MedicalResearch.com Interview with:
Wael A. Jaber, MD FACC, FAHA
Professor of Medicine
Cleveland Clinic Lerner College of Medicine
Fuad Jubran Endowed Chair in Cardiovascular Medicine
Heart and Vascular Institute
Cleveland Clinic Cleveland, OH
Medical Research: What is the background for this study? What are the main findings?
Prof. Jaber: Risk stratification of patients presenting with atrial fibrillation often includes a non-invasive evaluation for coronary artery disease. However, the yield of such testing in patients without angina or anginal-equivalent symptoms is uncertain. That is, how often do we find silent myocardial ischemia?
In our cohort of 1700 consecutive patients with atrial fibrillation, less than 5% had ischemia on nuclear stress testing, even though comorbidities were prevalent. Moreover, in patients with ischemia that had invasive coronary angiography, less than half had obstructive coronary artery disease.
MedicalResearch.com Interview with:
Prof. Dr. Holger Lode
Clinical Immunology, Pediatrics
University of Greifswald, Greifswald
Medical Research: What is the background for this study?
Response: Neuroblastoma is a cancer in childhood with one of the highest death rates. Standard treatment is already very intensive. It includes chemotherapy, surgery, radiation, high dose chemotherapy followed by autologous stem cell transplantation. However, the progress made in improving survival rates is still poor.
The use of an immune-modulatory treatment with a neuroblastoma specific monoclonal antibody ch14.18 (100 mg/m2 /cycle) in combination with cytokines and 13cis retinoic acid (13 cis RA) has shown benefit for patients with this disease [1]. This antibody targets ganglioside GD2 abundantly expressed on neuroblastoma with limited to no expression on healthy tissue. Low expression of GD2 on pain fibers is associated with an on-target side effect of the treatment, which is the induction of neuropathic pain. Approval of ch14.18 (dinutuximab) for the treatment of children with neuroblastoma has been provided by FDA.
In Europe, ch14.18 was not available for a long time. There were several reasons why the antibody in the US could not be given to children in Europe. Therefore a new development of this side of the Atlantic was initiated following the remanufacturing of the antibody in CHO cells [2] (dinutuximab beta) and was made available within clinical trials of the SIOPEN group. The SIOPEN group is a network of leading European pediatric oncology centers to improve outcome for children with neuroblastoma (http://www.siopen.org), similar to the COG (children`s oncology group in the USA; https://www.childrensoncologygroup.org).
Following the recloning procedure, ch14.18/CHO was first evaluated for safety in a Phase I study [3], which confirmed the tolerability and showed activity at a dosing regimen of 20 mg/m2 given by 8 hour infusions on 5 consecutive days. Dinutuximab beta is further developed by Apeiron Biologics.
The current way to apply 100 mg /m2 / cycle is by 4 short term infusions of 25 mg/m2/day each over 8 hrs on 4 consecutive days. The entire treatment consists of 5 cycles. The drawback is that STI is associated with a high amount of intravenous morphine required to make this treatment tolerable for patients. Also the rate of inflammatory side effects observed is substantial.
Clinical observation indicates that if patients treated by STI suffer from pain despite analgesic treatments, a decrease in speed of antibody infusion improves this on target toxicity. Therefore, we hypothesized that significant prolongation of the time of antibody infusion will improve tolerability of that treatment, but at the same time maintains clinical activity and efficacy in high risk neuroblastoma patients.
MedicalResearch.com Interview with:
Chiara Dall'Ora MSc
Nursing and Midwifery Sciences
University of Southampton
Medical Research: What is the background for this study? What are the main findings?
Response: There is a trend for healthcare employers to adopt longer shifts, typically 2 shifts per day each lasting 12 hours. This allows nurses to work fewer shifts each week. Changes are driven by perceived efficiencies for the employer, and anecdotal reports of improved work life balance for employees because they work fewer days per week. However, it is unclear whether these longer shits adversely affect nurses' wellbeing, in terms of burnout, job dissatisfaction, dissatisfaction with work schedule flexibility and intention to leave the job.
