Author Interviews, JAMA, Multiple Sclerosis / 31.12.2014

Dr. Richard Nash MD Colorado Blood Cancer InstituteMedicalResearch.com Interview with: Dr. Richard Nash MD Colorado Blood Cancer Institute   Medical Research: What is the background for this study? What are the main findings? Dr. Nash: Multiple sclerosis is an autoimmune disease of the central nervous system which causes significant disability and in some cases results in patients being wheel-chair bound or bed-ridden. It is a significant medical problem amongst young adults. We undertook this study because current Multiple sclerosis therapies were not adequate for effective long-term control of the disease in the majority of the patients. High-dose immunosuppressive therapy followed by autologous hematopoietic cell transplantation is an effective treatment for many hematological malignancies. It causes a profound immunosuppression. Based on this effect on the immunological system, we initiated a clinical trial of this treatment modified for autoimmune disorders. The study was supported by the Immune Tolerance Network and NIAID, NIH. In a phase 2 clinical trial of 25 patients all of whom were followed for at least 3 years, we demonstrated that 80% of patients had no evidence of disease activity. No other Multiple sclerosis treatments were given after the study treatment. Adverse events were similar to what we have observed for this treatment in patients with hematological malignancies. No significant acute neurological adverse events were observed. (more…)
Author Interviews, Cancer Research, PNAS, UCSD / 31.12.2014

MedicalResearch.com Interview with: Annie Samraj and Ajit Varki MDDr. Annie Samraj MD Postdoc Fellow Varki Lab and Ajit VAjit Varki MD Distinguished Professor of Medicine and Cellular & Molecular Medicine Co-Director, Center for Academic Research and Training in Anthropogeny (CARTA) Co-Director, Glycobiology Research and Training Center (GRTC) University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0687.arki MD Distinguished Professor of Medicine and Cellular & Molecular Medicine , Co-Director, Center for Academic Research and Training in Anthropogeny, Co-Director, Glycobiology Research and Training Center University of California, San Diego, La Jolla, CA Medical Research: What is the background for this study? What are the main findings? Dr. Varki: For the past decade, there has been increasing evidence that people who consume red meat (beef, pork, lamb) are at a higher risk for certain kinds of cancers. Although red meat is a high quality source of protein, iron and vitamins, too much consumption may be harmful to humans. While there are other hypotheses under consideration, we focused on a non-human sugar molecule called Neu5Gc in red meat that could explain the link to cancer risk. We extensively studied various foods and concluded that red meat (particularly beef) is rich in Neu5Gc. In contrast poultry, fish steaks and hen eggs have little or no Neu5Gc. From previous studies, we knew that animal-derived Neu5Gc could be incorporated into human tissues. In this study, we hypothesized that eating red meat could lead to inflammation if the body’s immune system targets the foreign Neu5Gc. Chronic inflammation is also known to instigate or promote tumor progression. To test this hypothesis, we used mice engineered to be similar to humans in that they lacked Neu5Gc, and also produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Tumor formation increased fivefold and Neu5Gc accumulated in the tumors, proving the hypothesis. None of the various control groups of mice showed this effect. (more…)
Author Interviews, JAMA, Surgical Research, Weight Research / 31.12.2014

Jeffrey A. Gusenoff, MD Associate Professor of Plastic Surgery Co-Director, Life After Weight Loss Program Co-Director, BodyChangers Director, Post-Bariatric Body Contouring Fellowship UPMC Department of Plastic SurgeryMedicalResearch.com Interview with: Jeffrey A. Gusenoff, MD Associate Professor of Plastic Surgery Co-Director, Life After Weight Loss Program Co-Director, BodyChangers Director, Post-Bariatric Body Contouring Fellowship UPMC Department of Plastic Surgery Medical Research: What is the background for this study? What are the main findings? Dr. Gusenoff: With the rise in massive weight loss patients from bariatric surgery or diet and exercise, more patients are choosing to have a thighplasty to remove excess skin of the inner thigh. Many techniques exist for treating this, but there aren't many studies that look into the safety of these procedures in massive weight loss patients. What we found is that  many patients have scars that go all the way down the thigh with a fairly high complication rate of almost 70%. (more…)
Author Interviews, JAMA, Smoking / 31.12.2014

Dr Hayden McRobbie MB ChB PhD Reader in Public Health Interventions Wolfson Institute of Preventive Medicine Barts and The London School of Medicine and Dentistry Queen Mary University of LondonMedicalResearch.com Interview with: Dr Hayden McRobbie MB ChB PhD Reader in Public Health Interventions Wolfson Institute of Preventive Medicine Barts and The London School of Medicine and Dentistry Queen Mary University of London Medical Research: What is the background for this study? What are the main findings? Dr. McRobbi: Varenicline is an effective smoking cessation aid that acts primarily to alleviate the symptoms of tobacco withdrawal discomfort, thereby making quitting easier. It also reduces the rewarding effects of cigarettes smoked which may enhance the drugs smoking cessation effect by reducing the enjoyment of smoking prior to quitting and preventing a lapse, after quitting, progressing to relapse. In some people the standard dose of varenicline (2mg/day) results in a decrease in the enjoyment of smoking prior to quitting and that these people appear to have higher quit rates that those that don’t experience this reaction to smoking. The randomised placebo controlled trial was designed to investigate whether increasing the varenicline dose (up to 5mg/day) in smokers who show no reaction to the standard dose improves treatment outcomes compared to remain on the standard dose. Medical Research: What are the main findings? Dr. McRobbi: Whilst the increased dose, compared with the standard dose, reduced the enjoyment of smoking prior to quitting it had no additional effect on alleviating tobacco withdrawal symptoms or smoking cessation rates at 12 weeks post quit date (26% vs. 23%). (more…)
Author Interviews, Diabetes / 30.12.2014

