MedicalResearch.com Interview with:
Prof. Francesca Mallamaci
Professor of Nephrology
Head of the Hypertension Unit at the Department of Nephro-Urology, CNR-IBIM Research on Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy
Medical Research: What is the background for this study? What are the main findings?
Dr. Mallamaci: It is well known that physical activity is beneficial both in normal individuals and in patients with heart failure which represent a high risk category of patients. We have scanty information about physical activity in dialysis patients. So the aim of our study was to test the effectiveness of a low-intensity, easy to implement, home exercise program on physical performance in about 300 dialysis patients in a multicenter, randomized, controlled clinical trial (EXCITE, ClinicalTrials.gov NCT01255969). What we found in our study was that dialysis patients who performed exercise improved their physical performance and this was documented by 2 well known and validated performance tests such as the Six Minute Walking Test and the Sit-to-stand-to sit test. We found also that after 2 year follow-up dialysis patients who were in the active exercise arm had a lower rate of hospitalization and a trend to a better survival, compared to dialysis patients in the control arm of the study.
MedicalResearch.com Interview with:
Marie-Christine Aubry, M.D.
Professor of Laboratory Medicine and Pathology
Consultant, Department of Laboratory Medicine and Pathology,
Mayo Clinic in Rochester, Minn.
Medical Research: What is the background for this study? What are the main findings?
Dr. Aubry: Up to 20% of patients will present with multifocal lung cancer or will develop a second lung cancer. The main clinical issue is distinguishing between independent primaries from true intrapulmonary metastases since this distinction will drive the therapy of the patient. Currently no ancillary studies allows for this distinction and the distinction is provider specific based on a combination of clinical, radiologic and pathologic assumptions. Based on our prior research using a method called mate pair sequencing , we observed that the probability of detecting identical chromosomal breakpoints in two unrelated tumors, from 2 different patients was basically zero. Similarly, when assessing different components within a single tumor, we always found identical chromosomal breakpoints between these components. We thus hypothesized that if two tumors within a patient were related, i.e. true metastasis, we should always find a number of identical chromosomal breakpoints between the tumors. And in contrast, if 2 tumors were truly independent primaries, we should not observe any chromosomal breakpoints in common.
We first studied a control group of patients that had
1- a primary lung cancer with a known distant metastasis (usually brain metastasis),
2- two lung cancers of different histologic subtype, adenocarcinoma and squamous cell carcinoma which are accepted as true independent primaries and
3- 1 tumor with different portions of the tumor being analyzed individually and compared as true relatedness.
There were thus a total of 11 pairs of tumors with predetermined status of independent primaries versus relatedness (ie metastasis or same tumor). The mate pair generated data showed a perfect concordance with this status. We then studied 11 pairs of lung tumors of similar histology (2 adenocarcinomas or 2 squamous cell carcinomas). The current gold standard for the distinction between independent primaries and intrapulmonary metastasis relies on a pathologist’s comparative morphologic assessment. In order to strengthen this gold standard, 2 pulmonary pathologists independently made this assessment. Interestingly, the pathologists agreed on the status of independent primaries and intrapulmonary metastasis in 9 (of 11) cases demonstrating the shortcomings of this gold standard. Furthermore, there were discordance between the pathologists’ prediction and the clinicians’ assessment in 3 of the 11 patients and the clinician could not come to a final assessment in 1 patient. The MP data was concordant with the pathology assessment in 8 of these 9 cases, and supported the pathologists’ prediction in 2 (of the 3) discordance with the clinical assumptions.
MedicalResearch.com Interview with:
Weian Zhao PhD
Assistant Professor at the Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Department of Biomedical Engineering, Edwards Lifesciences Center for Advanced Cardiovascular Technology and Department of Pharmaceutical Sciences at University of California, Irvine.
Medical Research: What is the background for this study?