We found that when nurses work 12 h shifts or longer they are more likely to experience high burnout, dissatisfaction with work schedule flexibility and intention to leave their job, compared to nurses working 8 h or less. All shifts longer than 8 hours are associated with nurses' job dissatisfaction.
MedicalResearch.com Interview with:
Jingyuan Fu, Ph.D.
Associate professor of genetics
University Medical Center Groningen
Netherlands
Medical Research: What is the background for this study? What are the main findings?
Dr. Jingyuan Fu: Abnormal blood lipid levels are important risk factors for cardiovascular diseases. Because of that, a common advice is to have a healthy lifestyle or take lipid-lowering drugs like statin to control the blood lipid level. However, the problem is only partially solved. Cardiovascular disease remains the No 1 cause of death globally, representing 31% of all global deaths. The primary purpose of the study is to look for a new solution in humans’ gut. Over millions of years, microbes and humans have formed a truly symbiotic relationship. Human body contains 10 trillion bacteria, 10x more than human cells. They help digest food and train our immune systems. As less than 30% of bacteria in human gut can be cultured, we know very little how they are and what they do in our gut. With the state-of-art deep sequencing technology, we are now able to see who are there. The research questions would be how much effect these bacteria could affect the blood lipids levels and which bacteria play important role. No such an analysis was done in large-scale human population.
Our study was the first to provide solid evidence for the associations between gut bacteria and blood lipids. Although we cannot conclude cause-effect relationship yet, it serves an important step in narrowing possible therapeutic targets.
MedicalResearch.com Interview with:
Jennifer W. Bea, PhD
Assistant Professor, Medicine
Assistant Research Scientist, Nutritional Sciences
University of Arizona Cancer Center
Tucson, AZ 85724-0524
Medical Research: What is the background for this study? What are the main findings?
Dr. Bea: The analysis was based on a subgroup of the largest study of post-menopausal women in the United States, Women's Health Initiative (WHI), which has been answering important questions about health and wellness among post-menopausal women since the 1990s. In the analysis, body mass index, a proxy for body fat, and actual body composition (i.e. fat and muscle mass) determined by an imaging technique called dual energy X-ray absorptiometry (DXA) were used to predict risk of death. In the younger post-menopausal women, aged 50–59 years, higher body fat increased risk of death by more than 2 times and the highest muscle mass decreased risk of death by almost 60%. Importantly, the relationships were reversed among the older women, aged 70–79 years (P < 0.05). These results were true in spite of BMIs in these groups spanning nearly the full range of possible BMIs (16.4–69.1kg/m2). These data indicate that BMI does not estimate mortality risk as well as we would hope among post- menopausal women.
MedicalResearch.com Interview with:
Ana C. Krieger, MD, MPH, FCCP, FAASM
Medical Director, Center for Sleep Medicine
Associate Clinical Professor
Departments of Medicine, Neurology and Genetic Medicine
Weill Cornell Medical College - Cornell University
Associate Attending
NewYork-Presbyterian Hospital
Rockefeller University Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Krieger: For many years, sleep researchers have been concerned about sleep deprivation in adolescents. Our study shows that high school students have shorter sleep duration on the nights following the spring Daylight Saving Time adjustment. This sleep loss was associated with a decline in daytime vigilance and cognitive performance on the week following DST.
MedicalResearch.com Interview with:
PD Dr. med. Christian Heiß
Sektion Angiologie
Oberarzt, Facharzt für Innere Medizin und Angiologie
Klinik für Kardiologie, Pneumologie und Angiologie
Universitätsklinikum Düsseldorf
Medical Research: What is the background for this study? What are the main findings?
Response: There is an extensive body of research which has shown that cocoa flavanols can improve healthy blood vessel function. However, for the most part, these investigations have focused on high-risk individuals like smokers and people that have already been diagnosed with conditions like hypertension and coronary heart disease. The purpose of the FLAVIOLA HEALTH study, published in BJN, was to find out whether the beneficial cardiovascular effects of cocoa flavanols would hold true for the general population.