Aramesh Saremi MD Phoenix VA Health Care System Health Research Scientist Phoenix, AZ 85012-1892MedicalResearch.com Interview with: Aramesh Saremi MD   Phoenix VA Health Care System Health Research Scientist Phoenix, AZ 85012-1892   Medical Research: What is the background for this study? What are the main findings? Dr. Saremi: Our study was a post-hoc analysis of the data that was available from VA cooperative study,  the Veterans Affair Diabetes Trial  (VADT).  The VADT was one of the  recent landmark studies examining the effect of intensive glycemic control on cardiovascular events  in older adults with type 2 diabetes. The main finding in the VADT and other two other landmark studies (ACCORD and ADVANCE ) was that intensive glycemic control does not reduce cardiovascular  disease events in people with type 2 diabetes of moderate to long duration.  However, our subsequent post-hoc analysis suggests that intensive glycemic control was associated with reduced risk of cardiovascular events in Hispanics, but not in non-Hispanic Whites or Blacks. (more…)
Author Interviews, Nature, Neurological Disorders / 30.12.2014

György Buzsáki, M.D., Ph.D. Biggs Professor of Neural Sciences NYU Neuroscience Institute New York University Langone Medical Center New York, NY 10016MedicalResearch.com Interview with: György Buzsáki, M.D., Ph.D. Biggs Professor of Neural Sciences NYU Neuroscience Institute New York University Langone Medical Center New York, NY 10016 Medical Research: What is the background for the NeuroGrid device? Dr. Buzsaki: The main form of communication among neurons in the brain occurs through action potentials (‘spikes’). Understanding the mechanisms that translate spikes of individual neurons into perceptions, thoughts, and actions requires the ability to monitor large populations of neurons at the spatial and temporal resolution of their interactions. We developed a novel, organic material-based, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) with neuron-size density electrodes capable of acquiring action potential of individual neurons from the surface of the brain. The NeuroGrid has several innovative characteristics that overcome limitations in current methods of surface recording: (i) light-weight and conformable architecture to establish stable electrical and mechanical contacts, thereby ensuring minimal damage to underlying tissue; (ii) efficient abiotic/biotic interface resulting in a high signal to noise ratio and the ability to resolve spikes. This is achieved by using conducting polymers as the interfacing material. Conducting polymers are mix conductors, they can conduct electronics and ionic currents hence they can efficiently transduce ion based neural activity into electronic signals (iii) scalable neuron-size density electrodes to allow isolation and characterization of multiple individual neurons’ action potential across the cortical surface. (more…)
Author Interviews, Heart Disease / 30.12.2014

MedicalResearch.com Interview with: Yan Liang, MD, PHD on behalf of co-authors Emergency and Intensive Care Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China Medical Research: What is the background for this study? What are the main findings? Response: The background of this study is mainly derived from the results of CURRENT-OASIS7 which has shown a 7-day 150 mg maintenance dose (MD) clopidogrel could reduce cardiovascular events among subgroup patients undergoing percutaneous coronary intervention (PCI) compared with the 75 mg/day regimen. We conducted a meta-analysis based on 17 randomized controlled trials to determine whether prolonging the high MD clopidogrel (≥150 mg) treatment period to at least 4 weeks could reduce major adverse cardiac events (MACEs) in the PCI patients with and without high on-clopidogrel platelet reactivity (HPR). Our study concluded that the high  maintenance dose clopidogrel was associated with a significant reduction in the risk of MACEs in PCI patients without increasing the rate of “Major/Minor bleeding” or “Any bleeding” in comparison with standard 75mg MD clopidogrel, and the “HPR Patients” subgroup were also benefited from such high MD treatment. (more…)
Author Interviews, Cancer Research / 30.12.2014

Paul Dent PhD Massey Cancer Center, Departments of Biochemistry and Molecular Biology Virginia Commonwealth University, Richmond, VA 23298MedicalResearch.com Interview with: Paul Dent PhD Massey Cancer Center, Departments of Biochemistry and Molecular Biology Virginia Commonwealth University, Richmond, VA 23298 Medical Research: What is the background for this study? What are the main findings? Dr. Dent: I have worked on understanding how the drug OSU-03012 (AR-12) kills cancer cells since 2005. The drug was originally advertised as an inhibitor of PDK1 in the PI3 kinase pathway. We found that PDK1 inhibition could not be the major way in which the drug worked. We found that the drug killed brain cancer cells through endoplasmic reticulum stress signaling. And in 2012 we published that OSU-03012 destabilized the chaperone protein GRP78, without significantly altering its transcription. Loss of GRP78 was responsible for the prolonged intense endoplasmic reticulum stress signal, that was toxic. In 2014 we published that OSU-03012 + Viagra / Cialis synergized to kill brain cancer cells. We hypothesized that Viagra / Cialis might enhance the anti-GRP78 effect of OSU-03012; and this was proven to be true. We discovered that the OSU-03012 + Viagra combination, but not OSU-03012 alone, reduced expression of other chaperone proteins, such as HSP70, GRP94. In mice, the combination was not toxic to "normal" tissues, but was toxic to tumor cells. In human patients the drug was found to be safe in a phase I trial, with plasma levels of up to 8 microM, and patients on trial for up to 9 months. (more…)
Annals Internal Medicine, Author Interviews, Colon Cancer, Race/Ethnic Diversity, University of Pennsylvania / 30.12.2014

