Author Interviews, Lancet, Nutrition, Sugar, Weight Research / 08.01.2016

MedicalResearch.com Interview with: Kawther Hashem MSc RNutr (Public Health) Nutritionist and Researcher Action on Sugar Wolfson Institute of Preventive Medicine, Queen Mary, University of London London UK Medical Research: What is the background for this study? What are the main findings? Response: The calculations showed that a 40% reduction in free sugars added to Sugar Sweetened Beverages (SSBs) over five years would lead to an average reduction in energy intake of 38 kcal per day by the end of the fifth year. This would lead to an average reduction in body weight of 1.20kg in adults,  resulting in a reduction in overweight and obese adults by approximately half a million and 1 million respectively. This would in turn prevent between 274,000-309,000 obesity-related type 2 diabetes over the next two decades. Policies such as this will reduce cases of overweight and obesity and type 2 diabetes, this will have a major clinical impact and reduce healthcare costs. (more…)
Author Interviews, Exercise - Fitness, Heart Disease, JAMA, Nutrition / 08.01.2016

MedicalResearch.com Interview with: Dalane W. Kitzman, M.D. Professor, Cardiology Sticht Center on Aging Gerontology and Geriatric Medicine Translational Science Institute Wake-Forest Baptist Health Winston-Salem, NC Medical Research: What is the background of the research? Dr. Kitzman: Heart Failure With Preserved Ejection Fraction (HFPEF) is a relatively recently recognized disorder.  It used to be thought that it was rare.  However, we now realize that HFPEF is the dominant form of heart failure in America.  It is also the fastest growing cardiovascular disorder.  Interestingly, this disorder occurs almost exclusively among older persons, particularly women.  The need is great because outcomes in persons with HFPEF (death, rehospitalization, health care costs) are worsening.  This stands in contrast to most other cardiovascular disorders which are on the decline and / or are experiencing greatly improved outcomes.  Remarkably, all of the large studies that have used medications in HFPEF that seemed they should be ‘sure bets’ showed no benefit for their primary outcomes.  Thus, this is also the only major cardiovascular disorder where there is no proven medication treatment.  That means physicians take ‘educated guesses’ in choosing treatment for this large group of patients. The main symptom in patients with chronic HFPEF is shortness of breath and and fatigue with exertion.  We showed in 2002 in JAMA that when we objectively measured this symptom with expired gas analysis (Peak VO2), this was as severely decreased in HFPEF as in patients with HFREF (severely reduced EF), the classic, well accepted form of heart failure.  That and other studies helped lead to acceptance of HFPEF as a true Heart Failure disorder. We first showed 5 years ago that 4 months of exercise training improves peak VO2 and quality of life in patients with HFPEF.  In fact, exercise remains the only proven means to improve these patients’ chronic symptoms. The goal of our study was to determine if weight loss diet also improved peak VO2 and quality of life in HFPEF patients, alone and in combination with exercise training.  This was based on the under-recognized fact that over 80% of Heart Failure With Preserved Ejection Fraction patients are overweight or obese.  It was already known that weight loss diet in other groups of older persons improves peak VO2 and quality of life.  And small studies of weight loss surgery in the other form of HF (HFREF) suggested that weight loss can improves symptoms, peak VO2, and quality of life.  However, there had never been a study of weight loss, by diet or other means, in HFPEF.  In fact, it had been thought, based on observational data, that weight loss diet might be contraindicated in HFPEF. So we recruited 100 overweight / obese patients age 60 years and older with this disorder from our community; 80% were women.  The exercise was standard exercise training that we’d previously shown was effective.  The meals for the weight loss diet were prepared in our metabolic kitchen by a regisered dietition.  Patients made out menus selecting preferred foods.  Well balanced, healthy, nutritious, but very palatable.  The portions were controlled so that there was a 350 caloric deficit per day deficit, on average.  Pateints made their own breakfast with guidance, unlimited of certain fruits and vegetables, and occasional “free days”, such as for holidays.  Patients loved the meals and wanted to continue after the 5 month study. (more…)
Author Interviews, Cost of Health Care, Primary Care / 07.01.2016

MedicalResearch.com Interview with: Sapna Kaul, Ph.D Huntsman Cancer Institute 2000 Circle of Hope Salt Lake City, UT 84112 Medical Research: What is the background for this study? What are the main findings? Dr. Kaul: The United States has the highest healthcare expenditures in the world, and close to one-third of these expenditures are believed to be unnecessary. One potential reason for these unnecessary expenditures is that patients may ask for medical services that are unnecessary. At the same time, primary care physicians (PCP) could find it difficult to refuse to prescribe unnecessary medical services as they may worry that it may compromise patient satisfaction. Also, there is a shortage of primary care workforce in the U.S. and PCPs may have insufficient time to effectively address patient requests. We investigated 2 types of unnecessary medical practices initiated by patient requests: (1) providing unnecessary specialty referrals, and (2) prescribing brand-name drugs when generic alternatives were available. To explore these practices, we used data on 840 U.S. PCPs from a national survey of physicians conducted in 2009. Over 50% of primary care physicians reported providing unnecessary specialty referrals and 39% prescribed brand-name drugs at patient requests. Several provider and organizational factors, such as physician specialty and solo/2-person practice, were related to reporting unnecessary practices. (more…)
Author Interviews, C. difficile, Hospital Acquired, Infections, Microbiome / 07.01.2016