The studies demonstrated that consumption of cocoa flavanols significantly improves several of the hallmarks of cardiovascular health, including increased flow-mediated vasodilation. Flow-mediated vasodilation is a sign of improved endothelial function and has been shown by some studies to be associated with decreased risk of developing cardiovascular disease. In addition, consuming flavanols decreased both systolic and diastolic blood pressure, and improved the blood cholesterol profile by decreasing total cholesterol, decreasing and increasing HDL cholesterol.
The results demonstrate that flavanols are effective at mitigating age-related changes in blood vessels, and could thereby reduce the risk of cardiovascular disease in healthy individuals.
MedicalResearch.com Interview with:
R. Scott Turner, MD, PhD
Director of the Memory Disorders Program
Georgetown University Medical Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Turner: The resveratrol trial originated from the extensive scientific literature demonstrating that caloric restriction (consuming only 2/3 usual calories) prevents or delays diseases of aging - including Alzheimer's disease (AD) in laboratory animals. The molecular mechanism is thought to involve sirtuins - a group of genes/proteins that sense energy balance to regulate gene expression. Sirtuins are activated by caloric restriction (a mild stressor) to express genes that promote resilience of the organism. Resveratrol is a potent activator of sirtuins - thus bypassing the requirement for caloric restriction. On the opposite side of the coin - caloric excess, midlife obesity, and diabetes are strong risk factors for Alzheimer's disease. And we have long-known that resveratrol is found in red grapes, red wine, and other foods that promote general health.
MedicalResearch.com Interview with:
Joshua W. Miller, PhD
Professor and Chair Dept. of Nutritional Sciences Rutgers
The State University of New Jersey
New Brunswick, NJ 08901
Medical Research: What is the background for this study? What are the main findings?
Response: In recent years, there has been a growing scientific literature on the associations between low vitamin D status in older adults and risk of Alzheimer's disease/dementia, cognitive impairment and decline, and brain atrophy. The vast majority of these studies have been conducted in predominantly white populations. The relatively unique aspect of our study was that over half of the cohort consisted of African Americans and Hispanics. What we found in our cohort (mean age ~75y, n=382 at baseline) was that participants with vitamin D deficiency (serum 25-hydroxyvitamin D <12 ng/ml) or vitamin D insufficiency (serum 25-hydroxyvitamin D between 12 ng/ml and <20 ng/ml) on average experienced faster rates of cognitive decline in episodic memory and executive function than participants with adequate vitamin D status. Importantly, the association between vitamin D status and the rate of decline in cognitive function was independent of race/ethnicity. However, the prevalence of low vitamin D status in the study participants was significantly higher in the African American and Hispanic participants compared with the White participants. This is most likely due to the fact that darker skin pigmentation reduces the ability of sunlight to induce vitamin D synthesis in the skin. It may also reflect differences in dietary intake of vitamin D and supplement use between the different race/ethnicity groups, though we did not assess this in our study. Thus, though the rate of cognitive decline in African Americans and Hispanics does not seem to be more or less affected by low vitamin D status than in Whites, because African Americans and Hispanics have a higher prevalence of low vitamin D status, as subpopulations they may be more prone to rapid cognitive decline in old age. Further studies addressing this possibility are needed.
MedicalResearch.com Interview with:
Monika Goyal, MD
Pediatric emergency medicine
Children’s National Hospital
Washington, DC
Medical Research: What is the background for this study? What are the main findings?
Dr. Goyal: Appendicitis is a painful surgical condition and adequate analgesia, particularly with opioids, are considered one of the mainstays of management. We found that almost half of all children diagnosed with appendicitis did not receive any analgesia. Furthermore, among the patients that did receive analgesia, there were marked racial differences with black children having lower rates of opioid medication receipt than white children, even after we took pain scores or acuity level into account.
MedicalResearch.com Interview with:
Wisit Cheungpasitporn, MD
Nephrology Fellow
Departments of Nephrology and Hypertension
Mayo Clinic, Rochester, MN
Program director: Suzanne Norby, MD
Co-authors: Charat Thongprayoon, MD, Andrew M. Harrison, BS and Stephen B. Erickson, MD
Project mentors: Stephen B. Erickson, MD Departments of Nephrology and Hypertension
Mayo Clinic, Rochester, MN
Medical Research: What is the background for this study?