Jeffrey H. Silber, M.D., Ph.D. The Nancy Abramson Wolfson Endowed Chair in Health Services Research Director, Center for Outcomes Research The Children's Hospital of Philadelphia Professor of Pediatrics, Anesthesiology & Critical Care The Perelman School of Medicine Professor of Health Care Management, The Wharton SchoolMedicalResearch.com Interview with: Jeffrey H. Silber, M.D., Ph.D. The Nancy Abramson Wolfson Endowed Chair in Health Services Research Director, Center for Outcomes Research The Children's Hospital of Philadelphia Professor of Pediatrics, Anesthesiology & Critical Care The Perelman School of Medicine Professor of Health Care Management, The Wharton School The University of Pennsylvania  Philadelphia, PA 19104 Medical Research: What is the background for this study? What are the main findings? Response: Differences in colon cancer survival by race is a well recognized problem among Medicare beneficiaries. We wanted to determine to what extent the racial disparity in survival is due to a racial disparity in presentation characteristics at diagnosis (such as advanced stage and the presence of chronic diseases) versus a disparity in subsequent treatment by surgeons and oncologists. To answer this question, we compared black colon cancer patients to three matched white groups: (1) “Demographics” match controlling age, sex, diagnosis year, and Survey, Epidemiology, and End Results (SEER) site; (2) “Presentation” match controlling demographics plus comorbidities and tumor characteristics including stage and grade; and (3) “Treatment” match including presentation variables plus details of surgery, radiation and chemotherapy. We studied Medicare patients 65 years of age and older diagnosed between 1991-2005 in the SEER-Medicare database. There were 7,677 black patients and 3 sets of 7,677 matched white controls. We found that difference in 5-year survival (black-white) was 9.9% in the demographics match. This disparity remained unchanged between 1991-2005. After matching on presentation characteristics, this difference fell to 4.9%. Finally, after additionally matching on treatment, this same difference hardly changed, moving to only 4.3%. So the disparity in survival attributed to treatment differences comprised only an absolute 0.6% of the overall 9.9% survival disparity. (more…)
Author Interviews, Cancer Research, Radiology / 29.12.2014

Ulas Sunar, Ph.D. Research Assistant Prof. Dept of Biomedical Engineering SUNY-University at BuffaloMedicalResearch.com Interview with: Ulas Sunar, Ph.D. Research Assistant Prof. Dept of Biomedical Engineering SUNY-University at Buffalo Medical Research: What is the background for this device? What are the main implications? Dr. Sunar: Most of ovarian cancer cases are not diagnosed until after the disease has spread in the abdominal cavity. A major challenge is to detect and remove dozens or hundreds of metastatic tumor nodules within the abdominal cavity. Fluorescence endoscopy can utilize the high sensitivity and specificity of fluorescence contrast and high resolution of endoscopic imaging. We are developing a clinically-relevant, fiber-based endoscopy system that allows both accurate fluorescence imaging and for projecting adaptive-shaped light for light-induced chemodrug delivery. The system can provide high contrast for improved demarcation and trigger drug release to destroy micrometastases. The system utilizes a highly sensitive camera and structured light illumination scheme with a projector for accurate fluorescence imaging of drug distribution, as well as allows light-triggered drug release and adaptive light delivery for optimized treatment of micrometastases. We expect that our novel illumination and drug release strategy will permit lower doxorubicin doses to be administered while simultaneously achieving more specific drug delivery in order to destroy the micrometastases and improve survival rates. (more…)
Author Interviews, Exercise - Fitness, Geriatrics, Memory / 29.12.2014

Scott M. Hayes, Ph.D. Associate Director Neuroimaging Research for Veterans Center Memory Disorders Research Center VA Boston Healthcare System Assistant Professor of Psychiatry Boston University School of MedicineMedicalResearch.com Interview with: Scott M. Hayes, Ph.D. Associate Director Neuroimaging Research for Veterans Center Memory Disorders Research Center VA Boston Healthcare System Assistant Professor of Psychiatry Boston University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Hayes:   Studies with rodents have demonstrated that physical activity positively impacts memory, whereas human studies have tended to emphasize a relationship with executive function—which refers to one’s ability to plan, organize, and manipulate information in one’s mind.  To clarify the relationship between fitness, cognition, and aging, we directly assessed cardiorespiratory fitness (heart and lung function) using the gold standard in the field, a graded treadmill test, and assessed both memory and executive functions in young and older adults.  Our results showed that cardiorespiratory fitness was positively associated with memory and executive functions in older adults, but not young adults.  In fact, on tests of executive functions, older adults with higher levels of cardiorespiratory fitness performed as well as younger adults. The impact of cardiorespiratory fitness may be age-dependent.  Young adults, who are at their peak in terms of memory performance, may exhibit minimal associations with cardiorespiratory fitness.  In contrast, cardiorespiratory fitness likely has a larger impact in older adults by attenuating age-related decline in memory. (more…)
Author Interviews, Breast Cancer / 29.12.2014

