch.com: What is the background for this study? Dr. Secemsky: Strategies to reduce bleeding, such as the selective use of procedural anticoagulants, have become an integral component of current percutaneous coronary intervention (PCI) practice to decrease adverse outcomes. For instance, previous randomized clinical trials had demonstrated that use of bivalirudin, a direct thrombin inhibitor, reduces major bleeding events following PCI among patients presenting with acute myocardial infarction (AMI) compared with unfractionated heparin (UFH). These findings resulted in a major increase in bivalirudin use during PCI. However, more recent trials have contradicted these results and created uncertainty as to the relative safety and effectiveness of bivalirudin therapy. In addition, current United States guidelines do not endorse a primary antithrombotic strategy during PCI, leaving the choice of procedural anticoagulant to the discretion of the physician operator. As such, we wanted to determine how bivalirudin was currently being used among United States PCI operators and how usage may have changed in light of these trial findings. (more…)
Author Interviews, Cancer Research, Technology, UCLA / 26.03.2016

MedicalResearch.com Interview with: Dr. David Wong D.M.D, D.M.S.C Professor Associate Dean for Research Director for UCLA Center for Oral/Head & Neck Oncology Research (COOR) Felix and Mildred Yip Endowed Chair in Dentistry UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Wong: The EFIRM technology is an electrochemical technology developed for the optimal detection of saliva targets for molecular diagnostics. It is a multiplexible platform (nucleic acid and proteins) that has sensitivity and specificity that comparable with PCR and luminex-based assays. It permits direct target detection in bio-samples without processing. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 26.03.2016

MedicalResearch.com Interview with: S. Hong Lee, PhD Queensland Brain Institute, The University of Queensland, Brisbane School of Environmental and Rural Science, University of New England, Armidale Australia  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies reported increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for schizophrenia tend to have children at an earlier or later age. We found evidence for a significant overlap between genetic factors associated with risk of schizophrenia and genetic factors associated with Age at First Birth (AFB). We observed a U-shaped relationship between schizophrenia risk and maternal AFB, consistent with the previously reported relationship between schizophrenia risk in offspring and maternal age when not adjusted for age of the father. (more…)
Allergies, Author Interviews, Genetic Research / 26.03.2016

MedicalResearch.com Interview with: Dr Gabrielle A. Lockett PhD Postdoctoral Research Fellow Asthma Genetics Laboratory, Faculty of Medicine, University of Southampton MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lockett: Season of birth has been known for decades to influence a huge range of traits, such as height and lifespan, as well as the risks of diseases such as allergy and schizophrenia. But until now the mechanism for season of birth effects was unknown. This study discovered that epigenetic marks (specifically DNA methylation) on the genome are associated with season of birth in 18-year-olds, suggesting that this could be a mechanism for such long-lasting birth season effects. Epigenetic marks on the genome are known to both influence gene expression and to change in association with environmental exposures. This study is the first to identify DNA methylation associated with season of birth. This discovery therefore extends our knowledge of environmental exposures that are able to affect the epigenome. The study also went on to further examine the genes identified to contain birth season-associated DNA methylation. Groups of these genes have functions related to development, cell death and the cell cycle, suggesting that season of birth alters the epigenetic regulation of these processes in particular. There was also suggestive evidence that season-associated DNA methylation could be on the functional pathway to allergic disease outcomes. (more…)
Author Interviews, Cancer Research, JAMA, Pediatrics / 25.03.2016