MedicalResearch.com Interview with: Casey M. Theriot, Ph.D. Assistant Professor Infectious Disease College of Veterinary Medicine Department of Population Health and Pathobiology North Carolina State University Raleigh, NC 27607 Medical Research: What is the background for this study? What are the main findings? Dr. Theriot: This study is an extension of the work we did in 2014 in our Nature Communications paper (Theriot et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection, 2014). We really wanted to know how different antibiotics that varied in their mechanism of action altered the gut microbiota in different ways and also in turn how this altered the bile acids present in the small and large intestine of mice. Primary bile acids are made by the host and are further converted to secondary bile acids by members of the microbiota in the large intestine. We know from previous work that secondary bile acids can inhibit the growth of C. difficile, but no one has looked in depth at the bile acid makeup in the actual gut before in the context of C. difficile. In this study we show that specific antibiotics that significantly alter the large intestinal gut microbiota and deplete all secondary bile acids allow for C. difficile to grow without any inhibition. We also showed that C. difficile spores are always germinating in the small intestine, which means in order to prevent this pathogen from colonizing the gut, we will have to target the growth of the pathogen. Moving forward the focus will be on trying to repopulate the gut with bacteria that are capable of restoring the secondary bile acid pools in order to inhibit C. difficile. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, PTSD, Vanderbilt / 07.01.2016

MedicalResearch.com Interview with: Mayur Patel, MD, MPH, FACS Assistant Professor of Surgery & Neurosurgery Vanderbilt University Medical Center Staff Surgeon and Surgical Intensivist Nashville VA Medical Center Medical Research: What is the background for this study? Dr. Patel: Post-traumatic stress disorder (PTSD) can occur in patients after the traumatizing events of critical illness. Survivors of critical illness have reported PTSD symptoms months to even years after critical illness, possibly related to nightmare-like experiences, safety restraints creating communication barriers, and protective mechanical ventilation causing feelings of breathlessness and fear of imminent death. But, the epidemiology of PTSD after critical illness is unclear with wide ranging estimates (0-64%) and largely fails to distinguish past PTSD from new PTSD specifically resulting from the critical care experience. Our study provides estimates on new cases of PTSD stemming specifically from the ICU experience. Pre-existing PTSD has rarely been systematically assessed in prior cohorts, and our work took extra effort to distinguish pre-existing PTSD from new PTSD cases. Civilian populations have dominated the literature of PTSD after critical illness, and this research is the first to also include the expanding and aging Veteran population.  (more…)
Author Interviews, Blood Clots, Endocrinology, Hormone Therapy, Pharmacology / 07.01.2016

MedicalResearch.com Interview with: Ida Martinelli MD, PhD A Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Italy  Medical Research: What is the background for this study? What are the main findings? Dr. Martinelli: Hormonal therapies are associated with an increased risk of venous thromboembolism. Patients with acute deep-vein thrombosis or pulmonary embolism require anticoagulation, but women of childbearing potential require also an adequate contraception, as oral anticoagulants cross the placenta potentially leading to embryopathy or fetal bleeding. This study was aimed to evaluate the safety of hormonal therapies together with anticoagulant therapies in terms of recurrent venous thrombosis and uterine bleeding. We demonstrated for the first time that women who take oral anticoagulants can safely use hormonal therapies, as their risk of recurrent venous thromboembolism or uterine bleeding is not increased. (more…)
Author Interviews, Gender Differences, Mental Health Research, Race/Ethnic Diversity / 07.01.2016

MedicalResearch.com Interview with: Silvia Sara Canetto, Ph.D., Professor Faculty in the Department of Psychology, and Affiliate Faculty in the Center for Women's Studies and Gender Research, Department of Ethnic Studies, and in the Human Development and Family Studies Department Colorado State University  Medical Research: What is the background for this study? Dr. Canetto: In the United States, older men of European descent (so called white men) have significantly higher suicide rates than any other demographic group. For example, their suicide rates are significantly higher than those of older men of African, Latino or Indigenous descent, as well as relative to older women across ethnicities. Behind these facts there is a cultural story, not just individual journeys of psychological pain and despair. Colorado State University’s Silvia Sara Canetto has spent a large portion of her research career seeking to uncover cultural stories of suicide. A professor in the College of Natural Sciences’ Department of Psychology, Canetto adds a new chapter to that story in an article recently published in the journal Men and Masculinities. The article features a critical review of theories and research on suicide among older men. (more…)
Author Interviews, Breast Cancer, Geriatrics, Mammograms / 07.01.2016