Dr. Cheungpasitporn: Uric acid has been linked to acute kidney injury (AKI) through crystal-dependent pathways and crystal-independent mechanisms, including reduced renal blood flow and glomerular filtration rate. Serum uric acid measurement has recently been examined as a marker for early AKI detection, especially in the setting of postoperative AKI following cardiovascular surgery. The effect of admission serum uric acid levels on the risk of in-hospital AKI in the general hospitalized patients, however, was unclear. Thus, we conducted a study to assess the risk of AKI in all hospitalized patients across different serum uric acid levels. The findings of our study data were recently published in Clinical Kidney Journal.
MedicalResearch.com Interview with:
Dr. Kristi Elisabeth Heiberg PhD Post.doc
Department of Medical Research
Baerum Hospital
Vestre Viken Hospital Trust
Medical Research: What is the background for this study?
Dr. Heiberg: This study is a long term follow-up of 60 patients who suffered from hip osteoarthritis and were treated with total hip arthroplasty (THA) approximately 5 years earlier. In a prior study, the patients participated in a RCT study, examining the effects of a supervised walking skill training program on physical functioning, pain and self-efficacy (1). The training program was performed between three and five months after surgery, and it was compared to a control group without supervised physiotherapy in the same time span. The results showed that immediately after the walking skill training intervention was completed, several outcome variables were statistically significant more improved in the training group than in the control group, and at one year after surgery the statistically significant effect on walking capacity (measured by the 6-min walk test) still sustained. Few long-term follow-up of RCTs regarding physical functioning in patients after total hip arthroplasty are previously published. Furthermore in another prior study, we examined the recovery of the total group of the same patients from preoperatively to one year after surgery (2). The results showed that the patients were statistically significant improved in all outcomes of physical functioning, pain and self-efficacy during the first year, but they still did not quite reach the level of healthy peers in walking capacity. In line with this, they also reported one year after surgery that they wanted to further improve their ability to walk and to participate in recreational activities (3). However, it seems that patients’ desires regarding physical activity are poorly understood and have received relatively little evaluation, although regular physical activity is considered to be one of the most important lifestyle behaviors affecting health. Only few prior studies have examined the long term recovery of physical functioning and the impact on physical activity.
Therefore, in this present 5-year follow-up study after total hip arthroplasty the aims were threefold.
MedicalResearch.com Interview with:
Patricia Sancho, PhD, Lecturer
Barts Cancer Institute - a Cancer Research UK Centre of Excellence
Queen Mary University of London
Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London
Medical Research: What is the background for this study? What are the main findings?
Dr. Sancho: Cancer cells commonly rely on glycolysis, the type of metabolism that does not use oxygen to generate their energy however, we have now found that not all cancer cells are alike when it comes to metabolism. Pancreatic Cancer Stem cells (PancCSCs) can make use of a more efficient form of metabolism, called oxidative phosphorylation or OXPHOS, which does use oxygen. OXPHOS uses a part of the cell called mitochondria and it is this which can be targeted with anti-diabetic drug, metformin. Some PancSCs are however able to escape this treatment by being much more flexible in their metabolism, leading to a recurrence of the cancer, but we also found a way to prevent such resistance and force all Pancreatic Cancer Stem cells to keep using OXPHOS.
MedicalResearch.com Interview with:
Mike Bancks, MPH
NHLBI Cardiovascular Disease Epidemiology & Prevention Pre-doctoral Fellow
University of Minnesota School of Public Health
banck005@umn.edu
Medical Research: What is the background for this study? What are the main findings?
Response: We chose to research this topic because marijuana is the most commonly used illicit drug in the United States and use can be expected to increase as the effort to legalize marijuana for recreational and medicinal use grows. We found that individuals who reported using marijuana in excess of 100 times during young adulthood had 40% greater risk for developing prediabetes by middle adulthood. However, we did not find an association between marijuana use and overt diabetes during this same period in adulthood, suggesting that marijuana use may be a risk factor for the early stage of diabetes.