MedicalResearch.com Interview with: Lee J. Helman, MD Senior Investigator Pediatric Oncology Branch Head, Molecular Oncology Section Acting Director, Center for Cancer Research and CCR Scientific Director for Clinical Research National Cancer Institute Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Helman: It was known that most gastrointestinal stromal tumors (GISTS) that occur in children and young adults do not contain cKIT or PDGFRA mutations that drive more than 90% of adult GIST tumors.  Since GISTs are quite rare in the pediatric and young adult population, we decided to establish a clinic at NIH that would allow us to study the most patients to try to define these tumors both clinically and molecularly. We were able to bring both patients and physicians interested in pediatric GIST from around the country to the NIH to begin to collect and study these patients. Of the 95 patients in this cohort study that lacked cKIT or PDGFRAmutations, 84 were found to have succinate dehydrogenase (SDH) deficient (SDH-deficient) GIST (75% due to SDH A, B, C, or D mutations, and 25% due to SDHC promoter hypermethylation. Since these tumors are driven by SDH loss and not due to KIT or PDGFR mutations, they do not generally respond to standard treatments for GIST that target these kinases. The mechanism of SDH-deficiency is important, since SDH mutations are commonly germ line and therefore require genetic counseling and family testing, while the SDHC promoter methylation is not a germ line alteration and therefore does not require genetic counseling.  Finally, any patient with SDH-deficient GIST is also at risk for development of paraganglioma and should be screened on a regular basis for these tumors.  (more…)
Author Interviews, Fertility, UCSF / 25.03.2016

MedicalResearch.com Interview with: Melissa Miller, PhD Postdoctoral fellow at both UC Berkeley and UC San Francisco  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Miller: This work builds on years of observed, but unexplained, phenomena within sperm cells which respond almost instantaneously to the presence of the steroid hormone progesterone. Typically, steroid signaling occurs through a long, slow process that involves the modification of gene amount within a cell. However, there is an alternative mechanism that is not well understood that works differently and is termed non-genomic progesterone signaling. We found that progesterone in human sperm cells binds to a protein called ABHD2 and activates its activity to clear the cell of the endogenous cannabinoid 2AG.  2AG is an inhibitor of sperm activation and its removal from the cellular membrane allows the sperm cells to change its motility so that it may reach and fertilize the egg. Men who’s sperm is unable to undergo this progesterone activated motility change are infertile. (more…)
Author Interviews, Ophthalmology, Vitamin C / 25.03.2016

MedicalResearch.com Interview with: Christopher J. Hammond, MD, FRCOphth Departments of Ophthalmology & Twin Research King's College London St. Thomas' Hospital London UK  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Hammond: Twin studies allow us to quantify the influence of genes vs environment on a trait and this study suggests 65% of variation of cataract progression is due to environmental factors. Vitamin C has long been linked to cataract because the lens of the eye is bathed in fluid rich in ascorbate, a derivative of vitamin C. We showed that, even in a relatively well-nourished UK population, those in the highest third of vitamin C dietary intake (equating to something like 3 times the RDA of 60mg) had a third less progression of lens opacities. (more…)
Author Interviews, HPV, JAMA, OBGYNE, Sexual Health, UCSD / 24.03.2016

MedicalResearch.com Interview with: Ryan K. Orosco, MD Division of Head and Neck Surgery Department of Surgery University of California, San Diego MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Orosco: Our group at UC San Diego is interested in HPV as it relates to diseases of the head and neck.  HPV is a well-publicized cause of cervical cancer, and awareness about its link to throat (oropharynx) cancer is rapidly increasing. Less well-known, is the relationship between HPV and benign (non-cancerous) diseases such as genital warts and papilloma of the throat.  As we strive to understand how to best care for patients with HPV-related disorders, it is important to understand the entire process of disease progression, which begins with HPV infection. Our group wanted to explore the relationship between HPV infection in the two most commonly infected body sites: oral and vaginal. (more…)
Author Interviews, End of Life Care, Geriatrics, Kidney Disease / 24.03.2016

