Medical Research Journals

25 Jun

Posted at 01:21h in Author Interviews, Cannabis, JAMA, Johns Hopkins
Ryan Vandrey, Ph.D. Associate Professor Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine Baltimore, MD 21224MedicalResearch.com Interview with: Ryan Vandrey, Ph.D. Associate Professor Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine Baltimore, MD 21224 Medical Research: What is the background for this study? What are the main findings? Dr. Vandrey: The background for the study was that I have had several conversations with individuals that led me to believe that there was insufficient regulation of products of all types being sold in medical cannabis dispensaries.  In order to evaluate that, we needed to do a study.  We decided to test edible products because that is a growing market, and, because it involves some level of manufacturing, there is greater chance for dose variability and inaccuracy.  The main finding was that the majority of products were purchased from retail stores selling cannabis products for medical use were significantly mislabeled with regards to the dose of THC and other cannabinoids.

25 Jun

Posted at 01:09h in Author Interviews, JAMA, Surgical Research, Technology
Vanita Ahuja, MD, MPH Department of General Surgery York Hospital, York, PennsylvaniaMedicalResearch.com Interview with: Vanita Ahuja, MD, MPH  Department of General Surgery York Hospital, York, Pennsylvania MedicalResearch: What is the background for this study? What are the main findings? Dr. Ahuja: Robotic-assisted surgery has been slowly accepted within the medical community. Felger et al. (1999), Falk et al. (2000), and Loumet et al. (2000) state that specific to cardiac surgery, the advantages of the robot in coronary artery bypass grafting (CABG) and valvular operations were demonstrated with increased visualization, ease of harvest, and quality of vascular anastomoses as early as 1999. However, Giulianotti, et al. (2003), Morgan et al. (2005), and Barbash et al. (2010) suggest that although safety and efficacy are supported, it is not conclusive yet that robot-assisted surgery is cost-effective, given the high cost of the robot itself, longer operating times, and the short life of the robotic instruments. The purpose of our paper was to compare outcomes of complications, length of stay (LOS), actual cost, and mortality between non-robotic and robotic-assisted cardiac surgery. In general surgery and subspecialties, the use of the robot has increased significantly over the past few years. It has been noted that robotic surgery improves on laparoscopic surgery by providing increased intra-cavity articulation, increased degrees of freedom, and downscaling of motion amplitude that may reduce the strain on the surgeon. The biggest growth in robotic surgery has been seen in the fields of gynecology and urology. Recently, Wright et al. reported an increase in robotic assisted hysterectomy from 0.5 percent of the procedures in 2007 compared to 9.5 percent in 2010 for benign disease. In their study, robotic assisted surgery had similar outcomes to laparoscopic surgery but higher total cost of $2,189 more per case. In urologic surgery, Leddy et al. reported in 2010 that radical prostatectomy remains the biggest utilization of robotic assisted surgery in urology with 1% in 2001 to 40% of all cases in 2006 performed in the United States. Utilizing a nationwide database from 2008-2011, subjects were propensity matched by 14 patient characteristics to reduce selection bias in a retrospective study. The patients were then divided into three groups by operation types: valves, vessels and other type. Univariate analysis revealed that robotic-assisted surgery, compared to non-robotic surgery, had higher cost ($39,030 vs. $36,340), but lower LOS (5 vs. 6 days) and mortality (1% vs. 1.9%, all p<0.001). For those who had one or more complications, robotic-assisted cardiac surgery had fewer complications (27.2%) to non-robotic cardiac surgery (30.3%, p < .001).

25 Jun

Posted at 00:46h in Author Interviews, Cancer Research, JAMA
Dr. Ayalew Tefferi, M.D.Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch.com Interview with: Dr. Ayalew Tefferi, M.D. Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch: What is the background for this study? What are the main findings? Dr. Tefferi: William Vainchenker discovered and reported an activating JAK2 mutation (JAK2V617F) in myelofibrosis and related myeloproliferative neoplasms in 2005 (Nature. 2005;434:1144-1148). This seminal observation led to the recognition of activated JAK-STAT as the potential disease-driving pathway in myeloproliferative neoplasms and development of several JAK inhibitors, including fedratinib, ruxolitinib and momelotinib, for treatment of myelofibrosis. In phase 2 studies, these JAK inhibitors showed similar activity in alleviating constitutional symptoms and reducing spleen size. However, none of them were able to induce complete or partial remissions or reversal of bone marrow fibrosis or significant lowering of JAK2 mutant allele burden. A subsequent phase 3 study provided the information required for FDA approval of ruxolitinib and the current phase 3 study was meant to do the same for fedratinib.

25 Jun

Posted at 00:04h in AHA Journals, Author Interviews, Lipids, Race/Ethnic Diversity
Carlos J. Rodriguez, MD, MPH Division of Public Health Sciences Department of Medicine Wake Forest School of Medicine Winston‐Salem, NC 27152MedicalResearch.com Interview with: Carlos J. Rodriguez, MD, MPH Division of Public Health Sciences Department of Medicine Wake Forest School of Medicine Winston‐Salem, NC 27152 MedicalResearch: What prompted you to study cholesterol in the Latino population? Please explain in detail. Dr. Rodriguez: Early in my career I noted that there were race-ethnic differences in the cholesterol profile between hispanics, african americans and non-hispanic whites. Hispanics are the largest ethnic minority group in the us yet prior studies of cholesterol in hispanics were relatively small, lacked adequate representation of diverse hispanic background groups for comparisons, and were not necessarily representative of nor generalizable to the hispanic population. The hispanic/latino adults in the hispanic community health study / study of latinos helped filled this critical gap. MedicalResearch: What do you think are the most significant findings from your study? What could have the greatest clinical implications and applications? Dr. Rodriguez: Several findings are important: less than half of those with high cholesterol were aware of their condition; less than a third of those with high cholesterol were being treated; and  among those receiving treatment, only two-thirds had cholesterol concentrations that were adequately controlled.