Dr. SikovMedicalResearch.com Interview with: William M. Sikov, MD Associate Chief of Clinical Research Program in Women's Oncology Women & Infants Rhode Island Associate professor of Medicine The Warren Alpert Medical School of Brown University Medical Research: What is the background for this study? What are the main findings? Dr. Sikov: The data presented at San Antonio this year are the first results from correlative studies performed on pretreatment tissue samples from patients treated on CALGB 40603, a 2 x 2 factorial randomized phase II study which tested the addition of carboplatin or bevacizumab to a standard neoadjuvant chemotherapy regimen consisting of weekly paclitaxel followed by dose-dense AC in patients with stage II-III triple breast cancer. Last year at San Antonio (and subsequently published in the JCO) we presented the primary endpoint of the study - pathologic complete response (pCR) - and reported that the addition of either carboplatin or bevacizumab significantly increased pCR rates compared to the control regimen. This year we reported results of a preplanned analysis which assessed the impact of intrinsic subtype (based on mRNA expression analysis) - especially the basal-like subtype - on the impact of the two agents on pCR rates. We also reported the effects of a number of previously published mRNA expression signatures on pCR rates and the benefits of adding carboplatin or bevacizumab. The findings reported were as follows: We had a higher percentage of basal-like cancers than we anticipated when the study was designed (87% vs. 70-80% expected), which we hypothesize is due to improvements in the ways we assess hormone receptor and HER2 status, and thus define triple-negative breast cancer, compared to 10-15 years ago. When we limit our analysis to the subset of patients with basal-like cancers, we continue to see a statistically significant increases in pCR rates with both carboplatin and bevacizumab. However, while the 13% of patients with non-basal-like cancers get essentially the same increase in pCR rates with carboplatin as do the basal-likes, non-basal-likes actually had a reduction in their pCR rates with the addition of bevacizumab - thus, there was a significant interaction between subtype and pCR benefit for bevacizumab but not for carboplatin. Among the mRNA signatures we assessed, higher expression of immune signatures  (indicating more tumor-infiltrating lymphocytes) correlated with higher pCR rates, but not greater pCR increments with either carboplatin or bevacizumab. Higher proliferation, lower estrogen, and higher TP53 mutation signaturss also correlated with higher pCR rates overall, and also with greater pCR increments with bevacizumab, but not carboplatin. (more…)
Author Interviews, JAMA, OBGYNE / 28.12.2014

Keith P. West, Jr., Dr.P.H., R.D. Professor and Director Program and Center in Human Nutrition Department of International Health Bloomberg School of Public Health Johns Hopkins University Baltimore, Maryland 21205MedicalResearch.com Interview with: Keith P. West, Jr., Dr.P.H., R.D. Professor and Director Program and Center in Human Nutrition Department of International Health Bloomberg School of Public Health Johns Hopkins University Baltimore, Maryland 21205 Medical Research: What is the background for this study? What are the main findings? Dr. West: Deficiencies in vitamins and minerals (micronutrients) that must be provided by the diet, are a major public health concern in undernourished societies.  In rural South Asia, where some 35 million babies are born each year, maternal micronutrient deficiencies are common and may increase risk of adverse pregnancy outcomes such as preterm birth, low birth weight or stillbirth and infant mortality.  Further, a newborn of low birth weight faces higher risks of poor postnatal growth, infection and mortality.  Where prenatal care exists, iron-folic acid supplements are often prescribed as standard care to prevent iron deficiency anemia.  But it is likely that many micronutrient deficiencies emerge from an inadequate diet, raising the possibility that a supplement that provides each day a recommended dietary allowance of most essential vitamins and minerals  could measurably improve the health of the mother, fetus and infant.  Because prenatal multinutrient supplements are rarely taken in low income countries, it is important to assess their potential to  improve health before recommending this practice.  We did this be conducting a large prenatal supplementation trial in rural Bangladesh, randomizing  44,567 pregnant women in their 1st trimester to receive a supplement with 15 vitamins and minerals or only iron and folic acid, followed their pregnancies and survival of their 28,516 infants to 6 months of age. Medical Research: What are the main findings? Dr. West:  The multiple micronutrient supplement had the effect of extending the length of gestation compared to the iron-folic acid supplement, by about 2 days on average.  This was enough to lower risk of preterm birth, below 37 weeks,  by 15%.  The extra time in the womb also allowed the fetus to grow a little larger, increasing birth weight (by 54 grams or about 2 ounces) as well as length and other measures of size, leading to a 12% reduction in low birth weight.  In addition, there was an 11% reduction in risk of stillbirth.  These are all indications of a healthier pregnancy.  Although we observed a 14% lower mortality from all causes in girls, there was not a similar effect in boys, leading to no overall effect.  We are continuing to investigate possible reasons for this difference. (more…)
Author Interviews, Heart Disease, Stroke / 28.12.2014

MedicalResearch.com Interview with: Torben Bjerregaard Larsen Associate professor, MD, PhD, FESC Aalborg University Hospital Department of Cardiology Aalborg Thrombosis Research Unit Denmark Medical Research: What is the background for this study? What are the main findings? Dr. Larsen: Heart failure is a major public health issue with an increasing prevalence. Heart failure is associated with an increased risk of stroke, also in patients without concomitant atrial fibrillation. However, recent prospective randomized controlled trials investigating the effect of antithrombotic therapy in heart failure patients in sinus rhythm revealed that the benefit of warfarin in reducing stroke was counterbalanced by an increased risk of bleeding. Whether subgroups within the heart failure population would benefit from antithrombotic therapy is currently unknown. Therefore, possible subgroups with a higher risk of stroke within the heart failure population must be identified. We investigated whether female sex was associated with a higher risk of stroke, since female sex has been associated with an increased stroke risk among patients with atrial fibrillation. In our study, we found an association between female sex and decreased stroke risk in heart failure patients in sinus rhythm which persisted after adjustment for concomitant cardiovascular risk factors. This association was attenuated with increasing age which could possibly be due to competing risks of death, since competing risk of death was substantial among males in the older age groups. (more…)
Author Interviews, HPV, Lancet, Vaccine Studies / 28.12.2014

MedicalResearch.com Interview with: Huachun Zou PhD on behalf of all authors. Melbourne Sexual Health Centre, Alfred Health, Carlton, VIC, Melbourne School of Population and Global Health University of Melbourne, Melbourne, VIC, Australia Medical Research: What is the background for this study? What are the main findings? Response: Anogenital human papillomavirus (HPV) infection and anal cancer are common among men who have sex with men (MSM) and preventable with the HPV vaccine. However, the optimal strategy for vaccinating MSM against HPV requires an accurate understanding of the age specific incidence of early HPV infection. In addition to understanding the optimal age at which to vaccinate young MSM, policy makers also need to know the vaccine coverage required in MSM. In this paper we aimed to provide estimates for the site specific incidence of HPV and to use this to estimate the probability of transmission per partner in a cohort of very young MSM aged 16 to 20 years. These data will assist governments in deciding what HPV vaccination strategy is likely to be the most effective in MSM. (more…)
Author Interviews, Breast Cancer, Johns Hopkins, Journal Clinical Oncology, Leukemia / 28.12.2014