MedicalResearch.com Interview with: Dr. Wouter R. Verberne Koekoekslaan 1 The Netherlands MedicalResearch.com: What is the background for this study? Dr. Verberne: The number of older patients with End Stage Renal Disease (ESRD) is increasing worldwide. When ESRD is approaching, patients need to be advised on the renal replacement therapy (RRT) necessary to remove toxic products and fluid from the body when their own kidneys are no longer able to do so. ESRD can be treated with kidney transplantation, hemodialysis or peritoneal dialysis. With increasing technical possibilities and with the widespread availability of dialysis treatment, age no longer limits dialysis treatment. It has been questioned whether older patients with ESRD, who often have multiple comorbidities, are likely to benefit from renal replacement therapy. Dialysis treatment comes with high treatment burden. Generally patients are treated in a dialysis facility 3 times per week, 3 to 4 hours per time. Patients with an anticipated poor prognosis on RRT may choose to forego dialysis and decide to be treated conservatively instead. Conservative management (CM) entails ongoing care with full medical treatment, including control of fluid and electrolyte balance and correcting anemia, and provision of appropriate palliative and end of life care. Shared decision making has been recommended to come to a joint decision on   renal replacement therapy by considering potential benefits and harms of all treatment options and the patient’s preferences. Data on outcomes, including survival and quality of life, are needed to foster the decision making. However, adequate survival data, specifically on older patients, are limited. A number of studies, predominantly from the United Kingdom, have determined survival of older patients managed conservatively compared with renal replacement therapy. In these studies, the numbers of recruited patients are generally small, the studies are performed in heterogeneous study populations, and there is significant variability in starting points used in survival analyses. We performed the first Dutch study in a large series of older patients slowly approaching ESRD, enabling the use of several starting points in survival analyses. The aims of the study were to compare survival in patients with ESRD ages ≥ 70 years old choosing either conservative management or renal replacement therapy and determine predictors of survival.  (more…)
Author Interviews, Coffee, Fertility, Lifestyle & Health, NIH, OBGYNE / 24.03.2016

MedicalResearch.com Interview with: Germaine M. Buck Louis, Ph.D., M.S. Office of the Director Division of Intramural Population Health Research Eunice Kennedy Shriver National Institute of Child Health and Human Development Rockville, Maryland 20852. MedicalResearch.com: What is the background for this study? What are the main findings? Response: To understand the association between couples’ lifestyles and risk of pregnancy loss.  Couples were recruited upon discontinuing contraception to try for pregnancy and followed daily for up to one year of trying or until pregnancy.  Pregnant women were followed daily for 7 weeks following conception then monthly. (more…)
Author Interviews, JAMA, Nutrition, Supplements / 23.03.2016

MedicalResearch.com Interview with: Judy Jou, MA PhD Candidate PhD Candidate in Health Services Research, Policy, & Administration Division of Health Policy and Management University of Minnesota, Twin Cities Minneapolis, MN  MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Use of complementary and alternative medicine (CAM) is rising among U.S. adults, but CAM is often poorly integrated into patients’ treatment and self-care routines. We analyzed nearly 7,500 responses from the 2012 National Health Interview Survey (NHIS) and found that over two-fifths of U.S. adults who used CAM during the past year did not disclose their complementary and alternative medicine use to their primary health care providers, with rates of disclosure varying by the type of CAM used. We also examined reasons for non-disclosure and found that, in contrast to prior studies, lack of provider-initiated conversation about  complementary and alternative medicine was the most commonly cited reason, rather than patients’ concerns about negative reactions from their providers regarding their complementary and alternative medicine use. (more…)
Author Interviews, End of Life Care, Heart Disease, JAMA / 22.03.2016

MedicalResearch.com Interview with: Colleen K. McIlvennan, DNP, ANP-BC Assistant Professor of Medicine Division of Cardiology Section of Advanced Heart Failure and Transplantation MedicalResearch.com: What is the background for this study? What are the main findings? Response: As technology continues to advance, more people are becoming eligible for advanced therapies for end-stage illness. One such therapy, the left ventricular assist device (LVAD) is an option for carefully selected individuals suffering from end-stage heart failure. Use of this innovative technology has expanded from its original indication as a bridge to transplantation to also include destination therapy, in which patients live with the device for the remainder of their lives. Significant focus has been placed on developing and expanding LVAD programs, with less thought about the eventual end-of-life process awaiting patients whose LVAD is indicated for destination therapy. We performed semi-structured interviews about experiences surrounding end of life with 8 caregivers of patients who died with an LVAD. There was a wide range of case histories represented by these patients; however, three main themes emerged that coalesced around feelings of confusion: 1) the process of death with an LVAD, 2) the legal and ethically permissible care of patients approaching death with an LVAD, and 3) the fragmented integration of palliative and hospice care. (more…)
Annals Internal Medicine, Author Interviews, Breast Cancer / 21.03.2016