24 Jun

Posted at 21:54h in Author Interviews, Heart Disease, JACC, University of Michigan
MedicalResearch.com Interview with: Jessica Parsh MD Hitinder Gurm MBBS Department of Internal Medicineb University of Michigan Health System Medical Research: What is the background for this study? What are the main findings? Response: Chronic kidney disease (CKD) is associated with adverse events after percutaneous coronary interventions (PCI). Estimated glomerular filtration rate (eGFR) is used for CKD stage classification and there are several widely used eGFR equations, including the Cockcroft-Gault, CKD-EPI, and MDRD. Others have shown that the CKD-EPI equation is more accurate, more precise and less bias. The current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the use of CKD-EPI. Even so, there remains wide variability among equation choice between different institutions as well as between different health care providers (physicians, pharmacists, etc). In addition, in a recent survey, up to 12% of providers were "unsure" of which equation they used. Furthermore, the FDA has no clear guidelines regarding equation selection for pharmacokinetic studies of novel medications and the equation used for development of a particular drug is not always clearly labeled on package inserts. Using data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium for almost 130,000 patients who underwent PCI, we investigated whether use of different eGFR equations would lead to discrepant eGFR output, how this would lead to CKD stage reclassification and whether CKD stage reclassification by a certain equation led to improved risk prognostication for adverse events. We also studied how calculation of eGFR by various equations would affect drug dosing recommendations for common renally-dosed antiplatelet and antithrombotic medications. We found that there was wide discrepancy among the eGFR output of the various equations and this led to significant CKD stage reclassification (with agreement on stage classification as low as 56% for CKD-EPI and Cockcroft-Gault). Further, our data from receiver operating characteristic analysis and net reclassification index analysis support CKD-EPI as superior for risk prognostication for renal adverse outcomes of acute kidney injury and new requirement for dialysis. In regards to drug dosing, agreement between all three equations on dosing adjustment was as low as 34% (bivalirudin with eGFR cutoff < 30 ml/min/1.732).

24 Jun

Posted at 21:33h in Author Interviews, Erectile Dysfunction, JAMA, Melanoma, NYU/NYMC, Pharmacology
Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York MedicalResearch.com Interview with: Dr. Stacy Loeb, MD, MSc Department of Urology, Population Health, and Laura and Isaac Perlmutter Cancer Center New York University, New York Medical Research: What is the background for this study? Dr. Loeb: A paper published last year suggested a relationship between use of (Viagra) and melanoma.  That study had only 142 cases of melanoma, and of these men 14 had used sildenafil.  This study got a lot of publicity leading numerous patients to express concern over whether erectile dysfunction drugs could cause melanoma. Our goal was to look more closely at this issue in a larger population from Sweden (including 4065 melanoma cases of whom 435 used any type of erectile dysfunction drug- Viagra, as well as Levitra and Cialis).  Sweden has a national health system so we were able to access prescription records for men across the entire country, which we linked to the national registries for melanoma and basal cell skin cancer.  

24 Jun

Posted at 21:20h in Author Interviews, Duke, Heart Disease, JAMA
Sean D. Pokorney, MD, MBA Division of Cardiology, Duke University Medical Center Duke Clinical Research Institute, Durham, North Carolina MedicalResearch.com Interview with: Sean D. Pokorney, MD, MBA Division of Cardiology, Duke University Medical Center Duke Clinical Research Institute, Durham, North Carolina Medical Research: What is the background for this study? Dr. Pokorney: About 350,000 people die of sudden cardiac death in the US each year. Patients who have weakened heart function, particularly those with heart muscle damage as a result of a heart attack, are more likely to experience sudden cardiac death.  Defibrillators have been around since the 1980s, and have prolonged countless lives.  A previous study showed that 87% of patients who had a cardiac arrest were eligible for an implantable-cardioverter defibrillator (ICD) beforehand but did not get an ICD implanted prior to their arrest.  The timing of ICD implantation is critical, as studies have not found a benefit to ICD implantation early after myocardial infarction (MI).  Guidelines recommend primary prevention ICD implantation in patients with an EF ≤ 35% despite being treated with optimal medical therapy for at least 40 days after an MI.  Given the need to wait for at least 40 days after an MI, ICD consideration is susceptible to errors of omission during the transition of post-MI care between inpatient and outpatient care teams.  Also, the benefit of ICDs remains controversial among older patients, as these patients were underrepresented in clinical trials. Medical Research: What are the main findings? Dr. Pokorney: We looked at Medicare patients discharged from US hospitals after a heart attack between 2007 and 2010.  We focused on those patients who had weak heart function, and this left us with a little over 10,300 patients from 441 hospitals for our study.  This was an older patient population with a median age of 78 years.  We looked to see how many of these patients got an ICD within the first year after MI, and how many patients survived to 2 years after their heart attack.  Only 8% of patients received an ICD within 1 year of their heart attack.  ICD implantation was associated with a third lower risk of death within 2 years after a heart attack, and this was consistent with the benefit that were seen in the randomized clinical trials.  Importantly, 44% of the patients in our study were over 80 years old, and we found that the relationship between ICD use and mortality was the same for patients over and under age 80 years.  Increased patient contact with the health care system through early cardiology follow-up or re-hospitalization for heart failure or MI was associated with higher likelihood of ICD implantation.  Rates of ICD implantation remained around 1 in 10 patients within 1 year of MI even among patients with the largest heart attacks and the weakest hearts (lowest ejection fractions), who were least likely to have improvement in their heart function over time.  Similarly, even after excluding patients at highest risk for non-arrhythmic death (prior cancer, prior stroke, and end stage renal disease), ICD implantation rates remained around 1 in 10 patients.

