Dr. Lan Ko[/caption]
Lan Ko MD PhD
Augusta University
Cancer Center
Augusta, GA 30912, USA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Lan Ko: Cancer development hijacks normal cell differentiation. Understanding the normal is where we could begin to unlock the secret of cancer. In normal breast tissue, stem or progenitor cells produce supporting stromal cells in normal breast development. In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendents so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer.
Each subgroup of breast tumor stromal cells has been previously described by other scientists. However, the connections among these cells were unclear in the past. Like blind men feeling elephant, we scientists are often obscured from seeing the entire picture. The finding of mutant breast tumor stromal cells using GT198 as a marker provides a critical puzzle piece that fits the rest of puzzle together. When cancer problems can be viewed in multiple aspects with great simplicity, their connections emerge. We now know why breast cancer stromal cells are important, and how should we target them.
Dr. RJT Mocking[/caption]
Dr. Roel JT Mocking
Program for Mood Disorders
Department of Psychiatry
Academic Medical Center
University of Amsterdam, The Netherlands
MedicalResearch.com: What is the background for this study?
Response: Omega-3 polyunsaturated fatty acid supplementation (popularly referred to as fish oil) is being promoted as (add-on) treatment for depression. Thus far, many studies have been performed that tested the effects of omega-3 fatty acids in depression. In order to overcome differences between these results of individual studies, a meta-analysis can be performed. A meta-analysis pools the results of all individual studies, and thereby provides a more definitive conclusion regarding the effect of omega-3 fatty acids in depression. Moreover, using the differences between the individual studies, a meta-analysis can point to factors that are associated with a better effect of the supplementation, for example supplementation dose or duration.
There have been meta-analyses performed previously, but they seemed to contain several inconsistencies. For example, they accidentally included the same study two or three times, which results in errors. In addition, these meta-analyses did not only include studies performed in patients with the psychiatric disorder "major depressive episode", but also subjects from the general population with less severe depressive complaints. This makes it more difficult to interpret the results. Therefore, we performed a meta-analysis that included only studies performed in patients with major depressive disorder, and corrected errors from earlier meta-analyses.
Dr. Emerson Perin[/caption]
Dr. Emerson C. Perin MD, PhD
Texas Heart Institute
Medical Director, BSLMC Catheterization Laboratory
Director, Research in Cardiovascular Medicine
Medical Director, Stem Cell Center
MedicalResearch.com: What is the background for this study?
Dr. Perin: Critical limb ischemia (CLI) is a devastating and debilitating disease characterized by reduced blood flow to the legs, frequently as a consequence of atherosclerosis. Patients with CLI have a poor prognosis and live with chronic pain and disability. The disease manifests clinically as pain during rest and compromised wound healing, often resulting in ulcers that don’t heal, which can lead to amputation. Moreover, Critical limb ischemia is a deadly disease, with an annual mortality rate of about 20%. The only effective treatment option is revascularization, but not all CLI patients are good candidates for this approach, and even for those who are, procedures can fail. These patients face a dismal prospect as no other effective treatment options are available. Clearly, new therapeutic strategies are desperately needed for this group of patients.
One of the most exciting new approaches for Critical limb ischemia patients who have no options is the concept of therapeutic angiogenesis—improving regional blood flow by facilitating the growth of blood vessels. This can be accomplished by delivering angiogenic factors to the area in need of improved blood supply. Hepatocyte growth factor (HGF) is a promising novel biologic for use in this way because it’s a powerful angiogenic agent that stimulates cell proliferation and migration. Delivering HGF into the ischemic limbs of patients with CLI may result in beneficial effects that help restore compromised blood flow to the area and encourage better healing of wounds. VM202 is a plasmid DNA that simultaneously expresses two isoforms of HGF, mimicking the way the body produces HGF. On the basis of favorable results from phase 1 clinical trials showing that gene therapy with VM202 was safe, well-tolerated, and potentially beneficial in patients with ischemic diseases, we conducted a phase 2, dose-escalation clinical trial in patients with Critical limb ischemia.