MedicalResearch.com Interview with: Professor Charles Hennekens MD Dr.P.H Sir Richard Doll Professor Senior Academic Advisor to the Dean Charles E. Schmidt College of Medicine Florida Atlantic University 777 Glades Road Boca Raton, FL 33431 Medical Research: What is the background for this study? What are the main findings? Prof. Hennekens: Randomized evidence indicates clear benefits of mammography in middle age and, at present, most guidelines recommend regular mammography for women up to age 74.  In collaboration with colleagues at Baylor Medical College and Meharry Medical School we were able to link the Surveillance, Epidemiology, and End Results (SEER) data to the Medicare administrative claims data.  We found that, up to 84 years, screening was more common among whites than blacks and women receiving regular annual screening mammography had lower risks of mortality from breast cancer. (more…)
Author Interviews, JAMA, Stroke / 07.01.2016

MedicalResearch.com Interview with: Michael F. Waters, MD, PhD Department of Neurology Department of Neuroscience McKnight Brain Institute University of Florida College of Medicine Gainesville, Florida Medical Research: What is the background for this study? What are the main findings? Dr. Waters: This study was based on a subgroup of medically managed patients with severe, symptomatic, intracranial, atherosclerotic disease. Historically we know that these patients have a very high rate of additional strokes, and multiple studies have attempted to determine the best management for these patients. In SAMMPRIS, we were able to prove that aggressive medical management was superior to stenting in these patients. However, certain patients in the medically managed group still had a very high rate of repeat strokes, as much as 30% of those with certain risk factors. This study was an attempt to identify those risk factors to determine which patients were at the greatest risk for another stroke. (more…)
Author Interviews, Cancer Research, Heart Disease, Pediatrics / 07.01.2016

MedicalResearch.com Interview with: Daniel A. Mulrooney, MD, MS Cancer Survivorship Jude Children's Research Hospital TN 38105-3678 Medical Research: What is the background for this study? What are the main findings?  Dr. Mulrooney:  This is a cross-sectional analysis performed in the St. Jude Lifetime Cohort Study (SJLIFE), an ongoing study designed to facilitate longitudinal evaluation of health outcomes among adults previously treated for childhood cancer.  Following patients over the life spectrum can be challenging making it difficult to understand the long-term health effects of childhood cancer therapy.  Previous studies have relied on self-report, registry, or death certificate data.  Our study is novel because we clinically evaluated cancer survivors on the St. Jude campus and identified substantial, asymptomatic cardiac disease (cardiomyopathy, coronary artery disease, valvular disease, and conduction/rhythm disorders).
  • Cardiomyopathy was present in 7.4% of survivors and newly identified by screening in 4.7%.
  • Coronary artery disease was present in 3.8% of survivors and newly identified by screening in 2.2%.
  • Valvular disease (regurgitation or stenosis) was present in 28% of survivors and newly identified by screening in 24.8%.
  • Conduction or rhythm abnormalities were present in 4.4% of survivors and newly identified by screening in 1.4%.
The prevalence of these cardiac findings might be expected in an older population but not necessarily in this young adult (median age at time of study 31 years, range: 18-60) population.    (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, OBGYNE, Pharmacology / 07.01.2016

MedicalResearch.com Interview with: Brittany M. Charlton, ScD Instructor Boston Children's Hospital and Harvard Medical School Researcher, Harvard Chan School Department of Epidemiology Boston, MA 02115   Medical Research: What is the background for this study? What are the main findings? Dr. Charlton: Even though oral contraceptives can be over 99% effective with perfect use, almost 10% of women become pregnant within their first year of use. Many more women will stop using oral contraceptives when planning a pregnancy and conceive within just a few months. In both of those examples, a woman may inadvertently expose her offspring during pregnancy to exogenous sex hormones. We conducted a nationwide cohort study in Denmark in order to investigate whether oral contraceptive use shortly before or during pregnancy was associated with an increased risk of major birth defects in the offspring. Our main finding was that there was no increased risk of having a birth defect associated with oral contraceptive exposure. These results were also consistent when we broke down the birth defects into different subgroups, like limb defects. (more…)
Author Interviews, Biomarkers, NEJM, OBGYNE / 06.01.2016

