AACR, Author Interviews, Cancer Research, Prostate Cancer / 04.09.2016
Dr. Alejandro Azofeifa[/caption]
Alejandro Azofeifa, DDS, MSc, MPH
Epidemiologist at the Substance Abuse and Mental Health Services Administration
MedicalResearch.com: What is the background for this study? What are the main findings?
Response:
-In the United States, marijuana is the most commonly used illicit drug. Because of certain state-level policies that have legalized marijuana for medical or recreational use, population-based data on marijuana use and other related indicators are needed to help monitor behavioral health changes in the United States.
- This SAMHSA surveillance report represents an overview of national estimates for marijuana use and other related indicators among the U.S. noninstitutionalized civilian population aged ≥12 years using 2002–2014 National Survey on Drug Use and Health data. The report includes at least seven important findings. Find more detailed information atSAMHSA surveillance report. Since 2002, marijuana use in the United States has increased among persons aged ≥18 years, but not among those aged 12–17 years. A decrease in the perception of great risk from smoking marijuana combined with increases in the perception of availability (i.e., fairly easy or very easy to obtain marijuana) and fewer punitive legal penalties (e.g., no penalty) for the possession of marijuana for personal use might play a role in increased use among adults.
Dr. Christian McNeely[/caption]
Christian A. McNeely, M.D.
Resident Physician - Internal Medicine
Barnes-Jewish Hospital
Washington University Medical Center
MedicalResearch.com: What is the background for this study?
Response: Prior research has demonstrated that readmission in the first 30 days after percutaneous coronary intervention (PCI) is common, reported around one in six or seven Medicare beneficiaries, and that many are potentially preventable. Since 2000, there have been significant changes in the management of coronary artery disease and the use of PCI. Additionally, in the last decade, readmission rates have become a major focus of research, quality improvement and a public health issue, with multiple resulting national initiatives/programs which may be affecting care. Therefore, in this study, we sought to examine contemporary trends in readmission characteristics and associated outcomes of patients who underwent PCI using the Medicare database from 2000-2012.
Dr. Adam Alani[/caption]
Adam G Alani, PhD
Associate Professor of Pharmaceutical Sciences
Department of Pharmaceutical Sciences
College of Pharmacy
Oregon State University-Oregon Health & Science University
Affiliate Assistant Professor
Department of Biomedical Engineering
School of Medicine at Oregon Health & Science University
Oregon State University-Portland Campus at OHSU
Portland Oregon
MedicalResearch.com: What is the background for this study?
Response: Current chemotherapeutic regimens while effective are difficult for patients and affect their quality of life. Our research tackles this issue by designing a nanotherapy that can deliver multiple chemotherapeutic agents by targeting the entire tumor microenvironment and not just the cancer cells and by reducing drug resistance. This, then is intended to simplify the treatment regimen, reduce drug related side effects and extends the life of the drugs by preventing resistance should the patient need it in the future. Thus, the ultimate underlying goal is to improve the patient’s quality of life by not just maximizing the drug’s efficacy but also trying to decrease its impact on the overall lifestyle of the individual.
Qing Shen[/caption]
Qing Shen, PhD student
Department of Medical Epidemiology and Biostatistics
Karolinska Institutet
MedicalResearch.com: What is the background for this study?
Response: Injury, either iatrogenic (for example, complications from medical procedures and drug treatment) or non-iatrogenic (for instance, suicidal behavior and accidents), is one of the leading causes of non-cancer mortality for patients diagnosed with cancer. Iatrogenic injuries are common in those with cancer and have been shown to increase mortality in some cancer patients. Increased risks of suicide and accidental death after diagnosis have been reported, and the diagnostic process of cancer has been recognized highly stressful. It is, however, unknown whether the risk of injuries is also increased during the time period before receiving the diagnosis. Actually confirming a diagnosis can often be difficult due to patients sometimes concealing information. This is why Motivational Interviewing is important. Anyway, we analysed the risks of injuries during the weeks before and after diagnosis using a nationwide study sample in Sweden.
Dr. Matt Maciejewski[/caption]
Matthew Leonard Maciejewski, PhD
Professor in the Division of General Internal Medicine
Department of Medicine
Duke University School of Medicine
Research Career Scientist and Director of the Health Economics and Policy Unit in the Center for Health Services Research in Primary Care
Durham VA Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: No study based on a US cohort undergoing current procedures has examined weight change comparing surgical patients and nonsurgical patients for as long as we have. This is the first study to report 10-year outcomes on gastric bypass patients and compare them to matched patients who did not get surgery. At 1 year, gastric bypass patients lost 31% of their baseline weight compared controls who only lost 1.1% of their baseline weight. At 10 years, gastric bypass had lost 28% of their baseline weight.