24 Jun

Posted at 20:42h in Anesthesiology, Author Interviews, BMJ, Surgical Research
Dr. Andrea Tricco Ph.D Dalla Lana School of Public Health University of TorontoMedicalResearch.com Interview with: Dr. Andrea Tricco Ph.D Dalla Lana School of Public Health University of Toronto Medical Research: What is the background for this study? What are the main findings? Dr. Tricco: We were commissioned by Health Canada to assess the safety and effectiveness of serotonin (5-HT3) receptor antagonists in patients undergoing surgery. In order to examine this research question, we conducted a systematic review and network meta-analysis including >450 studies. We found that more patients receiving granisetron plus dexamethasone experienced arrhythmia compared to all other interventions and placebo. No differences were observed regarding mortality and QT prolongation in meta‐analysis; no studies reported on PR prolongation or sudden cardiac death. Granisetron plus dexamethasone was often the most effective antiemetic, with the number needed to treat ranging from two to nine. We found that ondansetron plus droperidol intravenous (IV) was also a highly effective antiemetic for decreasing the risk of vomiting and post-operative nausea and vomiting (PONV).

24 Jun

Posted at 20:30h in Author Interviews, Biomarkers, Melanoma, Nature

MedicalResearch.com Interview with: Keiran Smalley, PhD. Scientific Director The Comprehensive Melanoma Research Center Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FL Medical Research: What is the background for this study? What are the main findings? Dr. Smalley: The major finding of this study is that some melanomas (those which are BRAF mutant and PTEN null)...

24 Jun

Posted at 16:04h in Author Interviews, Blood Pressure - Hypertension, Duke, Heart Disease, JACC
Satoru Kishi, MD Division of Cardiology Johns Hopkins University Baltimore, MarylandMedicalResearch.com Interview with: Satoru Kishi, MD Division of Cardiology Johns Hopkins University Baltimore, Maryland MedicalResearch: What is the background for this study? What are the main findings? Dr. Kishi: Blood pressure (BP) at the higher end of the population distribution may represent a chronic exposure that produces chronic injury to the cardiovascular system. Cumulative BP exposure from young adulthood to middle age may adversely influence myocardial function and predispose individuals to heart failure (HF) and other cardiovascular disease (CVD) later in life. The 2005 guidelines for the diagnosis and treatment of HF from the American College of Cardiology and American Heart Association highlight the importance of early recognition of subclinical cardiac disease and the importance of non-invasive tests in the clinical evaluation of heart failure. Our main objective was to investigate how cumulative exposure to high blood pressure from young to middle adulthood influence LV function. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, multiple repeated measures of BP and other cardiovascular risk factors was recorded over a 25 year time span, starting during early adulthood (ages 18-30).

24 Jun

Posted at 15:51h in Author Interviews, Cost of Health Care, JAMA, Weight Research

MedicalResearch.com Interview with: Dr. Yang Lin on behalf of all authors Department of Surgery, Division of Public Health Sciences Siteman Cancer Center, Washington University School of Medicine St Louis, Missouri Medical Research: What is the background for this study? What are the main findings? Dr. Lin: Overweight, obesity and associated chronic conditions are largely driving the...

24 Jun

Posted at 11:05h in Accidents & Violence, Annals Internal Medicine, Author Interviews, Brigham & Women's - Harvard, Pediatrics
MedicalResearch.com Interview with: Lois K. Lee, MD, MPH Division of Emergency Medicine Boston Children's Hospital Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Response: Motor vehicle crashes remain a leading cause of death for children and adults in the U.S. Seat belts are the single most effective protective device to decreased death and mitigate injuries in the event of a motor vehicle crash. Our study found that states with primary seat belt laws, where a motorist can be ticketed only for not wearing a seat belt, demonstrated a 17% decreased fatality rate, compared to states with secondary seat belt laws, where a motorist must be cited for another violation first before also getting ticketed for not wearing a seat belt. We found this difference was robust even after controlling for other motor vehicle safety legislation and state demographic factors. We found that although seatbelts prevent deaths, they don't completely stop injury so if you have been in an accident that wasn't your fault then you might want to look for a place like the Parnall Law Firm to see if they can help you get compensation for your injuries.