MedicalResearch.com Interview with: Stefan Verlohren, MD, PhD Consultant and Senior Lecturer Maternal-Fetal Medicine Klinik für Geburtsmedizin / Department of Obstetrics Charité Campus Mitte Berlin  Medical Research: What is the background for this study? What are the main findings? Dr. Verlohren: Preeclampsia affects 2–5% of pregnancies worldwide, and is a potentially life threatening syndrome for both mother and child. Treatment options for preeclampsia are very limited, with delivery being the only ‘cure’; however, early detection and monitoring are beneficial for improving maternal and fetal outcomes. Development of preeclampsia is very difficult to predict: its clinical presentation is variable and its signs and symptoms overlap with other conditions. There has been an unmet medical need for improved prediction of preeclampsia, i.e. predicting which women will develop preeclampsia and which will not. Women with suspected preeclampsia are often hospitalized until preeclampsia and related adverse outcomes are ruled out. Others who require hospitalization may be overlooked because their symptoms were nonspecific (e.g. headache). Preeclampsia has been linked with impaired function of the placenta. Placental development is highly dependent on blood vessel formation; before and during preeclampsia, levels of molecules involved in blood vessel inhibition or growth are altered in the maternal bloodstream. In particular, soluble fms-like tyrosine kinase-1 (sFlt-1) (a molecule that inhibits blood vessel growth) is increased and placental growth factor (PlGF) (a molecule that encourages blood vessel growth) is decreased. This study has established that the ratio of these two molecules (sFlt-1:PlGF) can be used to predict whether preeclampsia will develop or not. The sFlt-1:PlGF ratio can be calculated with a blood test (the Elecsys® sFlt-1 immunoassay and Elecsys® PlGF immunoassay). PROGNOSIS has validated the sFlt-1:PlGF ratio cutoff level of 38 for prediction of preeclampsia. For women with suspected preeclampsia, the Elecsys® immunoassay sFlt-1:PlGF ratio of 38 or below has a high negative predictive value to rule out preeclampsia or adverse fetal outcomes in the next week. A Elecsys® immunoassay sFlt-1:PlGF ratio of more than 38 indicates that preeclampsia or fetal adverse outcomes may develop in the next four weeks. In conjunction with other diagnostic and clinical information, the Elecsys® immunoassay sFlt-1:PlGF ratio can be used to guide patient management. (more…)
AHRQ, Author Interviews, Cost of Health Care / 06.01.2016

MedicalResearch.com Interview with: Asako Moriya, Ph.D. Service economist Center for Financing, Access and Cost Trends Agency for Healthcare Research and Quality (AHRQ). Rockville, Maryland  Medical Research: What is the background for this study? Dr. Moriya: While the Affordable Care Act (ACA) has increased insurance coverage and improved access to care among millions of Americans, the law’s potential impacts on the labor market are also important policy considerations. There was speculation that employers would reduce work hours to avoid the ACA employer mandate and also that ACA coverage expansion through Medicaid and the Health Insurance Marketplace would create work disincentives. We wanted to test these speculations using data from a nationally representative sample of approximately 60,000 households interviewed monthly up until June 2015. (more…)
Author Interviews, Cancer Research, Genetic Research, Personalized Medicine, Technology / 06.01.2016

MedicalResearch.com Interview with: Dr Bissan Al-Lazikani Team leader in computational biology The Institute of Cancer Research London Medical Research: What is the background for the canSAR database? What are the main uses for the tool? Dr. Al-Lazikani: Drug discovery is a difficult, time consuming and expensive venture that frequently ends in late stage drug failures - especially in oncology. As with any complex venture, decisions throughout the drug discovery pipeline can be empowered by having access to the right information at the right time. But for drug discovery this means bringing together billions of experimental data from very diverse areas of science spanning genomics, proteomics, chemistry and more. We developed canSAR to help guide our own drug discovery efforts by integrating these huge, diverse data and by analysing the data and deriving hidden links and knowledge from them. This means that we can answer questions in minutes that would have taken weeks using previously available public resources. But, more importantly, canSAR analyses and links these data in a way that allows us  to derive knowledge that was hidden before. For example, one of the main ways canSAR is used is to help select the best druggable targets for drug discovery. Using canSAR we were able to uncover many druggable cancer proteins that were previously overlooked, and we are delighted to see that several of these proteins are now the subjects of drug discovery and development projects both by us and by others. We took the decision to make canSAR publicly and freely available because we believe that cancer drug discovery is a vast challenge that requires openness and data sharing worldwide. It has been embraced by the community is being used by tens of thousands of cancer scientists worldwide, both in academia and industry, to generate hypotheses for experiments and select targets for drug discovery. (more…)
Author Interviews, Depression, OBGYNE, Pharmacology / 06.01.2016

