MedicalResearch.com Interview with:
David G. Kent, Ph.D
From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of Cambridge
Medical Research: What is the background for this study? What are the main findings?
Dr. Kent: Cancers are the result of the sequential acquisition of errors in the genetic code. Most studies have focused on the sum of these mutations (e.g., A+B+C = cancer) but no study in patients has asked the question of whether or not the order of genetic mutations impacts the disease (e.g., does A to AB equal B to BA). We studied patients with chronic blood disorders (known as myeloproliferative neoplasms, or MPNs) that are precursors to cancer to access the earliest stages of tumour development and studied whether or not the order of mutation acquisition impacted disease. We studied patients with mutations in two genes (JAK2 and TET2) and showed that the order of acquisition of these mutations impacted timing of clinical presentation, disease subtype, frequency of thrombotic events, and differed in their response to targeted therapy in the lab. (more…)
MedicalResearch.com Interview with:
Dr. Martin S. Schlumberger MD
Department of Nuclear Medicine and Endocrine Oncology
Centre de Référence Tumeurs Réfractaires de la Thyroïde
Institut Gustave Roussy and University Paris-Sud
Villejuif, France
Medical Research: What is the background for this study? What are the main findings?
Dr. Schlumberger: Patients with advanced refractory thyroid cancer is rare (4-5 patients/million population) but portends a poor prognosis with a median overall survival of 3-5 years from the diagnosis of metastases.
Before the availability of kinase inhibitors there was no effective treatment, and for this reason placebo was used as control in SELECT trial. This trial showed an improvement of PFS lenvatinib vs placebo (hazard ratio: 0.21; 99% CI: 0.14–0.31, P<0.001; median PFS: 18.3 vs 3.6 months, respectively) and objective response rate of 65% with some complete responses. Time to response was short (2 months).
Similar benefits were observed in naive patients and in patients who had been treated with another tyrosine kinase inhibitor, demonstrating the absence of cross resistance.
Toxicity was significant and could be controlled with dose reduction and symptomatic treatment.
Medical Research: What should clinicians and patients take away from your report?(more…)
MedicalResearch.com Interview with:
Omar A. Ibrahimi, M.D., Ph.D
Connecticut Skin Institute
Founding Medical Director
Stamford, CT 06905
www.ctskindoc.comMedical Research: What is the background for this study? What are the main findings?
Dr. Ibrahimi: The delivery of healthcare in a efficient and cost effective fashion is one of the largest themes in medicine today. Malpractice lawsuits have steadily increased with the cost of healthcare delivery. Mohs surgery involves the surgical removal, the tissue analysis and the reconstruction of a skin cancer all in a single visit that bundles multiple procedures in a cost effective manner that is proposed to be the gold standard for treating certain skin cancers.
Information regarding malpractice involving Mohs surgery is lacking. The only previous study that has been done was a survey of Mohs surgeons looking at how many had been involved in lawsuits and the reasons for being involved. Our study examined a legal database to identify all the lawsuits involving Mohs surgery and skin cancer. We were surprised to find that the majority of lawsuits involved non-Mohs surgeons as the primary defendant, mostly due to a delay of or failure in diagnosis, cosmetic outcome issues, lack of informed consent, and a delay of or failure in referral to a Mohs surgeon.(more…)
MedicalResearch.com Interview with:
Christopher Michael Petrilli MDDivision of General Internal Medicine
The Department of Medicine
University of Michigan, Ann Arbor, Michigan
Medical Research: What is the background for this study? What are the main findings?
Dr. Petrilli: Our team took note of the broad spectrum of physician attire that was worn in health care settings. We found a lack of specific guidance with regards to “appropriate” physician attire. Then we began to find anecdotal evidence that physician attire may be an important early determinant of patient confidence, trust and satisfaction. Studies have shown that patients are more compliant with their medications and treatment regimens when they perceive their doctors as being competent, supportive and respectful. Therefore, given the increasingly rushed patient–physician encounter, the ability to gain a patient’s trust and confidence are highly desirable. We hypothesized that if physician attire matched patients’ preferences and expectations, it would improve the overall patient experience.
Our findings supported our hypothesis. In general, we found that people prefer their physicians dress on the formal side -- and definitely not in casual wear. Doctors of either gender in suits, or a white coat, are more likely to inspire trust and confidence. But fashion takes a back seat when it comes to emergency, surgical or critical care, where data show clothes don't matter as much -- and patients may even prefer to see doctors in scrubs. In general, Europeans and Asians of any age, and Americans over age 50, trusted a formally dressed doctor more, while Americans in Generation X and Y tended to accept less-dressy physicians more willingly.
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MedicalResearch.com Interview with:
Alejandra Valenzuela-Iglesias
Ph.D. candidate
Department of Molecular Biology
University of Sonora Hermosillo, Sonora
MedicalResearch: What is the background for this study? What are the main findings?
