MedicalResearch.com Interview with:
Prof. Ze'ev Ronai Ph.D
Scientific Director
Sanford-Burnham's La Jolla
Medical Research: What is the background for this study? What are the main findings?
Prof. Ronai: There is an urgent need to find new approaches to treat melanoma in patients that are resistant to current therapeutic regimes—and this represents a significant percent of melanoma patients. We used samples from patients with drug resistant tumors to study the molecular basis of resistance and screened for genes involved in the process.
We have identified a new player in melanoma resistance to therapy—a molecular target, which provides the basis for clinical trials with drugs currently available to these targets. We found that JAK1 kinase is one target that is upregulated in the resistant tumors. Inhibiting JAK1 kinase can effectively overcome such resistance. (more…)
MedicalResearch.com Interview with:
Winfried Meissner, M.D.
Dep. of Anesthesiology and Intensive Care
Jena University Hospital
University Hospital Jena, Germany
Medical Research: What is the background for this study?
Dr. Meissner: Post-operative pain is managed inadequately worldwide. There are probably many reasons for this, one of which may be lack of evidence about outcomes of treatment in the clinical routine.
PAIN OUT was established as a multi-national research network and quality improvement project offering healthcare providers validated tools to collect data about pain-related patient reported outcomes and management after surgery. Patients fill in a questionnaire asking for pain intensity, pain interference and side effects of pain management. The questionnaire has now been translated into 20 languages. Data are collected electronically and clinicians are provided with feedback about management of their own patients, compared to similar patients in other hospitals. Furthermore, the findings are used for outcomes and comparative effectiveness research. PAIN OUT is unique in that outcomes of postoperative pain management can be examined internationally.
PAIN OUT was created in 2009 with funds from the European Commission, within the FP7 framework and has now been implemented in hospitals in Europe, USA, Africa and SE Asia. The findings allow us to gain insights as to how pain in managed in different settings and countries.
For this particular study, we compared management of pain in the US to other countries. We assessed a large group of patients who underwent different types of orthopedic surgery and compared their patient reported outcomes and management regimens. We included 1011 patients from 4 hospitals in the USA and 28,510 patients from 45 hospitals in 14 countries (“INTERNATIONAL”).
Medical Research: What are the main findings?
Dr. Meissner: Postoperative pain intensity of US patients was higher than in INTERNATIONAL patients; they felt more often negatively affected by pain-associated anxiety and helplessness, and more US patients stated they wished to have received more pain treatment. However, other patient-reported outcomes like time in severe pain or the level of pain relief did not differ.
We found that treatment regiments of American patients differed compared to INTERNATIONAL patients. More US patients received opioids, and their opioid doses were higher compared to INTERNATIONAL patients. In contrast, INTERNATIONAL countries use more nonopioid medications intraoperatively and postoperatively. Thus, under-supply with opioids cannot explain our findings.
Mean BMI of US patients was 30.3 while for INTERNATIONAL it was 27.4. However, insufficient evidence exists that this finding might account for differences in pain intensity.
Routine pain assessment was performed in almost all US patients, in contrast to about 75% in the INTERNATIONAL group. Obviously, routine pain assessment, as practiced in the United States, fails to result in lower postoperative pain. Perhaps it has the opposite effect by directing patients’ attention to the pain.
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MedicalResearch.com Interview with:
Howard L. Kaufman, MD, FACS
Rutgers Cancer Institute of New Jersey
New Brunswick, NJ
Medical Research: What is the background for this study? What are the main findings?
Response: The study clearly demonstrated that advanced melanoma patients achieved a significant improvement in both response rate and durable response rate with Talimogene laherparepvec, or T-VEC. T-VEC is the first oncolytic virus to show a clinical benefit in a randomized phase 3 clinical trial for the treatment of cancer. Patients who received T-VEC also had an improved progress-free and overall survival with nearly 11% obtaining a complete response. T-VEC is an oncolytic virus that mediates anti-tumor activity by directly killing injected tumor cells and by initiating a systemic immune response. Treatment was also associated with few side effects, which were mostly low grade fever, fatigue, chills, nausea and pain at the injection site.
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MedicalResearch.com Interview with:
Prof. Michael Breakspear MB BS, Ba(Hons), Bsc(Med), PhD
QIMR Berghofer Medical Research Institute
Royal Brisbane Hospital
Medical Research: What is the background for this study? What are the main findings?
Prof. Breakspear: The first 72 hours following complicated full-term or premature delivery of a newborn represents a critical window in which survival and long term brain development hangs in the balance. During this window of time, there does not currently exist a reliable, non-invasive, real-time measure of neuropathology that provides neurologists and neonatologists prognostic indicators of clinical outcome. We developed a tool that draws on techniques in physics used to characterize naturally occurring phenomena, such as earthquakes and avalanches, to analyze brain activity recordings of preterm infants. Our tool allows early identification of preterm infants at significant risk of developing poor long-term neurodevelopmental outcomes, such as cerebral palsy and learning difficulties at two years of age.
