MedicalResearch.com Interview with:
Jeffrey (Jerry) G. Jarvik MD MPH
Professor, Radiology, Neurological Surgery and Health Services
Adjunct Professor, Pharmacy and Orthopedics & Sports Medicine
Director, Comparative Effectiveness, Cost and Outcomes Research Center University of Washington Seattle, WA
Medical Research: What is the background for this study?
Dr. Jarvik: When I arrived at the Univ of WA over 20 years ago, my mentor, Rick Deyo, had just finished leading a project that was responsible for developing one of the first set of guidelines for the diagnosis and treatment of acute low back pain. These guidelines, published in a booklet by AHRQ (then called AHCPR), recommended that patients with acute low back pain not undergo imaging for 4-6 weeks unless a red flag was present. One of the exceptions was that patients older than 50 could get imaged immediately, the rationale being that older adults had a higher prevalence of potentially serious conditions such as cancer, infections, etc, that would justify the early imaging. As a practicing neuroradiologist, it was clear that a potential problem with this strategy is that the prevalence of age-related changes, which may or may not be related to back pain, also increases with age. So earlier imaging of older adults would almost certainly reveal findings, and these could easily start a series of unfortunate events leading to potentially poor outcomes and more healthcare resource use. Thus this policy of early imaging of older adults didn’t entirely make sense.
About 5 years ago, these guidelines hit home when I developed acute low back pain and since I was over 50 (barely) my doctor recommended that I get an imaging study. Being a knowledgeable patient and having a reasonable doctor, we mutually agreed not to get the study. I improved but that wasn’t the end of it. When we had the chance to apply for one of the CHOICE ARRA awards funded by AHRQ, we made answering this question of early imaging in older adults one of our primary goals.
MedicalResearch.com Interview with:
Marco Valgimigli, MD, PhD
Erasmus MC, Thoraxcenter,
Rotterdam The Netherlands
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Valgimigli: Interventional cardiologists can choose between two entry sites in order to perform a diagnostic coronary angiography and or a percutaneous coronary intervention, namely an artery which is in the groin called femoral artery or an artery which is located in the wrist which is called radial artery. The latter is more superficial and has small calibre as compared to the former. Femoral artery is the entry site which is most frequently used in the world especially in US where the use of radial artery is relatively limited.
Our study randomly allocated 8,404 patients to undergo diagnostic coronary angiography and PCI, if clinically indicated, either vie the femoral or the radial artery.
The main results of our study are that radial access reduced the composite of net adverse clinical events driven by a reduction of mortality and of major bleeding, including transfusions and need for surgical repair or the entry site.
MedicalResearch.com Interview with:
Jagpreet Chhatwal Ph.D.
Assistant Professor, Department of Health Services Research
Division of Cancer Prevention and Population Sciences
The University of Texas MD Anderson Center
Houston, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Chhatwal: More than two million people in the U.S. are infected with Hepatitis C (HCV), a virus found in the liver. In 2012, the Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force both recommended a one-time hepatitis C screening for baby boomers – people born between the years 1946 and 1964. Last year, the Food and Drug Administration approved the medications sofosbuvir and ledipasvir for Hepatitis C treatment. The newly approved oral regimen comes at a staggering price to payers – as much as $1,125 per day. As a result, several payers have questioned if the price is justified.
The study results show that using new therapies is cost-effective in the majority of patients. However, the budget required to treat all eligible patients would be $136 billion over the next five years. Compared with the old drugs, new therapies would cost an additional $65 billion, whereas the cost offsets would be only $16 billion.
MedicalResearch.com Interview with:
Pam R. Taub, MD, FACC
Assistant Professor of Medicine
UC San Diego Health System
Division of Cardiology Encinitas, CA 92024
Medical Research: What is the background for this study?
Dr. Taub: Epidemiological studies indicate that the consumption of modest amounts of dark chocolate (DC), which contains the natural cacao flavanol (-)-epicatechin (Epi,) is associated with reductions in the incidence of cardiovascular diseases (CVD). The health benefits of dark chocolate have been attributed to Epi. Clinical studies using cocoa and/or DC in normal volunteers or subjects with CVD have reported improvements in peripheral and coronary vascular endothelial function, blood pressure, lipids, insulin resistance, and inflammatory markers. The mechanism underlying these improvements is thought to be due to increased nitric oxide levels and improved endothelial function. We have also shown that capacity of Epi to favorable impact mitochondria under normal and disease states.