MedicalResearch.com Interview with: Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Elmore: Our team began studying diagnostic agreement among pathologists while interpreting breast biopsies in 2009. Early findings from the Breast Pathology Study (B-Path) were published in March 2015 in the Journal of the American Medical Association and indicated strong agreement among pathologists when diagnosing invasive breast cancer or benign breast tissue. Agreement, however, was much lower for ductal carcinoma in situ (DCIS) and atypia. Results from this study raised concerns that a high percentage of breast biopsies may be inaccurately diagnosed. These concerns were amplified in the media with statements like “as many as one-in-four biopsies are incorrectly diagnosed.” Statements like this inaccurately depicted the results of our study, which included a test set weighted heavily with DCIS and atypia cases. It is important to consider the percentage that each outcome category contributes to the overall number of biopsies in the U.S. population as we found that the agreement rate of pathologists varies drastically across these diagnostic categories. Atypia in Breast Tissue Elmore Image In the new work published in Annals of Internal Medicine, we have analyzed the B-Path results to reflect variation among diagnoses of women using U.S. population-adjusted estimates, In an effort to help physicians and patients better understand what the B-Path results mean for women, we have analyzed the B-Path results to reflect variation among diagnoses of women using U.S. population-adjusted estimates. When adjusted using population-based predictive value estimates, the B-Path results indicate that pathologists’ overall interpretations of breast biopsies would be confirmed by an expert panel 92 out of 100 biopsies, with more of the initial diagnoses over-interpreted rather than under-interpreted. Of concern, our results noted that among 100 breast biopsies given an initial diagnosis of atypia, less than half of these cases would be given a diagnosis of atypia after review by a panel of three experienced breast pathologists. Over half of the biopsies would be downgraded from atypia to a diagnosis of benign without atypia after review. (more…)
Author Interviews, Dermatology, JAMA, Parkinson's / 21.03.2016

MedicalResearch.com Interview with: Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital University of Copenhagen Hellerup, Denmark  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Egeberg: Rosacea skin shows an up-regulation of various cytokines (small proteins that are important in cell signalling), and displays increased activation and expression of matrix metalloproteinases (MMPs). Both rosacea and Parkinson’s disease have been associated with small intestinal bacterial overgrowth and Helicobacter pylori infection, and MMPs. MMPs are enzymes that are involved in tissue remodeling, organ development, and regulation of inflammatory processes. Parkinson’s is a progressive neurological disease that results from the gradual loss of brain cells that produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. Importantly, MMPs have also been implicated in the pathogenesis of Parkinson’s disease and other neurodegenerative disorders, and MMPs contribute to loss of dopamine producing brain cells. Rosacea is often characterized by flare-ups and remissions and typically presents as a redness on the cheeks, nose, chin or forehead. In our study, we found a significantly (approximately two-fold) increased risk of developing Parkinson's disease, a chronic and progressive movement disorder, among patients with rosacea. Also, we found that treatment with tetracycline, an oral antibiotic, was associated with a slightly decreased risk of Parkinson's disease. (more…)
Author Interviews, Cancer Research, Imperial College / 21.03.2016

MedicalResearch.com Interview with: Dr Olivier E Pardo PhD Team Leader Imperial College Division of Cancer Hammersmith Hospital London UK  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Pardo: Metastatic dissemination, the ability of tumour cells to go and colonise organs distant from the primary disease site, is the principal cause for failing to cure patients with cancer. This is particularly true in the case of breast cancer where resection of local disease offers good chances of cure but metastatic dissemination that may appear at a later stage carries very poor prognosis. Surgical resection is also the only true curative strategy for localised lung cancer. Hence, a better understanding of the mechanisms controlling the dissemination of tumour cells is likely to propose novel targets for combination therapy that will improve the survival of cancer patients. Here, we showed that an enzyme, named MARK4, controls the ability of lung and breast cancer cells to move and invade. When we lower MARK4 levels, it prevents cancer cells from moving by changing their internal architecture, making them unfit to invade. Consequently, these cells were unable to efficiently form metastasis in mouse cancer models. Confirming the role of this enzyme in cancer, we show that breast and lung cancer patients with increased levels of MARK4 in their tumours have poorer prognosis. We found that what controls the levels of MARK4 in cells is miR-515-5p, a small oligonucleotide sequence called a microRNA. When present in the cells, miR-515-5p prevents the expression of MARK4. Incidentally, the loss of miR-515-5p correlates with increased metastasis and poorer prognosis in mouse cancer models and patients, respectively. (more…)
Accidents & Violence, Author Interviews, Brigham & Women's - Harvard, Obstructive Sleep Apnea / 21.03.2016

