Author Interviews, NEJM, Opiods, Pharmacology / 29.01.2015

Richard C. Dart, M.D., Ph.D Denver Health & Hospital Authority Professor, University of Colorado School of MedicineMedicalResearch.com Interview with: Richard C. Dart, M.D., Ph.D Denver Health & Hospital Authority Professor, University of Colorado School of Medicine   Medical Research: What is the background for this study? What are the main findings? Dr. Dart: For the past two decades, prescription opioid medication abuse has increased significantly in the US. An estimated 25 million people initiated nonmedical use of pain relievers between 2002 and 2011.  In 2010 the number of death attributed to prescription opioid medications reached 16,651. The  RADARS® System (Researched Abuse, Diversion and Addiction Related Surveillance) has been monitoring prescription drug abuse and diversion for over 13 years. We use a “mosaic” approach, measuring abuse and diversion from multiple perspectives, to describe this hidden phenomenon as comprehensively as possible. For the current publication we used 5 separate RADARS® System programs to collect data and the study period was from January 2002 through December 2013. We noticed a substantial increase  of prescription drug abuse from 2002 through 2010, followed by a flattening or decrease in 2010 and, lastly, a decline in 2011 through 2013. We also noticed a similar pattern in opioid-related deaths. Nonmedical use did not change significantly among college students. (more…)
Author Interviews, Cost of Health Care, NEJM, University of Pennsylvania / 26.01.2015

Daniel Polsky PhD Executive Director, Leonard Davis Institute of Health Economics Professor of Medicine and Health Care Management Perelman School of Medicine and the Wharton School University of PennsylvaniaMedicalResearch.com Interview with: Daniel Polsky PhD Executive Director, Leonard Davis Institute of Health Economics Professor of Medicine and Health Care Management Perelman School of Medicine and the Wharton School University of Pennsylvania Medical Research: What is the background for this study? What are the main findings? Dr. Polsky: The Medicaid Fee bump, a provision of the Affordable Care Act (ACA), raised Medicaid payments to Medicare levels in 2013 and 2014 for selected services and providers expired on January 1, 2015 before policymakers had much empirical evidence about its effects.   The federally funded increase in reimbursements was aimed at expanding access to primary care for the growing number of Medicaid enrollees. The reimbursement increase expired at the end of 2014 in most states.  We found that this policy worked to increase the number of providers offering primary care appointments to Medicaid patients.  The Medicaid pay bump was associated with a 7.7 percentage points increase in new patient appointment availability without longer wait times.   This increase in availability was largest in the states where primary care physicians received the largest increase in their Medicaid reimbursements. (more…)
Author Interviews, Emory, NEJM / 22.01.2015

Ravi Mangal Patel, MD MSc Assistant Professor of Pediatrics Division of Neonatology Emory University School of MedicineMedicalResearch.com Interview with: Ravi Mangal Patel, MD MSc Assistant Professor of Pediatrics Division of Neonatology Emory University School of Medicine Medical Research: What is the background for this study? Response: We sought to understand the major causes of death and when these deaths occur among extremely premature infants (those born at 22 0/7 to 28 6/7 weeks of gestation). We evaluated a cohort of 22,248 extremely premature infants born at hospitals that were part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, a research network comprised of academic medical centers across the United States. We evaluated changes over time in survival by comparing in-hospital deaths among live births during three periods from 2000 to 2011. (more…)
Author Interviews, Kidney Disease, NEJM / 19.01.2015

MedicalResearch.com Interview with: David K. Packham, M.B., B.S., M.D Royal Melbourne Hospital Melbourne Renal Research Group VIC 3073, Australia, Medical Research: What is the background for this study? What are the main findings? Dr. Packham:  ZS-9 represents a new mechanism of action for addressing hyperkalemia. Unlike traditional nonspecific organic polymer cationexchangers, ZS-9 is a non-absorbed, inorganic crystalline potassium-selective cation exchanger that traps excess potassium in the gastrointestinal tract. It has been evaluated in three prospective, randomized, double-blind, placebo-controlled studies with over 1100 patients to date, representing the largest ever clinical development program for hyperkalemia. ZS-003 was the first of two pivotal Phase 3 studies that evaluated the safety and efficacy of ZS-9 in patients with hyperkalemia. In ZS-003, treatment of patients with an oral suspension of ZS-9 (2.5, 5, or 10 grams, three times a day) resulted in statistically significant and clinically meaningful reductions in serum potassium, compared with placebo, during the “acute phase” (first 48 hours), with 99 percent of patients achieving normal potassium levels with the highest 10 gram dose. During the next 12 days of the trial (the “maintenance phase”), ZS-9 (5 or 10 grams) given once daily could maintain the corrected potassium levels achieved during the acute phase. In contrast, patients who were randomized back to placebo after achieving normal potassium reverted back to hyperkalemia. The tolerability profile has been favorable, with adverse event rates from ZS-9 similar to that of placebo. (more…)
Author Interviews, Dengue, Infections, NEJM, Vaccine Studies / 13.01.2015