MedicalResearch.com Interview with: Dr. Judy Karp, Dr. Antonio Wolff and  Dr. Kala Visvanathan Breast Cancer Program Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore, MD 21287 Medical Research: What is the background for this study? What are the main findings? Response: The background for this study was the clinical observation from the Johns Hopkins Leukemia Program that a significant number of women with newly diagnosed acute myeloid leukemia had a personal history for breast and/or ovarian cancers.  This observation led to our examination of the large NCCN breast cancer database in a multidisciplinary and multi-institutional study.  The overarching finding in our study is that the risk of developing some form of leukemia following chemotherapy with or without radiation therapy, while small, continues to increase over at least 10 years without a plateau and is roughly twice what we thought it to be from previous breast cancer studies. (more…)
Aging, Author Interviews, Nature, Scripps / 27.12.2014

Paul Schimmel, Ph.D. Professor The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research Department of Molecular and Cell Biology, The Scripps Research Institute, La Jolla, California MedicalResearch.com Interview with: Paul Schimmel, Ph.D. Professor The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research Department of Molecular and Cell Biology, The Scripps Research Institute, La Jolla, California Medical Research: What is the background for this study? What are the main findings? Dr. Schimmel: Resveratrol (RSV) is thought to provide health benefits by activating a protective stress response. In the paper we described a new, previously missed mechanism for its action. This mechanism is activated at much lower concentrations of resveratrol than previously described or imagined. Consequently, other mechanisms, which appear to act at higher concentrations of resveratrol, are layered over a preexisting foundation set by the newly revealed mechanism. (more…)
Author Interviews, Heart Disease, Nutrition, Salt-Sodium / 27.12.2014

Jordi Salas-Salvadó Professor of Nutrition Human Nutrition Unit Department of Biochemistry & Biotechnology IISPV School of Medicine. Rovira i Virgili University CIBERobn, Instituto Carlos IIIMedicalResearch.com Interview with: Jordi Salas-Salvadó Professor of Nutrition Human Nutrition Unit Department of Biochemistry & Biotechnology IISPV School of Medicine. Rovira i Virgili University CIBERobn, Instituto Carlos III Medical Research: What is the background for this study? What are the main findings? Response: Excess sodium intake is associated with high blood pressure, a major risk factor for cardiovascular disease (CVD). The 2010 Dietary Guidelines for Americans recommended a sodium intake below 2300 mg per day (equivalent to less than 1 teaspoon of salt per day) in the general population. However it is unknown whether decreasing sodium intake below 2300 mg/d has an effect on CVD or all-cause mortality. The recent Institute of Medicine (IOM) explicitly concluded that studies on health outcomes are inconsistent in quality and insufficient in quantity to determine that sodium intake below 2300 mg/d may increase or decrease the risk of heart disease, stroke or all cause of mortality. (more…)
Author Interviews, Surgical Research, University Texas, Weight Research / 27.12.2014

Taylor S. Riall, MD, PhD Professor, John Sealy Distinguished Chair in Clinical Research Department of Surgery, University of Texas Medical Branch, Galveston, TXMedicalResearch.com Interview with: Taylor S. Riall, MD, PhD Professor, John Sealy Distinguished Chair in Clinical Research Department of Surgery, University of Texas Medical Branch, Galveston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Riall: In patients who have symptoms related their gallstones – most commonly sharp right upper quadrant abdominal pain (often associated with fatty meals), nausea, and vomiting - the current recommendation is to remove the gallbladder (perform cholecystectomy). However, in older patients there are multiple factors that make this decision difficult. Older patients have more associated medical problems (like diabetes, heart disease, etc.) making elective surgery higher risk. On the flip side, older patients are at higher risk of developing complications from their gallstones, and once they do, their mortality (death from gallbladder disease) and complications increase substantially. In recent study of Medicare beneficiaries with symptomatic gallstones, we found that fewer than 25% underwent elective removal of the gallbladder after an initial episode of pain or symptoms related to their gallbladder. We then developed a model that predicted the likelihood of these same patients requiring emergent gallstone-related complications if they did not have their gallbladder removed electively. This information prompted the current study. We sought to determine if the patients getting their gallbladders removed were the ones at highest risk for complications. Similar to the previous study, we found that only 22% of Medicare beneficiaries in this study (a different population) underwent elective gallbladder removal. We divided patients into three groups based on our risk prediction model – those with <30% risk, 30-60% risk, and >60% risk of requiring acute gallstone-related hospitalization. Please note that while we call the <30% risk group “low” risk, a 17% chance of hospitalization is actually a significant risk – much higher than seen in other medical conditions for which surgery or other interventions may be considered.
  • First, our model worked well – the ACTUAL hospitalization rate was 17%, 45%, and 69% in the two years after the first symptoms.
  • Second, whether patients had their gallbladder removed seemed unrelated to risk. 22% of patients in the lowest risk group, 21% in the middle risk group, and 23% in highest risk group had their gallbladder removed. Even more striking, in the healthiest patients – those with no medical problems and no reason not to perform elective surgery - cholecystectomy rates actually decreased with increasing risk of emergent admission. Cholecystectomy was performed in 34% of patients in the low risk group, 25% of patients in the moderate risk group, and 26% of patients in the highest risk group.
  • In addition, fewer than 10% of patients who didn’t have their gallbladder removed were ever seen by a surgeon, suggesting that this decision is being made at the level of the primary care or emergency physician and not necessarily patient choice.
(more…)
Author Interviews, Hearing Loss, HIV, JAMA, UCSD / 27.12.2014