MedicalResearch.com Interview with: Stefanos N. Kales, MD, MPH, FACP, FACOEM  Associate Professor, Harvard Medical School & Harvard TH Chan School of Public Health Director, Occupational Medicine Residency Division Chief OEM, Cambridge Health Alliance MedicalResearch: What is the background for this study? Dr. Kales: Up to 20% of all large truck crashes are due to drowsy or fatigued driving, which would account for almost 9,000 fatalities and up to 220,000 serious injuries. OSA is the most common medical cause of excessive daytime sleepiness or fatigue, and has been linked with negative impacts on attention, working memory, vigilance, and executive functioning. Past studies primarily of passenger car drivers have linked untreated OSA with a several-fold increased risk of motor vehicle accidents. They have also shown that effective treatment with CPAP reduces this risk close to that of unaffected drivers. Although commercial truck drivers undergo a biennial examination to determine their medical fitness to safely operate a vehicle, there are currently no mandatory standards for OSA screening or diagnosis, in part because there have been no large-scale studies evaluating the crash risk of commercial drivers diagnosed with OSA. Our study examined the results of the first large-scale employer program to screen, diagnose, and monitor OSA treatment adherence in the U.S. trucking industry  (more…)
Author Interviews, Depression / 21.03.2016

MedicalResearch.com Interview with: Theodore Henderson, MD, PhD Neuroluminance Ketamine Infusion Centers MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Henderson: Depression is a widespread problem. Psychotropic medications or therapy are the standard treatments, but they are often disappointing. Some studies have shown that the response rate to antidepressant medications is only 12-17% better than placebo response rate. Newer non-pharmacetical treatments, like transcranial magnetic stimulation, appear to have only a 50% response rate at best. The seminal study by Berman and colleagues in 2000 showed that sub-anesthetic dose infusions of the anesthetic, ketamine, produced a rapid antidepressant response. Many clinics across the United States focus on these rapid effects. Our clinic has been treating patients with treatment-resistant depression (defined as failing five or more antidepressants) for over three years. Our response rate is 80% based on multiple depression rating scales. We report here on 100 of the over 300 patients in our clinic who agreed to share their data in a research study. We treated patients with ketamine infusions no more frequently than once per week, unlike the clinical studies and many other ketamine clinics. We found our patients did equally well or better and received fewer treatments. The neurobiology of ketamine and its mechanism of action hold the key. Ketamine is a potent activator of the growth factor, brain derived neurotrophic factor (BDNF). This growth factor reverses the damage that depression causes to the brain – loss of synapses, dearborization of dendrites, and neuronal death. Ketamine’s ability to activate BDNF over time is responsible for a persistent antidepressant effect upon the brain. (more…)
Author Interviews, Biomarkers, Breast Cancer / 20.03.2016

MedicalResearch.com Interview with: Lan Ko MD PhD Augusta University Cancer Center Augusta, GA 30912, USA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lan Ko: Cancer development hijacks normal cell differentiation. Understanding the normal is where we could begin to unlock the secret of cancer. In normal breast tissue, stem or progenitor cells produce supporting stromal cells in normal breast development. In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendents so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer. Each subgroup of breast tumor stromal cells has been previously described by other scientists. However, the connections among these cells were unclear in the past. Like blind men feeling elephant, we scientists are often obscured from seeing the entire picture. The finding of mutant breast tumor stromal cells using GT198 as a marker provides a critical puzzle piece that fits the rest of puzzle together. When cancer problems can be viewed in multiple aspects with great simplicity, their connections emerge. We now know why breast cancer stromal cells are important, and how should we target them. (more…)
Author Interviews, Depression, Omega-3 Fatty Acids / 19.03.2016

