MedicalResearch.com Interview with:
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Dr. Ying Bao[/caption]
Dr. Ying Bao Sc.D., M.D
Assistant Professor of Medicine
Channing Division of Network Medicine
Department of Medicine
Brigham and Women's Hospital
Harvard Medical School,
Boston, MA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Nuts are rich in bioactive macronutrients, micronutrients, tocopherols and phytochemicals. Current epidemiological evidence has consistently linked increased nut consumption to reduced risk of several chronic conditions including cardiovascular diseases, type 2 diabetes, and inflammation. In contrast, evidence on nut consumption and cancer risk has been insufficient and equivocal.
Prostate cancer is the leading cancer among U.S. men, with approximately 220,800 new cases diagnosed in 2015. However, very few studies have investigated the association between nut intake and prostate cancer. Thus, in the current study, we followed 47,299 US men from 1986-2012, and examined
(1) whether consuming more nuts prevents getting prostate cancer, and
(2) whether consuming more nuts reduces death rates among non-metastatic prostate cancer patients.
During 26 years of follow-up, 6,810 men were diagnosed with prostate cancer, and 4,346 of these patients were without metastasis at diagnosis. We found no association between nut intake and being diagnosed with prostate cancer. However, among non-metastatic prostate cancer patients, those who consumed nuts 5 or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month.
Dr. Abigail Aiken[/caption]
Abigail R.A. Aiken, MD, MPH, PhD
Assistant Professor
LBJ School of Public Affairs
University of Texas at Austin
Austin, TX, 78713
MedicalResearch.com: What is the background for this study?
Response: As Zika began to emerge as an epidemic in Latin America and its links with microcephaly began to be realized, we were aware that women in the region who were already pregnant or who would become pregnant would have a very limited set of reproductive options. Research and media attention about the possible biological effects of Zika in pregnancy began to appear rapidly. But much less attention was been paid to the impacts of Zika on women. We followed the responses of governments and health organizations and when they began to issue advisories warning women to avoid pregnancy, we knew it would be important to investigate the impacts of those advisories. A country-wide policy that is impossible to follow if you are pregnant or cannot avoid pregnancy is an unusual and important public issue. Accurate data on abortion are very difficult to obtain in Latin America because in most countries, abortion is highly restricted. We wanted to provide a window on the issue of how women were responding to the risks of Zika and its associated advisories, so we worked with Women on Web (WoW), an online non-profit telemedicine initiative that provides safe medical abortion to women in countries where safe, legal abortion is not universally available.
Lindsay Kohler[/caption]
Lindsay Kohler MPH
Mel and Enid Zuckerman College of Public Health
Tucson, Arizona
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Several studies have reported that following health promotion guidelines for diet, physical activity, and maintenance of a healthy body weight may reduce the risk of getting cancer or dying from cancer. We performed a systematic review to examine the associations between established cancer prevention guidelines for diet and physical activity and cancer outcomes. We found that adhering to cancer prevention guidelines set forth by the American Cancer Society or the World Cancer Research Fund/American Institute for Cancer Research consistently reduced the risk of overall cancer incidence and mortality (10-61%) in the studies included in this review. In addition, higher adherence to the guidelines consistently reduced the risk of breast, colorectal, and endometrial cancers. Adherence to a pattern of healthy behaviors may significantly reduce cancer incidence and mortality.
Prof. Peter Johnson[/caption]
Peter Johnson MA, MD, FRCP
Professor of Medical Oncology
Cancer Research UK Centre
Southampton General Hospital
Southampton
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Johnson: Based upon retrospective series looking at the ability of interim PET to predict the outcomes of treatment, we aimed to test the idea of modulating treatment in response to an early assessment of the response to ABVD: could we safely reduce the amount of treatment by omitting bleomycin in the group who had responded well? Although the risk of severe toxicity from bleomycin is generally low, for the small number of patients who experience it, it can be life-changing or even fatal. We also wanted to test whether it might be possible to reduce the use of consolidation radiotherapy by comparison to our previous trials, and this seems to have worked too: we used radiotherapy in less than 10% of patients in RATHL, as compared to around half in our previous trials. We have seen better survival figures than in our previous studies with less treatment overall, so it feels as though we are on the right track.
Dr. Sunita Sah[/caption]
Sunita Sah MD PhD
Management & Organizations
Johnson Graduate School of Management
Cornell University
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sah: Physicians often recommend the treatment they specialize in, e.g., surgeons are more likely to recommend surgery than non-surgeons. Results from an observational study and a randomized controlled laboratory experiment found that when physicians revealed their bias toward their own specialty, patients were more likely to report increased trust in the physician’s expertise and take the treatment in accordance with the physician’s specialty. 