MedicalResearch.com Interview with:
Thomas N. Darling, MD, PhD
Department of Dermatology
Uniformed Services University of the Health Sciences
Bethesda, MD 20814
Medical Research: What is the background for this study? What are the main findings?
Dr. Darling: Many people with tuberous sclerosis complex (TSC) have skin tumors that can bleed or cause distress. Only surgical approaches were useful for treating these skin tumors in the past. Recently, drugs called mTOR inhibitors, including sirolimus, were shown to shrink internal tumors in those affected by tuberous sclerosis complex. We wanted to document what happens to the skin tumors in those being treated with oral sirolimus. We found that most patients taking oral sirolimus showed improvement in their skin tumors, and that these effects were maintained during a couple years of treatment. We did not observe any evidence for the skin tumors becoming resistant to the drug.
MedicalResearch.com Interview with:
Markus Jansson-Fröjmark PhD
Associate professor, clinical psychologist
Department of Psychology
Stockholm University
Medical Research: What is the background for this study? What are the main findings?
Response: There is ample evidence suggesting that how people regulate their emotions might influence several types of psychopathology, including anxiety and mood disorders. The purpose of our longitudinal investigation was therefore to examine the association between emotion regulation and how insomnia develops over time. Our main finding was that people whose ability to regulate their emotions had diminished were more likely to develop insomnia and that it was more likely to be persistent. A reduced ability to regulate emotions was associated with an 11% increased risk of developing a new bout of insomnia or reporting persistent insomnia. For anyone that has to deal with insomnia on a daily basis, they may find that is can effect a large part of their lives. Sleep is important for even, as it allows us all to function properly throughout the day. When it comes to Insomnia, there is medication out there that people can take that may help them with this issue. A popular method of treatment is through the use of medical marijuana. If this is something that you have been planning on trying, you would need to obtain your medical marijuana card in Cincinnati (if you live in this city) before you could start receiving product. Hopefully this will help with your insomnia and provide you with a better quality of sleep.
MedicalResearch.com Interview with:
Merja Nermes, MD
Dept. of Pediatrics
Turku University Hospital
Turku, Finland
Medical Research: What is the background for this study? What are the main findings?
Response: Earlier it was thought that exposure to pets early in childhood was a risk factor for developing allergic disease. Later epidemiologic studies have given contradictory results and even suggested that early exposure to pets may be protective against allergies, though the mechanisms of this protective effect have remained elusive. Our results are the first to show that specific bifidobacteria present in pets can be transferred to the infant gastrointestinal tract during a close contact. Bifidobacteria in general are a part of the microbiota in healthy breast fed infants, and many studies have shown that human-specific bifidobacteria have beneficial effects to health, e.g. lower the risk of allergic disease. The same might hold true for bifidobacteria of animal origin which may enhance and strengthen the development of the infants´ immune system to be protective against allergies.
Our results showed that animal-derived bifidobacteria were found in a higher proportion in infants of pet-keeping families than in those without such exposure. We also found that B. thermophilum (pet-derived Bifidobacterium) was associated with a lower risk for atopic sensitization at 6 months of age.
MedicalResearch.com Interview with:
Dr.Manuel Fernández-Real MD, PhD
Biomedical Research Institute of Girona (IDIBGI) CIBERobn
Obesity Hospital of Girona
Medical Research: What is the background for this study? What are the main findings?
Response: Obesity is an important determinant of increased cardiovascular risk. Increased fat mass has been assumed to constitute the main prominent contributor to changes in carotid intima-media thickness (c-IMT). A link among fat free mass and total blood volume, stroke volume and cardiac output has been also previously reported.
In this manuscript we describe that carotid intima-media thickness was positively associated with lean body mass in men (r =0.328, p <0.0001) and women (r = 0.268 p =<0.0001). c-IMT values increased across lean mass quartiles (p < 0.0001). Stepwise linear regression analysis showed that age and lean mass (but not fat mass or traditional cardiovascular risk factors) contributed to 46.2% of c-IMT variance in men (p=<0.0001).