Response: Breast cancer is one of the leading causes of cancer death in women all around the world. In recent years, there has been great interest in creating new therapies that will help to prevent or stop metastasis, but the therapies developed up until today are not completely effective. Metastasis is the main cause of death for a cancer patient because it implies that tumor cells have detached from the primary tumor and have colonized in one or more vital organs or tissues in the organism. For this to occur, the invasive tumor cells form actin-driven membrane protrusions called invadopodia. These protrusions possess proteolytic activity to degrade the basal membrane and extracellular matrix, which facilitates metastatic cancer cells to enter the bloodstream and spread to distant organs in the body. It has been shown that any dysregulation in the actin cytoskeleton leads to impaired invadopodia formation.
Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas.
Our study was a collaboration between Albert Einstein College of Medicine, University of Pittsburgh, and University of Sonora, lead by Dr. Jose Javier Bravo-Cordero and published in the European Journal of Cell Biology. We showed for the first time the role of profilin1 in invadopodia formation and function in human breast cancer cells MDA-MB-231. By using cell imaging techniques we unveiled the dynamic of the profilin1-depleted cells, finding that profilin1 can act as a negative regulator of breast cancer cell invasion, acting as a break in invadopodia turnover, by modulating the molecules involved in invadopodia maturation. The removal of profilin1 expression accelerates invadopodia maturation rate, explaining the invasive phenotype previously reported for this type of cells.
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MedicalResearch.com Interview with:
James J. DiNicolantonio, PharmD
Associate Editor BMJ Open Heart
Cardiovascular Research Scientist
Saint Luke's Mid America Heart Institute
Medical Research: What is the background for this study? What are the main findings
Response: There were 6 randomized controlled dietary trials performed before the government dietary fat recommendations were released. When we performed a systematic review and meta-analysis of the available trials at this time, there was no significant difference in all-cause mortality or cardiovascular heart disease mortality. In essence, there was no support from randomized controlled trials at the time to support a reduction in fat and saturated fat (and there still isn't from recent meta-analysis including newer trials).
The reductions in mean serum cholesterol levels were significantly higher in the intervention groups but this did not result in significant differences in cardiovascular heart disease or all-cause mortality. (more…)
MedicalResearch.com Interview with: Dr. Dixie-Lee Esseltine MD, FRCPC
Vice President, Oncology Clinical Research
Takeda.
MedicalResearch: What is Ixazomib?Dr. Dixie-Lee Esseltine: Ixazomib is an investigational, oral, once-weekly proteasome inhibitor (PI) that is being investigated in multiple Phase 3 trials in multiple myeloma (MM) and systemic light-chain (AL) amyloidosis. It is the first oral proteasome inhibitor to enter Phase 3 clinical trials.
Proteasome inhibition is a mechanism underpinning an established standard of care in the treatment of multiple myeloma. However, the current biweekly parenteral administration of proteasome inhibitors may pose challenges to patients. The ability to demonstrate that an oral, once-weekly PI can extend PFS would be a remarkably important finding in the effort to address these challenges. Early studies suggest ixazomib, has activity in MM patients, both as a single agent in relapsed patients and in combination in frontline patients.
Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. It was granted Breakthrough Therapy Designation for AL amyloidosis in the U.S. in 2014.
MedicalResearch: What is the design for this study? Dr. Dixie-Lee Esseltine: The TOURMALINE MM-1 study (C16010) is a phase 3, randomized, double-blind study comparing ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Patients were randomized to receive ixazomib 4.0mg days 1,8 and 15 or placebo with lenalidomide 25mg days 1-21 and dexamethasone 40mg days 1,8,15 and 22. Treatment was given every 28 days until disease progression or unacceptable toxicity. Evaluation was based on the International Myeloma Working Group (IMWG) Uniform Response Criteria.
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MedicalResearch.com Interview with:Wolfgang Sadee, Dr.rer.nat.
Felts Mercer Professor of Medicine and Chair, Pharmacology Director
and Elizabeth S Barrie, PhD
Center for Pharmacogenomics
The Ohio State University Columbus OH
MedicalResearch: What is the background for this study? What are the main findings?Dr. Sadee and Dr. Barrie: We have determined that two frequent genetic variants can interact in a way that lowers the carrier’s risk for a heart attack. These genetic variants are single nucleotide polymorphisms (SNPs) - single base changes in the DNA sequence - of the dopamine-beta hydroxylase gene (DBH), which converts dopamine to norepinephrine. Both act as hormones in the periphery and as neurotransmitters vital to the brain's activity central nervous system. Numerous studies had tested genetic variants in DBH for effects on brain functions. In contrast to expectations, however, our work demonstrates that our two genetic variants lower DBH activity primarily in the periphery, in tissues with sympathetic innervation mediated by norepinephrine, such as the heart, lung, and liver. As a result, we searched for genetic influence on risk of various diseases of the cardiovascular system and the lung, metabolic disorders, and more. Each of the two DBH variants alone was associated with a number of disease states; however, when considering both variants in combination, a strong protective effect on the risk for heart attacks was discovered in several clinical trials. Such combined effects arising from interactions between two genetic variants may be more common than currently realized, possibly providing a path towards effective biomarker panels for personalized medicine. (more…)
MedicalResearch.com Interview with:
Dr. Xiang (Shawn) Zhang PhD
Assistant Professor
Department of Molecular and Cellular Biology
Lester and Sue Smith Breast Center
Baylor College of Medicine Houston, Texas
Medical Research: What is the background for this study? What are the main findings?