23 Jun

Posted at 22:49h in Author Interviews, Cannabis, JAMA
MedicalResearch.com Interview with: Penny F. Whiting, PhD School of Social and Community Medicine, University of Bristol The National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West at University Hospitals, Bristol NHS Foundation Trust, Bristol UK Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom MedicalResearch: What is the background for this study? What are the main findings? Dr. Whiting: Cannabis is one of the most popular recreational drugs - only tobacco, alcohol and caffeine are more popular. It can result in an alteration to mood and a feeling of “high”. An estimated 141 million people use cannabis worldwide – this is equivalent to 2.5% of the world’s population. Cannabis has a long history of use for the relief of a wide variety of medical symptoms. There is evidence of its use for medical purposes going back to early Egyptian times. The pen-ts’ao ching the world’s oldest herbal book includes reference to cannabis as medicine for rheumatic pain, constipation, disorders of the female reproductive system, and malaria amongst others, this herbal book also contains the first reference to cannabis as a psychoactive drug. However, its use is controversial as it has been included as a controlled drug in the United Nations Single Convention on Narcotic Drugs since 1961, and the use of cannabis is illegal in most countries. Medical cannabis (or medical marijuana) refers to the use of cannabis or cannabinoids (any compound, natural or synthetic, that can mimic the actions of plant-derived cannabinoids) as medical therapy to treat disease or alleviate symptoms, this is different from CBD oil that also has been found to help with certain medical conditions, click to see details about CBD oil. Some countries have legalised medicinal-grade cannabis to chronically ill patients but in others its use remains illegal even for medicinal purposes. Canada and the Netherlands have government-run programmes where specialised companies supply quality controlled herbal cannabis. There are different strains of cannabis can help with aliments, those who are interested in finding out more about a list of low odor strains by GreenBudGuru.com might be interested in visiting or doing some research to find out more. These programmes have been running since 2001 and 2003 respectively. In the US around half of the states have introduced laws to permit the medical use of cannabis; other countries have similar laws. Kleijnen Systematic Reviews Ltd (see below) were commissioned by the Swiss Federal Office of Public Health to conduct a systematic review for the effects and adverse events of medical cannabis to inform policy decision making. Systematic reviews are studies of studies that offer a systematic approach to reviewing and summarising evidence. They follow a defined structure to identify, evaluate and summarise all available evidence addressing a particular research question. We were asked to focus on the following ten indications which were of particular interest to our commissioners: nausea and vomiting due to chemotherapy, patients with HIV/AIDS, chronic pain, spasticity in patients with multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, and Tourette’s syndrome. We only included randomised trials, the most robust design for evaluating the effects of an intervention. We included almost 80 trials (nearly 6500 participants). We had most evidence for chronic pain (28 trials), nausea and vomiting due to chemotherapy (28 trials) and spasticity due to MS or paraplegia (14 trials) with less than five studies included for each of the other indications and none for depression. With the exception of the nausea and vomiting due to chemotherapy population, studies general compared cannabinoids to placebo with only single studies for each indication comparing cannabinoid with an active comparator. In the nausea and vomiting population the majority of studies compared cannabinoids to an active comparator, most commonly prochlorperazine. Most trials reported greater improvement in symptoms with cannabinoids compared to control groups, however, these did not always reach statistical significance. Cannabinoids were also associated with a greater risk of short term adverse events, including serious adverse events. Common adverse events included dizziness, dry mouth, nausea, fatigue, sleepiness, and euphoria. Overall we found that there was moderate quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity and low-quality evidence to suggest that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep quality, and Tourette syndrome. When determining the quality of the evidence we considered the risk of bias in trials, the consistency of the evidence across the trials, the directness of the evidence (was the trials research question directly applicable to our review question), and the precision of the evidence.

23 Jun

Posted at 22:24h in Author Interviews, Heart Disease, Nature, Nutrition
MedicalResearch.com Interview with: Prof. Wilhelm Krek Institute of Molecular Health Sciences Zürich, Switzerland MedicalResearch: What is the background for this study? What are the main findings? Prof. Krek: Fructose and glucose are major components of dietary sugars consumed in the western world. A current prevailing view holds that glucose is used directly by various tissues as an energy source while fructose is first and foremost metabolized to fat by the liver arguing that these dietary sugars are metabolized differently despite having identical caloric values. Accordingly, overconsumption of fructose causes fatty liver disease and through dissemination of fat to peripheral organs such that adipose tissue contributes to obesity. The key enzyme in fructose metabolism is ketohexokinase (KHK). KHK-A and KHK-C are two isoforms of KHK that are produced through mutually exclusive alternative splicing of the KHK pre-mRNA. KHK-C displays a much higher affinity for fructose than KHK-A. Unlike other tissues that normally express KHK-A, the liver produces predominantly KHK-C providing a possible explanation of the above-noted pathologies upon overconsumption of fructose. Whether fructose metabolism is subject to signal-induced changes in alternative splicing of KHK isoform expression as a mechanism to mediate context-dependent changes in cell metabolism is not known. In this work, we identify the splicing factor SF3B1 as a key mediator of ketohexokinase alternative splicing and thus activator of fructose metabolism and further show that the SF3B1-KHK system is a direct target of regulation by hypoxia and promoter of heart disease. From the analysis of a series of genetic mouse models of pathologic cardiac hypertrophy and human samples of heart disease, we conclude that activation of the newly identified HIF1α-SF3B1-KHK-C axis and the ensuing promotion of fructose metabolism is essential for pathologic stress-induced anabolic growth and the development of heart disease.

