MedicalResearch.com Interview with:
Leora Horwitz, MD, MHS
Director, Center for Healthcare Innovation and Delivery Science
New York University Langone Medical Center
Director, Division of Healthcare Delivery Science
Department of Population Health, NYU School of Medicine
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Horwitz: We reviewed over 1500 discharge summaries from 46 hospitals around the nation that had been collected as part of a large randomized controlled trial (Telemonitoring to Improve Heart Failure Outcomes). All summaries were of patients who were admitted with heart failure and survived to discharge. We found that not one of them met all three criteria of being timely, transmitted to the right physician and fully comprehensive in content. We also found that hospitals varied very widely in their average quality. For instance, in some hospitals, 98% of summaries were completed on the day of discharge; in others, none were. In the accompanying Data Report, we show that summaries transmitted to outside clinicians and including more key content elements are associated with lower risk of rehospitalization within 30 days of discharge. This is the first study to demonstrate an association of discharge summary quality with readmission.
MedicalResearch.com Interview with: Anita Soni, PhD, MBA Survey Analyst/Statistician Project Officer, AHRQ Healthcare Data Analytics and Statistical Products Contract Center for Financing, Access and Cost Trends Agency for Healthcare Research and Quality Rockville, MD 20850 Medical Research: What is the background for this study? What are the main findings? Dr. Soni: The data used for this comes from...
MedicalResearch.com Interview with:
Jennifer Williams MSN, MPH, FNP-BC
National Center on Birth Defects and Developmental Disabilities
CDC, Atlanta, Georgia
Medical Research: What is the background for this study? What are the main findings?
Response: Neural tube defects are serious birth defects of the brain and spine that can cause significant disability and death. Studies have shown that taking 400 mcg of folic acid daily before and during pregnancy can reduce the prevalence of neural tube defects. Therefore, in 1992, the US Public Health Service (USPHS) recommended that all women of childbearing age in the United States who are capable of becoming pregnant consume 400mcg of folic acid per day to reduce the risk of neural tube defects. To help women meet this requirement, in 1998 the US Food and Drug Administration (FDA) mandated that folic acid be added to enriched grain products for the prevention of neural tube defects.
This study looks at how many neural tube defects have been prevented annually since folic acid fortification. Using data from birth defects tracking systems, researchers found that since folic acid fortification, the birth prevalence of neural tube defects has decreased by 35% in the United States, which translates to about 1,300 babies that are born each year without a neural tube defect who might otherwise have been affected. This study also reports that the number of babies born with a neural tube defect annually differs by the mother’s race/ethnicity. Hispanic mothers continue to be at the highest risk for having a baby with a neural tube defect.
MedicalResearch.com Interview with:
Jean-Claude Tardif MD
Professor of Medicine
Director of the Research Centre
Montreal Heart Institute Montreal, Quebec Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Tardif: Epidemiological and mechanistic studies have suggested that high-density lipoproteins (HDL) could have beneficial cardiovascular properties. However, several medications targeting HDL have failed in recent clinical trials, including the CETP inhibitor dalcetrapib in the dal-Outcomes trial. We hypothesized that dalcetrapib would be beneficial in the subset of patients with the appropriate genetic profile. We conducted the pharmacogenomic analysis of approximately 6000 patients from the dal-Outcomes study which showed that patients with the AA genotype at a specific genetic location (rs1967309) of the adenylate cyclase (ADCY9) gene benefited from a 39% reduction in cardiovascular events including cardiovascular death, myocardial infarction, stroke, unstable angina and the need for coronary revascularization when treated with dalcetrapib compared to placebo. In contrast, patients with the GG genotype had a 27% increase in cardiovascular events. We then obtained confirmatory evidence from the dal-Plaque-2 imaging study which revealed that patients with the protective genotype (AA) had a reduction in their carotid artery wall thickness and that those with the genotype associated with clinical harm (GG) had an increase in their wall thickness.
MedicalResearch.com Interview with:
Armen K. Goenjian, M.D., L.D.F.A.P.A., F.A.C.G.S.
Research Professor of Psychiatry
Department of Psychiatry and Biobehavioral Sciences
David Geffen School of Medicine at UCLA
Medical Research: What is the background for this study?