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MedicalResearch.com Interview with:
Meng Yang, PhD MPH
Research Fellow
Harvard T. H. Chan School of Public Health
Medical Research: What is the background for this study? What are the main findings?
Dr. Yang: There are nearly 3 million American men living with prostate cancer. However, there is very little information for patients and clinicians about how to manage patients’ lifestyles, like diet, after prostate cancer diagnosis to decrease the risk of death due to this disease and improve their survivorship.
The most important finding is that men initially diagnosed with prostate cancer without metastases whose diet was more “Westernized”, i.e. higher processed meats, refined grains, potatoes and high-fat dairy, had a significantly higher prostate cancer-related death and all cause mortality. Men whose diet was more “prudent”, i.e. higher intake of vegetables, fruits, fish, whole grains and healthy oils had a lower risk of death.
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MedicalResearch.com Interview with:
Yuyuan Li, PhD
Liaoning Provincial Key Laboratory of Brain Diseases
Institute for Brain Disorders, Dalian Medical University
College of Basic Medical Sciences, Dalian Medical University
Dalian ChinaMedical Research: What is the background for this study? What are the main findings?
Dr. Li: Traumatic brain injury (TBI) will become the leading cause of death and lifelong disability in the general population by the year 2020. Early determination of prognosis based on epidemiological data is the key to inform care of these patients. Neurobiochemical markers, like Ubiquitin C-terminal Hydrolase-L1 (UCH-L1) have shown a prognostic value for outcome prediction. Recently, several studies have investigated the correlation between serum UCH-L1 concentrations and TBI, however the results thus far have been inconsistent. In the present study, we conducted a systematic review and meta-analysis to evaluate the prognostic value of serum UCH-L1 concentrations after traumatic brain injury. Five studies (including 673 TBI and 1004 controls) were included in the meta-analysis and the overall results reveal that the serum UCH-L1 level was significantly higher in patients with traumatic brain injury compared to those of the control group. Importantly, there was no statistical evidence of a publication bias among the contributing studies from the result of Egger’s test either.
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MedicalResearch.com Interview with:
Christopher X WongMBBS MSc PhD
Clinical Research Fellow | Clinical Trial Service Unit, Oxford
Clinical Senior Lecturer | Centre for Heart Rhythm Disorders, Adelaide
Clinical Trial Service Unit, University of Oxford
Roosevelt Drive, Oxford
Medical Research: What is the background for this study? What are the main findings?Dr. Wong: Atrial fibrillation is an increasingly common heart rhythm disorder. This study demonstrates that even small increments in obesity are associated with a significantly increased risk of atrial fibrillation. Our data suggest that for every 1 unit reduction in body mass index there may be a 3-5% reduction in atrial fibrillation; for every 5 unit reduction, there may be 10-29% reductions. It should also be noted that this is likely to be a significant underestimate of the effect of weight reduction on atrial fibrillation rates as weight control has favourable effects on other risk factors for atrial fibrillation, such as hypertension and diabetes. Given the more than 45 million people with atrial fibrillation worldwide, even small but widespread reductions in obesity would thus help contain this ‘epidemic’ of atrial fibrillation.
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MedicalResearch.com Interview with:
R. Kenneth Marcus, FRSC & FAAAS
Professor of Chemistry
Clemson University
Medical Research: What is the background for this study? What are the main findings?
Prof. Marcus: We had previously shown that chromatographic columns formed from aligned capillary-channeled polymer (C-CP) fibers were highly effective in analytical scale and preparative separations of proteins from diverse media. The C-CP fibers are extracted from commodity fibers such as polyester, nylon, and polypropylene. The key aspects in using the C-CP fibers are very high bed porosity and rapid protein-surface mass transfer, this allows for very rapid separations. Packing of the fibers in narrow-bore polymer tubing (0.8 mm id x 1 cm long) allows them to be fixed to the end of a micropipette tip. Urine samples of 10 microliter-to-milliliter volumes can be spun through on a microcentrifuge, washed with DI-water, and then eluted with a solvent. Thus the proteins are isolated and pre-concentrated on the fiber surface. The elution solvent can be chosen based on the analytical method employed (e.g., MALDI- or ESI-MS). (more…)
MedicalResearch.com Interview with:
Dr. Renjie Chen PhD and Dr. Haidong Kan, PhDSchool of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, ChinaMedicalResearch: What is the background for this study? What are the main findings?
Response: Although several previous studies in developed countries with cleaner air have reported health benefits due to air filtration, no such interventional studies were conducted in a developing country with much severer air pollution problems. Our main findings suggested that even a short-term intervention (2 days) could significantly reduce indoor air pollution and improve cardiopulmonary health among healthy young adults. (more…)
MedicalResearch.com Interview with:
Yann Klimentidis Ph.D.