We previously conducted pilot study in five patients with heart failure and type II diabetes, and showed that in skeletal muscle (SkM) biopsies there is a severe reduction in mitochondrial volume and cristae, as well as, in structural/functional proteins. After treatment with Epi rich dark chocolate , there was a significant recovery of SkM mitochondrial cristae, structural/functional proteins (e.g. mitofilin), as well as in regulators of mitochondrial biogenesis. However, no studies have examined the capacity of Epi rich dark chocolate to enhance exercise capacity in normal subjects and assess its impact on mitochondrial and oxidative control systems.
Medical Research: What are the main findings?
Dr. Taub: Seventeen subjects were randomized to placebo (n=8) or DC groups (n=9) and consumed 2 squares of chocolate (20 g, provided by Hershey) for 3 months.
We showed in the chocolate group subjects had improved levels of HDL cholesterol and enhanced exercise capacity that is linked to the stimulation of SkM metabolic control endpoints which enhance mitochondrial function.
MedicalResearch.com Interview with:
Jay S. Kaufman, Ph.D
Canada Research Chair in Health Disparities
Department of Epidemiology, Biostatistics, and Occupational Health
McGill University
Montreal, Quebec Canada
Medical Research: What is the background for this study? What are the main findings?
Response: Published scientific articles speculate frequently about genetic predispositions in different racial groups as explanations for observed disease disparities. They infer this from the higher rates observed in racial minorities, even after adjusting for some social and behavioral measures. Taking the example of the racial disparity between blacks and whites in cardiovascular diseases (stroke, heart attack, heart failure, hypertension, etc), ours is the first published study to review all of the existing results from GWAS (genome-wide association studies) to see if they provide any support for this commonly stated position. To date, they do not. We performed an electronic literature search through the PubMed database to identify review articles and meta-analyses related to genetic risk factors for cardiovascular disease in samples that included populations of European and African ancestries. We focused our search on the 7-year period from January 1, 2007 to January 1, 2014, which corresponded to the rapid proliferation of large pooled GWAS activity. This search strategy yielded 197 review articles or meta-analyses. 68 of these articles contained relevant data, but very few reported significant associations in both racial groups, with just 3 variants meeting study-specific significance criteria. For most outcomes, there were too few estimates for quantitative summarization, but when summarization was possible, racial group did not contribute to heterogeneity. Most associations reported from genome-wide searches were small, difficult to replicate, and in no consistent direction that favored one racial group or another.
MedicalResearch.com Interview with:
Sameer Bansilal, MD, MS
Asst. Prof.- Medicine and Cardiology
Clinical Trials & Global Health Studies
Icahn School of Medicine at Mount Sinai
Medical Research: What is the background for this study? What are the main findings?
Dr. Bansilal: Our group has previously published data from FREEDOM, COURAGE and BARI showing that adherence to recommended therapies are low in diabetic (DM) patients. We have spent the last decade developing a potential solution to this- the Fuster-Ferrer polypill. This study was done to better inform the association between levels of medication adherence and long term major adverse cardiovascular events (MACE) in high risk diabetic patients.
We analyzed a U.S. health insurers’ claims data for 19,962 high risk diabetic subjects. Using proportion of days covered (PDC) for 1 year after first refill, we stratified patients as fully adherent (FA≥80%), partially adherent (PA ≥40- ≤79%) or non-adherent (NA <40%) and examined the associations with a primary cardiovascualr outcome measure of death, myocardial infarction, stroke and coronary revascularization. We found that only 34% participants were fully adherent to therapy. When compared to being non-adherent at 2 yrs follow up,, being fully adherent was associated with a 28% lower rate of MACE; being partially adherent was associated with a 21% lower rate of MACE. Efforts towards improving adherence in diabetic subjects may lead to substantial reductions in MACE.