23 Jun

Posted at 18:14h in Author Interviews, Clots - Coagulation, NEJM
MedicalResearch.com Interview with: Dr. Charles Pollack Jr., MA, MD, FACEP Thomas Jefferson University Clinical Professor of Emergency Medicine Philadelphia, PA 19107 MedicalResearch: What is the background for this study? What are the main findings? Dr. Pollack: There are currently no approved specific reversal agents for non–vitamin K antagonist oral anticoagulants. Idarucizumab, an antibody fragment, was developed to specifically reverse the anticoagulant effects of the oral thrombin inhibitor, dabigatran. RE-VERSE AD is an ongoing, global Phase III patient study initiated in 2014 to investigate idarucizumab in emergency settings in patients taking dabigatran. We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who either presented with serious bleeding (group A) or required an urgent invasive procedure (group B) which could not be delayed by eight hours. We intentionally designed the study with very broad inclusion criteria to reflect the types of patients who would require urgent anticoagulant reversal in real-world emergency settings. The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time. We also diligently collected clinical outcomes as secondary outcomes, being conscious that these may vary considerably due to the heterogeneity of the patients we included in the study. In our publication in the New England Journal of Medicine, we present the first results from the study, in an interim analysis of the data from the first 90 patients. The data showed that idarucizumab rapidly and completely reversed the anticoagulant effect of dabigatran in 88 to 98% of the patients who had had elevated clotting times at baseline. The reversal effect was evident within minutes. There were no safety concerns related to idarucizumab among the 90 patients involved in this study - including patients who were given idarucizumab on clinical grounds but were later found to have had normal results on clotting tests at baseline. This is consistent with the experience from the more than 200 volunteers who were administered idarucizumab in previous studies.

23 Jun

Posted at 10:59h in Author Interviews, Brigham & Women's - Harvard, Dermatology, Nature, Surgical Research
MedicalResearch.com Interview with: [caption id="attachment_26954" align="alignleft" width="200"]Dr. Alexander Golberg Ph.D. Center for Engineering in Medicine Department of Surgery, Massachusetts General Hospital Harvard Medical School, and Shriners Burns Hospital Boston, MA, 02114 Porter School of Environmental Studies Tel Aviv University, Israel Dr. Alexander Golberg[/caption] Dr. Alexander Golberg Ph.D. Center for Engineering in Medicine Department of Surgery, Massachusetts General Hospital Harvard Medical School, and Shriners Burns Hospital Boston, MA, 02114 Porter School of Environmental Studies Tel Aviv University, Israel MedicalResearch: What is the background for this study? What are the main findings? Dr. Golberg: Well, the population grows and becomes older. Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. We report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.

23 Jun

Posted at 10:35h in Author Interviews, Emory, Flu - Influenza, PLoS
MedicalResearch.com Interview with: Brooke Bozick Ph.D. Candidate Population Biology, Ecology, & Evolution Program Emory University MedicalResearch: What is the background for this study? Response: Previous research at the global scale has shown that air travel is important for the spread of disease. For example, much work has focused on the recent Ebola epidemic in Africa, identifying where this disease emerged and then using air travel networks to predict the path of spread from there. At a more local scale, other modes of transportation may be more important to structuring pathogen populations. We were interested in investigating seasonal influenza in the United States. Previous research has shown that once the winter influenza epidemic starts, it spreads very rapidly across the continental states, suggesting that the US may act as one large, well-mixed population. Previous work using genetic data to look for spatial structure at this scale didn’t identify any patterns. However, these studies used geographic proximity to define the distance between states; we wanted to see whether similar patterns existed at this spatial scale if we instead used movement data as a proxy for the distance between locations. Commuter movements have previously been shown to correlate with influenza timing and spread based on influenza-like-illness and mortality data. MedicalResearch: What are the main findings? Response: We found that spatial structure is detectable within the US. We used data on the genetic distance between sequences collected from different states and compared that to different measures of ‘distance’ between states—geographic proximity, the daily number of people flying between states and the daily number of commuters traveling between states using ground transportation—to see whether any correlations were present. Further, we did this for two different subtypes of seasonal influenza: A/H3N2 and A/H1N1. These subtypes have different epidemiological properties, so there was reason to believe that the observed patterns might differ depending on subtype. We found that some correlations were present for all the distance metrics studied, but that they were observed a greater proportion of the time when looking at commuter movements, and when looking at the A/H1N1 subtype. Since A/H1N1 is generally milder and spreads more slowly throughout the US compared to A/H3N2, we interpret this to mean that spatial structure is likely more easily detected in this subtype. If A/H3N2 spreads rapidly from coast to coast, any signature of spatial structure is likely obscured before we have a chance to observe it.

22 Jun

Posted at 22:35h in Author Interviews, Cancer Research, JAMA, NIH
MedicalResearch.com Interview with: Vinay Prasad, MD, MPH Medical Oncology Service, National Cancer Institute National Institutes of Health Bethesda, Maryland MedicalResearch: What is the background for this study? What are the main findings? Dr. Prasad: In medicine, there are two types of endpoints:  clinical endpoints and surrogate endpoints. Clinical endpoints, such as survival or quality of life, measure how a patient, feels, functions or lives.  In contrast, a surrogate endpoint is not a measure of patient benefit. Instead, it is merely hoped to correlate with one.  LDL levels are a surrogate for cardiovascular risk, for instance. Oncologists use and trust surrogate endpoints, such as response rate, progression free survival and disease free survival.  The majority of drug approvals and many guideline recommendations are based on improvements in surrogates.  Surrogates are assumed to correlate with overall survival, but we wanted to know if this was true, and under what circumstances. We reviewed all well done studies of surrogate-survival association.  We found that the majority--especially in the setting of metastatic disease--found a poor correlation between a surrogate and survival.  In fact, correlations were strong in only a handful of settings, such as adjuvant colorectal cancer.  Moreover, we found that correlations were always based on a subset of potentially informative literature, even when authors surveyed unpublished trials.  Missing data in these association studies raises the concern that correlations would be different if all data had been considered. Our overall conclusion was that most surrogate-survival correlations in oncology are based on weak evidence and are poor.