Response: Bone metastases present a major clinical problem for oncologists. They are very painful and unpleasant due to the ability of metastatic cells to dissolve bones, and if they spread to the spine or vertebrate bone they the spinal cord compression could cause paralysis. There is a gap in our knowledge about bone metastasis in breast cancer. We know a lot about when they are fully established and already dissolving the bone, but little about what happens early on, right after the cancer cells get there but before they start the bone-dissolving process.
In the study, we revealed that in the early stages, when there are only a few cancer cells, these cells tend to locate themselves in a microenvironment that is enriched in bone making cells called osteoblasts whose normal job is to help make new bones. The cancer cells appear to be surrounded by these bone-making cells before they acquire the ability to dissolve bones.
We also uncovered the pathway that gets activated when the cancer cells lodge into the bone-making cells, and helps them progress to more malignant metastases. The action is mediated by a class of proteins that helps bind the cancer cells to the bone tissue called heterotypic adherens junctions (hAJs) involving the adherens proteins E-cadherin (cancer-derived) and N-cadherin (bone-promoting). This then activates the mTOR pathway in cancer cells, which drives the progression from single cells to metastases.
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MedicalResearch.com Interview with:
Tom Shimabukuro, MD, MPH, MBA
Captain, U.S. Public Health Service
Deputy Director
Immunization Safety Office
Centers for Disease Control and Prevention (CDC)
Medical Research: What is the background for this study? What are the main findings?
Response: CDC conducted a study looking at reports of adverse events (possible side effects) following measles, mumps, and rubella (MMR) vaccination in adults. Researchers reviewed the Vaccine Adverse Event Reporting System (VAERS) database for U.S. reports of adults aged 19 years and older who received MMR vaccine from January 1, 2003 to July 31, 2013. During this period, VAERS received 3,175 U.S. reports after MMR vaccine in adults. The most common signs and symptoms for all reports were fever (19%), rash (17%), pain (13%), and joint pain (13%).
The study included adults only, a population for which there is limited safety data for this vaccine. This study further supports the MMR vaccine’s safety. Researchers did not find any new or unexpected safety concerns.
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MedicalResearch.com Interview with:
Molly B. Conroy MD, MPHAssistant Professor of Medicine, Epidemiology, and Clinical and Translational ScienceUniversity of Pittsburgh, Pittsburgh, PA,
Medical Research: What is the background for this study? What are the main findings?
Response: The background for the study is the fact that middle-aged women are at high risk for being physically inactive, which puts them at higher risk for heart disease, cancer, and other chronic health problems.
We compared an interventionist-led physical activity and weight loss program delivered in coordination with primary care to a booklet that women were asked to use to exercise by themselves at home. We found that women who received the interventionist-led program had significantly greater increases in physical activity at 3 months, compared to women who received booklet. At 12 months, women who received the interventionist-led program were still more active than they were before starting the program, although the difference between the 2 groups was no longer significant.
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MedicalResearch.com Interview with:
Prof. Kazem Rahimi DM MSc FESC
Associate Professor of Cardiovascular Medicine, University of Oxford ;Deputy Director, The George Institute for Global Health; James Martin Fellow in Healthcare Innovation, Oxford Martin School; Honorary Consultant Cardiologist, Oxford University Hospitals NHS Trust The George Institute for Global Health Oxford Martin School United Kingdom
Medical Research: What is the background for this study? What are the main findings?
Dr. Rahimi: Lowering blood pressure (BP) in individuals with diabetes is an area of current controversy. Although it is widely accepted that lowering blood pressure in people with diabetes and elevated blood pressure will reduce the risk of heart and circulatory problems, it is less certain whether diabetics whose blood pressure is not very high should be treated with blood pressure lowering drugs, and how far their blood pressure should be reduced. It is also less well known how blood pressure lowering affects a range of other potential health complications for diabetes patients, such as diabetic eye disease.
We found that each 10-mm Hg lower systolic blood pressure led to a lower risk of mortality, cardiovascular disease events, coronary heart disease events, stroke, albuminuria (the presence of excessive protein in the urine), and retinopathy (loss of vision related to diabetes). Although proportional effects of blood pressure lowering treatment for most outcomes studied were diminished below a systolic BP level of 140 mm Hg, data indicated that further reduction below 140 mm Hg led to a lower risk of stroke, retinopathy, and albuminuria, potentially leading to net benefits for many individuals at high risk for those outcomes.
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MedicalResearch.com Interview with:
Dihua Yu, M.D., Ph.D.