Assistant Professor
Mel and Enid Zuckerman College of Public Health
University of ArizonaMedical Research: What is the background for this study? What are the main findings?
Dr. Klimentidis: Previous studies have hinted at the possibility that genes which are associated with higher triglyceride levels may also be associated with lower type-2 diabetes. We set out to test this hypothesis in multiple prospective cohort studies, in European-Americans and in African-Americans. We found that on a collective basis, the alleles which are associated with higher triglycerides are also associated with reduced type-2 diabetes risk. We also identified some individual genetic variants which are driving this trend.
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MedicalResearch.com Interview with:
Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACS, Associate Professor, Department of Surgery
Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven, Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center
Program Director, Yale Interdisciplinary Breast Fellowship
Yale University School of Medicine Breast Centerm
New Haven, CT,
Medical Research: What is the background for this study? What are the main findings?
Response: Every year in the US, nearly 300,000 women are diagnosed with breast cancer -- the majority of these will have early stage breast cancer, and will opt for breast conserving surgery to remove their disease. The goal of this operation is to remove the cancer with a rim of normal tissue all the way around it (i.e., a margin), but sadly, 20-40% of women will have cancer cells at the edge of the tissue that is removed, often mandating a return trip to the operating room to remove more tissue to ensure that no further disease is left behind. No one likes to go back to the operating room -- so we asked the question, "How can we do better?". Surgeons have debated various means of obtaining clear margins. Some have advocated taking routine cavity shave margins -- a little bit more tissue all the way around the cavity after the tumor is removed at the first operation. Others have argued that this may not be necessary; that one could use intraoperative imaging of the specimen and gross evaluation to define where more tissue may need to be removed (if at all) -- i.e., selective margins. We conducted a randomized controlled trial to answer this question. We told surgeons to do their best operation, using intraoperative imaging and gross evaluation, and removing selective margins as they saw fit. After they were happy with the procedure they had performed and were ready to close, we opened a randomization envelope intraoperatively, and surgeons were either instructed to close as they normally would ("NO SHAVE"), or take a bit more tissue all the way around the cavity ("SHAVE").
Patients in both groups were evenly matched in terms of baseline characteristics. The key finding was that patients who were randomized to the "SHAVE" group half as likely to have positive final margins and require a re-operation than patients in the "NO SHAVE" group. On their postoperative visit, we asked patients, before they knew which group they had been randomized to, what they thought of their cosmetic results. While the volume of tissue excised in the "SHAVE" group was higher than in the "NO SHAVE" group, the distribution of patient-perceived cosmetic outcomes were identical in both groups. Complication rate was also no different between the two groups. We will be following patients for five years for long-term cosmetic and recurrence outcomes. (more…)
MedicalResearch.com Interview with:
Tanguy Seiwert, MD
Assistant Professor, Dept. of Medicine
Associate Director, Head and Neck Cancer Program
Section of Hematology/Oncology
Fellow, Institute for Genomics and Systems Biology
Speciality Chief Editor
Frontiers in Head and Neck Cancer
University of Chicago Chicago, IL 60637
Medical Research: What is the background for this study?
Dr. Seiwert: Recurrent/metastatic Head and Neck Squamous Cell Cancer (HNSCC) remains poorly treatable with a median OS of 10-13 months
There is evidence of a prominent immune escape observed in squamous cell carcinoma of the head and neck (SCCHN) suggesting that anti-PD1 agents (similar to e.g. melanoma) may be active.
Medical Research: What are the main findings?
Dr. Seiwert:
One in four patients with Head/Neck cancer treated with pembrolizumab showed marked tumor shrinkage (so called – partial/complete responses), and 57% of patients experienced any decrease in the size of their tumors.
Pembrolizumab is broadly active in both HPV(-) and HPV(+) types of squamous cell carcinoma of the head and neck.
Pemborliuzmab treatment is active in heavily pretreated squamous cell carcinoma of the head and neck patients.
Responses seem to be durable è 86% of responding patients remain in response.
Treatment overall was well tolerated with less than 10% of patients experiencing severe side effects (≥Grade 3).
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MedicalResearch.com Interview with:
David Katz, MDDivisions of Cardiology, and Neonatology,
University of Colorado School of Medicine
Aurora, Colorado
Medical Research: What is the background for this study? What are the main findings?
Dr. Katz: Sudden infant death syndrome (SIDS) is the leading cause of infant mortality in the US between 1 month and 1 year of life. This is the first large study to demonstrate an association between high altitude and SIDS. In particular there is a doubling of risk above 8,000 feet of elevation relative to below 6,000 feet.
Medical Research: What should clinicians and patients take away from your report?Dr. Katz: There is an association between high altitude residence and Sudden infant death syndrome (SIDS). The reason for this association is still unknown, but hypoxia may be the common link. While the population living above 8000 feet is small in the US, it is large worldwide. Better understanding this association is of great medical importance.