MedicalResearch.com Interview with: Anick Bérard PhD FISPE Research chair FRQ-S on Medications and Pregnancy and Director, Réseau Québécois de recherche sur le médicament (RQRM) and Professor, Research Chair on Medications, Pregnancy and Lactation Faculty of Pharmacy University of Montreal and Director, Research Unit on Medications and Pregnancy Research Center CHU Ste-Justine  Medical Research: What is the background for this study? What are the main findings? Dr. Bérard: Paroxetine (one of the most used antidepressant during pregnancy) has been studied extensively over the past 10-12 years. In 2005, a black box warning was put on the Paxil label to caution against use during pregnancy due to the increased risk of cardiac defects. The ACOG 2010 guidelines also suggested switching to other antidepressants during pregnancy. Over the past decade, many studies, including meta-analyses, were performed on on paroxetine use during pregnancy and the risk of cardiac malformations - but results were sometimes statistically significant or not, although a consistent increased risk was observed. It was thought that these variations could be explained by different study designs, patient populations, and because maternal depression was not always taken into account correctly. Hence, we undertook another meta-analysis (the most recent and updated) to quantify the risk of cardiac defects overall as well as specific cardiac defects associated with paoxetine use during pregnancy and to assess the impact of study designs, maternal depression and patient population on the effect of the risk. We found that women using paroxetine during the first trimester of pregnancy (critical time-window for malformations) were 23% more at risk of having a child with malformations (15 studies combined) - baseline risk of malformation is 3-5% and thus a 23% increased risk is 3.69-6.15% absolute risk; women using paroxetine during the first trimester of pregnancy were 28% more at risk of having a child with cardiac malformations (18 studies combined) - baseline risk of cardiac malformation is 1% and thus a 28% increased risk is 1.28% absolute risk. We found that paroxetine was increasing the risk of many specific cardiac defects as well. Although the estimates varied depending on the comparator group, study design, and malformation detection period, a trend towards increased risk was observed. (more…)
Addiction, Alcohol, Author Interviews / 06.01.2016

MedicalResearch.com Interview with: Kate Chitty PhD Postdoctoral Research Fellow Sydney Medical School School of Medical Sciences Pharmacology The University of Sydney  Medical Research: What is the background for this study? Dr. Chitty: Recreational poisonings, defined here as poisonings that occur as a result of using alcohol and/or illicit or prescribed drugs for recreational purposes or to induce acute rewarding psychoactive effects, represent a significant and potentially lethal form of harm attributed to drug use. There is limited information on hospital admissions for recreational poisonings separately from all hospital admissions for drug harms, despite a surge in overdose occurring at youth events. Identifying trends in recreational poisoning will enable better planning of drug and alcohol services and government initiatives to reduce harms and consequences associated with drug and alcohol use. (more…)
Author Interviews, HIV / 05.01.2016

  MedicalResearch.com Interview with: Dr. Christina Polyak MD MPH Acting Instructor with the University of Washington Clinical research physician at the U.S. Military HIV Research Program Walter Reed Army Institute of Research at WRAIR Bethesda, MD  20817 Medical Research: What is the background for this study? What are the main findings? Dr. Polyak:    Today, 35 million people are infected with HIV, the virus that causes AIDS.   (CTX)  is low-cost and widely utilized broad spectrum antibiotic used to prevent opportunistic infections in patients with HIV.  CTX prophylaxis is recommended by the World Health Organization (WHO) for HIV infected adults in settings with high infectious disease prevalence.   In these settings, the threshold for CTX discontinuation is undefined.  We designed a study to determine whether CTX discontinuation was non-inferior to continued CTX-prophylaxis in decreasing morbidity in adults with evidence of immune reconstitution (CD4 >350 and 18 months on ART).  Our findings show that combined morbidity/mortality was significantly higher in the CTX discontinuation arm (RR=2.27, 95% CI 1.52-3.38;p<0.001), driven by malaria morbidity.   This suggests that CTX discontinuation among ART-treated, immune-reconstituted adults in malaria-endemic regions resulted in increased incidence of malaria but not pneumonia or diarrhea.  These data helped inform and support the 2014 WHO CTX guidelines. (more…)
Author Interviews, Dermatology, Melanoma, Surgical Research / 05.01.2016

MedicalResearch.com Interview with: Jason B. Lee MD Professor , Clinical Vice Chair Department of Dermatology and Cutaneous Biology Director, Jefferson Dermatopathology Center Thomas Jefferson University Philadelphia, Pennsylvania  Medical Research: What is the background for this study? What are the main findings? Dr. Lee: When initially described, Clark et al. suggested that dysplastic nevi were intermediate lesions that lie biologically on a spectrum between benign and malignant. As such, they were to be histologically graded as mild, moderate, and severe (or a combination thereof), with mild presumably closer to benign and severe closer to malignant. In this paradigm, adopted by most dermatologists, these nevi are routinely excised based on histologic grading and margin status. Recent outcomes of follow-up and excision studies of dysplastic nevi suggest that they are over treated as there have been very low rates of melanoma on re-excision. An alternative approach considers dysplastic or eponymously Clark nevi as common acquired nevi, typically in fair skin individuals, and rejects the entire notion that they are intermediate lesions as there exists no formal proof of their intermediate status. This approach omits grading and margin status entirely, providing the clinician an explicit recommendation for excision only for those cases of diagnostic uncertainty. In this study, excision recommendation rate of dysplastic/Clark nevi was determined along with analysis of excision outcomes in a laboratory where non-grading histologic diagnostic approach to these nevi has been adopted. The excision recommendation rate, representing the diagnostic uncertainty rate, was 11.1%. Out of 80% of the cases returned for excision, only 2.0% of the cases were interpreted as melanoma on excision; all were in situ or thin melanomas. This excision rate is much lower than in prior reports, which vary from 22-52%, while still capturing melanomas within this subset of lesions. (more…)
Author Interviews, Pharmacology / 04.01.2016