MedicalResearch.com Interview with:
Megan Colleen McHugh, PhD
Research Assistant Professor
Center for Healthcare Studies
Feinberg Institute for Public Health and Medicine and Emergency Medicine
Northwestern University
Medical Research: What is the background for this study? What are the main findings?
Dr. McHugh: There have been many large efforts to improve the delivery of health care in the U.S., for example, the Robert Wood Johnson Foundation’s Aligning Forces for Quality Program and the Institute for Healthcare Improvement’s 100,000 Lives Campaign. One of the challenges to understanding whether these programs work is that the intervention “dose” – the quality and quantity of the intervention – often varies across different participating sites.
As evaluators of multi-site quality improvement programs, we want to better understand how to measure the dose of a quality improvement intervention at participating sites. We identified four different approaches to measuring dose. These approaches resulted in different conclusions about which sites are “low dose” and “high dose” intervention sites.
Medical Research: What should clinicians and patients take away from your report?
Dr. McHugh: The main audience for this paper is program evaluators. They should take away the following:
1) Variation in dose scores across intervention sites suggests that dose may be a contributor to the effectiveness of a quality improvement intervention.
2) It is feasible to measure the dose of a quality improvement intervention, but measuring QI dose presents many challenges, including subjective decisions about which approach to measurement to use and the need for extensive data collection.
MedicalResearch.com Interview with:
Brian A. Primack, MD, PhD
Associate Professor of Medicine, Pediatrics, and Clinical and Translational Science
Director, Center for Research on Media, Technology, and Health
Assistant Vice Chancellor for Research on Health and Society
University of Pittsburgh School of Medicine
Pittsburgh, PA 15213
Medical Research: What is the background for this study?
Dr. Primack: Adolescents and young adults who have never smoked traditional cigarettes are now using e-cigarettes. It is unclear whether these people are at risk for progression to traditional cigarette smoking. Therefore, we followed 694 non-smokers ages 16-26 who did not intend on taking up smoking for 1 year.
Medical Research: What are the main findings?
Dr. Primack: At baseline, only 16 of the 694 participants had used e-cigarettes. However, those individuals were significantly more likely to start smoking traditional cigarettes by the 1-year follow-up. In fully adjusted models, baseline e-cigarette use was independently associated with both progression to smoking (AOR = 8.3, 95% CI = 1.2-58.6) and to susceptibility (AOR = 8.5, 95% CI = 1.3-57.2).
MedicalResearch.com Interview with:
Chan-Won Kim, M.D.
Clinical Associate Professor
Center for Cohort Studies
Kangbuk Samsun Hospital
Sungkyunkwan University School of Medicine
Seoul, South Korea
Medical Research: What is the background for this study?
Dr. Chan-Won Kim: In modern society, inadequate sleep either in quantity or in quality is a common problem and widely recognized as a potential determinant of adverse health outcomes including cardiovascular health. Very long or very short duration of sleep are associated with an increased risk for clinical cardiovascular events such as coronary heart disease and strokes. In these previous studies, however, it was possible that extreme sleep duration or poor sleep quality was a consequence of previous co-morbidities such as depression and obesity, and it was still unclear if these co-morbidities were really responsible for the effects of sleep disturbances. Therefore, we evaluated the association of sleep duration and quality with early markers of subclinical arterial disease in asymptomatic apparently healthy men and women.
Medical Research: What are the main findings?
Dr. Chan-Won Kim: In our study, we found that sleep duration had a U-shaped association with two early markers of vascular disease. Both short and long sleep duration were associated with a greater amount of calcification in the coronary arteries, a very good measure of subclinical atherosclerosis that predicts the risk of a heart attack. We also found a similar pattern of association with arterial stiffness, a marker of vascular aging. For both markers, we found the lowers risk in study participants who reported 7 hours of sleep. In addition, poor subjective sleep quality was also associated with these markers of vascular disease. Few studies had explored these associations before, and they were inconsistent partly because of small sample sizes. Our research also indicates that these associations were present irrespective of traditional risk factors such as hypertension, hypercholesterolemia, or diabetes.