Response: Post-traumatic stress disorder (PTSD) is a psychiatric disorder that develops after exposure to a traumatic event such as rape, war, natural disaster, and accident. Symptoms include recurrent intrusive traumatic memories, flashbacks, nightmares, hyper-vigilance, jumpiness, and anxiety.
Dopaminergic and serotonergic systems have been implicated in PTSD. Catechol-O-methyltransferase (COMT) is an enzyme that degrades dopamine, an important brain neuro-hormone that regulates human behavior, thoughts and emotions. Tryptophan hydroxylase is the rate limiting step in the synthesis of serotonin, another important neuro-hormone that regulates arousal, sleep, anxiety, and mood. This study evaluated the association of four COMT gene loci, and the joint effect of COMT and tryptophan hydroxylase 2 (TPH-2) genes on PTSD symptoms.
MedicalResearch.com Interview with:
Keiran Smalley, PhD.
Scientific Director, The Comprehensive Melanoma Research Center
Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FL
Medical Research: What is the background for this study? What are the main findings?
Dr. Smalley: Although many patients with BRAF mutant melanoma respond very well to BRAF inhibitors and the BRAF/MEK inhibitor combination, resistance is commonplace and the majority of those treated ultimately fail therapy. Most studies to date have focused upon the genetic changes that are associated with acquired BRAF and BRAF/MEK inhibitor resistance. We decided to take a different approach and to use proteomics to comprehensively map all of the signaling changes associated with resistance. Our study showed that melanoma cells with resistance to BRAF and BRAF/MEK inhibition were highly invasive and aggressive. This aggressive phenotype was driven through a cell surface receptor called EphA2, and this became upregulated in both melanoma cell cultures and in patient tumors following BRAF inhibitor treatment. As this suggested that the resistant cells would be more metastatic, we then performed animal experiments and analyzed tumors from melanoma patients receiving BRAF inhibitor. These studies showed an increase in EphA2 expression in the metastatic tumors that was lacking in the primary tumors. When we looked at cohorts of melanoma patients who received either a BRAF inhibitor or an older chemotherapy drug, we found that more of the BRAF inhibitor treated patients seemed to develop disease at new sites. Together this suggested that BRAF inhibition may switch the cancer cells to being more metastatic.
MedicalResearch.com Interview with:
Nenad Bursac PhD
Rooney Family Associate Professor of Biomedical Engineering
Associate Professor of Medicine Duke University
Medical Research: What is the background for this study? What are the main findings?
Dr. Bursac: Researchers have tried for a long time to coax human muscle cells (obtained from needle biopsies) into contracting muscle fibers in a dish in order to be able to study human muscle physiology ex vivo. We are the first group that succeeded by carefully optimizing culture conditions including methods to expand and then culture cells in three-dimensional hydrogel matrices under passive tension. By doing so, we made first human muscle model that in response to electrical stimulation generates classical muscle contractile responses (twitch and tetanus). We have also shown that these engineered muscles (that we call "myobundles") contract in response to acetylcholine as it naturally happens when neurons in our body activate muscle. We demonstrated reproducibility and robustness of the approach by generating functional myobundles with similar properties from 10 independent donor muscle samples. We further went to show that myobundles have intact signaling characteristic of native muscle and respond to diverse set of drugs as human muscles do in clinics.
MedicalResearch.com Interview with:
Dr Christos Pliatsikas PhD
Lecturer in Cognitive Psychology School of Psychology
University of Kent Canterbury Kent
Medical Research: What is the background for this study? What are the main findings?
Response: It has been proposed that lifelong bilingualism preserves the white matter structure of older bilinguals because of the increased cognitive demands that come with handling two languages for their entire life. We wanted to extend this by investigating whether active (or "immersive") bilingualism in younger late bilinguals would give similar results.
We showed increased white matter integrity (or myelination) in several white matter tracts that have also been shown to be better preserved in older lifelong bilinguals, compared to monolinguals. Based on our findings, we propose that any benefit of bilingualism to the brain structure is simply an effect of actively handling two languages without presupposing lifelong usage- our participants were only about 30 years old and had been active bilinguals for only about 7-8 years. In other words, immersive bilingualism, even in late bilinguals, leads to structural changes that can bring about benefits in older age, by assisting in the preservation of the white matter structure in the brain.