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MedicalResearch.com Interview with:
Dr. Samson Y. Gebreab, Ph.D., M.Sc.
Lead Study Author and Research Scientist
National Human Genome Research Institute
Bethesda, Maryland
Medical Research: What is the background for this study?
Dr. Gebreab: It is well known that African Americans hold a commanding lead in cardiovascular disease (CVD) mortality and morbidity compared to whites and other ethnic groups. Furthermore, the risk for developing CVD begins early in life and extends over a lifecourse. Previous studies have indicated the influence of both childhood and adult socioeconomic status (SES) on CVD risk. However, the impact of lifecourse socioeconomic status (both childhood and adulthood) on CVD risk in African American population is not fully understood. The purpose of our study was to investigate the associations of different measures of lifecourse socioeconomic status with cardiovascular disease risk in African Americans and whether the associations were modified by sex and/ or age after controlling for known cardiovascular disease risk factors. We analyzed 10-year follow-up data of African American adults who were participating in Jackson Heart Study, Jackson, MS.
Medical Research: What are the main findings?Dr. Gebreab: Our findings highlights that among those of lower socioeconomic status, women and younger (<=50 years old) African Americans are at increased risk of CVD, including heart disease and stroke compared to their counterparts of higher socioeconomic status groups.
African American women in the lowest socioeconomic status, had more than twice the risk of developing cardiovascular disease than those in the highest socioeconomic status group.
African Americans of 50 years and younger in the lowest socioeconomic status group had more than three times higher risk of experiencing a cardiovascular disease event than those in the highest socioeconomic status group.(more…)
MedicalResearch.com Interview with:
Prof. Dr. Robert Sanders MD
Assistant Professor, Anesthesiology & Critical Care Trials & Interdisciplinary Outcomes Network (ACTION)
Department of Anesthesiology
University of Wisconsin, Madison, WI
Medical Research: What is the background for this study? What are the main findings?
Dr. Sanders: While it is known that chronic raised blood pressure exerts important effects on long term health outcomes, it is unclear how pre-operative blood pressure levels effect risk from surgery. In this study we show that after adjustment for other diseases, high blood pressure does not increase perioperative risk. Rather low blood pressure is associated with an increase in risk of death following surgery and anesthesia.
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MedicalResearch.com Interview with:
Bruno M. Heleno MD
The Research Unit for General Practice and Section of General Practice
Department of Public Health
University of Copenhagen
Medical Research: What is the background for this study? What are the main findings?Dr. Heleno: False positive mammography causes psychological distress. Several observational studies have shown this, and their results have been summarized in systematic reviews. However, it was unclear whether women requiring invasive tests (needle or surgical biopsy) were more distressed than women only requiring non-invasive procedures (clinical examination or imaging). Contrary to previous research, we found that these two groups of women were equally distressed during the 36 months of follow-up in our cohort. The best estimate for the difference for 12 related measures of distress was always close to zero.
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MedicalResearch.com Interview with:
Ruben A. Mesa, MD, FACP
Consultant Hematologist Chair, Division of Hematology & Medical Oncology
Deputy Director, Mayo Clinic Cancer Center
Professor of Medicine Mayo Clinic Cancer CenterNCI Designated Comprehensive Cancer Center
Scottsdale, AZ
Medical Research: What is the background for this study? What are the main findings?
Dr. Mesa: Myelofibrosis is a rare and chronic blood cancer associated with significantly reduced quality of life and shortened survival. In patients with this disease, spleen enlargement (splenomegaly) is a very common and debilitating symptom – and as the disease progresses, the body slows production of important blood cells.
The results presented at ASCO were from the PERSIST-1 study, which is a Phase 3 registration-directed trial designed to compare pacritinib — an investigational oral multikinase inhibitor with specificity for JAK2 and FLT3 – to best available therapy (exclusive of a JAK inhibitor) in patients with myelofibrosis — regardless of their platelet counts. Data from this study showed that compared to best available therapy, pacritinib resulted in a significantly higher proportion of patients with spleen volume reduction and control of disease-related symptoms, regardless of platelet levels at the time of enrollment.
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MedicalResearch.com Interview with:
Brodie Nolan, MD BSc
PGY3 Emergency Medicine Resident
University of Toronto, Faculty of Medicine
Medical Research: What is the background for this study? What are the main issues?
Dr. Nolan: Police are commonly encountered in the emergency department (ED). They support EMS, transport patients, are a source of collateral information for health care professionals, and help provide a safe environment for hospital staff. However, there is a potential for conflict due to the nature of police investigation and the emergency physician’s duty to protect patients’ confidentiality and personal health information. Any disclosure of patient information to police without consent could potentially violate the patient’s right to privacy of personal health information.