Hubert L. & Olive Stringer Distinguished Chair in Basic Science
Professor and Deputy Chair
Department of Molecular and Cellular Oncology
Co-Director, Center of Biological Pathways
The Univ. Texas MD Anderson Cancer Center Houston, TX 77030
Medical Research: What is the background for this study?Dr. Yu: Transforming growth factor β (TGF-β) functions as a tumor suppressor in premalignant cells but may also function as a metastasis promoter in cancer cells. This study aimed to understand how the growth factor makes this switch between tumor suppressor to tumor promoter.Medical Research: What are the main findings?
Dr. Yu: We reported that 14-3-3ζ overexpression (14-3-3ζ+++) can switch TGF-β’s function from tumor suppressor to metastasis promoter by changing Smad partners. Specifically, 14-3-3ζ+++ led to destabilization of p53, a Smad determinant in pre-malignant cells, thus disrupting p53/Smad complex, and consequently inhibiting TGF-β-induced p21 expression and cytostatic function in non-malignant human mammary epithelial cells (HMECs). On the contrary, 14-3-3ζ+++ stabilized Gli2, a Smad partner in cancer cells, and Gli2 complexed with Smads to promote TGF-β-induced parathyroid hormone-related protein (PTHrP) expression, which enhanced breast cancer bone metastasis. Remarkably, both transcriptomic analyses and clinical pathology data indicated that 14-3-3ζ+++ is associated with the loss of TGF-β’s tumor suppressor function and the gain of its metastasis promoter function by changing contextual partners of Smads. Taken together, we have identified 14-3-3ζ as a novel molecular switch of TGF-β’s function by altering Smad partners from p53 in pre-malignant cells to Gli2 in cancer cells. The study provided important answers to the long-standing questions of how and when TGF-β switches its functional roles from a tumor suppressor to a metastasis promoter. The findings established a scientific base for a new strategy of selectively targeting TGF-β signaling in cancer by inhibiting the cancer-specific Smad partner without blocking TGF-β’s tumor suppressor function in normal tissues.
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MedicalResearch.com Interview with:
Prof.dr. Judith K. Sluiter Principal Investigator
Manager KMKA: Kenniscentrum Medische Keuringen in Arbeid
Nationaal secretaris voor ICOH (International Commission on Occupational Health)
Coronel Instituut voor Arbeid en Gezondheid, Academisch Medisch Centrum / UvA Meibergdreef Amsterdam
Medical Research: What is the background for this study?
Prof. Sluiter: Professional footballers contain a group of employees working in a job with specific job demands. The occupational guidance and prevention of decreased work functioning of workers in these kinds of jobs should receive more attention. The mental health of professional footballers receive less attention compared to their physical health. We studied the prevalence of self-reported mental health problems and psychosocial difficulties in a group of current and former professional footballers, and we explored the association between having had psychosocial stressors and the health conditions under study.
Medical Research: What are the main findings?
Response: The response rate was 29% with available data from 253 footballers. In current players, the prevalence of mental health complaints ranged from 5% (burnout) to 26% (anxiety/depression). In former players, the prevalence ranged from 16% (burnout) to 39% (anxiety/depression). A small percentage of players had low self-esteem (3-5%). One quarter to two-fifth of the players showed adverse nutrition behaviour. Small but significant association between experiencing lower social support (OR=1.1) and having had recent life events (OR=1.4-1.6) and mental health complaints were found in current players. Having had severe injuries was associated with better nutrition behavior. In former players, having had life events showed a preventive effect on smoking (OR=0.4) and having had previous surgery was significantly associated with current smoking behavior (OR=1.9).
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MedicalResearch.com Interview with:
A/Prof Manuela Ferreira PhD
Senior Research Fellow, Musculoskeletal Division
Associate Professor, Sydney Medical School
The George Institute for Global Health Sydney AustraliaMedicalResearch: What is the background for this study? Dr. Ferreira: Our study was set up to look at the common triggers for sudden and moderate to severe episodes of back pain.
It included 1,000 participants with this condition. Participants were interviewed in the first week their pain episode occurred in and were asked to describe their physical and psychosocial activities in the 3 days preceding pain onset.
MedicalResearch: What are the main findings?Dr. Ferreira: The results of the study have shown that sudden attacks of back pain are more likely to be triggered in the morning, between 8 am and 11 am.
Being distracted while engaged in manual tasks, manual tasks performed in an awkward posture, or those involving objects not close to the body and lifting heavy loads were activities that most likely would trigger a new episode of back pain, even following very brief exposure (i.e. less than 2 hours). If you feel like this is you, you should visit a round rock chiropracter to aid progress!
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MedicalResearch.com Interview with:
Erin L. Kelly PhD Post Doctoral Scholar
Health Services Research Center
University of California, Los Angeles, California
MedicalResearch: What is the background for this study? What are the main findings?Dr. Kelly: Mental health facilities can be hazardous workplaces. Nationally, compared to their counterparts in other healthcare settings, mental health workers are at the highest risk for patient assaults. Many studies have focused on predictors for assault such as gender, years of experience, or the position that staff hold in the hospital, which can account for a small amount of violence. However, psychiatric care is largely about relationships. Our study examined how conflicts with patients and coworkers, and how people react to conflict, influences their risk of assault.