Prof. Bruce Guthrie[/caption]
Prof. Bruce Guthrie
Primary Care Medicine and Honorary Consultant NHS Fife
University of Dundee
Dundee, Scotland
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Guthrie: Most drug-related harm is caused by commonly prescribed drugs with moderate risk. This prescribing is not always inappropriate, because risk of harm may be outweighed by benefit in an individual, but we have previously shown that high-risk prescribing like this is common and highly variable between primary care practices, consistent with it being improvable. We therefore developed a complex intervention combining education, informatics to make it easy to identify and review patients, and a small financial incentive to review. We evaluated this intervention in a cluster-randomised trial in 33 Scottish primary care practices, targeting nine measures of high-risk non-steroidal anti-inflammatory drug (NSAID) and antiplatelet prescribing (for example, prescription of an NSAID to someone with chronic kidney disease; prescription of an antiplatelet to someone taking an anticoagulant without also prescribing a gastroprotective drug).
The intervention reduced the targeted prescribing by just over one third, and this reduction was sustained in the year after the intervention (including the payment to review) ceased. We also observed reductions in related hospital admissions with gastrointestinal bleeding and heart failure, although not acute kidney injury which was reduced but not statistically significantly.
Prof. Jack Cuzick[/caption]
Professor Jack Cuzick, PhD, FMedSci, FRCP(hon)
Director, Wolfson Institute of Preventive Medicine and
Head, Centre for Cancer Prevention
Queen Mary University of London.
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Cuzick: Ductal carcinoma in situ (DCIS) is a very early form of breast cancer, where cancer cells are present in milk ducts, but have not spread to the surrounding breast tissue. It is estimated that approximately a fifth of all screen-detected breast cancers are DCIS, with around 4,800 people diagnosed with DCIS in the UK each year.
Our IBIS-II DCIS trial looked at 2,980 postmenopausal women with DCIS in 14 countries, who were either given anastrozole or tamoxifen for five years after surgery.
The two groups had a similar number of cases of the disease recurring, whether they took tamoxifen or anastrozole. Those who took anastrozole had an 11 per cent lower rate of recurrence of DCIS or invasive cancer than those who took tamoxifen, but this difference was not significant. The similar NSABP B-35 trial found a 29% reduction with anastrozole and the combined analysis of the two trials indicated a significant 21% reduction.
The key difference between the two groups were in the side effects of the medication. Women who took anastrozole experienced fewer womb and ovarian cancers and non melanoma skin cancers, and fewer deep vein thromboses and gynecological issues, compared with those who took tamoxifen. However more fractures and musculoskeletal side effects were seen among those receiving anastrozole.
Dr. Chin Yo Lin[/caption]
MedicalResearch.com Interview with:
Chin-Yo Lin, Ph.D.
University of Houston
Center for Nuclear Receptors and Cell Signaling
Department of Biology and Biochemistry
Science and Engineering Research Center (SERC)
Houston, TX 77204-5056
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Lin: Many studies have established that alcohol consumption is a risk factor for breast cancer. Breast cancers associated with drinking tend to be hormone receptor-positive, the type is commonly treated with the drug tamoxifen which blocks the actions of estrogen in driving tumor growth in pre-menopausal women. Alcohol consumption has also been shown to increase the risk of disease recurrence in patients. Our study shows that alcohol can enhance the effects of estrogen by increasing cancer cell division and also reduce the efficacy of tamoxifen. The key mechanistic insight from the study is that alcohol treatment of breast cancer cells increased the expression of BRAF, a cancer-causing gene that is commonly mutated and activated in other types of cancers.
Dr. Ariel Drori[/caption]
Dr. Ariel Drori MD
Hadassah Medical Center
MedicalResearch.com: What is the background for the ThoraXS device?
Dr. Drori: The initial recognition of the need for a device like ThoraXS first came to me on an operational deployment during my reserve service where I serve as a military doctor. While serving on the Gazan border, I was called to a battle scene to treat a soldier who was suffering from pneumothorax after being shot in the chest. A quick evacuation by helicopter meant that I didn't have the time to perform the entire procedure and I was forced to hand over a partially-treated patient whose condition was unstable.