Unfortunately, it is not uncommonly the case that patients in the emergency department for whom the police have an interest are unable or unwilling to provide consent. Education for emergency medicine residents on police-physician exchanges is variable however it is important to understand the legislation surrounding these practices to ensure patients’ rights are protected and avoid any potential for litigation.
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MedicalResearch.com Interviews with:
Dr. Sunil M. Kurian Ph.D.
Lead- Biomarker Discovery at the Laboratory of Functional Genomics and Cell Therapy
The Scripps Research Institute and Transplant Genomics Inc. and
Dr. John J. Friedewald, MD
Associate Professor of Medicine and Surgery
Northwestern University’s Feinberg School of Medicine and a transplant nephrologist at Northwestern Memorial Hospital and the Kovler Organ Transplant Center
Editor’s note: These interviews are based on two abstracts presented at the American Transplant Congress 2015.MedicalResearch: What is the background for these studies?
Response: Previous studies by the scientific founders of Transplant Genomics Inc. helped lay the groundwork for the company’s development of genomic biomarker tests for kidney transplant graft status and demonstrated feasibility as noninvasive monitoring tools that could enable differential diagnosis of graft status in kidney transplant recipients.1-3
These included a study involving five transplant centers published in the American Journal of Transplantation.4 In that study, peripheral blood gene expression profiling was used to classify kidney graft recipients into three key categories of graft status based on gene expression signatures – clinical acute rejection, acute dysfunction no rejection, and stable graft performance - with very high predictive accuracy.
STUDY A: Validation of Blood and Biopsy Gene Expression-Based Molecular Diagnostics for Subclinical Acute Rejection: Comparing DNA Microarrays vs. Next-Generation RNA SequencingMedicalResearch: What are the main findings?
Response: The current study presented recently at the 2015 American Transplant Congress5 validated that gene expression signatures as indicators of kidney graft status can be detected as robustly with RNA sequencing as with microarrays, with implications for reduced cost of analysis, faster turnaround times and improved throughput for sample processing.
In this study, we substantiated RNA sequencing as an alternative data generation platform for analyzing gene expression profiles in peripheral blood and tissue from kidney transplant recipients. The data validated that gene expression signatures for subclinical acute rejection (a histological acute cellular rejection in the presence of a normal or stable serum creatinine that is associated with decreased graft survival), clinical acute rejection and stable graft performance can be detected as robustly with RNA sequencing as with microarrays.
MedicalResearch: What should clinicians and patients take away from your report?Response: The key point of this study is that gene expression profiles generated and validated using microarray technology have been successfully translated to a technology platform based on RNA sequencing. Sequencing has the potential to offer advantages such as reduced cost of analysis, faster reporting back to the clinician and improved throughput for sample processing. In addition, it could facilitate development of kits enabling standardized assay performance on local lab-based sequencing systems and expansion of test use worldwide.
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MedicalResearch.com Interview with:
Nathan Clark, PharmD
Clinical pharmacy supervisor, anticoagulation and anemia management services and
Thomas Delate, PhD
Clinical research scientist
Kaiser Permanente ColoradoMedicalResearch: What is the background for this study? What are the main findings?
Response: Patients with a history of blood clots are commonly prescribed warfarin, an anticoagulant, to decrease the body’s ability to form additional clots. Clinicians typically stop the use of warfarin in patients to reduce the risk of serious bleeding when invasive procedures, such as colonoscopy or orthopedic surgery are scheduled. However, when warfarin interruptions occur, patients are exposed to an increased risk of blood clots three to five days before and five or more days after invasive procedures. Bridge therapy with another, faster acting anticoagulant is often initiated in an attempt to reduce the patients’ risk for developing blood clots during that gap.
Bridging has been a part of standard therapy for venous thromboembolism (VTE) patients undergoing invasive procedures for many years. But only limited data outlining the rates of bleeding and VTE recurrence were available to help clinicians analyze the risks and benefits of bridge therapy.
We examined the electronic medical records of 1,178 patients with VTE who underwent 1,812 invasive diagnostic or surgical procedures between January 2006 and March 2012 that required the interruption of warfarin therapy. Study patients were categorized into three groups based on their annual risk of VTE recurrence without anticoagulant therapy. Within those groups, a total of 555 patients – 28.7 percent of low-risk, 33.6 percent of moderate-risk and 63.2 percent of high-risk patients – received bridging anticoagulant therapy. The 1,257 patients who did not receive bridge therapy interrupted their warfarin use and received no other anticoagulants during the perioperative period. The use of bridge therapy resulted in a 17-fold higher risk of bleeding without a significant difference in the rate of blood clot formation compared to patients who didn’t receive bridge therapy. In addition, there were no significant differences in the rates of blood clot occurrence or death between the bridged and non-bridged patient groups. (more…)
MedicalResearch.com Interview with:
Dr. Marie C. Leger, MD, PhD
Assistant Professor
Ronald O. Perelman Department of Dermatology
NYU Langone Medical Center
Medical Research: What inspired this study? How did it come about?