In our study, 70% of staff at a large public mental hospital were assaulted in a single year, which is closer to the lifetime assault rate for mental health workers. We also found that the likelihood of assault is predicted by conflicts when we also include stress reactions to conflict as a moderator. We found that workers who reported being less reactive to conflict but experienced a great deal of conflict, with staff or patients, were at the highest risk of assault. This could mean that people who aren't afraid of conflict with patients are more likely to jump in with agitated patients or that people who are insensitive to conflict are missing important social cues and being assaulted more often. However, despite the similarity in the relationships of staff conflict and patient conflict with assault risk, it’s possible that the direction of the relationship between staff conflict and assault may be different. For example, mental health staff who have a lot of conflict with their co-workers may be isolated and therefore a target for assault by patients.
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MedicalResearch.com Interview with:Tassaneewan Laksanasopin
PhD Candidate
Molecular and Microscale Bioengineering Lab
Columbia University
Medical Research: What is the background for this study? What are the main findings?
Response: We miniaturized and integrated all components needed for blood test (similar to ELISA) to be run on a smartphone accessory for point-of-care testing of infectious diseases. The device simultaneously detects three infectious disease markers for HIV, treponemal syphilis and nontreponemal syphilis from a finger prick of blood in just 15 minutes. In a blinded experiment in three health clinics in Rwanda, local health care workers obtained diagnostic results from 96 patients enrolled in prevention of mother-to-child transmission and voluntary counseling programs. The test performance from our triplexed test was 92-100% sensitivity and 79-92% specificity compared to the gold standard of lab-based HIV ELISA, Treponema pallidum haemagglutination and rapid plasma reagin. Importantly, patient preference for the dongle was 97% compared to lab-based tests, with most pointing to the convenience of obtaining quick results with a single finger prick. This work suggests coupling microfluidics with recent advances in consumer electronics can make certain lab-based diagnostics accessible to almost any population with access to smartphones.
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MedicalResearch.com Interview with:
Andres Moreno De Luca, MD
Investigator and Resident Physician
Autism & Developmental Medicine Institute
Department of Radiology Geisinger Health System
Danville, PA 17822
Medical Research: What is the background for this study? What are the main findings?Response: The main finding of our study is that family background contributes to the variability in cognitive, behavioral, and motor performance seen in children with 16p11.2 deletions, and perhaps other genetic syndromes, and this may be attributed in part to genetic background effects.
In the general population the best predictor of a child’s outcomes in traits such as cognitive ability, height, BMI, etc. is the biparental mean performance in such domains and this is due in part to genetic background. For example, if a child’s parents have IQ scores of 130 and 110, it is expected that the child will have an IQ within 2 standard deviations of 120 (bi-parental mean). However, when studying individuals with genetic conditions, most researchers tend to overlook the influence of familial/genetic background on the affected child’s outcomes and commonly attribute the manifestations (or lack thereof) to the genetic mutation alone.
This creates confusion when studying children with neurodevelopmental disorders, such as autism, which show significant clinical variability, as some children with a specific genetic mutation (e.g. deletion 16p11.2) may have intellectual disability without autism, while other children with the same mutation may have autism without intellectual disability. Based on these observations, some researchers have argued that deletion 16p11.2 is incompletely penetrant. However, our study showed that the 16p11.2 deletion has a detrimental effect on cognitive and behavioral performance for all children, but the clinical status (affected vs. unaffected) and ultimate performance level is influenced by the parental performance.
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MedicalResearch.com Interview with:
Torsten Olbers MD, PhD
Assistant Professor of Surgery
Sahlgrenska University Hospital
Gothenburg, Sweden
Medical Research: What is the background for this study? What are the main findings?
Dr. Olbers: Until now there has been no consensus regarding preferred bariatric procedure for patients with a body mass index (BMI) above 50 kg/m2. We report on the 5-year outcomes from a randomized clinical trial of gastric bypass and duodenal switch published online by JAMA Surgery on February 4th.
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MedicalResearch.com Interview with:
Ezequiel Morsella, Ph.D.
Associate Professor of Neuroscience Department of Psychology
San Francisco State University Assistant Adjunct Professor
Department of Neurology University of California, San Francisco
Boardmember, Scientific Advisory Board
Institute of Cognitive Neurology (INECO), Buenos Aires
Medical Research: What is the background for this study? What are the main findings?
Dr. Morsella: Previous studies have demonstrated that, under certain experimental conditions, conscious processes in the brain can function in a way that resembles reflexes. In past research, a single ‘high-level’ thought (e.g., the name of a visually-presented object) was triggered involuntarily by external stimuli. The current research is the first to trigger, not one, but two high-level unintentional conscious thoughts. In this experiment, participants were presented with an object (e.g., the picture of a star) and instructed to not subvocalize (i.e., name in one’s head but not aloud) the name of the object nor count the number of letters comprising the name of the object. On many trials, participants experienced both cognitions (e.g., “STAR” and “4”), even though these thoughts were against the intentions of the participant. Thus, this is the first demonstration of external control of two thoughts in the stream of consciousness. This research is based in part on the pioneering investigations of Wegner, of Gollwitzer, and of Ach.