dr-peter-torre Dr. Peter Torre III PhD Associate Professor, Audiology Director, Recreational Noise Exposure and Hearing Lab San Diego State UniversityMedicalResearch.com Interview with: Dr. Peter Torre III PhD Associate Professor, Audiology Director, Recreational Noise Exposure and Hearing Lab San Diego State University Medical Research: What is the background for this study? What are the main findings? Dr. Torre: The primary purpose of our study was to evaluate hearing sensitivity in HIV+ and HIV- adults. And subsequently, in HIV+ adults only, to examine whether HIV disease variables or treatment was associated with hearing sensitivity. The main findings were that HIV+ adult had poorer hearing for both the lower and higher frequencies compared with HIV- adults, although we did not find any significant associations between HIV variables and treatment variables with hearing loss. (more…)
Author Interviews, Heart Disease / 26.12.2014

Jiun-Ling Wang MD Associated professor at Medical school in I-Shou University infectious disease doctor at E-DA Hospital, Kaohsiung , TaiwanMedicalResearch.com Interview with: Jiun-Ling Wang MD Associated professor at Medical school in I-Shou University infectious disease doctor at E-DA Hospital, Kaohsiung , Taiwan Medical Research: What is the background for this study? What are the main findings? Dr. Wang: Some study showed increase cardiovascular death in azithromycin user. But there lacks of data in other antibiotics in the treatment for respiratory tract infections. So we used the Taiwan National Health Insurance Database to perform a nationwide, population-based study comparing the risks of ventricular arrhythmia and cardiovascular death among patients using these antibiotics. And we find azithromycin, and moxifloxacin were associated with higher risk of ventricular arrhythmia cardiovascular death than amoxicillin/clavunate. (more…)
Author Interviews, Dermatology, Smoking, Weight Research / 26.12.2014

MedicalResearch.com Interview with: Seong Jin Jo, MD, PhD Department of Dermatology Seoul National University College of Medicine Seoul Korea. Medical Research: What is the background for this study? What are the main findings? Response: Hair graying is a natural aging process, but some people develop hair graying in their youth. In this study of young Korean males, we found that obesity, smoking, and family history were significantly associated with premature hair graying. (more…)
Author Interviews, JAMA, Pediatrics / 26.12.2014

Seetha Shankaran MD Director, Neonatal-Perinatal Medicne Children's Hospital of Michigan and Hutzel Women's Hospital Detroit, MIMedicalResearch.com Interview with: Seetha Shankaran MD Director, Neonatal-Perinatal Medicne Children's Hospital of Michigan and Hutzel Women's Hospital Detroit, MI Medical Research: What is the background for this study? What are the main findings? Dr. Shankaran: The background for this study is that term newborn infants born following lack of blood flow and oxygen to the brain are at high risk for death or disability, including motor and developmental handicaps. Hypothermia (lowering the core body temperature to 33-34°C for 72 hours has been shown to decrease the rate of death or disability to 44 to 55%. Hypothermia is currently the only proven therapy to reduce these devastating outcomes. The hypothermia therapy provided to term newborns was based on laboratory experiments that demonstrated that in animal models subjected to hypoxia and ischemia, cooling reduced brain injury. In the NICHD Neonatal Research Network (a group of academic centers across the US), in 2005 we reported the first trial of whole-body cooling to 33.5°C for 72 hours and noted a reduction in death or disability in infancy.  When the infants in the study where followed to childhood, we noted that this reduction in death or disability continued to childhood. Recent laboratory experiments have demonstrated that brain injury continues for days or weeks after the hypoxic-ischemic injury. Other laboratory experiments noted that cooling for a greater depth than 33-34°C (as long as the temperature does not decrease much lower) can reduce brain injury further. Based on this information, in the NICHD Neonatal Research Network we designed a study, among term infants with moderate or severe encephalopathy to compare longer cooling and deeper cooling to see if death or disability can be reduced. Term infants with moderate or severe encephalopathy were randomly assigned at <6 hours of age to 4 groups of therapy; 33.5°C for 72 hours, 32.0°C for 72 hours, 33.5°C for 120 hours and 32.0°C for 120 hours. The  goal was to compare death or disability rates between the 2 durations of cooling (72 hours vs. 120 hours) and 2 depths of cooling (33.5 C vs. 32.0°C) and was designed to recruit 726 infants. A independent data safety and monitoring committee was appointed by the director of NICHD to monitor safety events after the first 50 infants were enrolled and then following the enrollment of every 25 infants. The safety events monitored included mortality in the neonatal intensive care unit (NICU), cardiac arrhythmia, persistent acidosis and major vessel bleeding or thrombosis. The study was started in October 2010. Medical Research: What is the background for this study? What are the main findings? Dr. Shankaran: In November 2013 the study was closed by the data safety and monitoring committee after 8 reviews of study data, following recruitment of 364 neonates because of emerging safety concerns as well as futility analyses. The NICU death rates were 7% (7 of 95) for the 33.5°C for 72 hour group, 14% (13 of 90) for the 32.0°C for 72hr group, 16% (15 of 96) in the 33.5°C for 120 hour group and 17% for the 32.0°C for 120 hour group. The adjusted risk ratio (95% CI) for death for the 120 hour vs. the 72 hour was not significantly different 1.37 (0.92-2.04) nor was it significantly different for the 32.0°C group compared to the 33.5°C group 1.24 (0.69-2.25).  The safety outcomes were similar between the 120 vs. 72 hour groups and the 32.0°C vs. the 33.5°C groups, except that major bleeding occurred among 1% in the 120 group vs. 3% in the 72 hours group, RR 0.25 (0.07-0.91). Futility analyses noted that the probability of detecting benefit of longer cooling, deeper cooling or both for death in the NICU was <2%. The follow -up of infants enrolled into the study for 18 months is on-going. (more…)
Author Interviews, Blood Pressure - Hypertension, Case Western, Dermatology, JAMA, Weight Research / 26.12.2014

Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, IllinoisMedicalResearch.com Interview with: Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, Illinois Medical Research: What is the background for this study? Dr. Silverberg: Previous studies found associations between obesity and atopic dermatitis (AD). However, little was known about the association between AD and metabolic risk factors, such as central obesity and high blood pressure. (more…)
Author Interviews, JACC, Surgical Research / 26.12.2014

Dr. Mary T. Hawn Center for Surgical, Medical Acute Care Research, and Transitions, Birmingham Veterans Affairs Medical Center University of Alabama at Birmingham, BirminghamMedicalResearch.com Interview with: Dr. Mary T. Hawn MD, MPH Center for Surgical, Medical Acute Care Research, and Transitions, Birmingham Veterans Affairs Medical Center Section of Gastrointestinal Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama Medical Research: What is the background for this study? What are the main findings? Dr. Hawn: Cardiac risk factors and surgical risk factors contribute to the development of postoperative adverse cardiac events, but the relative contribution of each has not been quantified. In this study, we sought to determine the incremental risk of surgery following coronary stent placement on adverse cardiac events. To answer this question we used a retrospective cohort study of VA patients with coronary stents placed during 2000-2010 undergoing non-cardiac surgery within two years of stent placement matched to patients with coronary stents not undergoing surgery.  The patients were matched on stent type (drug-eluting versus bare metal) and cardiac risk factors at the time of stent placement.  Our outcome of interest was a composite variable of myocardial infarction and coronary revascularization occurring within 30 days of surgery.  We calculated adjusted risk differences over time from stent placement using generalized estimating equations. When comparing the two cohorts, we found a higher rate of composite cardiac events in the surgical cohort compared to the cohort not undergoing surgery. The main findings in the study were that the incremental risk of surgery was greatest when the surgery occurred in the first 6 weeks following stent placement and decreased to approximately 1% after 6 months, where it remained stable out to 24 months. Surgical characteristics associated with a significant reduction in the incremental risk after 6 months following stent placement included elective, inpatient procedures, and in the setting of a drug eluting stent. (more…)
Author Interviews, Heart Disease, Statins / 26.12.2014

Beth Taylor, PhD Director of Exercise Physiology Research Department of Preventive Cardiology Hartford Hospital Hartford, CT 06102MedicalResearch.com Interview with: Beth Taylor, PhD Director of Exercise Physiology Research Department of Preventive Cardiology Hartford Hospital Hartford, CT 06102 Medical Research: What is the background for this study? Dr. Taylor:  Statins reduce incidence of cardiac events, and thus are extremely effective drugs. However, they may cause muscle side effects such as pain, weakness and soreness (i.e., statin myalgia) in up to 10% of patients. One potential mechanism underlying statin myalgia may be the depletion of Coenzyme Q10, a mitochondrial transport element used in energy production, as statin therapy produces a 30-50% reduction in intramuscular Coenzyme Q10. Seven previous studies to date have produced conflicting results, yet CoQ10 supplementation is used by many patients and recommended by many clinicians despite the absence of definitive results. The purpose of the present study was to assess the effect of CoQ10 on muscle pain, muscle strength and aerobic performance in confirmed myalgics (i.e., patients who tested positive for  myalgia during a randomized, double-blinded cross-over trial of statin therapy vs. placebo to confirm myalgia prior to CoQ10 treatment). Medical Research: What are the main findings? Dr. Taylor:  The first main finding was that after our randomized double-blind cross-over run-in phase, only 35.8% of patients experienced myalgia on simvastatin and did not experience it on placebo, what we term true or confirmed statin myalgia, and 17.5% of patients had no symptoms on simvastatin or placebo which could have been because the dose we selected was too low.  However, 29.2% experienced pain on placebo but not on simvastatin and 17.5% experienced pain on both simvastatin and placebo during the confirmation phase. Secondly, we found that Coenzyme Q10 supplementation had no effect on the incidence and severity of myalgia, time to onset of pain, muscle strength, or aerobic performance.  Serum levels of CoQ10 went up, suggesting dosing worked, and LDL-C went down similarly in both groups, suggesting the statin was not compromised. Therefore we did not find an observable effect of CoQ10 on any muscle outcome. Finally, there were no reductions from baseline in muscle strength or aerobic performance when statins were combined with placebo in our verified statin myalgics. This is notable because while there have been observational reports of decreased muscle strength and aerobic performance in statin myalgics, there have been few rigorous assessments of muscle strength and aerobic performance with statins and myalgia. In our previous study, the The Effect of STatins On Skeletal Muscle Performance (STOMP) trial , we randomized healthy, statin-naïve patients to atorvastatin 80 mg daily or placebo for 6 months, confirming myalgia via a challenge-dechallenge protocol. In that study, we also found no significant differences in the two groups  in muscle and exercise performance, and thus the present results confirm those findings. (more…)
Author Interviews, HIV, JAMA / 26.12.2014