Dr. Leger: As a dermatologist at NYU, I have taken care of several patients with tattoo reactions--some of them mild (like longstanding itching for example) and some of them more severe (like long term reactions to a particular color that can severely disfigure the tattoo) and wondered how common it was for people to have adverse tattoo reactions or complications. There were lots of case reports in the literature but only a few larger studies examining how common these kinds of complaints were--and these were all European studies. We decided to do a quick survey to give us a better idea of how common it is for people to have problems with their tattoos.
Medical Research: What do you think is the most important takeaway from this study for the consumer?Dr. Leger: Tattoos have risks associated with them--which is part of their appeal I'm sure--but I do think it's important for people to know that long term tattoo reactions (including for example, itching, scaling, swelling) may be more common than we realize. A recent Danish study shows that these kinds of reactions can be quite distressing for people and significantly impact their quality of life.
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MedicalResearch.com Interview with:
Aaron P. Thrift, Ph.D.
Assistant Professor, Department of Medicine
Dan L. Duncan Cancer Center
Baylor College of Medicine
Houston, TX 77030-3498
Medical Research: What is the background for this study? What are the main findings?
Dr. Thrift: Greater attained adult height is associated with increased risk of all cancers combined; however, the association may differ by cancer site and between women and men. For colorectal cancer, epidemiological studies suggest that the association with height may be stronger for women than for men. We used data from over 10,000 patients with colorectal cancer and over 10,000 population-based controls and conducted multiple analyses, including using Mendelian randomization (which incorporates genomic data with traditional approaches) to overcome potential issues of confounding and bias in observational studies, to further examine the association between height and risk of colorectal cancer. Overall, we found that taller height was associated with increased risk of colorectal cancer (8% increased risk per 10cm increase in height). When we examined women and men separately, our results strongly suggest that height is causally associated with colorectal cancer risk for women, whereas there was weaker evidence for a causal association between height and colorectal cancer risk for men.
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MedicalResearch.com Interview with:
Akrit Sodhi, M.D., Ph.D.
Assistant Professor of Ophthalmology
Retina Division
Wilmer Eye Institute
Johns Hopkins Medical Institutions
Medical Research: What is the background for this study? What are the main findings?Dr. Sodhi: Diabetic eye disease is the most common cause of severe vision loss in the working age population in the developed world, and proliferative diabetic retinopathy (PDR) is its most vision-threatening sequela. In proliferative diabetic retinopathy, retinal ischemia leads to the upregulation of angiogenic factors that promote neovascularization. Therapies targeting vascular endothelial growth factor (VEGF) delay the development of neovascularization, in some, but not all diabetic patients, implicating additional factor(s) in proliferative diabetic retinopathy pathogenesis. In our study, we demonstrate that the angiogenic potential of aqueous fluid from PDR patients is independent of VEGF concentration, providing an opportunity to evaluate the contribution of other angiogenic factor(s) to PDR development. We identified angiopoietin-like 4 (ANGPTL4) as a potent angiogenic factor whose expression is upregulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. Expression of ANGPTL4 was increased in the aqueous and vitreous of PDR patients, independent of VEGF levels, correlated with the presence of diabetic eye disease, and localized to areas of retinal neovascularization. Inhibition of ANGPTL4 expression reduced the angiogenic potential of hypoxic Müller cells; this effect was additive with inhibition of VEGF expression. An ANGPTL4 neutralizing antibody inhibited the angiogenic effect of aqueous fluid from proliferative diabetic retinopathy patients, including samples from patients with low VEGF levels or receiving anti-VEGF therapy. Collectively, our results suggest that targeting both ANGPTL4 and VEGF may be necessary for effective treatment or prevention of proliferative diabetic retinopathy and provide the foundation for studies evaluating aqueous ANGPTL4 as a biomarker to help guide individualized therapy for diabetic eye disease.
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MedicalResearch.com Interview with:
Jessica Castner, PhD, RN, CEN
Assistant Professor
University at Buffalo, New York
Medical Research: What is the background for this study? Dr. Castner: There are groups of people more likely to visit the emergency department (ED) frequently. One of these groups are people insured by Medicaid, the insurance for those with low incomes. By finding what factors increase the risk for frequent emergency department use, healthcare leaders can target interventions to design a more effective and accessible healthcare delivery system. With approximately 12 million ED visits each year related to behavioral health issues, we wanted to investigate how smoking, substance abuse and psychiatric diagnoses increased the risk for repeat ED use for adults insured by Medicaid.