The reality of constant combat injuries mixed with a rising number of daily civilian terror attack casualties led us to understand that we need to provide a cheap, easy to use, robust and reliable solution that on the one hand can withstand the most extreme combat conditions and on the other, be used by any paramedic and in any pre-hospital and hospital setting.
This line of thought eventually led to the adoption of ThoraXS's simple yet sophisticated mechanical mechanism that ticks all the boxes.
Dr. Jonathan Davis[/caption]
Jonathan P. Davis , Ph.D.
Associate ProfessorThe Ohio State University Medical Center
Department of Physiology & Cell Biology.
Columbus, OH 43210
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Davis: Myocardial infarction (MI) is a leading cause of heart failure and death in the US. Since the infarcted heart does not contract as well, therapeutics have been designed (i.e. positive inotropes) to help the heart contract better. While current positive inotropes help the patients in the short-term, they have detrimental long-term effects (“feel better but die sooner”). There is a dire need to be able to increase cardiac contraction without the deleterious side effects. We have achieved this goal by engineering the Ca2+-dependent switch in the heart, troponin C, to be able to better bind Ca2+. Combining gene therapy with our smartly formulated TnC, we demonstrated that our novel strategy not only protected the mouse from the negative consequences of an MI, but was also therapeutic when given after the MI.
MedicalResearch.com Interview with: [caption id="attachment_22743" align="alignleft" width="200"] Riley Steiner[/caption] Riley Steiner MPH Epidemiologist in the Division of Adolescent and School Health Centers for Disease Control and Prevention MedicalResearch.com: What is the background for this study? What are the main findings? Response: Using data from the 2013 national Youth Risk Behavior Survey (YRBS), our analysis looks at...
Dr. Alanna Chamberlain[/caption]
Alanna Chamberlain, PhD
Assistant Professor of Epidemiology
Mayo Clinic College of Medicine
MedicalResearch.com: What is the background for this study?
Dr. Chamberlain: The number of elderly individuals in the US will double by the year 2050 and these individuals will become increasingly frail as they get older. Frailty has been recognized by doctors and researchers as an important contributor to poor health and declines in quality of life among older adults. However, it is difficult to measure frailty because it’s not due to a single condition. Instead, multiple health problems tend to accumulate over time until a person becomes increasingly frail. It is important to understand how frailty develops as patients age and how changes in frailty are related to outcomes. To address these questions, we followed individuals over 8 years to identify changes in frailty over time, to describe how people cluster (follow similar trajectories of frailty over time), and to examine how these changes relate to emergency department visits, hospitalizations, and death in a large population from Olmsted County, MN.
Dr. Sarah de Ferranti[/caption]
Dr. Sarah de Ferranti MD MPH
Boston Children’s Hospital
Director, Preventive Cardiology Program
Assistant Professor of Pediatrics
Harvard Medical School
MedicalResearch.com: What are the main findings?
Dr. de Ferranti: Familial hypercholesterolemia, or FH, is a genetic condition that causes severely elevated cholesterol levels from birth and is a leading cause of early heart attack. It is generally slowly progressive without symptoms until there is serious heart disease in the 3rd and 4th decade of life, making it important to look for it at a young age. Prior to this analysis it was thought that FH affected about 1 in 500 adults. The current study used data from 36,949 adults who took part in the 1999-2012 National Health and Nutrition Examination Survey (NHANES) and extrapolated to the 210 million U.S. adults aged 20 years and older. We identified cases of probably or definite Familial hypercholesterolemia in our analysis by using a combination of high levels of low-density-lipoprotein cholesterol (considered “bad” because it contributes to plaque buildup in arteries) and early heart disease in a person or close relative.
Dr. Sanjit Konda[/caption]
Sanjit Konda, MD
Assistant professor of Orthopaedic surgery
NYU Langone Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Konda: We serendipitously found that we could identify periarticular fractures associated with deep knee wounds with the use of a CT-scan. We published a study in the Journal of Orthopaedic Trauma showing that a CT scan could identify a traumatic arthrotomy of a joint better than a saline load test, which at the time was considered the diagnostic gold standard. When we presented that work, we received criticism that we were subjecting patients to a high dose of radiation for a diagnostic test; however, our rationale at the time was that the saline load test was a painful, invasive procedure using a needle, and that we would trade a bit of radiation for lack of invasive procedure.