We also compared weight loss at 4 years for Veterans who received the 3 most common procedures (gastric bypass, sleeve gastrectomy, and adjustable gastric banding). At 4 years, patients undergoing gastric bypass lost more weight than patients undergoing sleeve gastrectomy or gastric banding. Given that few high quality studies have examined sleeve gastrectomy to 4 years, the 4-year sleeve outcomes contribute to filling this important evidence gap as the sleeve gastrectomy is now the most commonly performed bariatric procedure worldwide.
Dr. Marlous Hall[/caption]
Dr Marlous Hall PhD
Senior Epidemiologist
Leeds Institute of Cardiovascular and Metabolic Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It is well known that death rates following heart attacks have fallen considerably over recent decades. Many studies have looked at the effect of medications and invasive strategies, and their association with better clinical outcomes is clear.
However, a big question remains: why have heart attack deaths fallen? Is it due to increased use of medications and treatment, is the risk of patients simply lower over time due to things like earlier diagnosis or are patients generally healthier with fewer comorbidities such as diabetes? Answering this is not straightforward - as gold standard studies like clinical trials on historic data cannot be done.
An alternative approach is to look for patterns in data observed from routine care to look at all these factors together. This study used a large and rich dataset covering heart attack care in the UK (Myocardial Ischaemia National Audit Project (MINAP)). This dataset was linked to outcome data from the Office for National Statistics to allow us to look at all the different factors that could influence the change in mortality over time.
Dr. N. Nick Knezevic[/caption]
N. Nick Knezevic, MD, PhD
Vice Chair for Research and Education
Associate Professor of Anesthesiology and Surgery at University of Illinois
Advocate Illinois Masonic Medical Center
Department of Anesthesiology
Chicago, IL 60657
MedicalResearch.com: What is the background for this study?
Response: Even though serious efforts have been undertaken by different medical societies to reduce opioid use for treating chronic non-cancer pain, still many Americans seek pain relief through opioid consumption. The purpose of this study was to accurately assess compliance of chronic opioid consuming patients in an outpatient setting and evaluate if utilizing repeated urine drug testing could improve compliance.
Dr. John Batsis[/caption]
John A. Batsis, MD, FACP, AGSF
Associate Professor of Medicine and The Dartmouth Institute
Geisel School of Medicine at Dartmouth
Section of General Internal Medicine - 3M
Dartmouth-Hitchcock Medical Center
Lebanon, NH
MedicalResearch.com: What is the background for this study?
Response: In 2011, the Centers for Medicare and Medicaid implemented a regulatory coverage benefit to cover 22 brief, targeted 15-minute counseling visits by clinicians over the course of a 12-month period for Medicare beneficiaries with a body mass index exceeding 30kg/m2. This was an important policy determination in tackling the obesity epidemic in the United States. An emphasis on the importance of counseling, or intensive behavioral therapy, in a primary care setting set the foundation for this benefit.
Yet, it was unclear how and if this benefit (which would be free of charge without a copay or deductible for beneficiaries) was being implemented in clinical care. We therefore identified fee-for-service Medicare claims for the years 2012 and 2013 to determine whether the G0477 code (Medicare Obesity benefit code) was billed. We additionally explored the rate of uptake of the Medicare benefit in relation to the prevalence of obesity using the 2012 Behavior Risk Factor Surveillance System data.
Prof. Paul Morgan[/caption]
Professor B. Paul Morgan
Director, Systems Immunity Research Institute
Institute of Infection and Immunity
School of Medicine
Cardiff University
MedicalResearch.com: What is the background for this study?
Response: Inflammation is a normal response of the body to infection or injury; however, it is well known that inflammation also has a dark side and when it escapes normal controls can cause disease. Some illnesses, like rheumatoid arthritis, have been known for many years to be caused by rogue inflammation and most of the drugs used to treat work by suppressing the inflammation (anti-inflammatories). More recently, it has become clear that inflammation is behind many other diseases that were previously thought of as diseases of ageing caused by wear and tear and lifestyle - these include heart disease and some brain diseases, notably Alzheimer's disease the commonest cause of dementia. Evidence that inflammation is one of the drivers of disease has come from many sources, including some where it was noticed that people on long-term anti-inflammatory drugs for other reasons appeared to be protected from developing Alzheimer's disease.
A problem is that Alzheimer's disease, despite the name, is not a single disease but rather a group of conditions with similar symptoms, and inflammation is likely to be a cause in only some of the patients; further, most of the inflammation might be occurring very early in the disease, even before symptoms are obvious. So, there is an urgent need for a simple test or set of tests that can be used in individuals with the very earliest hints of Alzheimer's disease - mild memory loss - that will pick out those who have brain inflammation and are most likely to develop Alzheimer's disease. It might then be possible to treat this select group with anti-inflammatory drugs that will reduce brain inflammation and slow or stop progression of the disease.