Gustavo Dayan, MD Director, Clinical Development Sanofi Pasteur Discovery Drive Swiftwater, PA 18370MedicalResearch.com Interview with: Gustavo Dayan, MD Director, Clinical Development Sanofi Pasteur  Discovery Drive Swiftwater, PA 18370 Medical Research: What is the background for this study? What are the main findings? Dr. Dayan: This is the first dengue vaccine efficacy trial conducted in Latin America. The trial met its primary objective showing an efficacy of 60.8% against symptomatic VCD (virologically confirmed dengue) after a 3-dose vaccination schedule. Serotype-specific efficacy was also demonstrated against all four serotypes. Furthermore, the dengue vaccine candidate effectively reduced hospitalization due to dengue by 80.3% and severe dengue disease by 95.5% over the 25-month study period. (more…)
Author Interviews, Breast Cancer, Mayo Clinic, NEJM / 03.01.2015

MedicalResearch.com Interview with: Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined. As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them. Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up. This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort). This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women. Medical Research: What should clinicians and patients take away from your report? Dr. Hartmann: There are about 100,000 US women each year diagnosed with atypical hyperplasia via breast biopsy. Although strictly speaking, atypical hyperplasia is a benign finding, it is associated with a sizable risk of a later breast cancer. Physicians from numerous disciplines care for women with high-risk benign breast issues, including gynecologists, family physicians, internists, surgeons and oncologists. These practitioners, and the patients themselves, need information about the absolute risk of breast cancer occurring over time after a diagnosis of atypical hyperplasia. This information is provided in the NEJM report. Also, current guidelines should be updated to include this high-risk population and specifics about their absolute risk, and that the risk level qualifies these patients for screening MRI. Moreover, from the standpoint of risk reduction, four previously conducted breast cancer prevention trials included women with atypical hyperplasia. These trials used hormonal therapies (anti-estrogens) and showed that, in women with atypical hyperplasia, the use of such medications could lower the risk of a later breast cancer by 50% or more. Yet, other research has shown that women are quite reluctant to take such medications, primarily because of fear of side effects. In the NEJM report, we detail specific numbers of side effects that actually occurred in women who used these anti-estrogens (as opposed to the number of side effects seen in women taking placebo) and show that most of the side effects occurred quite uncommonly. Thus, we hope that the combination of information provided in this report on (i) actual risks of breast cancer and (ii) actual risks of side effects will help patients and practitioners make informed decisions on the best treatment approaches for women with atypical hyperplasia. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Hartmann: First, women with atypical hyperplasia should be included in future prospective trials of novel imaging strategies (they were not included in trials of MRI, which had been limited to women with hereditary risk). Second, efforts should continue to predict which women with atypical hyperplasia are at highest risk, especially in the first 5-10 years after their biopsy, so they can be cared for optimally. Our research team, and others, continue to study the underlying molecular pathways that drive the progression from atypical hyperplasia to cancer; identifying such processes would not only aid in risk prediction but also identify driving pathways that could be blocked pharmaceutically. Citation: upcoming NEJM publication discussing: Women with Atypical Hyperplasia are at Higher Risk of Breast Cancer MedicalResearch.com Interview with: Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern  – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined.  As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them.  Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up.  This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort).  This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women. (more…)
Author Interviews, Erasmus, NEJM, Stroke / 02.01.2015