Prof. Chris Semsarian[/caption]
Professor Chris Semsarian
MBBS PhD MPH FRACP FAHMS FAHA FHRS FCSANZ
Professor of Medicine, University of Sydney
Cardiologist, Royal Prince Alfred Hospital
NHMRC Practitioner Fellow
Head, Molecular Cardiology Program
Centenary Institute,
Newtown NSW Australia
MedicalResearch.com: What is the background for this study?
Response: Sudden cardiac death is a tragic and devastating event at all ages, and especially in the young (aged under 35 years). Understanding the causes and circumstances of SCD in the young is critical if we are to develop strategies to prevent SCD in the young. Our study represents the first prospective, population-based study of SCD in the young across two nations, Australia and New Zealand.
Dr. Guang Yang[/caption]
Guang Yang, Ph.D.
Assistant Professor
NYU Langone School of Medicine
Alexandria Center for Life Sciences
New York, NY 10016
MedicalResearch.com: What is the background for this study? How common is the problem of long-lasting behavioral deficits after repeated anesthesia exposure in neonates?
Response: Each year, in the United States alone, more than 1 million children under 4 years of age undergo surgical procedures that require anesthesia. Many lines of evidence from animal studies have shown that prolonged or repeated exposure to general anesthesia during critical stages of brain development leads to long-lasting behavioral deficits later in life. The results from human studies are less clear, although some studies suggest a higher incidence of learning disabilities and attention-deficit and hyperactivity disorders in children repeatedly exposed to procedures requiring general anesthesia. To date, there has been no effective treatment to mitigate the potential neurotoxic effects of general anesthesia.
Dr. Thomas Gaziano[/caption]
Thomas Andrew Gaziano, MD, MSc
Department of Cardiology
Assistant Professor
Harvard Medical School
MedicalResearch.com: What is the background for this study?
Response: Heart failure (HF) is the leading cause of admissions to hospitals in the United States and the associated costs run between $24-47 billion annually. Targeting neurohormonal pathways that aggravate the disease has the potential to reduce admissions. Enalapril, an angiotensin converting enzyme-inhibitor (ACEI), is more commonly prescribed to treat HF than Sacubitril/Valsartan, an angiotensin-receptor/neprilysin inhibitor (ARNI). The latter was shown to reduce cardiovascular death and hospitalizations due to heart failure in a multi-country, randomized clinical (PARADIGM-HF), compared to Enalapril. In order to assess the cost-effectiveness of Sacubitril/Valsartan, compared to Enalapril, in the United States, we created a model population with population characteristics equivalent to the population in the PARADIGM-HF trial. Using a 2-state Markov model we simulated HF death and hospitalizations for patients with a left ventricular ejection fraction (LVEF) of 40% or less.
Dr. Jonathan Hsu[/caption]
Jonathan Hsu, MD, MAS, FACC, FAHA, FHRS
Assistant Professor
Cardiac Electrophysiology, Division of Cardiology
University of California, San Diego (UCSD)
MedicalResearch.com: What is the background for this study?
Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and imparts significant stroke risk. In patients with AF determined to be at intermediate to high risk for thromboembolism, anticoagulation with warfarin (a vitamin K antagonist) or the newer non-vitamin K antagonist oral anticoagulants clearly reduces morbidity and mortality compared to aspirin. We sought to evaluate practice patterns of cardiovascular specialists in the United states to determine how often AF patients at risk for stroke are prescribed aspirin over oral anticoagulation, and predictors of this practice.
Dr. Gregory Marcus[/caption]
Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS
Director of Clinical Research
Division of Cardiology
Endowed Professor of Atrial Fibrillation Research
University of California, San Francisco
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We and others have previously demonstrated that, despite the observation that African Americans on average exhibit more risk factors for atrial fibrillation, they demonstrate a substantially reduced risk of the disease. This suggests that, if we could understand the mechanism underlying this apparent paradox, we might learn something fundamentally important to atrial fibrillation that would be relevant to treating or preventing the disease regardless of race.
Building on our previous work demonstrating that, among African Americans, more European ancestry (determined by genomic testing) was a statistically significant predictor of atrial fibrillation, we sought to identify the gene(s) that might underlie this observation. The analysis took two forms.
First, we examined if any differences among several well-established single nucleotide polymorphisms (SNP) associated with atrial fibrillation might mediate the race-atrial fibrillation relationship. One such SNP statistically mediated (rs10824026) up to about a third of the race-atrial fibrillation relationship. It’s important to mention that a causal relationship cannot be proven here.