MedicalResearch.com Interview with:
Professor Marianna Virtanen PhD
Unit of Expertise for Work and Organizations
Finnish Institute of Occupational Health
Helsinki, Finland.
Medical Research: What is the background for this study? What are the main findings?
Professor Virtanen: Risky alcohol use is common among working populations but the contribution of work-related factors such as long working hours has rarely been studied. In the present study we performed the first systematic analysis on published studies regarding long working hours and risky alcohol use and added unpublished individual participant data to the analyses. Altogether 61 studies were included in the cross sectional analysis and 20 studies in the prospective analysis. The pooled cross sectional analysis showed 11% higher alcohol use associated with long working hours. In the prospective analysis we found that working 49-54 hours a week was associated with a 13% increase in the probability of new-onset risky alcohol use and working 55 hours or more with a 12% increased risk.
MedicalResearch.com Interview with:
Javaid Iqbal, MD, MSC (Candidate)
Institute of Medical Sciences, and
Women’s College Research Institute/Women’s College Hospital
University of Toronto, Toronto Canada
What is the background for this study? What are the main findings?
Dr. Iqbal: A woman’s racial/ethnic background predicts her participation in breast cancer control program (i.e., awareness and screening). The ultimate objective of breast cancer control program is to detect cancer at an optimal stage, which is stage I, because women with stage I breast cancer survive longer. Given the racial/ethnic diversity of North America, this poses questions such as “what predicts stage I breast cancer in the multiethnic North American population?”, “what predicts its survival?”, and “does a woman’s ethnic background plays a role in predicting an early stage, and survival?”
We studied 373,563 women diagnosed with invasive breast cancer in the United States between 2004 and 2011. We followed these women for 7 years and recorded whether or not they died of breast cancer, or whether they are still alive. We then divided all women into different ethnic groups, in particular white, black, Chinese, Japanese, and Indian/Pakistani (South Asian). For each racial/ethnic group, we estimated proportions of women who were diagnosed with stage I breast cancer, and risk of death at 7 years. Our aim was to determine if the racial/ethnic differences in early stage breast cancer, and its survival were better explained by intrinsic biological differences in tumor characteristics, or by differences in early-detection of breast cancer.
We found that a woman’s racial/ethnic background predicted the diagnosis of stage I breast cancer, as well as her risk of dying at 7 years after breast cancer. A black woman was less likely than a white woman to be diagnosed with stage I breast cancer. A black woman was also more likely than a white woman to die of stage I breast cancer 7 years after her diagnosis. The Japanese and Chinese women were more likely than white women to be diagnosed with stage I breast cancer. The risk of death at 7 years was lowest for Indian or Pakistani (South Asian) women. Furthermore, even for small sized (2.0) breast cancers the risk of death at 7 years was higher for black women (9%), compared to white women (5%). Compared to white women, small sized breast cancers in black women were more aggressive at diagnosis, and had spread to lymph nodes and other organs.
MedicalResearch.com Interview with:
Terisa P. Gabrielsen, PhD, NCSP
Assistant Professor, School Psychology
Dept. of Counseling Psychology and Special Education
Brigham Young University, Provo, UT 84602
Medical Research: What is the background for this study? What are the main findings?
Dr. Gabrielsen: One of the keys to improving outcomes for individuals with outcomes is to begin intervention as early as possible, which means we need to identify autism symptoms as early as possible, preferably during the early toddler years. The current study grew out of a screening feasibility study to see what would happen if pediatricians followed the AAP guidelines for screening every child for autism at ages 18 and 24 months as part of their regular pediatric care appointments. That study was conducted in a large, independent community pediatrics practice. We found that universal screening of 796 patients helped to identify 10 toddlers with autism who had not previously been referred for evaluations. Physicians had previously identified 3 others with autism in the group, and toddlers with other delays, such as language delays, were also identified through the screening process. We wondered what some possible causes were for the low rate of autism referrals and designed the current study to look for what information was available to a pediatrician during the timespan of a typical pediatric exam. We found that even in toddlers with autism, a brief (10-minute) sample contains an overwhelming ratio of typical behaviors (averaging 89%) compared to infrequent atypical behaviors (11%) that would indicate the presence of autism. We had autism experts identifying the behaviors from videos of the evaluations of children in the previous study, so they had many luxuries that a clinician doesn't have during an exam (i.e., ability to focus on one aspect of development, ability to rewind and re-view behaviors). After watching the 10-minute video observations, we asked our experts, "Would you refer this child for an autism evaluation?" We found that even the experts missed referring a child for an autism evaluation 39% of the time when the only data available were the brief observations.