There are many problems associated with frequent emergency department use, including less than ideal continuity of care, crowding, and cost. Every year, there are over 136 million visits to United States EDs, and 12 million are linked to some sort of behavioral health issue. Unlike primary care, the patient is not likely to see a healthcare provider in the emergency department who knows them or one who may not have access to their complete and up-to-date records. The patient might get conflicting guidance or have tests ordered that duplicate tests recently done in other settings.
Frequent emergency department visitors also contribute to crowded EDs, where demand outstrips capacity. Studies have shown an association with increased morbidity and mortality for patients treated in the ED during these times of crowding.
Medical Research: What are the main findings?
Dr. Castner: The main findings of our study include helping to dispel the myth of “inappropriate emergency department use.” Our research analyzed the 2009 Medicaid claims for Erie and Niagara County. Our findings indicate that there is a positive relationship between outpatient visits and frequent emergency department use. In other words, people who are sicker and have more complex illnesses use all services more – both the emergency department and their outpatient care provider. In addition, we found that smoking, substance abuse, and psychiatric diagnoses all substantially increased the odds of frequent emergency department use – or ED bouncebacks. The most surprising finding was that healthy individuals were four times more likely to be frequent ED users if they smoked.
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MedicalResearch.com Interview with:
Evgeniya Sokolovskaya, DO, MD
Monmouth Medical Center
Long Branch, NJ 07740.
Medical Research: What is the background for this study? What are the main findings?
Dr. Sokolovskaya: As the utilization of diagnostic imaging has continued to increase in recent years, the workload of radiologists has correspondingly risen. Radiologists are under pressure to increase productivity by increasing workload volume. Previous studies have shown that increasing the number of reporting exams per day can affect the accuracy of radiologic interpretations, increase an error rate and degrade radiologists’ performance in the detection of pathology as viewing time per study decreases. The purpose of this pilot study was to determine if faster reporting speed when reading CT imaging studies of the Abdomen and Pelvis, results in higher number of misses and interpretation errors. The results of our study showed that the number of major misses and interpretation errors significantly increased at the faster reporting speed.
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MedicalResearch.co Interview with:
Katherine Ornstein, PhD MPH
Assistant Professor
Brookdale Department of Geriatrics and Palliative Medicine
Institute for Translational Epidemiology
Icahn School of Medicine at Mount Sinai
New York, NY 10029
Medical Research: What is the background for this study? What are the main findings?
Dr. Ornstein: There is an increased focus on the need to support caregivers and families, particularly at the End of Life (EOL). They play a critical role in the care process and decision making, yet this can be a very high stress role with an increased risk for negative consequences. Hospice services, which are increasing, are focused on palliative rather than curative care and include medical services, symptom management, spiritual counseling, social services and bereavement counseling delivered by an interdisciplinary team of professionals for dying patients. An important part of the hospice service is the provision of support to families during illness and after death. Prior research suggests that hospice (which is cost saving, has benefits to patients), may also be beneficial to families. Yet these studies have been largely limited to patients with cancer, have failed to adequately control for differences between patients who do or do not use hospice.
Overall, there was an increase in depressive symptoms after death. However, surviving spouses of those who used hospice were more likely to have a decrease in depressive symptoms. We found that the positive benefit of hospice was much stronger when we looked at least 1 year after death.
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MedicalResearch.com Interview with:Dr. Leonard Petrucelli Ph.D
Mayo Clinic
Jacksonville, FL 32224
MedicalResearch: What is the background for this study?Dr.Petrucelli: According to the ALS Association, more than 30,000 Americans live with amyotrophic lateral sclerosis (ALS), a condition that destroys motor neuron cells that control essential muscle activity such as speaking, walking, breathing and swallowing. After Alzheimer’s disease, frontotemporal dementia (FTD) is the most common form of early onset dementia. It is characterized by changes in personality, behavior, and language due to loss of neurons in the brain’s frontal lobe. Once considered rare, frontotemporal dementia is now thought to account for up to 10 to 15 percent of all dementia cases, according to the Alzheimer’s Association.
In 2011, Mayo investigator Rosa Rademakers, Ph.D., identified the most common genetic mutation known to cause ALS and FTD, namely a repeat expansion in the gene C9ORF72. The C9ORF72 repeat expansion leads to the generation of toxic RNA species that form abnormal foci, as well as inclusions of c9RAN proteins in affected cells in the central nervous system. Prior to this research study lead by Leonard Petrucelli, Chair of the Department of Neuroscience at the Mayo Clinic Florida, no animal model existed that fully recapitulated the known clinicopathological features of what is now collectively referred to as c9FTD/ALS. Without such an animal it has remained difficult to identify important mechanisms by which the repeat expansion leads to neurodegeneration and putative therapeutic targets that may mitigate disease in patients where currently there are no curative treatments.