Perhaps more remarkable was the observation that the disease-associated alleles of the SNPs most closely associated with atrial fibrillation in multiple studies were actually significantly more common among African Americans, pointing to the complex nature of both the race-atrial fibrillation relationship as well as the genetics of atrial fibrillation.
Finally, leveraging the ancestral relationships, we performed a genome wide admixture mapping study with the hope of reducing the penalty for multiple hypothesis testing incurred in conventional genome wide association studies. While several loci revealed associations with atrial fibrillation with small p values, none met our criteria for genome wide significance.
Dr. Gregg Fonarow[/caption]
Gregg C. Fonarow, MD, FACC, FAHA
Eliot Corday Professor of Cardiovascular Medicine and Science
Director, Ahmanson-UCLA Cardiomyopathy Center
Co-Chief of Clinical Cardiology, UCLA Division of Cardiology
Co-Director, UCLA Preventative Cardiology Program
David Geffen School of Medicine at UCLA
Los Angeles, CA, 90095-1679
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Fonarow: Angiotensin receptor neprilysin inhibitors (ARNI) have been demonstrated to reduce mortality in patients with heart failure with reduced ejection fraction. However, to date, the population level impact of optimal implementation of this therapy in the United States has not been evaluated.
This new analysis estimates that as many 28,484 deaths in heart failure with reduced ejection fraction patients annually could be prevented or postponed with optimal use of angiotensin receptor neprilysin inhibitors (with sensitivity analyses demonstrating a range of 18,230 to 41,017).
Dr. Kenneth Cusi[/caption]
Kenneth Cusi, M.D., F.A.C.P., F.A.C.E.
Professor of Medicine
VAMC staff
Chief, Division of Endocrinology, Diabetes and Metabolism
The University of Florida
Gainesville, FL 32610-0226
MedicalResearch.com: What is the background for this study?
Dr. Cusi: Many patients with prediabetes or Type 2 Diabetes Mellitus (T2DM) are not diagnosed with Nonalcoholic steatohepatitis (NASH), a disease that is the second cause of liver transplantation in the United States. It is also associated with worse cardiovascular disease and harder to control T2DM. We had done in this population a proof-of-concept study published in Nov 2006 in the NEJM. But we lacked a larger, long-term study for definitive proof. This is the largest SINGLE center study, and the longest ever (3 years).
NASH is an overlooked problem for perhaps as many as one-third of patients with Type 2 Diabetes Mellitus. There is now a safe and effective treatment option for patients with T2DM and NASH – pioglitazone will become for NASH what metformin is to the treatment of T2DM: a safe, effective, the “backbone therapy" to which other treatments will be added.
Dr. Brian Haas[/caption]
Brian W. Haas PhD
Department of Psychology
Interdisciplinary Neuroscience Graduate Program
University of Georgia, Athens, GA
MedicalResearch.com: What is the background for this study?
Response: A burgeoning body of evidence highlights the role of several key genes within the oxytocin signaling pathway linked to sociability. Although many studies strongly supports the role of OXTR in the phenotypic expression of sociability in humans, the roles of other oxytocin pathway genes, such asOXT, has received relatively little attention.
Dr. Taulant Muka[/caption]
Taulant Muka, MD, MPH, PhD
Postdoctoral Researcher
Department of Epidemiology
Erasmus University
Rotterdam, The Netherlands
MedicalResearch.com: What is the background for this study?
Response: Hot flashes, night sweats and vaginal dryness are very common symptoms of menopause, affecting up to 80% of women. Despite the availability of a wide range of pharmacological treatments and the best effort of health care professionals, good control of menopausal symptoms and their adverse effects remains elusive for much of the women. Some women choose hormone replacement therapy to treat menopausal symptoms, but for many others estrogen is not an option as long as some research suggests that it may rise the risk for breast cancer and heart disease. Therefore, 40 to 50% of women in Western countries choose to use complementary therapies, including plant-based therapies. These are many plant based-therapies that have been suggested to improve menopausal symptoms, but there is little guidance about which plant-based therapy is effective.
Dr. Peter Ganz[/caption]
Peter Ganz, MD
Chief, Division of Cardiology
Director, Center of Excellence in Vascular Research
Zuckerberg San Francisco General Hospital
Maurice Eliaser Distinguished Professor of Medicine
University of California, San Francisco
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ganz: The research described in the JAMA paper involved measuring 1,130 different proteins in nearly 2000 individuals with apparently stable coronary heart disease, who were followed up to 11 years. Initially, two hundred different proteins were identified whose blood levels could be related to the risk of heart attacks, strokes, heart failure and death, and ultimately a combination of nine proteins was selected for a risk prediction model, based on their combined accuracy and sensitivity.