21 Jun

Posted at 13:30h in Author Interviews, Heart Disease, JACC
MedicalResearch.com Interview with: José C. Nicolau, MD, PhD, FACC Professor -University of São Paulo Medical School Director - Acute Coronary Disease Unit, Heart Institute MedicalResearch: What is the background for this study? Dr. Nicolau: Previous studies, mainly performed in patients undergoing percutaneous coronary intervention (PCI), have shown that concomitant use of proton-pump inhibitors (PPIs) diminishes the antiplatelet effect of the drug clopidogrel. This diminished response to clopidogrel has in turn been associated with an increased risk of stent thrombosis and ischemic events. Our paper presented results from a secondary analysis performed in patients enrolled in the TRILOGY ACS randomized clinical trial. Our study is the first to examine the influence of interactions between PPIs and clopidogrel or the newer, more potent antiplatelet drug prasugrel, as well as correlations with platelet reactivity and clinical outcomes in high-risk patients who were receiving medical management without revascularization following acute coronary syndrome (ACS).

21 Jun

Posted at 13:00h in Anesthesiology, Author Interviews, Emergency Care, JAMA
MedicalResearch.com Interview with: Christoph Czarnetzki MD, MBA Division of Anesthesiology Geneva University Hospitals Geneva, Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Czarnetzki: In the US, about 40 million patients undergo a general anesthetic each year, and approximately 12,000 broncho-aspirate. Broncho-aspiration of gastric juice may lead to acute respiratory distress syndrome, carrying a 40% mortality rate. The risk is increased 10-fold in patients undergoing emergency surgery. Trauma patients may have ingested food before their accident, or have swallowed blood from oral or nasal injuries. Also, gastric emptying is delayed due to head injury, stress, pain, and opioid medication. Non-trauma patients may have delayed gastric emptying due to paralytic ileus and critical illness, leading to significant residual stomach content even after long fasting periods. Erythromycin, a macrolide antibiotic, and motilin receptor agonist induces antral contractions, and increases the lower esophageal sphincter tone, which is an important barrier against gastro-esophageal reflux. Although gastric emptying properties of erythromycin are well known, its efficacy in patients undergoing emergency surgery has never been investigated before to our knowledge. In our study we included 132 patients undergoing general anesthesia for emergency procedures and we could show that erythromycin increased the proportion of clear stomach and decreased acidity of residual gastric liquid. Dependent of the definition of empty stomach (less than 40 ml and absence of solid food or completely empty stomach) the absolute risk reduction ranged from 17% to 24%, equivalent to a number needed to treat of four to six patients to produce one completely cleared stomach. Erythromycin was particularly efficacious in non-trauma patients. Adverse effects were minor.

21 Jun

Posted at 12:53h in Author Interviews, Diabetes, Endocrinology, JAMA
MedicalResearch.com Interview with: Francis de Zegher, MD, PhD Department of Development and Regeneration, University of Leuven Leuven, Belgium & Lourdes Ibáñez, MD, PhD Hospital Sant Joan de Déu, University of Barcelona Barcelona, Spain Medical Research: What is the background for this study? Response: Hyperinsulinemic androgen excess is the most frequent hormonal disorder of adolescent girls. It seems to be mainly driven by an excessive and/or inappropriate storage of fat due to a chronically positive energy balance. The traditional approach (not approved by FDA or EMA) is to silence the ovaries by giving an oral contraceptive. An alternative approach is to change the storage of fat by giving an insulin-sensitizing combination of generics in low dose.

21 Jun

Posted at 12:41h in AHA Journals, Author Interviews, Heart Disease, Social Issues
Jaana Halonen Ph.D Finnish Institute of Occupational Health Kuopio, FinlandMedicalResearch.com Interview with: Jaana Halonen Ph.D Finnish Institute of Occupational Health Kuopio, Finland MedicalResearch: What is the background for this study? What are the main findings? Dr. Halonen: Research on predictors of cardiovascular disease has increasingly focused on exposures to risk factors other than the conventional behavioral and biological ones, such as smoking, hypertension, dyslipidaemia, or diabetes. One of the potential predictors beyond the conventional risks is exposure to childhood psychosocial adversities. Previous studies have found that people who had experienced financial difficulties, serious conflicts and long-term disease in the family in childhood have a higher level of cardiovascular risk factors and increased cardiovascular morbidity in adulthood, but the underlying mechanisms linking childhood exposure to adult disease remain unclear. It is possible that childhood adversity sets an individual on a risk pathway leading to adverse future exposures. An important source of adversity experienced in adulthood is residence in a socioeconomically disadvantaged neighborhood. However, no previous study had examined the combined effect of childhood psychosocial adversity and adult neighborhood disadvantage on cardiovascular disease risk. We found that exposure to childhood psychosocial adversity and adult neighborhood disadvantage in combination was associated with a doubling of the risk of incident cardiovascular disease in adulthood when compared to the absence of such exposures. This association was not explained by conventional cardiovascular risk factors. Neither childhood psychosocial adversity nor adult neighborhood disadvantage alone were significantly associated with incident CVD, although they were associated with CVD risk factors.