MedicalResearch.com Interview with:
Gustavo Dayan, MD
Director, Clinical Development
Sanofi Pasteur Discovery Drive
Swiftwater, PA 18370
Medical Research: What is the background for this study? What are the main findings?
Dr. Dayan: This is the first dengue vaccine efficacy trial conducted in Latin America. The trial met its primary objective showing an efficacy of 60.8% against symptomatic VCD (virologically confirmed dengue) after a 3-dose vaccination schedule. Serotype-specific efficacy was also demonstrated against all four serotypes. Furthermore, the dengue vaccine candidate effectively reduced hospitalization due to dengue by 80.3% and severe dengue disease by 95.5% over the 25-month study period.
MedicalResearch.com Interview with:
Teresa Waters PhD
Professor and Chair, Preventive Medicine
University of Tennessee Health Science Center
Memphis TN
Medical Research: What is the background for this study? What are the main findings?
Dr. Waters: On October 1, 2008, Medicare implemented the Hospital-Acquired Conditions (HACs) Initiative, a policy penalizing hospitals for eight complications of hospital care, also known as never events. Under the HACs Initiative, hospitals could no longer justify a higher level Medicare MS-DRG when caring for a patient who developed 1 of the 8 never events. This Initiative was one in a series of CMS payment reforms intended to increase emphasis on value-based purchasing.
We found that Medicare's nonpayment policy was associated with significant improvements in the time trends for central line associated blood stream infections (CLABSIs) and catheter associated urinary tract infections(CAUTIs). For these outcomes, our data from the National Database of Nursing Quality Indicators showed that introduction of the Medicare policy was associated with an 11% reduction in the rate of change in central line associated blood stream infections and a 10% reduction in the rate of change in CAUTIs. We did not find any relationship between introduction of the policy and significant changes in injurious falls or hospital acquired pressure ulcers (two other important never events covered by the policy). We hypothesized that the Hospital-Acquired Conditions Initiative may have a great effect for conditions where there is strong evidence that better hospital processes yield better outcomes or where processes are more conducive to standardization.
MedicalResearch.com Interview with: James Louis Januzzi, Jr, MD, FACC, FESC Director, Cardiac Intensive Care Unit Director, Dennis and Marilyn Barry Fellowship in Cardiology Research Massachusetts General Hospital Boston, MA, 02114. Medical Research: What is the background for this study? What are the main findings? Dr. Januzzi: Evaluation for suspected or proven acute coronary syndrome is...
MedicalResearch.com Interview with:
Oleh Taratula, Ph. D.
Assistant Professor of Pharmaceutics
Department of Pharmaceutical Sciences
College of Pharmacy Oregon State University
Corvallis, OR 97331-3507
Medical Research: What is the background for this study? What are the main findings?
Dr. Taratula: Our research group is focused on the development of novel nanotechnology-based approaches to treat different cancers, including ovarian cancer. For many cancers, surgery is a first choice of treatment. For example, only optimal surgical resection of most abdominal metastases can significantly reduce ovarian cancer recurrence and, therefore, improve patient survival. However, it is challenging to remove most of the cancer tumors and residual cancer cells eventually may lead to cancer relapse. Therefore, our aim is to develop a nanomedicine platform, which could help surgeons achieve maximal tumor resection, using the intraoperative guidance with real-time near infrared (NIR) fluorescence signal. Moreover, we expect that the same nanoplatform could further enhance surgical outcomes by combinatorial phototherapy to be performed intraoperatively after tumor resection to eradicate unresected cancer cells.