This got us thinking of ways we could decrease the amount of radiation in the CT yet maintain the same diagnostic accuracy of identifying penetrating joint injuries. Collaborating with Dr. Soterios Gyftopoulos, an assistant professor in the Department of Radiology at NYU Langone, we were able to successfully reduce the amount of radiation in these CT scans and still get good bony images. We then thought, if we can get a CT scan that shows us good bony detail and is safer, then why shouldn’t we be doing it on every joint fracture, not just these arthrotomy cases? We then applied this to our current research protocol, REDUCTION(Reduced Effective Dose Using Computed Tomography In Orthopaedic Injury) in which we reduced the average amount of radiation from 0.43 msV to 0.03 msV, or down to the average dose given in a routine chest X-ray. After running a comparison study with our ultra-low dose radiation protocol compared to conventional CT scans, we found we were able to obtain nearly the exact same types of images for various joint fractures and locations without sacrificing any diagnostic accuracy in most cases. We gave sets of these CT scans to orthopaedic surgeons to analyze, and found we achieved 98 percent sensitivity and 89 percent specificity with the ultra-low dose CT scans when occult fractures, or those that could not be seen on an X-ray, were removed from our analysis.
Dr. Ellen Flint[/caption]
Dr Ellen Flint
Lecturer in Population Health
MRC Strategic Skills Fellow
Department of Social & Environmental Health Research
London School of Hygiene & Tropical Medicine
London
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Flint: Globally, physical inactivity is a major cause of obesity, chronic disease and premature mortality. Improving population levels of physical activity is therefore a key public health policy aim, in high and middle income countries. In the past, functional active travel was a key source of physical activity for many people. However, since the mass adoption of private motorised travel in the 20th century, the vast majority (63%) of working adults in the UK commute to by car. Using UK Biobank data from more than 150,000 middle-aged adults, we found that those who commuted to work via cycling or walking had significantly lower body fat percentage and lower body mass index (BMI) compared to adults who commuted by car. The strongest associations were seen for adults who commuted via bicycle. For the average man in the sample (age 53 years; height 176.7cm; weight 85.9kg), cycling to work rather than driving was associated with a weight difference of 5kg or 11lbs (1.71 BMI points). For the average woman in the sample (age 52 years; height 163.6cm; weight 70.6kg), the weight difference was 4.4kg or 9.7lbs (1.65 BMI points). Even people who commuted via public transport also showed significant reductions in BMI and percentage body fat compared with those who commuted only by car. This suggests that even the incidental physical activity involved in public transport journeys may be important. The link between active commuting and obesity reduction was independent of other factors such as income, area deprivation, urban or rural residence, education, alcohol intake, smoking, general physical activity, dietary energy intake and overall health and disability. If you're often using public transport, particularly around the New York Area, check out this babylon schedule.
Dr. Anna Clara Hollander[/caption]
Anna-Clara Hollander PhD
Division of Social Medicine, Department of Public Health Sciences
Karolinska Institutet, Stockholm, Sweden.
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The humanitarian crises in Europe, the Middle East, north Africa, and central Asia have led to more displaced people, asylum seekers, and refugees worldwide than at any time since the second world war. Refugees are known to be at an increased risk of mental health problems, such as post-traumatic stress disorder and other common mental disorders, compared to non-refugee migrants, but little is known about their risk of psychosis.
The aim of the study was to determine the risk of schizophrenia and other non-affective psychotic disorders among refugees, compared to non-refugee migrants, and the general Swedish population. We used a linked national register data to examine more than 1.3 million people in Sweden, and tracked diagnoses of non-affective psychotic disorders among the population. The cohort included people born to two Swedish-born parents, refugees, and non-refugee migrants from the four major refugee generating regions: the Middle East and north Africa, sub-Saharan Africa, Asia, Eastern Europe and Russia.