Dr. Zhao: Bloodstream infections are a major cause of illness and death. In particular, infections associated with antimicrobial-resistant pathogens are a growing health problem in the U.S. and worldwide. According to the Centers for Disease Control & Prevention, more than 2 million people a year globally get antibiotic-resistant blood infections, with about 23,000 deaths. The extremely high mortality rate for blood infections is due, in part, to the inability to rapidly diagnose and treat patients in the early stages. The present gold standard to detect a blood infections, is a blood culture and it takes 2-5 days for the detection and the identification of the bacteria. Recent molecular diagnosis methods, including polymerase chain reaction, can reduce the assay time to hours but are often not sensitive enough to detect bacteria that occur at low concentrations in blood, as is common in patients with blood infections. Therefore, less expensive and less technically demanding methods are urgently needed for the rapid and sensitive identification of blood infections.
MedicalResearch.com Interview with:with
Stuart M. Sprague, DO, FACP, FASN, FNKF
Chairperson, Division of Nephrology and Hypertension
NorthShore University HealthSystem
Evanston, Illinois 60201
Medical Research: Congratulations, Dr. Sprague, on your presentation of another successful phase 3 clinical trial program at the recently concluded Annual Meeting of the American Society of Nephrology. Your presentation unveiled a new vitamin D repletion therapy that effectively controls secondary hyperparathyroidism in chronic kidney disease. Can you give us a little background for the presented studies?
Dr. Sprague: Thanks! Vitamin D insufficiency is a big problem in chronic kidney decease (or CKD): it afflicts more than 20 million adults in the United States who have stages 1 through 4 CKD. Its prevalence increases with CKD severity and it drives secondary hyperparathyroidism. The studies which I presented evaluated a novel therapy to treat secondary hyperparathyroidism (SHPT) arising from vitamin D insufficiency in patients diagnosed with stage 3 or 4 CKD. This new therapy is a modified-release formulation of calcifediol.
Medical Research: Can you tell us more about vitamin D insufficiency?
Dr. Sprague: Vitamin D insufficiency is a condition in which the body has low vitamin D stores. It is characterized by inadequate blood levels of the vitamin D, known as 25-hydroxyvitamin D. An estimated 70-90% of CKD patients have vitamin D insufficiency, which can lead to SHPT and resultant debilitating bone diseases. Vitamin D insufficiency has also been associated with increased mortality in CKD.
MedicalResearch.com Interview with: Alexander Janke BS School of Medicine at Wayne State University Medical Research: What is the background for this study? What are the main findings? Response: Health insurance by itself does not guarantee quality healthcare; patients need accessible primary care options. Without them, patients newly-enrolled in health insurance may not be able...
MedicalResearch.com Interview with:
Dr. Lars H. Lund
Department of Medicine, Karolinska Institutet
Department of Cardiology, Karolinska University Hospital
Stockholm, Sweden
Medical Research: What is the background for this study?
Dr. Lund: Heart Failure and Preserved Ejection Fraction is common and associated with poor prognosis and there is no therapy.
Beta-blockers reduce mortality in Heart Failure and Preserved Ejection Fraction and we hypothesized that they may be associated with reduced mortality also in Heart Failure and Preserved Ejection Fraction.
MedicalResearch.com Interview with:
Anne Stephenson MD, PhD
Division of Respirology
The Toronto Adult Cystic Fibrosis Centre
St. Michael's Hospital Toronto, ON
Medical Research: What is the background for this study? What are the main findings?
Dr. Stephenson: Cystic Fibrosis is progressive genetic disease that results in very thick secretions in various organs such as the lungs, pancreas, and digestive tract. Over time, these thick secretions damage organs in particular, the lungs, which results in respiratory failure due to recurrent chest infections. Cystic Fibrosis patients are also at high risk for malnutrition due to the inability to absorb food which is associated with poor survival. In the 1960s, people with Cystic Fibrosis died at a very young age and in fact, parents who had a child born with Cystic Fibrosis at that time were told that there was a 50% chance their child would not live to attend kindergarten. Over the last several decades, we have seen a significant increase in the survival of individuals with CF. Individuals born with Cystic Fibrosis today can expect to not only attend kindergarten, but complete high school, perhaps attend college or university, have a career, get married or have children as people are living well into adulthood with this disease. The median age of survival in Cystic Fibrosis today is approximately 50 years of age in Canada which is quite remarkable.