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MedicalResearch.com Interview with:
Alexandra Gonçalves, MD, PhD
Postdoctoral Research Fellow
Cardiovascular Department
Brigham and Women's Hospital
Boston, MA 02115
MedicalResearch.com: What is the background for this study?Dr. Gonçalves: Excessive alcohol consumption is associated with alcoholic cardiomyopathy, while light to moderate drinking might have benefits in the risk of heart failure (HF). However, the cardiovascular mechanisms and the alcohol dosage associated with risks or potential benefits are uncertain. Furthermore, the variation in the toxic and protective effects of alcohol by sex remains controversial, as women may be more sensitive than men to the toxic effects of alcohol on cardiac function, developing alcoholic cardiomyopathy at a lower total lifetime dose of alcohol compared to men. In this study we assessed the associations between alcohol intake and cardiac structure and function by echocardiography, in elderly men and women in the large, community-based Atherosclerosis Risk in Communities (ARIC) Study.
MedicalResearch.com: What are the main findings?Dr. Gonçalves: We studied 4466 participants (76±5 years and 60% women) with alcohol consumption ascertained, who underwent transthoracic echocardiography. Participants were classified into 4 categories based on self-reported alcohol intake: non-drinkers, drinkers of up to 7 drinks per week, ?7 to 14 and ? 14 drinks per week. In both genders, increasing alcohol intake was associated with larger left ventricular (LV) diastolic and systolic diameters and larger left atrial diameter. In men, increasing alcohol intake was associated with greater LV mass and higher E/E’ ratio. In women, increasing alcohol intake was associated with lower LV ejection fraction. (more…)
MedicalResearch.com Interview with: Yana Vinogradova, Research Fellow
Division of Primary Care
School of Medicine
University of NottinghamMedical Research: What is the background for this study? What are the main findings?
Response: Combined oral contraceptives are an effective method of birth control but do have measurable side effects. One – common to all combined contraceptives and sometimes fatal – is an increased risk of venous thromboembolism (VTE). A number of earlier studies investigated VTE risks for different types of hormonal contraceptives, but all were performed some years ago or had insufficient data to analyse newer preparations, while some included only healthy users and others did not adequately control for lifestyle and health issues. The data used for this study were representative of the UK population and covered all currently prescribed drugs, with results adjusted for the widest possible range of available relevant factors.
We found that the venous thromboembolism risks of combined oral contraceptives appear to fall into two distinct groups. Newer drugs containing gestodene, desogestrel, drospirenone or cyproterone were associated with risks of VTE between 1.5 and 1.8 times higher than both the older compositions containing norethisterone or levonorgestrel and the relatively newer norgestimate. While our findings are statistical associations between different compositions and venous thromboembolism risks, they do represent more comprehensive and reliable information for doctors making evidence-based prescribing decisions. (more…)
MedicalResearch.com Interview with:
Lewis J. Smith, MD
Professor of Medicine and Associate Vice President for Research
Northwestern University and the Feinberg School of Medicine
Chicago, IL 60611
Medical Research: What is the background for this study? What are the main findings?
Dr. Smith: We previously observed in a survey of more than 1,000 patients with asthma that those consuming soy isoflavones in their diet had better lung functioning than their counterparts who consumed little or none. Using a more detailed soy questionnaire, we confirmed the observation in a different group of patients with asthma, and followed that up with laboratory studies. In cell culture studies, we saw that genistein, the major soy isoflavone, at levels that are achieved in individuals consuming a high soy diet, reduces eosinophilic inflammation, a key feature in asthma. In addition, people who consume more soy products, mostly in Japan and parts of China, generally have less asthma than in western countries. Although these data indicate a potential beneficial effect of soy isoflavones in patients with asthma and nutritional supplements are commonly used by people to treat and prevent disease and improve their health, there was little direct data to prove that the supplement is actually effective. As a result, we explored the effects of a soy isoflavone supplement in 386 adults and children aged 12 or older with poorly controlled asthma. All were taking medicine to treat their asthma – either corticosteroids or leukotriene modifiers – but none consumed soy more than once a week. In the randomized, double-blind study, half of the participants took a soy isoflavone supplement twice daily for six months, and the other half took a placebo. We found that the supplement, though able to increase blood levels of genistein, did not improve lung function, symptoms or measures of inflammation in these individuals.
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MedicalResearch.com Interview with:
Prof. Ze'ev Ronai Ph.D
Scientific Director
Sanford-Burnham's La Jolla
Medical Research: What is the background for this study? What are the main findings?
Prof. Ronai: There is an urgent need to find new approaches to treat melanoma in patients that are resistant to current therapeutic regimes—and this represents a significant percent of melanoma patients. We used samples from patients with drug resistant tumors to study the molecular basis of resistance and screened for genes involved in the process.
We have identified a new player in melanoma resistance to therapy—a molecular target, which provides the basis for clinical trials with drugs currently available to these targets. We found that JAK1 kinase is one target that is upregulated in the resistant tumors. Inhibiting JAK1 kinase can effectively overcome such resistance. (more…)