Application of these findings to samples of patients with stable coronary heart disease demonstrated that some of those who were deemed clinically stable instead had a high risk of adverse cardiovascular outcomes, while other patients with the same clinical diagnosis had a very low risk. Thus, individuals who all carried the same clinical diagnosis of stable coronary heart disease had a risk of an adverse cardiovascular event that varied by as much as 10-fold, as revealed by analysis of the levels of the nine proteins in their blood. Given such large differences in risk and outcomes, patients could reasonably opt to be treated differently, depending on their level of risk. We hope that in the future, management of patients with stable angina will at least in part rely on risk assessment based on levels of blood proteins.
Dr. Mikhail Kolonin[/caption]
Mikhail Kolonin, PhD, Associate Professor
Director, Center for Metabolic and Degenerative Diseases
Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research
The Brown Foundation Institute of Molecular Medicine
University of Texas Health Science Center at Houston
Houston, TX 77030
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Epidemiology studies have indicated that in obese patients progression of prostate, breast, colorectal, and other cancers is more aggressive. Adipose (fat) tissue, expanding and undergoing inflammation in obesity, directly fuels tumor growth. Adipose tissue is composed by adipocytes and stromal/vascular cells, which secrete tumor-trophic factors. Previous studies by our group have demonstrated that adipose stromal cells, which support blood vessels and serve as adipocyte progenitors, are recruited by tumors and contribute to cancer progression. Mechanisms underlying stromal cell trafficking from fat tissue to tumors have remained obscure. We discovered that in obesity a chemokine CXCL1, expressed by cancer cells, attracts adipose stromal cells to tumors.
Dr. Gregoire Boulouis[/caption]
Dr. Gregoire Boulouis MD MS
Research Fellow at Massachusetts General Hospital / Harvard Med. School
Boston, Massachusetts
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Boulouis: Hemorrhagic Stroke or Intracerebral hemorrhage (ICH) still has a poor prognosis. A substantial proportion of patients will experience ongoing intracranial bleeding and their hematomas will grow in size in the first hours following presentation, a phenomenon called 'hemorrhage epxansion'. Patients with hemorrhage expansion have been shown to have significantly worse clinical outcome. If all baseline ICH characteristics (location, initial hemorrhage volume, ..) are non modifiable at the time of diagnosis, hemorrhage expansion, however, represents one of the few potential targets to improve outcome in ICH patients. An accurate selection of patients at high risk of expansion is needed to optimize patients' selection in expansion targetted trials and, eventually, to help stratifying the level of care at the acute phase.
In this study, we investigated whether the presence of non-contrast Computed Tomography hypodensities within the baseline hematoma, a very easily and reliably assessed imaging marker, was associated with more hemorrhage expansion.
A total of 1029 acute phase ICH patients were included ; approximately a third of them demonstrated CT hypodensities at baseline. In this population, CT hypodensities were independently associated with hemorrhage expansion with an odds ratio of 3.42 (95% CI 2.21-5.31) for expansion in fully adjusted multivariable model.
Dr. Alan Fayaz[/caption]
Dr Alan Fayaz
MA MBBS MRCP FRCA FFPMRCA
Consultant in Anaesthesia and Pain Medicine
University College London Hospital NHS Foundation Trust
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Fayaz: Despite fairly well established negative consequences of chronic pain (social, psychological, biological) very little is known about the burden of chronic pain in the United Kingdom. For example healthcare costs relating to chronic pain in the USA outstrip those of Cancer and Cardiovascular disease, and yet the profile of chronic pain (as disease in its own right) is not nearly as well established as either of those conditions. Surprisingly, prior to our study, there was little consensus regarding the prevalence of chronic pain in the UK. The purpose of our review was to synthesise existing data on the prevalence of various chronic pain phenotypes, in the United Kingdom, in order to produce accurate and contemporary national estimates.
Dr. John Mafi[/caption]
John N. Mafi, MD, MPH
Assistant Professor of Medicine
Division of General Internal Medicine and Health Services Research
UCLA David Geffen School of Medicine
Los Angeles, CA 90024
Affiliated Adjunct in Health Policy
RAND Corporation
Santa Monica, CA 90401
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Mafi: The U.S. healthcare system faces a looming shortage of primary care physicians, with some estimates as high as 20,000 physicians by the year 2020. In addition, fewer and fewer trainees enter primary care careers because of the harder work and lower salaries. Combine this with the passage of the Affordable Care Act and the millions of newly insured patients looking for a primary care provider, and you have created a perfect storm where timely access to primary care becomes essentially unachievable.