MedicalResearch.com Interview with: Dr. Roel JT Mocking Program for Mood Disorders Department of Psychiatry Academic Medical Center University of Amsterdam, The Netherlands  MedicalResearch.com: What is the background for this study? Response: Omega-3 polyunsaturated fatty acid supplementation (popularly referred to as fish oil) is being promoted as (add-on) treatment for depression. Thus far, many studies have been performed that tested the effects of omega-3 fatty acids in depression. In order to overcome differences between these results of individual studies, a meta-analysis can be performed. A meta-analysis pools the results of all individual studies, and thereby provides a more definitive conclusion regarding the effect of omega-3 fatty acids in depression. Moreover, using the differences between the individual studies, a meta-analysis can point to factors that are associated with a better effect of the supplementation, for example supplementation dose or duration. There have been meta-analyses performed previously, but they seemed to contain several inconsistencies. For example, they accidentally included the same study two or three times, which results in errors. In addition, these meta-analyses did not only include studies performed in patients with the psychiatric disorder "major depressive episode", but also subjects from the general population with less severe depressive complaints. This makes it more difficult to interpret the results. Therefore, we performed a meta-analysis that included only studies performed in patients with major depressive disorder, and corrected errors from earlier meta-analyses. (more…)
Author Interviews, Cancer Research / 19.03.2016

MedicalResearch.com Interview with: Douglas.A. Lauffenburger PhD Ford Professor of Biological Engineering, Chemical Engineering, and Biology Head, Department of Biological Engineering Massachusetts Institute of Technology Cambridge, MA 02139  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lauffenburger: We aimed to advance understanding concerning causes of tumor resistance to kinase inhibitor drugs, which limits effectiveness for many therapeutics even when indicated by specific genetic mutations in the new ‘personalized medicine’ paradigm.  We discovered a new mechanism underlying this resistance at least for a number of otherwise promising drugs currently in clinical use as well as further clinical trials.  Our discovery was based on realizing that the same oncogenic signaling driving tumor cell proliferation and invasiveness at the same time activates proteolytic shedding of receptor tyrosine kinases not involved in the targeted oncogenic pathway, shutting down additional signaling inputs.  Thus, when the targeted pathway is inhibited by the intended drug, this shedding is concomitantly diminished — now permitting “bypass" pathways to be activated downstream of these alternative receptor inputs.  Moreover, we showed that measurement of a set of key shed receptors (primarily AXL and MET, in our examined case of MEK pathway inhibitors for melanoma and triple-negative breast tumors) in patient blood serum samples could predict effectiveness of these inhibitors: when the shed levels were high, the drugs were less effective because of the correspondingly great potential for bypass signaling upon drug treatment.  In follow-up mouse experiments, we demonstrated increased effectiveness of a MEK inhibitor when combined with either an AXL inhibitor or a proteolysis inhibitor, thereby confirming the mechanism and proving an avenue for overcoming it. (more…)
Author Interviews, Immunotherapy / 19.03.2016