Results showed 3,704 cases of non-affective psychotic disorders during the 8.9 million person years of follow up. Refugees granted asylum were on average 66% more likely to develop schizophrenia or another non-affective psychotic disorder than non-refugee migrants. In addition, they were up to 3.6 times more likely to do so than the Swedish-born population. Incidence rates for non-affective psychosis were 385 per million in those born in Sweden, 804 per million in non-refugee migrants, and 1264 per million in refugees.
The increased rate in refugees was significant for all areas of origin except sub-Saharan Africa, for whom rates in both groups were similarly high relative to the Swedish-born population. One possible explanation is that a larger proportion of sub-Saharan Africa immigrants will have been exposed to deleterious psychosocial adversities before emigration, irrespective of refugee status. Alternatively post-migratory factors, such as discrimination, racism, and social exclusion may explain these high rates.
Overall, our findings are consistent with the hypothesis that increased risk of non-affective psychotic disorders among immigrants is due to a higher frequency of exposure to social adversity before migration, including the effects of war, violence, or persecution.
Dr. Sarah Tartoff[/caption]
Sara Y. Tartof, PhD, MPH
Kaiser Permanente Southern California Department of Research & Evaluation
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Tartof: The flu is a highly contagious respiratory infection that can cause serious complications, hospitalizations and, in some cases, even death. Some people, such as older adults, young children and people with certain health conditions, are at high risk for serious complications. In addition to recommending annual flu vaccination for people 6 months of age and older, the Centers for Disease Control and Prevention recommends that hospitalized patients who are eligible receive the flu vaccine before discharge.
Historically, inpatient rates of vaccination have been low. There has been concern among surgeons that vaccinating patients while they are in the hospital can contribute to increased risk of vaccine-related fever or muscle pain, which might be incorrectly attributed to surgical complications. However, there have been no data to support that concern. The objective of this study was to provide clinical evidence that would either substantiate or refute concerns about the safety of perioperative vaccination.
Dr. Nipun Shrestha[/caption]
Dr Nipun Shrestha MBBS, MPH
Health Research and Social Development Forum
Thapathali, Kathmandu, Nepal
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: These days our work in the offices isn't the same as it used to be. Almost everybody is working with a computer nowadays and that makes you sit still all day. We do not need to move from our chair to do most of the things. This is not just the case in developed countries but for developing countries as well.
One would argue though we are sitting in the office hours but we are regularly doing lots of exercises. However researchers have found that sedentary behavior is an independent risk factor for many chronic diseases like diabetes, cardiovascular diseases and cancer. So breaking up time that we spend sitting is important.
There are many commercial innovations available in the market which are being advertised heavily by the manufacturers. The evidence on effectiveness of such innovation is however not available.
We found that there is limited evidence on effectiveness of interventions that aim to reduce sitting at work. There is some evidence that sit-stand desk may reduce sitting at work between 30 minutes to 2 hours without any adverse effects.
Dr. Daniel Murphy[/caption]
Daniel R. Murphy MD MBA
Assistant Professor - Interim Director of GIM at Baylor Clinic
Department of Medicine
Health Svc Research & General Internal Medicine
Baylor College of Medicine
Houston, TX, US
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Murphy: Electronic health records (EHRs) have enabled a large number of messages to be transmitted to physicians each day, including new types of messages that were not present in the pre-EHR era. Lack of support and policies to assist physicians with this workload creates opportunities for important information, such as abnormal tests results, to be missed among the vast amount of other information. We found that primary care physicians (PCPs) at three clinics using commercial EHRs received an average of 77 messages per day, of which only about 20% were test results. Specialists received an average of 29 total messages per day. Extrapolating time needed to process these messages from prior work suggests that PCPs would require an average of 67 minutes per day to process these messages.
Dr. Mairead Black[/caption]
Dr Mairead Black MBChB, MRCOG, MSc
Clinical Lecturer, Obstetrics and Gynaecology
School of Medicine and Dentistry, Division of Applied Health Sciences
University of Aberdeen
Aberdeen Maternity Hospital, Cornhill Road
Aberdeen
MedicalResearch.com: What is the background for this study?