Many advocate for expanding the role of nurse practitioners and physician assistants to mitigate the physician shortage. But this is controversial as most doctors believe nurse practitioners provide inferior care to doctors and many feel that expanding their role would worsen the value and efficiency of the U.S. healthcare system.
While studies suggest they provide similar quality of care to physicians, few have actually evaluated whether they provide greater amounts of inefficient or low value care. Low value care is important because it can harm patients (antibiotics for colds don’t help patients and have harmful side effects) and they can raise healthcare costs. In this context, we used a large national database on ambulatory visits to compare the quality and efficiency of care among nurse practitioners, physician assistants, and physicians in the U.S. primary care setting.
In our 15 year analysis of nearly 29,000 patients who saw either a nurse practitioner, physician assistant, or a physician, we found similar rates of inappropriate antibiotic use for colds, unnecessary imaging (such as x-rays, CT scans, and MRI scans) for back pain and headache, and potentially necessary referrals to specialists for these same three conditions.
Dr. Morgan Freiman[/caption]
J. Morgan Freiman, MD
Infectious disease research fellow
Boston Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Freiman: There are 130-150 million persons infected with chronic HCV with 75% of all cases occurring in low- and middle- income countries (LMICs). Diagnosis is a 2-step process that starts with screening for exposure with an assay that detects antibodies to HCV (anti-HCV), followed by nucleic acid testing (NAT) for persons with reactive anti-HCV to measure HCV ribonucleic acid (RNA) and confirm active viremia.
In LMICs diagnostic capacity is low, and fewer than 1% of patients are aware of their infection. Additionally, a significant proportion of patients who test positive for anti-HCV are lost to follow-up before nucleic acid testing. The 2-step diagnostic process is thus a major bottleneck to the HCV cascade of care. Testing for hepatitis C virus core antigen (HCVcAg) is a potential replacement for NAT.
Our systematic review evaluated the accuracy of diagnosis of active HCV infection among adults and children for 5 commercially available HCVcAg tests compared with NAT. We found that HCVcAg assays with signal amplification have high sensitivity, high specificity, and have the potential to replace NAT in settings with high HCV prevalence.
Dr. Steven Woloshin[/caption]
Steven Woloshin, MD
Professor of The Dartmouth Institute
Professor of Medicine
Professor of Community and Family Medicine
New Hamphsire
MedicalResearch.com: What is the background for this study?
Dr. Woloshin: Drug companies are required by law to post results of trials used to support drug applications to the FDA on the clinicaltrials.gov website - but it is not clear whether posted results are complete and accurate. Recent studies attempting to validate posted results by comparing them to corresponding peer reviewed medical journal publications suggest that discrepancies are relatively common. But it is which source is more likely to be correct. We tried to validate posted results against an arguably better gold standard, the drug approval packages from the FDA (ie, the medical and statistical reviews posted on the drugs@fda.gov website). FDA reviews have an advantage over peer reviewed publications: unlike medical journal editors and peer reviewers, FDA has access to the individual participant data from the trials. This means FDA can see all the trials and all the outcomes (avoiding sleective publication) and it means FDA can independently reanalyze according to what they believe to be the best statistical practices (data can be analyzed in many ways - and different decisions, for example, how to account for missing data, can yield very different results).
Dr. James Freeman[/caption]
Dr. James V. Freeman MD
Assistant professor of cardiology and
Assistant Clinical Professor of Nursing
Internal Medicine
Yale School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Freeman: Randomized trials of left atrial appendage (LAA) closure with the Watchman device have shown varying results, and its cost-effectiveness compared to anticoagulation has not been evaluated using all available contemporary trial data.
We used a Markov decision model to estimate lifetime quality-adjusted survival, costs, and cost-effectiveness of LAA closure with Watchman, compared directly with warfarin and indirectly with dabigatran, using data from the long-term (mean 3.8 year) follow-up of PROTECT AF and PREVAIL randomized trials. Using data from PROTECT AF, the incremental cost-effectiveness ratios (ICER) compared to warfarin and dabigatran were $20,486 and $23,422 per quality adjusted life year (QALY), respectively. Using data from PREVAIL, LAA closure was dominated by warfarin and dabigatran, meaning that it was less effective (8.44, 8.54, and 8.59 QALYs, respectively) and more costly.