MedicalResearch.com Interview with: Jonathan D. Newman, MD, MPH Instructor of Medicine The Leon H Charney Division of Cardiology and The Center for the Prevention of Cardiovascular Disease New York University School of Medicine NY, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Newman: Outdoor fine air pollution (PM2.5 defined...
MedicalResearch.com Interview with Filippo Calzolari PhD Institute of Stem Cell Research, ISF-N Helmholtz Zentrum München Neuherberg Germany MedicalResearch: What is the background for this study? What are the main findings? Dr. Calzolari: Despite their amazing complexity, life-long production of new neurons occurs in only a few well-circumscribed areas in adult mammalian brains, thanks to the...
MedicalResearch.com Interview with: Jaspreet Ahuja, Nutritionist
USDA, Agricultural Research Service
Nutrient Data Laboratory
Beltsville, MD 20705
MedicalResearch: What is the background for this study? What are the main findings?
Response: Most sodium in the U.S. diet comes from commercially processed and restaurant foods. Sodium reduction in these foods is key to several recent public health efforts. In this paper, we provide an overview of a program led by Nutrient Data Laboratory, USDA, in partnership with CDC and FDA to monitor sodium contents in commercially processed and restaurant foods in United States.
We track about 125 highly consumed, sodium-contributing foods, termed “Sentinel Foods” annually using information from food manufacturers and periodically by nationwide sampling and laboratory analyses. In addition, we monitor over 1,100 other commercially processed and restaurant food items, termed “Priority-2 Foods,” biennially using information from food manufacturers. These foods serve as indicators for assessing changes in the sodium content of commercially processed and restaurant foods in the U.S. In addition to sodium, we are monitoring related nutrients (potassium, total dietary fiber, total and saturated fat, total sugar) because their levels may change when manufacturers and restaurants reformulate their products to reduce their sodium content.
We sampled all Sentinel Foods nationwide and reviewed all Priority-2 Foods in 2010–2013 to determine baseline sodium concentrations. The results of sodium reduction efforts, based on re-sampling of the Sentinel Foods or re-review of P2Fs, will become available in 2015 on our website. The updated data are also released in USDA food composition databases, National Nutrient Database for Standard Reference and Food and Nutrient Database for Dietary Studies.
MedicalResearch.com Interview with:
Colleen K. McIlvennan, DNP, ANP
Assistant Professor of Medicine
University of Colorado, Division of Cardiology
Section of Advanced Heart Failure and Transplantation
Medical Research: What is the background for this study?
Response: Destination therapy left ventricular assist device (DT LVAD) patients are often older with significant comorbidities that preclude heart transplantation. As such, the decision to get a DT LVAD is arguably more complicated than the decision to receive a temporary LVAD in anticipation of a transplant. Centers offering LVADs often require the identification of a caregiver prior to proceeding with the implant. Caregivers are commonly female spouses of DT LVAD patients, who are also older with co-morbidities. Understanding their perspective in DT LVAD decision making is extremely important as they are at particular risk for experiencing stress and caregiver burden due to the increased demands on caregiving with DT LVAD.
Medical Research: What are the main findings?
Response: We performed semi-structured qualitative interviews with 17 caregivers: 10 caregivers of patients living with DT LVAD, 6 caregivers of patients who had died with DT LVAD, and 1 caregiver of a patient who had declined DT LVAD. Throughout the interviews, the overarching theme was that considering a DT LVAD is a complex decision-making process.
Additionally, three dialectical tensions emerged:
1) the stark decision context, with tension between hope and reality;
2) the challenging decision process, with tension between wanting loved ones to live and wanting to respect loved ones’ wishes; and
3) the downstream decision outcome, with tension between gratitude and burden.
MedicalResearch.com Interview with:
Prof. David Newby
British Heart Foundation Professor of Cardiology
University of Edinburgh
Director of the Wellcome Trust Clinical Research Facility
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Newby: The diagnosis of angina (chest pain) due to coronary heart disease can be very challenging and we often get it wrong. We have a wide range of tests that can try and identify patients with angina due to coronary heart disease. However, even with these tests, we fail to identify 1 in 3 patients who go on to have heart attacks. So we need better tests.