MedicalResearch.com Interview with: Dr. Emerson C. Perin MD, PhD Texas Heart Institute Medical Director, BSLMC Catheterization Laboratory Director, Research in Cardiovascular Medicine Medical Director, Stem Cell Center  MedicalResearch.com: What is the background for this study? Dr. Perin: Critical limb ischemia (CLI) is a devastating and debilitating disease characterized by reduced blood flow to the legs, frequently as a consequence of atherosclerosis. Patients with CLI have a poor prognosis and live with chronic pain and disability. The disease manifests clinically as pain during rest and compromised wound healing, often resulting in ulcers that don’t heal, which can lead to amputation. Moreover, Critical limb ischemia is a deadly disease, with an annual mortality rate of about 20%. The only effective treatment option is revascularization, but not all CLI patients are good candidates for this approach, and even for those who are, procedures can fail. These patients face a dismal prospect as no other effective treatment options are available. Clearly, new therapeutic strategies are desperately needed for this group of patients. One of the most exciting new approaches for Critical limb ischemia patients who have no options is the concept of therapeutic angiogenesis—improving regional blood flow by facilitating the growth of blood vessels. This can be accomplished by delivering angiogenic factors to the area in need of improved blood supply. Hepatocyte growth factor (HGF) is a promising novel biologic for use in this way because it’s a powerful angiogenic agent that stimulates cell proliferation and migration. Delivering HGF into the ischemic limbs of patients with CLI may result in beneficial effects that help restore compromised blood flow to the area and encourage better healing of wounds. VM202 is a plasmid DNA that simultaneously expresses two isoforms of HGF, mimicking the way the body produces HGF. On the basis of favorable results from phase 1 clinical trials showing that gene therapy with VM202 was safe, well-tolerated, and potentially beneficial in patients with ischemic diseases, we conducted a phase 2, dose-escalation clinical trial in patients with Critical limb ischemia. (more…)
Author Interviews, NEJM, Pharmacology / 18.03.2016

MedicalResearch.com Interview with: Prof. Bruce Guthrie Primary Care Medicine and Honorary Consultant NHS Fife University of Dundee Dundee, Scotland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Guthrie: Most drug-related harm is caused by commonly prescribed drugs with moderate risk. This prescribing is not always inappropriate, because risk of harm may be outweighed by benefit in an individual, but we have previously shown that high-risk prescribing like this is common and highly variable between primary care practices, consistent with it being improvable. We therefore developed a complex intervention combining education, informatics to make it easy to identify and review patients, and a small financial incentive to review. We evaluated this intervention in a cluster-randomised trial in 33 Scottish primary care practices, targeting nine measures of high-risk non-steroidal anti-inflammatory drug (NSAID) and antiplatelet prescribing (for example, prescription of an NSAID to someone with chronic kidney disease; prescription of an antiplatelet to someone taking an anticoagulant without also prescribing a gastroprotective drug). The intervention reduced the targeted prescribing by just over one third, and this reduction was sustained in the year after the intervention (including the payment to review) ceased. We also observed reductions in related hospital admissions with gastrointestinal bleeding and heart failure, although not acute kidney injury which was reduced but not statistically significantly. (more…)
Author Interviews, Breast Cancer, Lancet / 18.03.2016

MedicalResearch.com Interview with: Professor Jack Cuzick, PhD, FMedSci, FRCP(hon) Director, Wolfson Institute of Preventive Medicine and Head, Centre for Cancer Prevention Queen Mary University of London. MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Cuzick: Ductal carcinoma in situ (DCIS) is a very early form of breast cancer, where cancer cells are present in milk ducts, but have not spread to the surrounding breast tissue. It is estimated that approximately a fifth of all screen-detected breast cancers are DCIS, with around 4,800 people diagnosed with DCIS in the UK each year. Our IBIS-II DCIS trial looked at 2,980 postmenopausal women with DCIS in 14 countries, who were either given anastrozole or tamoxifen for five years after surgery. The two groups had a similar number of cases of the disease recurring, whether they took tamoxifen or anastrozole. Those who took anastrozole had an 11 per cent lower rate of recurrence of DCIS or invasive cancer than those who took tamoxifen, but this difference was not significant. The similar NSABP B-35  trial found a 29% reduction with anastrozole and the combined analysis of the two trials indicated a significant 21% reduction. The key difference between the two groups were in the side effects of the medication. Women who took anastrozole experienced fewer womb and ovarian cancers and non melanoma skin cancers, and fewer deep vein thromboses and gynecological issues, compared with those who took tamoxifen. However more fractures and musculoskeletal side effects were seen among those receiving anastrozole. (more…)
Author Interviews, Mental Health Research, PTSD / 18.03.2016

MedicalResearch.com Interview with: Donna L. Littlewood PhD Student School of Psychological Sciences University of Manchester, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: Every year over 800,000 people die by suicide, and for every individual’s death, it is estimated that another 20 people will make a suicide attempt. Therefore, to be able to prevent suicide, we need to understand the different factors that can combine to make an individual think about ending their own life. Recent research indicates that nightmares are associated with suicidal thoughts and behaviours, and that this association is independent of other related suicide risk factors, such as, depression and PTSD. However, it is now important for research to examine the mechanisms that underpin this association, as this information will support the development of clinical interventions to prevent subsequent suicide attempts and deaths (more…)
Alcohol, Author Interviews, Breast Cancer, Genetic Research, PLoS / 18.03.2016