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MedicalResearch.com Interview with:
Prof. Ran Kornowski, M.D, FACC, FESC on behalf of the coauthors
Chairman - Division of Cardiology,
Rabin Medical Center, Petah-Tikva, Israel
Medical Research: What is the background for this study?
Prof. Kornowski: Over the years, the PCI procedure went-through many progresses. Among those are some angioplasty techniques, generalize use of stents and drug eluting stents, and adjuvant novel antithrombotic therapy. Unmistakably, these were associated with an overall improved PCI outcome. As many of the data on PCIs’ adverse outcomes predictors come from predates studies, we sought to update this matter.
Medical Research: What are the main findings?
Prof. Kornowski: This study confirms the influence of advanced age, diabetes-mellitus and urgent settings (i.e. acute coronary syndromes) on PCI long term outcome. However, we found that their effect extent is modest while supplementary predictors such as anemia (even mild), chronic kidney injury and echocardiographic findings of left ventricular dysfunction have a greater effect on contemporary PCI prognosis.
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MedicalResearch.com Interview with:
Ashok K. Shetty, Ph.D.
Professor and Director of NeurosciencesInstitute for Regenerative Medicine and Department of Molecular and Cellular Medicine Texas A&M Health Science Center College of Medicine, Temple, TX Research Career Scientist, Central Texas Veterans Health Care System (CTVHCS), Temple, TX
Medical Research: What is the background for this study?
Prof. Shetty: Hippocampus is a region in the brain important for maintaining functions such as learning, memory and mood. However, this region is highly vulnerable to aging and brain insults. Previous research has shown that diminished function in the dentate gyrus region of the hippocampus is one of the key reasons for memory impairments seen in old age. Dentate gyrus is also one of the few regions in the brain where neural stem cells generate new neurons on a daily basis, also referred to as "adult neurogenesis". Studies have suggested that a significant fraction of newly born neurons mature, get incorporated into the existing hippocampus circuitry and contribute to learning, formation of new memories, and normal mood. However, with aging, the dentate gyrus shows decreased function with some conspicuous structural changes, which include reduced production of new neurons, diminished microvasculature implying reduced blood flow, and occurrence of hypertrophy of astrocytes and activated microglia, signs of chronic low-level inflammation. Because alterations such as reduced neurogenesis, decreased blood flow and brain inflammation can contribute to memory and mood impairments, the idea that drugs that are efficacious for mitigating these changes may preserve memory and mood function in old age has emerged. Such drugs may be prescribed to the aging population if they are efficacious for maintaining normal cognitive and mood function in old age with no or minimal side effects.
Medical Research: What is the rationale for choosing resveratrol for preventing age-related memory dysfunction in this study?Prof. Shetty: Administration of resveratrol, a naturally occurring polyphenol found in the skin of red grapes, red wine, peanuts and some berries, appeared suitable for counteracting age-related detrimental changes in the hippocampus. This is because, previous studies have shown that resveratrol has ability to promote the formation of new capillaries (through pro-angiogenic effects) and to suppress oxidative stress and inflammation (via antioxidant and antiinflammatory effects) with no adverse side effects. Other studies have also reported that resveratrol can mediate extension of the life span and delayed onset of age related diseases. More importantly, a recent human study suggested that a reasonably lower dose of resveratrol intake for 26 weeks is good enough to improve memory performance as well as hippocampus functional connectivity in 23 healthy overweight older individuals (Witte et al., J. Neurosci., 34: 7862-7870, 2014).
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MedicalResearch.com Interview with:
Ann Marie Navar-Boggan, MD PhD
Fellow, Cardiovascular Disease
Duke University School of MedicineMedical Research: What is the background for this study? What are the main findings?
Response: In this study of adults from the Framingham Offspring Study, we evaluated the impact of prolonged exposure to elevated cholesterol in early adulthood and future risk of coronary heart disease. In adults aged 55, the duration of time a person has been exposed to a non-HDL of >=160 mg/dL was associated with increased risk of coronary heart disease, and that risk was above and beyond the risk conferred by lipid levels at age 55. Every 10 years spent with a non-HDL of 160 or above was associated with a 39% increased future risk of coronary heart disease. We also looked at the association between prior average blood cholesterol between the age of 35 and 55, and found that every 10 mg/dL increase in prior average cholesterol above 125 mg/dL was associated with a 33% increased risk of coronary heart disease. These findings were particularly notable because the vast majority of adults with prolonged exposure to hyperlipidemia would not have been identified by the guidelines for statin therapy.