21 Jun

Posted at 11:13h in Author Interviews, Breast Cancer, JAMA, Race/Ethnic Diversity, Surgical Research, University Texas
Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TXMedicalResearch.com Interview with: Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Bedrosian: There have been a number of reports on the rates of Breast Conserving Therapy (BCT) and mastectomy among women with early stage breast cancer. These reports have been discordant, with some suggesting that index mastectomy rates have increased and others suggestion Breast Conserving Therapy rates have actually increased. We hypothesized that these differences in reporting may be due to data source (ie tertiary referral centers vs population based studies) and turned to the NCDB, which captures 70% of cancer cases in the US and as such provides us with the most comprehensive overview on patient treatment patterns.

21 Jun

Posted at 10:34h in Author Interviews, BMJ, Imperial College
Mr. Angus Turnbull Imperial College School of Medicine, London UKMedicalResearch.com Interview with: Mr. Angus Turnbull Imperial College School of Medicine, London UK Medical Research: What is the background for this study? What are the main findings? Mr. Turnbull: Autopsy has been used to advance medical knowledge and understanding of pathological processes for millennia but increasing evidence indicates its decline in the UK and elsewhere. This study not only confirms that but suggests autopsy for learning purposes has almost disappeared. In the United Kingdom autopsy is divided into medico-legal autopsy (that required by law under the jurisdiction of HM Coroner) and consented autopsy (performed with the consent of the bereaved or their family). Over the past half-century, small single site studies have noted a marked decline in consented autopsy rates, however there has been no study for over 20 years to determine the extent of the decline nationwide. This study examined all acute NHS Trusts within England, NHS Boards in Scotland and Wales and Social Care Trusts in Northern Ireland. We found that the average autopsy rate (the percentage of adult inpatient deaths which under go consented autopsy) in the United Kingdom in 2013 was only 0.7%. The study showed that in nearly a quarter (23%) of all NHS Trusts in the United Kingdom, consented autopsy is now extinct. These findings may have implications for training, for research and for learning from mortality – a key aspect of patient safety.

19 Jun

Posted at 16:41h in Author Interviews, Lancet
MedicalResearch.com Interview with: Dr. Stephan Glund Ph.D. Boehringer Ingelheim Pharma GmbH & Co. KG Transl. Medicine & Clin. Pharmacology Medical Research: What is the background for this study? What are the main findings? Dr. Glund: There are currently no specific reversal agents available for any of the non-Vitamin K antagonist oral anticoagulants (NOACs). We are working on the development of idarucizumab, a specific reversal agent to dabigatran, the first approved NOAC. The study now published in The Lancet investigated, for the first time in healthy volunteers, the reversal of the anticoagulant effect of dabigatran by idarucizumab. Our study in healthy male volunteers showed that idarucizumab led to immediate, complete and sustained reversal of the anticoagulant effect of dabigatran. Participants first received dabigatran and then idarucizumab. The specific reversal agent was given two hours after the last dose of dabigatran, when dabigatran concentrations were at peak levels. After a five-minute infusion of idarucizumab, anticoagulation was immediately reversed back to baseline levels. The reversal effect was sustained for more than 24 hours for all doses of 2g and above. Idarucizumab was well tolerated by the study participants. In addition, our study also showed that administration of idarucizumab reversed dabigatran-induced inhibition of wound-site fibrin formation, which plays a key role in the blood clotting mechanism. This suggests that idarucizumab might also reverse impaired haemostasis due to dabigatran anticoagulation at a wound site.

19 Jun

Posted at 11:08h in Author Interviews, BMJ, Chocolate, Heart Disease
Professor Phyo Kyaw Myint MBBS MD FRCP(Edin) FRCP(Lond) Clinical Chair in Medicine of Old Age Epidemiology Group, Division of Applied Health Sciences University of Aberdeen ScotlandMedicalResearch.com Interview with: Professor Phyo Kyaw Myint MBBS MD FRCP(Edin) FRCP(Lond) Clinical Chair in Medicine of Old Age Epidemiology Group, Division of Applied Health Sciences University of Aberdeen Scotland Medical Research: What is the background for this study? What are the main findings? Response: The research was carried out by academics from the Universities of Aberdeen, Manchester, Cambridge and East Anglia, as well as the Lancashire Teaching Hospital, the Medical Research Council Epidemiology Unit, Cambridge and the Academic Medical Centre, Amsterdam. It has been published online in the journal Heart. The team base their findings on almost 21,000 adults taking part in the EPIC-Norfolk study, which is tracking the impact of diet on the long term health of 25,000 men and women in Norfolk, England, using food frequency and lifestyle questionnaires. The researchers also carried out a systematic review of the available international published evidence on the links between chocolate and cardiovascular disease, involving almost 158,000 people—including the EPIC study participants. The EPIC-Norfolk participants (9214 men and 11 737 women) were monitored for an average of almost 12 years, during which time 3013 (14%) people experienced either an episode of fatal or non-fatal coronary heart disease or stroke. Around one in five (20%) participants said they did not eat any chocolate, but among the others, daily consumption averaged 7 g, with some eating up to 100 g. Higher levels of consumption were associated with younger age and lower weight (BMI), waist: hip ratio, systolic blood pressure, inflammatory proteins, diabetes and more regular physical activity —all of which add up to a favourable cardiovascular disease risk profile. Eating more chocolate was also associated with higher energy intake and a diet containing more fat and carbs and less protein and alcohol. The calculations showed that compared with those who ate no chocolate higher intake was linked to an 11% lower risk of cardiovascular disease and a 25% lower risk of associated death. It was also associated with a 9% lower risk of hospital admission or death as a result of coronary heart disease, after taking account of dietary factors. And among the 16,000 people whose inflammatory protein (CRP) level had been measured, those eating the most chocolate seemed to have an 18% lower risk than those who ate the least. The highest chocolate intake was similarly associated with a 23% lower risk of stroke, even after taking account of other potential risk factors. Of nine relevant studies included in the systematic review, five studies each assessed coronary heart disease and stroke outcome, and they found a significantly lower risk of both conditions associated with regular chocolate consumption. And it was linked to a 25% lower risk of any episode of cardiovascular disease and a 45% lower risk of associated death. The study concluded that cumulative evidence suggests higher chocolate intake is associated with a lower risk of future cardiovascular events.