MedicalResearch.com Interview with: Prof. Daniel F. Klessig Boyce Thompson Institute for Plant Research, Department of Plant Pathology and Plant-Microbe Biology Cornell University, Ithaca, New York  MedicalResearch: What is the background for this study? Prof. Klessig: Acetyl salicylic acid, commonly called aspirin, has been the most widely used drug worldwide for more than a century. Currently, 80 million pounds of aspirin are produced worldwide every year and almost 30 billion tablets are consumed annually in the US alone. Long before German pharmacologist Johann Buchner identified the salicylic acid derivative salicin in 1828 as the ingredient in willow bark that is responsible for its therapeutic effects, different cultures throughout the world were, and many still are, using a variety of plants rich in salicylic acid derivatives, such as willow, wintergreen, and meadowsweet, to treat pain, fever, swelling, and other maladies. Aspirin also is used to reduce the risk of heart attack, stroke, and certain cancers. One might expect that aspirin’s mechanisms of action would be well understood, given its extraordinarily widespread use and the fact that it was first synthesized by the Bayer chemist Felix Hoffmann over 100 years ago. The prevailing view in the biomedical community has been that aspirin works primarily, if not exclusively, by irreversibly inhibiting the enzymatic activities of cyclooxygenases 1 and 2 (COX1 and COX2), thereby disrupting the synthesis of inflammation-inducing prostaglandins. However, this assumption ignores two important facts.
  • First, aspirin is rapidly converted to salicylic acid (SA) in the body. Indeed, almost all aspirin is metabolized to SA within an hour after ingestion.
  • Second, SA and many of its natural plant derivatives are rather poor inhibitors of COX1 and COX2 as compared to aspirin, yet SA and aspirin have nearly the same beneficial pharmacological effects. Thus, there must be additional targets through which aspirin/SA exerts its many effects. Over the past two decades, a number of proteins whose activities are altered by aspirin/SA have been identified; however, their relevance as aspirin/SA targets has been called into question due to the very high, non-physiological levels of aspirin/SA required to alter their activities.
In light of our unexpected discovery that SA mediates its physiological effects in plants via many targets, and given that SA is a key hormone produced by all plants, we hypothesized that there might be multiple targets through which SA acts in animals, regardless of whether it is obtained in low to moderate levels via the diet or in moderate to high doses through herbal-based medicines or aspirin usage. (more…)
Author Interviews, Prostate Cancer, Race/Ethnic Diversity / 04.01.2016

MedicalResearch.com Interview with: Benjamin A. Rybicki, Ph.D Department of Public Health Sciences Henry Ford Health System Detroit, MI  Medical Research: What is the background for this study? What are the main findings? Dr. Rybicki: Inflammation of the prostate gland—prostatitis—is a complex and heterogeneous condition. Two separate meta-analyses have estimated about a 60% increased risk of prostate cancer associated with clinical prostatitis.  Most prostatitis, however, is asymptomatic and not fully captured in prevalence surveys. In fact, over 50% of surgical prostate specimens demonstrate some histological evidence of chronic inflammation, which has been generally shown to decrease risk of prostate cancer. The race of a patient may also be a factor as far as how inflammation influences prostate cancer risk. African American men are at greater risk for prostate cancer and demonstrate higher levels of circulating prostate specific antigen (PSA), which can confound the relationship between inflammation and prostate cancer. In adjusted analyses, African American men with clinical chronic prostatitis had a significant 53% decreased risk of prostate cancer compared with African American men without prostatitis. Clinical prostatitis did not significantly increase prostate cancer risk in white men overall, but it was associated with a significant 3.5-fold increased risk in those who had no evidence of histologic prostatic inflammation. In addition, the investigators found that clinical prostatitis increased prostate cancer risk nearly 3-fold in white men with a low PSA velocity and nearly 2-fold in white men with more frequent PSA testing. PSA level and PSA density did not significantly modify the effect of clinical prostatitis on prostate cancer risk. (more…)
Author Interviews, Heart Disease, JAMA, Stanford, Surgical Research / 04.01.2016

MedicalResearch.com Interview with: Dr. Mary Hawn MD MPH Chair, Department of Surgery Stanford School of Medicine Stanford, California Medical Research: What is the background for this study? What are the main findings? Dr. Hawn: Patients with known coronary artery disease are at higher risk for adverse cardiac events in the peri-operative period.  Revascularization with coronary stents does not appear to mitigate this risk and in fact, may elevate the risk if surgery is in the early post-stent period.  Drug eluting stents pose a particular dilemma as these patients require 12 months of dual anti platelet therapy to prevent stent thrombosis, thus elective surgery is recommended to be delayed during this period.  In contrast, bare metal stents with early epithilialization are not at the same risk for stent thrombosis with anti platelet cessation.   In our retrospective cohort study, however, we observed that stent type was not a major driver of adverse events in the early post-stent period and that underlying cardiac disease and acuity of the surgery explained most of the risk.  We undertook this study to determine the influence of the underlying indication for the stent procedure on surgical outcomes over time following the stent. (more…)
Author Interviews, JAMA, Mental Health Research / 04.01.2016