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MedicalResearch.com Interview with:
Adam E. Singer, MPhil
Pardee RAND Graduate School, RAND Corporation
Santa Monica, CA
MedicalResearch: What is the background for this study? What are the main findings?Response: In 1997, the Institute of Medicine (IOM) released a seminal report on the state of end-of-life care in the US that called for major changes in the organization and delivery of end-of-life care. Many of the IOM’s indictments have ostensibly been addressed since that time through the expansion of palliative care and hospice, along with a greater focus on symptom management in both policy and practice. This study was designed to ask whether end-of-life symptoms have become less prevalent from 1998 to 2010 for the population as a whole and also for subgroups that died suddenly or had cancer, congestive heart failure (CHF), chronic lung disease, or frailty.
The study found that many alarming symptoms were common in the last year of life and affected more people from 1998 to 2010. For example, in the whole population, pain affected 54% in 1998 and 61% in 2010 (a 12% increase). Depression affected 45% in 1998 and 57% in 2010 (a 27% increase). Periodic confusion affected 41% in 1998 and 54% in 2010 (a 31% increase). Depression and periodic confusion also became more prevalent in subgroups with CHF and/or chronic lung disease and frailty. In addition, nearly all other symptoms in the whole population and in each of the subgroups trended toward increases in prevalence from 1998 to 2010, although most of these trends did not reach statistical significance. The one exception is that there were no significant changes in the subgroup with cancer.
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MedicalResearch.com Interview with:
Jonetta L. Johnson, PhD, MPH
Epidemiologist
Division of Reproductive Health, CDC.
Medical Research: What is the background for this study?
Dr. Johnson: Achieving adequate gestational weight gain (GWG) is important for optimal health of the infant and mother. Women who gain below or above Institute of Medicine (IOM) recommendations are more likely to experience maternal complications and negative infant birth outcomes. Realizing the importance of gestational weight gain to maternal and infant health, the IOM established recommendations for gestational weight gain based on a woman’s prepregnancy body mass index (BMI) in 1990 and updated them in 2009. Trends in GWG are particularly of interest since prepregnancy BMI has increased over time in the U.S and little data was available on how gestational weight gain has changed over time.
Medical Research: What are the main findings?
Dr. Johnson: Our findings show that from 2000-2009, the majority of women did not gain weight within IOM GWG recommendations and that women were more likely to gain outside recommendations in more recent years. In fact, from 2000–2009, there was a gradual decrease (1.0 percentage point every 2 years) in women gaining within IOM gestational weight gain recommendations and a gradual increase (0.8 percentage points every 2 years) in women gaining above IOM recommendations while the percentage of women gaining weight below IOM recommendations remained relatively constant. Although there were slight differences in mean gestational weight gain by BMI group, gestational weight gain was about 31 pounds on average. The decreasing percentage of women gaining within IOM recommendations during our study period may be influenced by increases in prepregnancy BMI during the same time period because women in higher BMI groups are recommended to gain less weight during pregnancy compared to women in lower BMI groups. Thus, even with no change in gestational weight gain over time, an increase in the proportion of women who are obese could result in a decrease in the proportion of women gaining within gestational weight gain recommendations. (more…)
MedicalResearch.com Interview with:Dr Sandra L Jackson PhD
Atlanta VA Medical Center, Decatur, GA, Nutrition and Health Sciences, Graduate Division of Biological and Biomedical Sciences Emory University, Atlanta, GA, USA
Medical Research: What is the background for this study? What are the main findings?
Dr. Jackson: Lifestyle change programs are aimed to improve health, yet little is known about their impact once translated into clinical settings. The Veterans Health Administration (VA) MOVE! program is the largest lifestyle change program in the U.S. Participation is a key challenge of the program, as only 13% of the eligible population participated. However, among patients who did not have diabetes at baseline, we found that MOVE! participation was associated with lower diabetes incidence.
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MedicalResearch.com Interview with:Steven C. Hill, PhD
Center for Financing, Access and Cost Trends
Agency for Healthcare Research and Quality
Rockville, MD 20850
MedicalResearch: What is the background for this study? Dr. Hill: The Affordable Care Act offers two major ways to extend health coverage to more Americans: through expanding state Medicaid programs and through the Marketplace. States can expand Medicaid coverage to adults with family incomes at or below 138 percent of the federal poverty guidelines (approximately $16,242 for an individual and $33,465 for a family of four in 2015).
At the time of the study, 23 states had not yet expanded their Medicaid programs. In those states, poor adults typically continue to have very limited access to Medicaid. However, adults with incomes at or above the poverty guidelines who lack access to affordable insurance elsewhere are eligible for premium tax credits in the Marketplace. If these low-income adults purchase silver plans, then they are also generally eligible for cost sharing reductions.
MedicalResearch: What was the methodology for study? Dr. Hill: The study used data from then Agency for Healthcare Research and Quality’s Medical Expenditure Panel Survey (MEPS) to determine family out-of-pocket health care spending in 2005 – 2010 for uninsured, low-income adults who lived in the states that had not yet expanded Medicaid under the Affordable Care Act at the time of the study. The study focused on those who would have been eligible for Medicaid if their states expanded eligibility (income at or below 138 percent of poverty guideline), and whose incomes were high enough to be eligible for premium tax credits and cost sharing reductions through the Health Insurance Marketplace (at or above poverty guidelines). The study then compared those data with the following simulated scenarios for these adults: coverage in a Marketplace silver plan with financial assistance; and enrolling in expanded Medicaid.