Dr. Black: The commonest reason for performing a planned Cesarean Section (CS) in high-income countries is a history of a previous CS. However, there is very little information available on childhood health outcomes of birth after a previous .
MedicalResearch.com: Why might vaginal birth be beneficial?
Dr. Black: If a baby is born naturally, it is exposed to various processes of labour and birth which may help their immunity and ability to avoid or fight future illness.
Dr. Michael Miedema[/caption]
Michael D. Miedema, MD, MPH
Minneapolis Heart Institute Foundation
Abbott Northwestern Hospital
Minneapolis, MN
MedicalResearch.com: What is the background for this study?
Dr. Miedema: Heart disease is the leading cause of death in the United States. With increasing risk factors like obesity and diabetes more population level prevention efforts are needed. Heart of New Um Project (HONU) was created as a demonstration project to test prevention of cardiovascular disease by reducing modifiable risk factors across the entire community. HONU interventions focus on improving health by reaching individuals in health care, worksites, and the community settings but also creating healthier environment and a social movement around being healthy to enable individuals to make healthier choices. Example interventions in health care, worksite, and the broader community include:
Dr. Shaun Desai[/caption]
Shaun C. Desai, MD
Assistant Professor
Facial Plastic and Reconstructive Surgery
Department of Otolaryngology - Head & Neck Surgery
Johns Hopkins University School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Desai: Estimates of the rate of revision septorhinoplasty and the risk factors associated with revision are unknown because the current published literature is limited to small, retrospective, single-surgeon studies with limited follow-up time. The purpose of this study is to determine the overall revision rates of patients undergoing a septorhinoplasty procedure (for functional or cosmetic reasons) and to determine risk factors for the revision. We found that the overall revision rate was 3.3% (5,775 patients of a total of 175,842 patients undergoing the procedure) with an average time to revision at 1 year. Risk factors for revision surgery included female gender, younger age, a history of anxiety or autoimmune disease, cosmetic indications, and more complicated initial surgery (i.e. cleft rhinoplasty).
Dr. Joost Sluijter[/caption]
Joost P.G. Sluijter, PhD, FESC
Associate Professor
Department of Cardiology
Experimental Cardiology Laboratory
UMC Utrecht
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sluijter: Cell transplantation therapy for ischemic heart disease has entered the arena of clinical trials more than a decade ago. Multiple cell types have been used since these first endeavors, and there is accumulating evidence that different cell types positively influence the damaged heart through paracrine and/or regenerative mechanisms. One of the most promising cell types to be used are the cardiac-located stem cells. Cardiac stem cells (CSCs) have been found to reside in the adult heart and can differentiate towards all cell types that are needed in the normal functional heart. These cells have shown great potential as a regenerative therapeutic upon myocardial infarction (MI) in animal models and are currently being tested in some clinical studies. However, although promising, no systematic overview and subsequent meta-analysis of preclinical data exists to date for this cell type and if they are consistently effective. Our systematic approach, yielded 80 studies and included over 1900 animals, confirms the consistent effect of CSCs and provides us with a first comprehensive overview of pre-clinical MI studies in an unbiased and systematic manner. Nowadays we are aware of a failure in therapeutic effect size for the translation axis, where we try to bridge fundamental findings from the lab to the bedside. This means that effects we observe in our initial studies on cardiac performance are slowly getting less successful when we are getting closer to a real clinical scenario.
Through our meta-analysis, we observed a consistent therapeutic effect of Cardiac stem cells therapy on cardiac function after MI, where 12% of functional improvements is observed in rodents, and only an 8% improvement was still present in large animal models. From previous observations, we know that this leaves a 3-4% of effect in a patient population. In addition to the difference in effect size between small and large animal models, also a difference in study quality and attrition bias was observed. Interestingly, although additional support to the idea that Cardiac stem cells are efficacious in preclinical studies were observed, we did not find any influence of immunosuppression, cell source, comorbidity of CSC donors, culture methods, or model of ischemia on the outcomes.