The study shows that if you add CTCA to a clinic consultation, you clarify the diagnosis in 1 in 4 patients, alter the investigations in 1 in 6 and change the subsequent treatments in 1 in 4. This did appear not only to increase the use of coronary revascularisation but also reduce the risk of subsequent heart attacks by 38-50%.
MedicalResearch.com Interview with:
Ricardo Stein, MD, ScD
Exercise Cardiology Research Group, Cardiology Division
Federal University of Rio Grande do Sul, Hospital de Clinicas de Porto Alegre,
Porto Alegre, RS, Brazil
MedicalResearch: What is the background for this study?
Dr. Stein: Patients with a recent myocardial infarction (MI) present a reduction in functional capacity expressed as a decrease in peak oxygen consumption (VO2 peak). The impact of a Tai Chi Chuan (TCC) cardiac rehabilitation program for patients recovering from recent MI has yet to be assessed. Our goal was to evaluate functional capacity after a TCC-based cardiac rehabilitation program in patients with recent non complicated MI.
MedicalResearch: What are the main findings?
Dr. Stein: After the 12-week study period, participants in the Tai Chi Chuan group experienced a significant 14% increase in VO2 peak from baseline (21.6 ± 5.2 to 24.6 ± 5.2 mL.Kg-1.min-1), whereas control participants had a non-significant 5% decline in VO2 peak (20.4 ± 5.1 to 19.4 ± 4.4 mL.Kg-1.min-1). There was a significant difference between the two groups (P<0.0001).
As a primary outcome, CPET results for the TCC and control groups at baseline and after the 12-week intervention period leading to a significant difference in peak VO2 (5.2 mL.Kg-1.min-1; 95% CI, 2.8 to 7.7, in favor to TCC group). This difference remained significant after adjustment to baseline measurements, age, gender, diabetes, and smoking (4.1 mL.Kg-1.min-1; 95% CI, 2.6 to 5.6, in favor to TCC group).
Summarizing:
- We observed a significant increase in VO2 peak in TCC group participants.
- Our results provide important information data from a randomized clinical trial of Tai Chi Chuan in patients with a history of recent MI.
- Tai Chi Chuan can be an attractive alternative to cardiac rehabilitation for patients who don't have access to conventional cardiac rehabilitation programs.
MedicalResearch.com Interview with:
Barnaby C. Reeves, D.Phil.
Professor of Health Services Research, Clinical Trials & Evaluation Unit
School of Clinical Sciences, University of Bristol
Bristol Royal Infirmary Bristol
Medical Research: What is the background for this study?
Response: Variable decisions are made about when to transfuse patients after cardiac surgery. The circumstances of particular patients influence decisions about whether to give a transfusion.
Transfusion is a life-saving intervention when a patient is experiencing life-threatening bleeding but most patients have only one or two units of red cells transfused. These transfusions are given at varying levels of anaemia. Some doctors prefer to give a transfusion after cardiac surgery when a patient is only mildly anaemic, believing that the transfusion will promote recovery, while other doctors prefer to wait to transfuse until a patient is substantially anaemic, believing that a transfusion may do more good than harm and is wasteful if it is not needed. Therefore, we carried out a randomized controlled trial comparing restrictive (transfuse when haemoglobin <7.5 g/dL) and liberal transfusion thresholds (transfuse when haemoglobin <9.0 g/dL).*
Medical Research: What are the main findings?
Response: We obtained written informed consent before surgery but only randomized participants after surgery, in intensive care, if their Hb dropped below 9 g/dL. (Hence, we recruited over 3,500 patients but randomized only 2007.) This design avoids ‘diluting’ any difference between groups by including participants who would not usually be ‘considered’ for transfusion.
The primary outcome was the occurrence of one or more serious complications: heart attack, stroke, acute kidney injury, bowel infarction, infection; this included/involved 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group. This slight difference – more in the restrictive group – was not statistically significant.
We then compared the percentages of patients who died; these were 4.2% in the restrictive group and 2.6% in the liberal group. The difference in this secondary outcome was of borderline statistical significance. Frequencies of other secondary outcomes (infections, ischaemic events, days in critical care and hospital, pulmonary complications) were not different in the two groups.