19 Jun

Posted at 10:51h in Author Interviews, General Medicine, JAMA, Outcomes & Safety
Samuel Pannick, MA, MBBS, MRCP Imperial Patient Safety Translational Research Center, National Institute for Health Research and Imperial College London, London, England West Middlesex University Hospital National Health Service Trust, Middlesex, EnglandMedicalResearch.com Interview with: Samuel Pannick, MA, MBBS, MRCP Imperial Patient Safety Translational Research Center, National Institute for Health Research and Imperial College London West Middlesex University Hospital National Health Service Trust Middlesex, England Medical Research: What is the background for this study? What are the main findings? Response: Improving the quality of general medical ward care is a recognized healthcare priority internationally. Ward teams have been encouraged to structure their work more formally, with regular interdisciplinary team meetings and closer daily collaboration with their colleagues. Some early studies suggested that these changes might benefit patients, and help ward teams work more efficiently. However, team interventions on medical wards have been reported with numerous different outcome measures, and prior to this study, it was unclear what their objective benefits were. We showed that there is little agreement on the objective outcomes that best reflect the quality of interdisciplinary team care on general medical wards. Changes to interdisciplinary care aren’t reflected in the outcome measures that researchers choose most often, like early readmission rates or length of stay. Complications of care - although harder to record - might have more promise as a measure of the quality of inpatient team care in these specific medical areas.

19 Jun

Posted at 10:39h in Author Interviews, Immunotherapy, Melanoma, Nature
MedicalResearch.com Interview with: Chiara Martinoli, PhD Medical Oncology of Melanoma European Institute of Oncology Milan, Italy MedicalResearch: What is the background for this study? What are the main findings? Dr. Martinoli: The recent advent of new immunomodulatory drugs and targeted therapies is changing the therapeutic algorithm for metastatic melanoma patients. Immunomodulation with the anti-CTLA-4 antibody ipilimumab improves survival but is not devoid of potential risks. There is an urgent need for biomarkers to identify patients best suited to receive this therapy, in order to maximize treatment benefit and spare toxicities. In this study, by analyzing pre-therapy hematological parameters of a large group of metastatic melanoma patients treated with ipilimumab, we showed that neutrophil-to-lymphocyte ratio is strongly and independently associated to patient outcome. Patients with a low baseline neutrophil-to-lymphocyte ratio had a double-reduced risk of disease progression and a two-to-four-fold reduced risk of death, regardless of age, sex and LDH.

19 Jun

Posted at 10:30h in AHA Journals, Author Interviews, Cleveland Clinic, Stroke
Dr. Ken Uchino, MD Cleveland Clinic Main Campus Cleveland, OH 44195MedicalResearch.com Interview with: Dr. Ken Uchino, MD Cleveland Clinic Main Campus Cleveland, OH 44195 Medical Research: What is the background for this study? What are the main findings? Dr. Uchino: Stroke center designation started in 2003 and more hospitals have been certified as primary stroke centers over time. We asked the question how many are certified now? What are the characteristics of the hospitals that are certified? In 2013, nearly a third (23%) of acute short-term adult general hospitals with emergency departments were certified as stroke centers. 74% of the stroke centers were certified by the Joint Commission, a non-profit organization that certifies health care facilities and programs. 20% were certified by state health departments. States varied in percentages of hospitals that were certified, ranging from 4% in Wyoming to 100% in Delaware. Not unexpectedly larger hospitals and hospitals in urban locations were more likely to be certified as stroke centers. But a hospital being located in a state with so-called “stroke legislation” more than tripled the chance of being a certified stroke centers, even accounting for other factors. These states passed legislation to promote stroke centers and mandated stroke patients to be preferentially transported to qualified hospitals.

18 Jun

Posted at 21:15h in Author Interviews, Cannabis, Columbia, Lancet
Deborah S. Hasin, Ph.D. Professor of Epidemiology Columbia University New York, New York 10032MedicalResearch.com Interview with: Deborah S. Hasin, Ph.D. Professor of Epidemiology Columbia University New York, New York 10032 MedicalResearch: What is the background for this study? What are the main findings? Dr. Hasin: The background for the study was the need to identify the causes of the marked increase in marijuana use among U.S. adolescents over the last several years, given that early adolescent marijuana use leads to a number of adverse health and psychosocial consequences, including cognitive decline, into adulthood. We had two main findings from the study:
  1. A comparison of the rates of adolescent marijuana use between states that ever passed a medical marijuana law and those that did not revealed that states with such laws had higher rates of teen marijuana use, regardless of when they passed the law; and
  2. When we compared the rates of teen marijuana use in these states before and after passage of the laws, we did not find a post-passage increase in the rates of teen marijuana use. This suggests that some common factor may be causing both the laws to be passed and the teens to be more likely to smoke marijuana in the states that passed these laws.