Prof. Roger Nitsch[/caption]
Roger M. Nitsch, MD
Professor and Director
Institute for Regenerative Medicine · IREM
University of Zurich Campus Schlieren
Switzerland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The main finding is that treatment with aducanumab resulted in an unprecedented reduction of brain amyloid plaques in patients with Alzheimer's disease. The removal of amyloid from patients brains were both dose- and time-dependent. We also observed initial hints for stabilized brain functions in patients receiving aducanumab. In contrast, patients in the placebo group continued to declined as usual in this stage of Alzheimer's disease.
The main safety finding in 22% of all treated patients was ARIA - an Amyloid-Related Imaging Abnormality - suggestive of fluid shifts in the brains. In most cases, ARIA occurred in the absence of clinical signs and resolved spontaneously. In one third of the ARIA cases, patients experienced transient headaches. None of the patients had to hospitalized because of ARIA.
Dr. Jim Lambert[/caption]
James R. Lambert, PhD.
Department of Pathology
University of Colorado Anschutz Medical Campus
Aurora, CO
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Our laboratory has been investigating a novel small molecule drug, AMPI-109, as a targeted therapeutic agent for triple-negative breast cancer (TNBC). We demonstrated that AMPI-109 is a potent inducer of apoptosis in TNBC cells and that its cell killing activities are largely specific for the TNBC subtype of breast cancer. Through our efforts to identify the molecular mechanism of AMPI-109 action in TNBC cells we identified the oncogenic phosphatase, PRL-3 as a mediator of AMPI-109 action and as a potential direct target of the drug in TNBC cells.
Our studies have defined PRL-3 as an oncogenic driver of triple-negative breast cancer as exemplified by knocking down PRL-3 using shRNAs, or treating TNBC cells with AMPI-109, ultimately results in TNBC cell apoptosis. We thus became interested in elucidating the mechanisms whereby loss of PRL-3 expression, or function, results in cell death. During the course of these investigations we noted that at early times following PRL-3 knock down TNBC cells undergo a period of cell senescence followed by induction of apoptosis. This dynamic reprogramming of triple-negative breast cancer cell fate was determined to be mediated through signaling events mediated by an autocrine tumor necrosis factor receptor 1 (TNF-R1) feedback loop. TNF-R1, which binds the pro-inflammatory cytokine TNFα, is a widely studied mediator of both cell survival and cell death yet the precise molecular mechanism controlling this toggling effect of TNF-R1 on TNBC cells remained largely unknown.
In this report, we demonstrate that PRL-3 is transcriptionally regulated by the pro-inflammatory NF-ĸB pathway in triple-negative breast cancer cells, and that PRL-3 knock down elicits an autocrine TNF-R1 feedback loop that results in cell cycle arrest and senescence as a pre-determinant to engaging apoptosis of TNBC cells. These studies reveal a previously undescribed mechanism for how PRL-3 influences TNBC cell growth and further increase our understanding of the role of TNFα signaling in the disease.
Dr. Jim Hu[/caption]
Jim C. Hu, MD
Ronald Lynch Professor of Urologic Oncology
Weill Cornell Medicine
New York, NY 10065
MedicalResearch.com: What is the background for this study?
Response: Initial results from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a large-scale randomized controlled trial of prostate cancer screening in the United States, radically changed the landscape of prostate cancer screening insofar as it led the United States Preventative Services Task Force (USPSTF) to recommend against routine screening with prostate-specific antigen (PSA). Though many subsequent studies have continued to investigate the role of PSA in screening, there is a paucity of data examining the use of digital rectal examination (DRE) for screening in the PSA era. Indeed, the USPSTF recommendation did not explicitly address DRE, calling for further research to evaluate the role of periodic DRE in prostate cancer screening. Likewise, while recent guidelines from the National Comprehensive Cancer Network (NCCN) recommend use of PSA in all men who elect screening, the role of digital rectal examination is equivocal.
We sought to evaluate the value of digital rectal examination and PSA for detection of clinically significant prostate cancer and prostate cancer-specific (PCSM) and overall mortality in a secondary analysis of the PLCO.
Prof. Francine Ducharme[/caption]
Francine M. Ducharme, MD, FRCPC
Professor, Departments of Paediatrics and Social and Preventive Medicine
University of Montreal
Associate Director of Clinical Research and Knowledge Transfer, Research Centre, CHU Ste-Justine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The management of asthma attacks in preschoolers has been the subject of much recent debate. The results of a study published in 2009 had shaken the pediatric world. The study reported that preschool children with viral-triggered flare-ups did not respond to standard treatment and, suggesting that this was due to their young age. Such finding was particularly worrisome as the majority of asthma-related emergency room visits and hospitalizations involve preschool children.