Jared Baeten, MD PhD Professor, Departments of Global Health and Medicine Adjunct Professor, Department of Epidemiology University of Washington Seattle, WA 98104MedicalResearch.com Interview with: Jared Baeten, MD PhD Professor, Departments of Global Health and Medicine Adjunct Professor, Department of Epidemiology University of Washington Seattle, WA 98104 Medical Research: What is the background for this study? What are the main findings? Dr. Baeten: The medication tenofovir disoproxil fumarate is used widely for the treatment of HIV-1 infection and, more recently, as pre-exposure prophylaxis (PrEP) to protect against HIV-1 infection for at-risk HIV-1 uninfected persons.  Its use has been associated with declines in the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by HIV-1 infected persons, but limited data are available for risk when used as PrEP for HIV-1 prevention. Using data from the largest randomized, placebo-controlled trial of PrEP, among heterosexual women and men in Africa, eGFR changes were assessed during prospective follow-up in those receiving pre-exposure prophylaxis and compared to those receiving placebo.  PrEP use resulted in a small (-1.59 mL/min/1.73m2, 95% CI -2.44, -0.74) but statistically significant decline in eGFR that was non-progressive over a median of 18 months and a maximum of 36 months of follow-up.  PrEP use was not accompanied by a substantial increase in the risk of clinically relevant (≥25%) eGFR decline. (more…)
Author Interviews, Heart Disease, NYU / 26.12.2014

Dr. Glenn I. Fishman MD Professor; William Goldring Professor of Medicine Vice Chair Research Dept of Medicine Director of the Leon H. Charney Division of Cardiology NYU LangoneMedicalResearch.com Interview with: Dr. Glenn I. Fishman MD Professor; William Goldring Professor of Medicine Vice Chair Research Dept of Medicine Director of the Leon H. Charney Division of Cardiology NYU Langone Medical Research: What is the background for this study? What are the main findings? Dr. Fishman: Sudden cardiac arrest (SCA) due to life-threatening ventricular arrhythmias is one of the leading causes of death in the US. Conditions that predispose to SCA can be acquired, as in atherosclerotic coronary artery disease, or inherited in the form of mutated cardiac ion channels, i.e. ion channelopathies. Mutations in the SCN5A cardiac sodium channel gene have been linked to progressive cardiac conduction disorders as well as atrial and ventricular arrhythmias. Understanding the mechanistic basis for lethal arrhythmias in cardiac sodium channelopathy patients has been limited in part due to the lack of adequate model systems that replicate human physiology. To address this limitation, we have developed the first genetically modified porcine model of an inherited channelopathy. A mutation in the SCN5A gene first identified in a child with the arrhythmic condition Brugada syndrome was introduced into the pig genome. Mutant pig hearts displayed conduction abnormalities and ventricular fibrillation bearing striking resemblance to the human condition. (more…)
Author Interviews, Case Western, Nature, Neurological Disorders / 26.12.2014

Bradley T. Lang, PhD Researcher, Jerry Silver Lab Department of Neurosciences Case Western Reserve University School of MedicineMedicalResearch.com Interview with: Bradley T. Lang, PhD Researcher, Jerry Silver Lab Department of Neurosciences Case Western Reserve University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Lang: In the late 1980’s, Jerry Silver, PhD, discovered the presence of chondroitin sulfate proteoglycans in the developing nervous system, which form barriers to prevent aberrant growth. He has been building on this finding for more than 30 years, attempting to understand why the adult spinal cord is incapable of regenerating, or why axons don’t grow where they don’t. He has found that the glial scar, which surrounds the site of neural trauma, is incredibly rich in proteoglycans, which prevent regeneration in the spinal cord. In 2009 we collaborated with a group at Harvard to discover the very first receptor for chondroitin sulfate proteoglycans, protein tyrosine phosphatase-sigma, or PTPsigma. Medical Research: What are the main findings? Dr. Lang: The findings in this paper are twofold. We first describe a novel mechanism of regeneration failure, where regenerating axons become stabilized within a gradient of chondroitin sulfate proteoglycan, completely preventing motility. This finding helps explain why axons persist in the vicinity of the glial scar after injury indefinitely, with little to no regeneration potential—they are simply embedded within the scar. We were able to model this interaction in a petri dish to screen for drugs that were capable of promoting motility. The second finding in the manuscript is the discovery and characterization of a novel peptide therapeutic that binds to the receptor for chondroitin sulfate proteoglycans and releases inhibition. Most importantly, this drug was given systemically, similar to a daily insulin injection, avoiding complications due to direct nervous system infusion/injection. After several weeks of treatment (which began 1 day after injury), rats with severe spinal cord injury regained coordinated locomotion, bladder control, and/or balance. In total, 21/26 treated animals regained some function. (more…)
Author Interviews, Education, Stroke / 26.12.2014

dr-gustavo-saposnikMedicalResearch.com Interview with: Gustavo Saposnik, MD, MSc., FAHA, FRCPC Director, Stroke Outcomes Research Center Co-Director, Stroke Program - Research & Innovation Associate Professor & Clinician Scientist Departments of Medicine (Neurology) and Health Policy, Management and Evaluation (HPME) St. Michael’s Hospital University of Toronto Medical Research: What is the background for this study? What are the main findings? Dr. Saposnik: There is some controversy around worse outcomes at the beginning of academic year. Physicians recently graduated from medical schools begin their training and assume responsibilities for patient care in teaching hospitals, usually bearing the first-line duty for managing patients. Consequently, less experienced staff having new roles may influence access to care and contribute to adverse outcomes in patients managed at the beginning of academic year - the so-called “July Effect”. for example, increase of medication errors and in-hospital mortality in July has been reported from teaching hospitals. In our large cohort study, comprising 10,319 stroke patients, 882 (8.5%) were admitted in July. Those patients were 28% less likely to receive thrombolysis (clot-buster treatment) (12% vs. 16%; odds ratio (OR), 0.72; 95% confidence interval (CI), 0.59-0.89) and 22% less likely to receive stroke unit care (62% vs. 68%; 0.78; 0.68-0.90). July admissions were not associated with either of higher death at 30 days (adjusted OR, 95% CI; 0.88, 0.74-1.03) or poor functional outcome (0.92, 0.74-1.14). Results remained consistent in the sensitivity analysis by including both July and August as part of the ‘July effect’. (more…)