MedicalResearch.com Interview with: Josephine Mollon MSc Department of Psychosis Studies Institute of Psychiatry, Psychology, and Neuroscience King’s College London London, England  Medical Research: What is the background for this study? What are the main findings? Dr. Mollon: Psychotic symptoms, such as hallucinations and delusions, are core features of psychotic disorders. A significant minority of the general population also reports subclinical psychotic experiences. Evidence suggests that these experiences may lie on a continuum with clinically significant psychotic symptoms. For example, cognitive deficits, which are a hallmark of psychotic disorders, are also seen in people with subclinical psychotic experiences. We used population-based survey data to characterize cognitive functioning in adults with psychotic experiences while adjusting for important sociodemographic characteristics and investigating the effect of age. The 171 (9.7%) adults with psychotic experiences showed significant memory and verbal deficits, but not IQ or processing speed deficits. Only participants 50 years and older with psychotic experiences showed medium to large impairments in general IQ, verbal knowledge, working memory and memory after adjusting for socioeconomic status, cannabis use, and common mental disorders. (more…)
Author Interviews, Beth Israel Deaconess, CT Scanning, JAMA, Neurological Disorders, Stroke / 04.01.2016

MedicalResearch.com Interview with: Sandeep Kumar, MD Assistant Professor of Neurology Harvard Medical School Director, Inpatient Stroke Service Department of Neurology, Stroke Division Beth Israel Deaconess Medical Center Boston, MA 02215 Medical Research: What is the background for this study? What are the main findings? Dr. Kumar: Transient deficits that start suddenly and typically last for a few minutes to a few hours are the hallmark of a transient ischemic attack (TIA) or a minor ischemic stroke. In this single-center observational study, we have reported similar clinical presentation in some patients with intracerebral hemorrhage (ICH) that are difficult to distinguish from cerebral ischemia based only on clinical signs and symptoms. (more…)
Author Interviews, CMAJ, Opiods / 04.01.2016

Medical Research: What is the background for this study? What are the main findings? Response: Surveillance of the harms associated with chronic opioid use is imperative for clinicians and policy-makers to rapidly identify emerging issues related to this class of medications.  However, data regarding opioid-related deaths is difficult to obtain in Canada as it is collected by local coroners and is not widely available to researchers.  We conducted a validation study to evaluate whether regularly collected vital statistics data collected by Statistics Canada can be used to accurately identify opioid-related deaths in Canada. We compared deaths identified from charts abstracted from the Office of the Chief Coroner of Ontario to those identified using several coding algorithms in the Statistics Canada Vital Statistics database.  We found that the optimal algorithm had a sensitivity of 75% and a positive predictive value of 90%. When using this algorithm, the death data obtained from the Vital Statistics database slightly underestimated the number of opioid-related deaths in Ontario, however the trends over time were similar to the data obtained from the coroner’s office. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, Medicare, OBGYNE / 04.01.2016

MedicalResearch.com Interview with: Dr. Sarah Elizabeth Little, MD Obstetrics/Gynecology Department of Obstetrics and Gynecology Brigham and Women's Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Little: This study investigates the variation in cesarean delivery rates across hospital services areas (a geographic unit designed by the Dartmouth Atlas to represent local markets for primarily hospital-based medical services). We looked at whether variation in cesarean delivery rates was related to broader variation in overall medical spending and utilization in that area, which we measured with Medicare spending and hospital use at the end-of-life. We found that an area’s cesarean delivery rate was correlated with these other measures; in other words, the hospital services areas that are doing the most cesarean deliveries are the same ones that are spending more and doing more to non-obstetric patients as well. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Surgical Research, Testosterone / 04.01.2016

MedicalResearch.com Interview with: Quoc-Dien Trinh MD Assistant Professor, Harvard Medical School Brigham and Williams Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. Trinh: Among elderly Medicare beneficiaries with metastatic prostate cancer, surgical castration is associated with lower risks of any fractures, peripheral arterial disease, and cardiac-related complications compared to medical castration using GnRH agonists. (more…)
Author Interviews, Duke, Heart Disease, Kidney Disease / 03.01.2016

MedicalResearch.com Interview with: Renato D. Lopes MD, MHS, PhD Duke University Medical Center Duke Clinical Research Institute Durham, NC 27705   John P. Vavalle, MD, MHS Assistant Professor of Medicine Division of Cardiology UNC Center for Heart & Vascular Care Medical Research: What is the background for this study? What are the main findings?  Dr. Lopes: Patients with varying degrees of underlying renal failure who presented for primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI) were studied as part of the APEX-AMI trial. Baseline renal dysfunction portends a worse prognosis in patients undergoing PCI. However, the association between clinical outcomes and angiographic results with baseline renal function in this population of STEMI patients is not clearly defined.  We report the results of a trial population with a full spectrum of underlying renal function (normal to dialysis dependent) and developed a prediction model for the development of acute kidney injury following primary percutaneous coronary intervention. In summary, patients with worse underlying renal function had worse angiographic outcomes, higher mortality, and were less likely to be treated with evidence-based medications.  The rate of acute kidney injury (AKI) after PCI appears to increase with worsening underlying renal function, except for those with Class IV chronic kidney disease where the rate of AKI was lowest.  Our novel prediction model for the development of AKI found that the strongest predictors of AKI were age and presenting in Killip Class III or IV. (more…)
Author Interviews, OBGYNE, Surgical Research / 03.01.2016