We also carried out some pre-specified sensitivity analyses for the primary outcome and all-cause mortality. The two most important ones aimed to avoid dilution of the difference between groups as a result of patients having transfusions or outcome events before randomization. Excluding patients who were transfused before randomization shifted the treatment effect to favour the liberal threshold more strongly, for both the primary outcome and mortality. Excluding patients who experienced an outcome event in the first 24 hours after randomization did not change the treatment effect for either outcome.
Dr. Ana Ramírez-Boscá, MD
Department of Dermatology and Clinical Research Unit and
Vicente Navarro-López, MD
Clinical Research Unit and Infectious Diseases Unit
Centro Dermatológico Estético, Alicante, Spain
MedicalResearch: What is the background for this study? What are the main findings?
Response: Infections have been related with the pathogenesis of guttate psoriasis, however antibiotic treatment does not improve prognosis nor does it affect the evolution of the disease. The association between psoriasis and other infectious diseases has been reported as well, although in these cases there is scarce information on the causative microbial likely involved and the role of these bacteria in the pathogenesis of this skin disease.
MedicalResearch: What are the main findings?
Response: Bacterial DNA may be detected in bloodstream of a significant proportion of patients with active plaque psoriasis. Increased levels of pro-inflammatory cytokines in patients with presence of bacterial DNA but not in patients without presence of bacterial genomic fragments suggest a role of bacterial DNA translocation in inducing an inflammatory response.
[caption id="attachment_12680" align="alignleft" width="300"]
Guttate Psoriasis
MedicalResearch.com Interview with:
Stella Yi, Ph.D., MPH, Assistant Professor
Department of Population Health
New York University School of Medicine
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Yi: Self-blood pressure monitoring has been shown to be an effective tool for improving blood pressure control, however most studies have only included white race participants. We were interested in assessing whether distribution of self-blood pressure monitors (intervention) would improve blood pressure and hypertension control over usual care (control) in a 9-month period in a predominantly Hispanic, uninsured population. Systolic blood pressure improved over time in both the intervention (n=409) and the control (n=419) arms by 14.7 mm Hg and 14.1 mm Hg, respectively, as did hypertension control; 39% of study participants overall achieved control at the end of follow-up. However there were no statistical differences between the outcomes in the intervention and usual care groups.
MedicalResearch.com Interview with:
Harold P. Erickson Ph.D.
James B. Duke Professor, Department of Cell Biology
Duke Univ. Med. Center Durham, NC 27710
MedicalResearch: What is the background for this study?
Dr. Erickson: In Jan 2012 a paper reported the discovery of irisin, a hormone reportedly lopped off a precursor in muscle and sent through the bloodstream to fat tissue, where it turned white fat into brown fat. Brown fat burns calories, and is what hibernating animals – and even human babies -- use to keep warm. Turning on brown fat had exciting promise for obesity, diabetes, etc. Dozens of labs around the world jumped on the discovery and started trials in animals and humans of how irisin levels in blood were altered by exercise and a variety of metabolic challenges.
MedicalResearch: What are the main findings? Early reports.
Dr. Erickson: The follow-up studies from different labs reported a huge range of values for the level of irisin in blood, so they could not all be right. And most of them failed to find any significant effect of exercise. In 2013 two papers criticized the irisin study. A commentary article by Harold Erickson (Adipocyte 2:289-93) reported two substantial flaws in the original study. A research paper by S. Raschke, J. Eckel and colleagues (PloS one 8:e73680) concluded that humans did not make significant amount of irisin. The human gene for irisin has a deleterious mutation in the start codon, and Raschke et al showed that this reduced irisin expression to only 1% the level with the normal start. These two reports may have slowed new labs entering the field, but many groups already invested continued to publish.
Sabine Roza MD[/caption]
MedicalResearch.com Interview with:
Sabine Roza MD Ph.D. and
Ayesha Sajjad MD, Phd student
Department of Child and Adolescent Psychiatry & Psychology
Department of Psychiatry, Erasmus MC,
Rotterdam, The Netherlands.
Medical Research: What is the background for this study? What are the main findings?