Diederik Dippel MD, PhD Senior Consultant in Neurology Erasmus MC University Medical Center Rotterdam The NetherlandsMedicalResearch.com Interview with: Diederik Dippel MD, PhD Senior Consultant in Neurology Erasmus MC University Medical Center Rotterdam The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Dippel: MR CLEAN is the first randomized clinical trial to show that intra-arterial treatment of ischemic stroke to get the clot out, really works. It leads to more recovery and less handicap. Previous studies had shown that intra-arterial treatment leads to recanalization, but the final proof that the treatment leads to recovery more often than standard treatment was lacking. With standard treatment, less than 1 out of 5 recovers without handicap, but with this new treatment, this will be 1 out of 3. The treatment did not lead to more complications than standard treatment. The rate of symptomatic intracranial hemorrhage was similar in both arms. Our study differs from previous, neutral trials.
  • First, we required patients to have an intracranial arterial occlusion confirmed by neuro-imaging.
  • Second, we used third generation thrombectomy devices, such as retrievable stents in most of the cases.
  • Third, our trial was conducted in a country with a very good infrastructure, which allowed rapid transfer to intervention centers, which are spread throughout the country. Our rate of iv tPA in Dutch hospitals is over 11% on average.
  • Last, all intervention centers participated, and almost no patients were treated outside the trial. Moreover, reimbursement of the treatment was conditional on participation in the trial. (more…)
Author Interviews, NEJM / 19.12.2014

natalie_walkerMedicalResearch.com Interview with: Natalie Walker, Ph.D. National Institute for Health Innovation School of Population Health, University of Auckland Auckland, New Zealand Medical Research: What is the background for this study? What are the main findings? Dr. Walker: Cytisine is a plant-based alkaloid and is structurally similar to nicotine.  It is found in various plants from the Legume Family (Fabaceae), the third largest plant family on earth.  Cytisine is currently manufactured by Sopharma Ltd, Bulgaria (Tabex®) and Aflofarm Pharma, Poland (Desmoxan®) as a smoking cessation treatment, with the cytisine used in the tablets taken from a plant called Golden Rain (Laburnum anagyroides).  Cytisine has been available with and without prescription for smoking cessation since the 1960s, largely in Eastern Europe.   Cytisine is not currently registered for use in any Western countries (although regulatory approval is currently been sought for the USA , UK and Japan).             We know from trial evidence that cytisine is better than a placebo for helping people quit smoking.  Cytisine is also one of the most affordable smoking cessation medicines available. It is much cheaper than nicotine patches, gum and/or lozenges and other smoking cessation medicine such as varenicline. This means smokers and governments are more likely to afford cytisine, especially those from low and middle income countries. However, we don’t know if cytisine is as good as nicotine patches and/or gum or lozenges, one of the most commonly used smoking cessation treatments in many western countries. We therefore undertook a pragmatic non-inferiority trial to answer this question, with recruitment of 1310 adult daily smokers who were motivated to quit, undertaken using the New Zealand national Quitline. Smokers were randomised to receive the standard 25 days of cytisine treatment or 8 weeks of nicotine patches and/or gum or lozenges.  Both groups received standard Quitline behavioural support.  Follow-up occurred at one week and one, two, and six months. At all time points, cytisine was found to be better at helping people quit smoking than nicotine patches and/or gum or lozenges.  This finding was consistent irrespective of ethnicity, age, alcohol consumption, degree of cigarette dependence or whether participants smoked factory-made cigarettes or roll-your-owns. For reasons unknown, cytisine helped more women quit smoking than nicotine patches, gum and/or lozenges.  For men the effectiveness of the two products was similar.  Cytisine use made people less likely to relapse back to smoking. Those who did smoke when using cytisine didn’t enjoy smoking as much, and reduced the number of cigarettes they smoked.  Self-reported, non-medically verified adverse events were more common in those that used cytisine. Three out of every 10 people who used cytisine reported an adverse event, compared to 2 out of every 10 that used nicotine patches, gum and/or lozenges.  However the majority of reported side effects were mild and self-limiting. More people in the cytisine group experienced nausea, vomiting and sleep disturbances (e.g. bad dreams). (more…)
Author Interviews, Breast Cancer, NEJM / 16.12.2014

Prudence A. Francis, M.D Associate Professor , Peter MacCallum Cancer Centre Melbourne, AustraliaMedicalResearch.com Interview with: Prudence A. Francis, M.D Associate Professor, Peter MacCallum Cancer Centre Melbourne, Australia Medical Research: What is the background for this study? What are the main findings? Response: The background for this study was the observation that premenopausal women diagnosed with hormone receptor positive breast cancer under age 35, had an increased risk of recurrence, as compared with older premenopausal women. We postulated that this might be because this age group was less likely to enter menopause after receiving chemotherapy, and so their ovaries were continuing to produce estrogen, which might have the effect of stimulating any remaining cancer cells. The main findings were that while not all premenopausal women benefit from the addition of treatment with ovarian function suppression to , the women who underwent chemotherapy and remained premenopausal (median age 40) did have improved breast cancer outcomes. This same group of women had even further improvement in recurrence rates if the ovarian suppression was combined with an aromatase inhibitor exemestane, as compared with tamoxifen. The effects of including ovarian suppression were particularly striking in women under 35 years of age. Those premenopausal women who did not receive chemotherapy (median age 46) after discussion with their doctor, did well with tamoxifen alone and do not appear to benefit from ovarian suppression currently. (more…)
Author Interviews, Brain Injury, NEJM / 13.12.2014