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MedicalResearch.com
Hailey Winetrobe, MPH, CHES
Project Manager
NIDA Transitions to Housing Study
School of Social Work
University of Southern California
MedicalResearch: What is the background for this study? What are the main findings?Response: Homeless young adults are a very vulnerable population with high healthcare needs. However, because of their housing instability and very low income, many homeless young adults may not have health insurance and/or access to healthcare services. Prior research regarding this population’s health insurance coverage was mostly outdated. Additionally, with the implementation of the Affordable Care Act (ACA), homeless young adults may now qualify for health insurance coverage (i.e., if there is a relationship, by being a dependent on their parent’s health insurance until 26 years old; and via Medicaid expansion in states choosing to expand). As such, this study aimed to update homeless young adults’ rates of health insurance coverage prior to the full implementation of the ACA (i.e., before Medicaid expansion) and to determine if there was an association between insurance and use of healthcare services.
We found that 70% of homeless young adults did not have health insurance in the prior year. Of those with health insurance, 46% reported coverage through their parents, and 34% through Medicaid (not mutually exclusive). Over half (52%) of the sample received healthcare in the prior year. Furthermore, in a multivariable logistic regression model controlling for demographic characteristics, homeless young adults with health insurance, compared to their peers who did not have health insurance, had 11 times the odds of receiving healthcare in the prior year.
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MedicalResearch.com Interview with:
Pauline Mendola, PhD, Investigator
Epidemiology Branch
Division of Intramural Population Health Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH
Rockville, MD 20852
Medical Research: What is the background for this study? What are the main findings?
Dr. Mendola: Asthma is the most common chronic disease in pregnancy and both asthma and maternal race/ethnicity are associated with adverse pregnancy outcomes. Since the prevalence of asthma also varies by race/ethnicity, we wanted to assess whether asthma was an important contributor to racial/ethnic disparities in pregnancy outcomes. We examined the joint impact of maternal race/ethnicity and asthma status on the risk of obstetric and neonatal outcomes.
In general, maternal asthma did not impact the risk of obstetric and neonatal complications within racial/ethnic groups. However, compared to mothers of the same race/ethnicity without asthma, White and Hispanic asthmatic mothers were more likely to have infants born small-for gestational age or admitted to the NICU. White women with asthma were also at increased risk of preeclampsia and maternal hemorrhage and Hispanic mothers with asthma were more likely to have infants with apnea. Despite their increased risk of maternal asthma and neonatal and obstetric complications, maternal asthma did not impact the risk of complications among Black women or their infants.
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MedicalResearch.com Interview with:
Christa Van Dort PhD
Department of Anesthesia, Critical Care, and Pain Medicine,
Department of Brain and Cognitive Sciences,
Picower Institute for Learning and Memory,
Massachusetts General Hospital, Harvard Medical School Boston, MA, 02114
Medical Research: What is the background for this study? What are the main findings?
Dr. Van Dort: Sleep is crucial for survival and maintenance of health. Inadequate sleep and sleep disorders impair many brain and body functions such as executive function, the immune system and memory consolidation. The benefits of sleep are dependent on normal sleep physiology and patterns. Natural sleep is composed of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep alternating every 90 min in humans. Each stage provides different benefits, for example deep NREM sleep is associated with feeling rested and REM sleep is important for learning. Current sleep aids do not effectively restore normal sleep physiology or timing and as a result do not fulfill the important functions of natural sleep. To develop new strategies for reproducing natural sleep, we aimed to understand each component of sleep (NREM and REM sleep) individually and then in combination. Cholinergic neurons have been hypothesized to control REM sleep for many years but no one had been able to test this directly due to limited methodology. Optogenetics solved this problem by giving us the ability to activate selectively the cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT).
The primary finding of this study was that cholinergic neurons in the PPT and LDT are sufficient to drive REM sleep from NREM sleep. These cholinergic neurons were important for initiation of REM sleep but not the duration of REM sleep. Understanding REM sleep control is an important first step in reproducing normal sleep patterns and by itself could enhance learning and memory.
(more…)
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MedicalResearch.com Interview with:
David G. Kent, Ph.D
From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of Cambridge
Medical Research: What is the background for this study? What are the main findings?
Dr. Kent: Cancers are the result of the sequential acquisition of errors in the genetic code. Most studies have focused on the sum of these mutations (e.g., A+B+C = cancer) but no study in patients has asked the question of whether or not the order of genetic mutations impacts the disease (e.g., does A to AB equal B to BA). We studied patients with chronic blood disorders (known as myeloproliferative neoplasms, or MPNs) that are precursors to cancer to access the earliest stages of tumour development and studied whether or not the order of mutation acquisition impacted disease. We studied patients with mutations in two genes (JAK2 and TET2) and showed that the order of acquisition of these mutations impacted timing of clinical presentation, disease subtype, frequency of thrombotic events, and differed in their response to targeted therapy in the lab. (more…)