We conducted this large cohort study in which children aged 1 to 17 years with a moderate or severe asthma attack were treated using the established evidence-based therapy adjusted to the severity of exacerbation assessed by the Pediatric Respiratory Assessment Measure (PRAM), administered rapidly. We explored the determinants of the failure of emergency therapy. Age was not a factor. Instead, in addition to attack severity and symptoms between attacks, it was rather the presence of respiratory viral infection or fever triggering the attack that was more often associated with treatment failure, i.e., higher hospitalization rates, more returns to the emergency room, and reduced speed of recovery over the 10 days after discharge. Viral detection occurred more frequently in preschoolers (67%) than in older children (46%) with asthma.
Nevertheless, the results confirm the overall effectiveness of standard treatment, adjusted to the severity of the attack and administered early, in the vast majority of children, regardless of age and viral detection. Indeed, although a failure rate of nearly 40% was expected in this group of children with moderate to severe attack, only 17% of the participants did not respond to standard treatment. This rate was significantly higher (19%) in children with viral infection compared to uninfected children (13%).
MedicalResearch.com Interview with: MS WEI DU, First author Third Year Medical Student DUKE-NUS Medical School and DR BAN LEONG SNG, Senior Author Senior Consultant...
Dr. Ben Wheeler[/caption]
Dr. Ben Wheeler MB ChB(Otago) DCH CCE FRACP
Senior Lecturer / Paediatrician / Paediatric Endocrinologist
Department of Women’s & Children’s Health : Te Tari Hauora Wāhine me te Tamariki
Dunedin School of Medicine
MedicalResearch.com: What is the background for this study?
Response: Vitamin D is essential for calcium and bone metabolism. It is unique among vitamins in that it is mainly derived from synthesis in the
skin after exposure to UV-B radiation. In the absence of fortification, few foods are rich in vitamin D, including human milk, which contains very low amounts. Breastfeeding infants in higher latitude countries such as New Zealand, much of North America and
Central/Northern Europe are at risk of vitamin D deficiency.
The most profound manifestation of vitamin D deficiency in growing children is rickets, characterized by bone deformities, impaired growth, biochemical abnormalities, and depending on the severity of deficiency, seizures. Studies also identified a number of common factors that potentially affect the risk of rickets, including darker pigmented skin, maternal vitamin D deficiency during pregnancy, season of birth, and age.
A potential alternative strategy to improve the vitamin D status of breastfed infants is high-dose vitamin D supplementation to pregnant and lactating women. This would be attractive from a compliance perspective, promote exclusive breastfeeding, and treat both the mother and her infant.
Thus, the primary aim of this randomized, placebo-controlled study was to determine the effect of two different monthly doses of maternal vitamin D supplementation on the vitamin D status of non–vitamin D–supplemented breastfed infants and their mothers.
Dr. Karla Evans[/caption]
Karla K. Evans, Ph.D.
Lecturer, Department of Psychology
The University of York
Heslington, York UK
MedicalResearch.com: What is the background for this study?
Response: This research started after initially talking to radiologists and pathologists about how they search a radiograph or micrograph for abnormalities. They talked about being able to tell at the first glance if the image had something bad about it. Jokingly, they talked about “having the force” to see the bad. We wanted to know whether this hunch after the brief initial viewing was real and to systematically test it. We collected radiographic and micrographic images, half of them that had signs of cancer in them and half of them that didn't, and we briefly presented them (250 millisecond to 2000 milliseconds) to radiologists or pathologistsrespectively. They simply had to report whether they would recall the patient or not and try localize on the outline the location of the abnormality. We first reported these finding in the following paper.
Evans et al. (2013) The Gist of the Abnormal: Above chance medical decision making in the blink of an eye. Psychonomic Bulletin & Review (DOI) 10.3758/s13423-013-0459-3
In addition to finding that radiologists and pathologists can indeed detect subtle cancers in a quarter of a second we also found that they did not know where it was in the image leading us to conclude that the signal that they were picking up must be a global signal (i.e. the global image statistic or the texture of the breast as a whole) rather than the result of a local saliency. This led me to start further exploring this signal in order to characterize it when I moved to University or York, UK to establish my own lab.
Dr. Aaron Kesselheim[/caption]
Aaron S. Kesselheim, M.D., J.D., M.P.H.
Associate Professor of Medicine at Harvard Medical School
Director, Program On Regulation, Therapeutics, And Law (PORTAL)
Division of Pharmacoepidemiology and Pharmacoeconomics
Brigham and Women's Hospital
Boston MA 02120
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It has been previously reported that the number of new cardiovascular drugs approved by the U.S. Food and Drug Administration (FDA) has declined in recent years. So we sought to empirically assess trends in the development of new cardiovascular therapeutics.