MedicalResearch.com Interview with:
Dr. Abhay Lodha, MBBS, MD, DM, MSC
Assistant Professor, Department of Pediatrics and Community Health Sciences, University of Calgary,
Staff Neonatologist and Clinical Epidemiologist, Section of Neonatology, Alberta Health Services, Chairman, CME
Foothills Medical Centre, Calgary, Alberta, Canada
Medical Research: What is the background for this study? What are the main findings?
Dr. Lodha: Apneic episodes (cessation of breathing) occur in the premature infants. Caffeine is the most commonly used medication for apnea of prematurity. Normally caffeine started on day 3 of life for apnea. However, there is no strong evidence that starting caffeine on day 1 or 2 life has some extra advantages in premature infants. Our study has a large number of premature infants. Our study determined the association of early initiation of caffeine therapy in very preterm neonates and neonatal outcomes.
The main finding of our study was that early use of caffeine was associated with a reduction in the rate of death or bronchopulmonary dysplasia and patent ductus arteriosus. We did not find any adverse impact on any other outcomes.
MedicalResearch.com Interview with:
Boback Ziaeian MD
Cardiology Fellow, UCLA Division of Cardiology
PhD Candidate, UCLA Fielding School of Public Health
Medical Research: What is the background for this study? What are the main findings?
Dr. Ziaeian: Heart failure is projected to increase dramatically over the coming decade due to an aging population improved medical therapies that prolong heart failure survival. Spending for heart failure is projected to increase from $20.9 billion in 2012 to $53.1 billion in 2030. Despite the magnitude of the impact of heart failure on the US population and economy, our understanding of the factors associated with the highest cost heart failure hospitalizations is limited.
Our study provides a descriptive analysis of how certain patient and hospital factors are associated with increased medical costs nationally. The top 20% of heart failure hospitalizations average $28,500 per hospitalization compared to $3,000 for the lowest 20%. Overall, patients with more medical conditions (such as obesity, lung disease, and peripheral vascular disease) have much higher costs associated with hospital care. As expected, sicker patients receiving more invasive procedures such mechanical ventilation or blood transfusions incurred higher costs. Certain hospital characteristics were also associated with higher costs. Hospitals in urban centers were higher cost compared to more rural hospitals. Hospitals in the Northeast and West Coast of the US were higher in cost compared to the Midwest and South. The reasons for this disparity in medical costs requires further research to better understand.
MedicalResearch.com Interview with:
Dr. Patrice Carter
Diabetes, Nutrition & Lifestyle Research Associate
Diabetes Research Centre (Broadleaf) University of Leicester
Leicester General Hospital Leicester UK
Medical Research: What is the background for this study? What are the main findings?
Dr. Carter: Type 2 diabetes is a growing concern, worldwide prevalence is expected to increase to 552million by 2030. Prevalence is closely linked to increasing obesity rates which are associated to environmental changes that have led to more sedentary lifestyles and poor-quality dietary intake. Consumption of fast food has previously been linked to the obesity epidemic and consumption is associated with low adherence to dietary recommendations.
We analysed data of over 10,000 individuals to investigate the association between screen detected type 2 diabetes and the number of fast food outlets in their neighbourhood.
In summary we found the mean number of fast food outlets in areas with high social deprivation as compared to low social deprivation; mean number of outlets was 3.53 (SD 4.83) and 0.91 (1.89) respectively. The number of fast food outlets was positively associated with screen-detected type 2 diabetes (OR=1.05; 95% CI 1.04, 1.07; p<0.001). In addition, we used these data to calculate that for every additional two outlets we would expect to see one more diabetes case, assuming a 7% prevalence of undiagnosed type 2 diabetes in neighbourhoods with no outlets and approximately 200 residents in a 500m radius, and assuming a causal relationship.
MedicalResearch.com Interview with:
Prof Simon Stewart PhD
Mary MacKillop Institute for Health Research, Australian Catholic University,
Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia
Medical Research: What is the background for this study? What are the main findings?