MedicalResearch.com Interview with: Gabriele Saccone, MD Department of Neuroscience Reproductive Sciences and Dentistry School of Medicine University of Naples Federico II Naples, Italy Vincenzo Berghella, MD Department of Obstetrics and Gynecology Division of Maternal-Fetal Medicine Thomas Jefferson University Philadelphia, PA 19107, USA Medical Research: What is the background for this study? What are the main findings? Dr Saccone: Preterm birth (PTB) is the number one cause of perinatal mortality in many countries, including the US. The annual societal economic burden associated with Preterm birth in the US was at least $26.2 billion in 2006, or about $51,600 per infant born preterm. Defining risk factors for prediction of PTB is an important goal for several reasons.
  • First, identifying women at risk allows initiation of risk-specific treatment.
  • Second, it may define a population useful for studying particular interventions.
  • Finally, it may provide important insights into mechanisms leading to Preterm birth.Prior surgery on the cervix, such as cone biopsy and LEEP procedures, is associated with an increased risk of spontaneous PTB. History of uterine evacuation for abortion, by either induced termination of pregnancy (I-TOP) or treatment of spontaneous abortion (SAB) by suction dilation and curettage (D&C) or by dilation and evacuation (D&E), which may involve mechanical and/or osmotic dilatation of the cervix, has been associated with an increased risk of PTB in some studies, but not in others. Our systematic review and meta-analysis pooled data from 36 studies including 1,047,683 women with prior abortion. We found that history of surgical abortion is an independent risk factor for Preterm birth and also other obstetric complications including low birth weight and small for gestational age, while prior medical abortion with first-trimester mifepristone or mid-trimester misoprostol was not associated with an increased risk of PTB. The biological plausibility to explain our findings is not completely clear. However, three main hypotheses can be made.
  • The increased risk of Preterm birth could result from the overt or covert infection following surgically uterine evacuation,
  • as well as from mechanical trauma to the cervix leading to increased risk of cervical insufficiency.
  • Moreover, surgical procedures including curettage during D&E may result in scar tissue that may increase the probability of faulty placental implantation.
(more…)
Author Interviews, Breast Cancer, Immunotherapy, PLoS / 02.01.2016

MedicalResearch.com Interview with: David Gallego Ortega, PhD Group Leader, Tumour Development Group Cancer Division Garvan Institute of Medical Research Conjoint Lecturer, St Vincent’s Clinical School, Faculty of Medicine, UNSW, Australia National Breast Cancer Foundation and Cure Cancer Foundation Australia Fellow  Medical Research: What is the background for this study? What are the main findings? Dr. Ortega: We have identified a protein that 'goes rogue’ in breast cancer. The protein, called Elf5, ‘tricks' the immune system producing inflammation so that the immune cells now help the breast cancer cells to spread throughout the body. Cancer spread, or metastasis, is the ultimate cause of death of breast cancer patients, so we are very excited about our discovery because it opens the door to explore anti-inflammatory drugs that can be combined with existing therapies. We have found that luminal breast cancer patients that present high levels of Elf5 progress earlier in their disease. The Luminal subtype is the most common type of breast cancer, so these therapies will potentially benefit to 2/3 of all breast cancer patients. (more…)
Author Interviews, BMJ, Urinary Tract Infections / 02.01.2016

MedicalResearch.com Interview with: Ildikó Gágyor MD Senior researcher in primary care Department of General Practice University Medical Center Göttingen Göttingen, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Gágyor: Uncomplicated urinary tract infection is a common problem for women. Affected patients are usually treated with antibiotics to combat both unpleasant symptoms and to combat infection. However, prescription of antibiotics for a self-limiting condition, contributes to increased resistance rates posing a serious long-term threat to public health. In a double blind randomised controlled trial we examined whether symptomatic treatment of uncomplicated urinary tract infection with ibuprofen reduces the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications. In all, 494 women were randomly assigned to receive: either ibuprofen for three days and antibiotics only if symptoms are persistent; or antibiotic treatment with fosfomycin. Results showed that antibiotic use could be reduced significantly: of the 248 women in the ibuprofen group two thirds recovered without antibiotics and one third received antibiotics subsequently. Women in the ibuprofen group had a higher symptom burden but in both groups, symptoms decreased within the first week (Figure 1). Six cases of pyelonephritis occurred, one in the fosfomycin group, five in the ibuprofen group. (more…)