Dr. Roza: WHO guidelines recommend six months of exclusive breastfeeding followed by partial breastfeeding until two years for overall optimum growth and development of children. However, the role of breastfeeding duration on child cognitive development remains a topic of continual debate. Previous research has shown mixed results on the role of breastfeeding duration and exclusivity on child IQ. Several methodological differences in study design inhibit comparisons of these studies and thus limit their generalizability. Furthermore, the association of breastfeeding with child cognitive development is subject to confounding by various factors especially maternal IQ. Therefore, we aimed to study the association between breastfeeding duration and breastfeeding exclusivity with non-verbal IQ in children. We used data the Generation R Study, which is a prospective cohort study from fetal life until young adulthood. Due to the large variability in ethnic backgrounds in our study participants, we focused on non-verbal IQ. In a large sample of 3761 children aged on average 6 years, we found an initial advantage of 0.32 points in non-verbal IQ for every increasing month of breastfeeding, which strongly attenuated after adjustments were made for child factors, maternal factors, sociodemographic factors, parental lifestyle and maternal IQ. Similar attenuation of effect sizes was observed for breastfeeding duration as a categorical variable and duration of exclusive breastfeeding.
MedicalResearch.com Interview with:
Theodore J. Cicero, PhD
Professor, Vice Chairman for Research
Department of Psychiatry, Washington University
St Louis, Missouri
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Cicero: Prescription opiate abuse (eg Vicodin, Percocet, OxyContin) has reached epidemic proportions in this country over the past decade. Although most people swallow the drugs whole, a relatively large number either chew the drugs to produce an immediate delivery of large quantities of drugs or they crush them and/or dissolve them in some solvent which makes them useful for intranasal (eg snorting) or intravenous administration. Non-oral routes, particularly injection, represent the most serious public health risk due to a high incidence of infection, including Hepatitis C and HIV, and the much greater severity of abuse. In an effort to reduce these practices, drug companies are introducing so-called abuse deterrent formulations (ADF) which are resistant to crushing or dissolving in an aqueous solution. In one such important effort, the company responsible for distributing one of the most widely abused prescription opiates, OxyContin, introduced an ADF in 2010. Although the abuse deterrent formulations was highly successful in reducing abuse of OxyContin by either chewing, crushing, or dissolving in water, there was none-the-less a clear limit to how effective it was. For example, some people simply switched to the oral route of administration or never did snort or inject the drug, whereas a small number found ways to defeat the abuse deterrent formulations and persisted in harmful patterns of abuse. Unfortunately, there was also an unintended result. ADF-OxyContin caused many individuals to abandon the use of OxyContin - a good thing - in favor of other opiates (a bad thing). Most serious, however, was that 70% of those who switched drugs moved from OxyContin to heroin abuse. Although by no means the only factor, the abuse deterrent formulations has contributed to the wide-spread reports of heroin abuse in suburban and rural Caucasian male and females, a group here-to-fore not the typical heroin users (i.e. poor minorities, living in large urban centers).
MedicalResearch.com Interview with: Matthijs A. Velders, MD PhD Uppsala Clinical Research Center Uppsala, Sweden. Medical Research: What is the background for this study? What are the main findings? Dr. Velders: Outcomes in patients with ST-elevation myocardial infarction have been substantially improved by early reperfusion with primary percutaneous coronary intervention, but recurrent events after the acute...
MedicalResearch.com Interview with:
Matthew B. Yurgelun, MD
Instructor in Medicine
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Yurgelun: Germline mutations in the TP53 gene are linked to Li-Fraumeni syndrome, which is an inherited syndrome associated with a 73-100% lifetime risk of cancer. Classically, cancers linked to Li-Fraumeni syndrome include early-onset breast cancer, leukemias, soft tissue sarcomas, brain cancer, and adrenocortical cancer, although recent data have shown an increased risk of colorectal cancer as well. Our study’s primary aim was to determine the frequency of germline TP53 mutations in patients with early-onset colorectal cancer.
We studied 457 patients from the multinational Colon Cancer Family Registry who were diagnosed with colorectal cancer at age 40 or younger, and found that 1.3% carried a germline alteration in the TP53 gene. None of these individuals had personal or family histories of cancer that fulfilled clinical criteria for Li-Fraumeni syndrome.