Prof. Stewart: Atrial fibrillation (AF) is the most common irregular heart beat and a major cause of deadly and disabling stroke and chronic heart failure. Atrial fibrillation has become a major public health issue that is putting increasing pressure on health care systems worldwide. In an attempt to reduce re-hospitalisations and death due to Atrial fibrillation, we designed the randomised controlled trial the Standard versus Atrial Fibrillation-spEcific managemenT strategY (SAFETY); a home-based, nurse-led, AF-specific management programme delivered to patients who have been hospitalised with Atrial fibrillation and involved individualised AF management. Half of participants (n=168) were given this intervention and the other half (n=167) underwent standard post-hospital management. All participants were followed-up over 24 months with specific clinic visits scheduled at 12 months and 24 months. We found that patients in the intervention group had proportionately more days alive and out of hospital compared to patients who received standard management (reflecting a combination of less hospital stay and prolonged survival). Further, when intervention patients did go to hospital, the length-of-stay of their admission was shorter than for patients under standard management.
MedicalResearch.com Interview with:
Dr. T. Jared Bunch, M.D
Medical Director for Heart Rhythm Services
Intermountain Healthcare network.
Medical Research: What is the background for this study? What are the main findings?
Dr. Bunch: Approximately 5 years ago we found that atrial fibrillation was associated with all forms of dementia, including Alzheimer's disease. At that time we did not know the mechanisms behind the association. One hypothesis that we had was brain injury in patients with atrial fibrillation is in a spectrum, large injuries result in strokes and repetitive small injuries result in dementia. In this regard, we anticipated that anticoagulation effectiveness and use may impact dementia risk. Early this year we published in HeartRhythm Journal that atrial fibrillation patients with no history of dementia that have used warfarin, but had high percent times outside of the therapeutic range were much more likely to develop dementia. We gained some insight from this trial in that we saw much higher risks of the patients were either over or under anticoagulated.
Amongst our atrial fibrillation patients using warfarin nearly one third are also taking aspirin, typically due to the presence of coronary artery disease or a prior myocardial infarction. We hypothesized since these patients were using two agents that increase risk of bleed that over anticoagulation with warfarin may be an even great risk for dementia. This is was we found. The patients over anticoagulated greater than 30 percent of the time were nearly 2 and a half times more likely to develop dementia compared to those that were over anticoagulated less that 10 percent to the time.
MedicalResearch.com Interview with:
Prof Gavin D. Perkins MD
Clinical Professor in Critical Care Medicine Warwick Clinical Trials Unit Co-Director of Research;
Warwick Medical School and Heart of England NHS Foundation Trust
Medical Research: What is the background for this study?
Prof. Perkins: Each year around 30,000 people in the United Kingdom suffer out of hospital cardiac arrests and less than one in twelve of those returns home alive. Early high quality Cardio- Pulmonary Resuscitation (CPR – ventilation and chest compressions) is critical to survival. However maintaining high quality chest compressions during resuscitation is difficult for crews of emergency vehicles, especially if they are on their own, because of fatigue and the need to perform other actions. Chest compression is particularly difficult in moving vehicles.
A number of mechanical devices, suitable for out of hospital use, have been developed over the years to improve the quality of chest compressions and therefore attempt to improve patient outcomes. Some NHS organisations decided to purchase devices to use although there is limited evidence of their effectiveness. To equip all emergency vehicles in the NHS would cost tens of millions of pounds plus costs for on-going training and maintenance. This prompted the UK Joint Royal College Ambulance Liaison Committee to advise against the purchase of further mechanical chest compression devices until further research had been carried out.
The aim of this trial was to compare the effects of the mechanical chest compressions (LUCAS-2) device versus standard manual chest compressions (crew using their hands) on survival.
MedicalResearch.com Interview with:
Dr Guillaume Geri, MD
Medical Intensive Care Unit
Cochin Hospital Paris, France
Medical Research: What is the background of the study? What are the main findings?
Dr. Geri: Culprit coronary artery occlusion is the main cause of out-of-hospital cardiac arrest. This has been well demonstrated since pioneer study of Spaulding et al in the New England Journal of Medicine in 1997. Several studies highlighted the favorable prognostic impact of an immediate successful PCI in cardiac arrest patients but inclusion biases or the lack of data on in-hospital management limit the generalization of such findings.
In this large French cohort of out-of-hospital cardiac arrest patients who were admitted after successful return of spontaneous circulation from 2000 to 2012, those who received immediate PCI had better short- and long-term survival than those who did not undergo the procedure, new data presented here concluded.