MedicalResearch.com Interview with: Chin-Yo Lin, Ph.D. University of Houston Center for Nuclear Receptors and Cell Signaling Department of Biology and Biochemistry Science and Engineering Research Center (SERC) Houston, TX 77204-5056  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lin: Many studies have established that alcohol consumption is a risk factor for breast cancer. Breast cancers associated with drinking tend to be hormone receptor-positive, the type is commonly treated with the drug tamoxifen which blocks the actions of estrogen in driving tumor growth in pre-menopausal women. Alcohol consumption has also been shown to increase the risk of disease recurrence in patients. Our study shows that alcohol can enhance the effects of estrogen by increasing cancer cell division and also reduce the efficacy of tamoxifen. The key mechanistic insight from the study is that alcohol treatment of breast cancer cells increased the expression of BRAF, a cancer-causing gene that is commonly mutated and activated in other types of cancers. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Pulmonary Disease, Surgical Research, Technology / 18.03.2016

MedicalResearch.com Interview with: Dr. Ariel Drori MD Hadassah Medical Center  MedicalResearch.com: What is the background for the ThoraXS device? Dr. Drori: The initial recognition of the need for a device like ThoraXS first came to me on an operational deployment during my reserve service where I serve as a military doctor. While serving on the Gazan border, I was called to a battle scene to treat a soldier who was suffering from pneumothorax after being shot in the chest.  A quick evacuation by helicopter meant that I didn't have the time to perform the entire procedure and I was forced to hand over a partially-treated patient whose condition was unstable. The reality of constant combat injuries mixed with a rising number of daily civilian terror attack casualties led us to understand that we need to provide a cheap, easy to use, robust and reliable solution that on the one hand can withstand the most extreme combat conditions and on the other, be used by any paramedic and in any pre-hospital and hospital setting. This line of thought eventually led to the adoption of ThoraXS's simple yet sophisticated mechanical mechanism that ticks all the boxes. (more…)
Author Interviews, Gastrointestinal Disease, Heart Disease, Pharmacology / 18.03.2016

MedicalResearch.com Interview with: Giuseppe Gargiulo MD Research fellow in Cardiology Inselspital, University of Bern, Bern, Switzerland  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Gargiulo: Every year millions of people with coronary artery disease are treated worldwide with percutaneous coronary intervention (PCI). Consequently, they receive a dual  (DAPT) in order to prevent thrombotic life-threatening complications, such as stent thrombosis. DAPT often consists of aspirin and clopidogrel, but some studies have questioned the efficacy of clopidogrel in case of concomitant therapy with proton-pump inhibitors (PPI) due to pharmacodynamic interactions. Indeed, clopidogrel is a pro-drug needing to be activated, and this could be potentially affected by PPI. This is a relevant topic given that many patients treated with DAPT commonly receive also a PPI to prevent gastrointestinal complications (ulceration and bleeding) or due to pre-existing gastric disease. Some studies demonstrated that the use of a PPI, mainly omeprazole, was associated with an increased risk of cardiovascular adverse events, indeed the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) discouraged the concomitant use of omeprazole and clopidogrel. On the contrary, some other studies did not confirm this finding. We performed a detailed analysis of the impact of PPI therapy on the 2-year clinical outcomes of 1970 patients undergoing PCI with stent implantation enrolled in the PRODIGY trial (a randomized trial comparing 2 DAPT regimens: 6-month versus 24-month DAPT). In our study population, 738 patients (38%) were treated with a PPI (lansoprazole 90%) concomitantly to DAPT. We found that the ischemic and bleeding events at 2 years of follow-up were similar in patients treated with or without a PPI, irrespective of DAPT duration (6-month or 24-month). These findings support the concept that the concomitant use of PPI, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcomes. (more…)