Our data published in Nanoscale is the first step towards our main goal. At this point, by utilizing naphthalocyanine, we have developed a single-agent-based nanomedicine platform capable of both NIR fluorescence imaging and combinatorial phototherapy. Naphthalocyanine is a commercially available compound, but its potential clinical application is limited by low water solubility and aggregation. Especially, aggregation diminishes the imaging ability and phototherapeutic efficacy of this compound. To address these shortcomings, we discovered that the loading of naphthalocyanine into the dendrimers significantly enhances water solubility, prevents aggregation and preserves imaging and therapeutic abilities. Our data demonstrated that naphthalocyanine-based nanoplatform can generate a NIR fluorescence signal in the cancer tumors, required for elimination of autofluorescence from healthy tissue and body fluids. Furthermore, our results also indicated that the developed nanoplatform is an efficient therapeutic agent which, upon exposure to NIR light, destroys chemotherapy-resistant ovarian cancer tumors by producing both heat and toxic reactive oxygen species.
Finally, many organic fluorophores, including naphthalocyanine, can undergo photobleaching under exposure to light, which could be misinterpreted as a lack of fluorescence signal during the surgery. We demonstrated that the dendrimer encapsulated naphthalocyanine exhibits extremely high photostability and could overcome the above mentioned issue.
MedicalResearch.com Interview with:
Kasia Joanna Lipska MD, MHS
Assistant Professor of Medicine (Endocrinology)
Yale School of Medicine
New Haven, CT 06520-8020
Medical Research: What is the background for this study? What are the main findings?
Dr. Lipska: Diabetes is common and affects about 1 in 4 older adults (65 years or more). For younger adults with diabetes, most guidelines suggest lowering blood sugar levels to a hemoglobin A1c below 7%. However, in older patients, especially those with complex medical problems, the benefits of this strategy are unclear. What’s more, this strategy can cause harm. Aiming for a hemoglobin A1c below seven increases the risk for hypoglycemia. And older adults are especially susceptible to this risk. As a result, many guidelines suggest that treatment should be more cautious for these vulnerable elders and that aiming for “tight” blood sugar control may not be worth the risk.
Medical Research: What are the main findings?
Dr. Lipska: We looked at diabetes treatment of older adults using nationally representative data from 2001 to 2010. We found that 62% of older adults with diabetes had a hemoglobin A1c below 7%. But what’s really striking is that this proportion was similar for patients who were relatively healthy, for those with intermediate health, and for those with poor health. What’s more, the use of insulin or sulfonylureas (drugs that increase the risk for hypoglycemia) was common and similar across these groups.
MedicalResearch.com Interview with:
Caroline Attardo Genco, PhD
Professor Department of Medicine, Section of Infectious Diseases Department of Microbiology
Boston University School of Medicine
Boston MA
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Genco: Atherosclerosis is a common cardiovascular disease associated with heart attack and stroke. Although it has been shown that a diet high in fat as well as exposure to certain bacteria can cause atherosclerosis (the buildup of fats, cholesterol, and other substances on artery walls which can restrict blood flow), we have for the first time identified distinct gene pathways that are altered by these different stimuli. One of these bacteria, Porphyromonas gingivalis, is found in the mouth of humans with periodontal disease. Another is the bacteria Chlamydia pneumoniae, which causes pneumonia. We found that even though these three different stimuli all cause atherosclerosis, the gene pathways are distinct depending upon stimulus. This is the first study that has performed side-by-side comparison of genome-wide gene expression changes to address this issue.
In this study, we used four experimental groups to compare genome-wide expression changes in vascular tissue. The first group was subjected to Porphyromonas gingivalis, while the second group received Chlamydia pneumoniae. The third group was placed on a high-fat Western style diet, while the fourth group was the control group. In collaboration with the Clinical and Translational Science Institute (CTSI) at Boston University, we performed genome-wide microarray profiling and analysis of vascular tissue from all groups to reveal gene pathways altered in vascular tissue by each treatment group.
These findings may explain how specific infections or high-fat diet may cause atherosclerotic plaques to undergo changes that affect their size and stability and may ultimately lead to a heart attack.