The researchers examined the association between immediate PCI and survival at 30 days, 2 years and 10 years, and evaluated other potential predicting factors. Furthermore, they used a propensity score method to analyze the impact of PCI on 30-day and long-term survival in matched patients.
Overall, 1,722 patients (71.5% male; median age, 59.9 years) were analyzed during a median 2 year follow-up. OHCA (out-of-hospital cardiac arrest ) was witnessed in 86.7% of patients, and occurred in a public space in 32.2% of patients and with an initial shockable rhythm (eg, ventricular fibrillation/ventricular tachycardia) in 54.6% of cases.
MedicalResearch.com Interview with:
Pietro Cottone, Ph.D.
Associate Professor
Departments of Pharmacology and Psychiatry
Laboratory of Addictive Disorders
Boston University School of Medicine Boston, MA 02118
Medical Research: What is the background for this study? What are the main findings?
Dr. Cottone: Binge-eating disorder affects over ten million people in the USA and it is characterized by excessive consumption of junk food within brief periods of time, accompanied by loss of control, uncomfortable fullness and intense feelings of disgust and embarrassment. Increasing evidence suggests that binge-eating disorder can be regarded as an addiction behavior.
Memantine, a neuroprotective drug which blocks the glutamatergic system in the brain, is an Alzheimer's disease medication, and it has been shown potential to treat a variety of addictive disorders.
We first developed a rodent model of binge eating by providing a sugary, chocolate diet only for one hour a day, while the control group was given the standard laboratory diet. Rats exposed to the sugary diet rapidly develop binge eating behavior, observed as a 4 fold increase in food intake compared to controls. Furthermore, binge eating rats are willing to work to a much greater extent to obtain just the cue associated with the sugary food (not the actual food), as compared to controls. In addition, binge eating subjects exhibit compulsive behavior by putting themselves in a potentially risky situation in order to get to the sugary food, while the control group obviously avoids that risk.
We then tested whether administering memantine could reduce binge eating of the sugary diet, the strength of cues associated with junk food as well as the compulsiveness associated with binge eating. In addition, we studied which area of the brain was mediating the effects of memantine, by injecting the drug directly into the brain of binge eating rats.
Our data show that memantine was able to block binge eating of the sugary diet, the willingness to work to obtain a cue associated with junk food, as well as the risky behavior of rats when the sugary diet was provided in a potentially unsafe environment. When we injected the drug directly into the nucleus accumbens of rats, they stopped binge eating. Importantly, the drug had no effects in control rats eating a standard laboratory diet.
Dr. Springer[/caption]
Matthew L. Springer, Ph.D.
Associate Professor of Medicine
Division of Cardiology
Cardiovascular Research Institute
Broad Center of Regeneration Medicine and Stem Cell Research
Center for Tobacco Control Research & Education
Helen Diller Family Comprehensive Cancer Center
University of California, San Francisco
Medical Research: What is the background for this study? What are the main findings?
Dr. Springer: The general public is aware that cigarette secondhand smoke is harmful. However, many people who actively avoid tobacco secondhand smoke don't feel the need to avoid marijuana secondhand smoke; they don't consider it harmful because there's no nicotine and because we who tell them to avoid tobacco smoke don't tell them to avoid marijuana smoke. However, secondhand smoke from tobacco and marijuana is very similar in chemical composition (4000-7000 chemicals depending on whom you ask), aside from the nicotine and the THC (the psychoactive drug in marijuana).
We and others have shown that brief exposure to tobacco secondhand smoke, such as 30 minutes, at real-world levels impairs vascular function in humans. We developed a way to study vascular function (measured as arterial flow-mediated dilation; FMD) in living rats, and recently published that even one minute of sidestream smoke from the burning tips of tobacco cigarettes, a well-accepted model for secondhand smoke, is enough to start detecting impairment of FMD. The main findings of the current study are that in laboratory rats, FMD was substantially impaired by a 30 minute exposure to marijuana secondhand smoke, when measured 10 minutes after the end of exposure. Impairment was comparable to that resulting from exposure to tobacco sidestream smoke, although whereas impairment from tobacco smoke was temporary and had normalized by 40 minutes later, FMD was still impaired 40 minutes after the end of exposure to marijuana smoke. Smoke from marijuana lacking THC still impaired FMD, showing that