MedicalResearch.com Interview with: [caption id="attachment_22924" align="alignleft" width="133"] Dr. Kristian Filion[/caption] Kristian B. Filion, Ph.D., FAHA Assistant Professor of Medicine, Division of Clinical Epidemiology, McGill University Principal Investigator, Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital Associate Member, Department of Epidemiology, Biostatistics, and Occupational Health, McGill University MedicalResearch.com: What is the background for this study? What...
MedicalResearch.com Interview with: [caption id="attachment_22792" align="alignleft" width="186"] Dr. Paul Gurbel[/caption] Paul A. Gurbel, M.D. Director, Inova Center for Thrombosis Research and Drug Development Director, Cardiovascular Medicine Research Director, Interventional Cardiology Inova Heart and Vascular Institute Falls Church, VA Professor of Medicine, Johns Hopkins University School of Medicine Adjunct Professor of Medicine, Duke University School of Medicine MedicalResearch.com: What is the background for...
Dr. Daniel Cherkin[/caption]
Dr. Daniel C. Cherkin PhD
Senior Investigator
Group Health Research Institute
Seattle, WA
MedicalResearch.com: What is the background for this study?
Dr. Cherkin: Chronic low back pain is a widespread, costly, and potentially disabling problem. It’s the most common cause of pain of any kind. It affects eight in 10 Americans at some point in their lives. In recent years, the United States has been spending more on back pain treatments—but unfortunately with worse results in how much pain bothers people and interferes with their lives. Group Health is addressing the problem in several ways, including this innovative research.
MedicalResearch.com: What are the main findings?
Dr. Cherkin: In a randomized controlled trial involving more than 300 patients at Group Health, we found that training in a kind of mindfulness meditation—mindfulness-based stress reduction (MBSR)—led to meaningful improvements in functioning and chronic low back pain at six months and one year. MBSR, which is becoming increasingly popular and available in the United States, involves training in observing, acknowledging, and accepting thoughts and feelings including pain. The training also includes some easy yoga poses to help participants become more aware of their bodies. Results with mindfulness-based stress reduction were significantly better than with usual care (whatever patients would be doing for their back pain if they weren’t in the study, including medications and physical therapy—but not mindfulness meditation or cognitive behavioral therapy). And results with mindfulness-based stress reduction were very similar to those with cognitive behavioral therapy (CBT). CBT includes education about chronic pain, relationships between thoughts and emotional and physical reactions, instruction and practice in changing dysfunctional thoughts, setting and working towards behavioral goals, relaxation skills, activity pacing, and pain coping strategies. Prior studies had already proven that CBT helped adults of various ages with back pain.
Dr. Sari Reisner[/caption]
Dr. Sari L. Reisner PhD
Research Fellow in the Department of Epidemiology
Harvard T.H. Chan School of Public Health
Associate Scientific Researcher in the Division of General Pediatrics
Boston Children’s Hospital/ Harvard Medical School
MedicalResearch.com: What are the main findings?
Dr. Reisner: Transgender youth—including adolescent and young adult transgender women assigned a male sex at birth who identify as girls, women, transgender women, transfemale, male-to-female, or another diverse gender identity on the transfeminine spectrum—represent a vulnerable population at-risk for negative mental health and substance use/abuse outcomes.
Although community surveys of transgender people in the United States have found a high prevalence of depression, anxiety, and substance use relative to the general adult U.S. population, studies typically utilize screening instruments or sub-threshold symptom questions and do not use diagnostic interviews. Diagnostic interview data are scarce among young transgender women; such data are important to establish guidelines for diagnosis and treatment for this youth group given their complex life experiences.
The aim of this study was to report the prevalence of mental health, substance dependence, and co-morbid psychiatric disorders assessed via a diagnostic interview in an at-risk community-recruited sample of young transgender women. This observational study reported baseline finding from a diverse sample of 298 sexually active, young transgender women ages 16-29 years (mean age 23.4; 49.0% Black, 12.4% Latina, 25.5% White, 13.1% other minority race/ethnicity) enrolled in Project LifeSkills, an ongoing randomized controlled HIV prevention intervention efficacy trial in Chicago and Boston, between 2012-2015 (NIMH-funded, multiple PIs: Rob Garofalo, MD, MPH & Matthew Mimiaga, ScD, MPH).
Dr Marlene Grenon[/caption]
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.
Dr. Cameron Stewart[/caption]
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.
MedicalResearch.com Interview with: [caption id="attachment_22896" align="alignleft" width="175"] Dr. Eric Chow[/caption] Eric J. Chow, MD, MPH Hematology-Oncology Attending physician, Seattle Childrens Hospital Assistant professor of Pediatrics, University of Washington School of Medicine Member of the Clinical Research and Public Health Sciences Divisions Fred Hutchinson Cancer Research Center MedicalResearch.com: What is the background for this study? Dr. Chow: Adverse effects on...
Dr. Eric Secemsky[/caption]
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.
Dr. David Wong[/caption]
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.
Dr. Hong Lee[/caption]
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.
Dr. Gabrielle Lockett[/caption]
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.
Dr. Lee Helman[/caption]
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.
Dr. Chris Hammond[/caption]
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.
Dr. Ryan Orosco[/caption]
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.
Dr-Germaine M. Buck-Louis[/caption]
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.
Judy Jou[/caption]
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.
Dr. Colleen McIlvennan[/caption]
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.
Dr. Joann Elmore[/caption]
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.
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.
Dr. Alexander Egeberg[/caption]
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.
Dr. Olivier Pardo[/caption]
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.
Dr. Stefanos Kales[/caption]
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
Dr. Lan Ko[/caption]
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.
Dr. RJT Mocking[/caption]
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.