MedicalResearch.com Interview with: Dr. Brett E. Skolnick PhD Department of Neurosurgery Cushing Neuroscience Institute Hofstra North Shore–LIJ School of Medicine, Manhasset, NY Medical Research: What is the background for this study? What are the main findings? Dr. Skolnick: The experimental evidence for a role of progesterone is based on extensive non-clinical studies in non-primate species (4 animal species such as rat, mice) the majority of which indicate that progesterone has a variety of neuroprotective properties. The animal models of injury in traumatic brain injury (TBI) have included models of blunt trauma, fluid percussion injury, cortical aspiration but similar effects have been seen stroke models and models of spinal cord injury. In these experiments progesterone has been shown to reduce cerebral edema thus limiting the effects or preventing intracranial pressure increases which can lead to secondary injury. Progesterone has also been shown to exert anti-inflammatory, anti-apopotic and perhaps even anti-oxidant effects. All of these effect are postulated to work synergistically to prevent cell death which could result in improved functional outcomes. Two small single center clinical trials provided the support in traumatic brain injury patients that progesterone could have impact on functional outcomes in larger, properly powered trials.  The results of which are summarized in the NEJM article. In the current trial evaluated the Glasgow Outcome Scale and the extended version of the Glasgow Outcome scale at 6 months following injury. These scales are well validated scales that are used to determine the degree of recovery in terms of disability and handicap due to TBI rather than the degree of impairment. The GOS has 5 levels: death, vegetative state, severe disability, moderate disability and good recovery with death and vegetative state typically collapsed because they are considered equally undesirable. The Extended GOS takes the three best levels of recovery and subdivides these into a upper and lower category to increase the granularity of the outcome measure. Progesterone was administered within 8 hour of injury (loading dose followed by continuous infusions) for a total of 120 hours.  Careful assessments were performed to ensure optimal patient management during the trial to provide the best background to evaluate the impact of the addition of progesterone or placebo (1  to 1 randomization).  No effect was seen on the GOS or the extended GOS. In addition a fairly new approach of categorizing patients based on prognostic factors known at time of randomization (such as Age, baseline GCS, pupillary response, hypoxia, hypotension, Marshall Classification or presence/absence of subarachnoid hemorrhage) as developed by Hukkelhoven and colleagues was used. This was expected to tease out improvements, if they existed in subgroups of patients where perhaps progesterone could work better in the most severe or less severe traumatic brain injury patients. But again no effects were seen. The unfavorable outcomes (see NEJM paper for details) were essentially identical between progesterone and placebo groups whether they had the worst prognosis or the best prognosis. (more…)
Author Interviews, Genetic Research, NEJM, NIH / 13.12.2014

Dr. Constantine A. Stratakis, M.D., D.Sc National Institutes of Health, Clinical Research Center Bethesda, MD 20892-1862MedicalResearch.com Interview with: Dr. Constantine A. Stratakis, M.D., D.Sc National Institutes of Health, Clinical Research Center Bethesda, MD 20892-1862 Medical Research: What is the background for this study? What are the main findings? Dr. Stratakis: We have been working for years on the genetics of pituitary tumors in association with other conditions. A few years ago (attached), we studied for the first time a series of pediatric giants that we sequenced for then known genes. We found a few MEN1 and AIP mutations but all mutations were present in older kids with gigantism. This left out the youngest among the giants without any genetic defect. This was the first time I realized that I was dealing with a different disease. We started looking for additional genetic defects and when we found the Xq26 microduplications in 3 kindreds. We contacted the custodians of the largest series in the world - Dr. Beckers in Liege. He screened his cases, once we gave him the coordinates, and boom - it was there... The most significant thing here is that this is a new disease really: the early pediatric gigantism is almost exclusively due to Xq26 microduplications unless it is part of a family with another syndrome (AIP, MEN1, Carney complex). If there is no family history and you are dealing with a toddler with gigantism, based in these data, there is a more than 80% chance of having an Xq26 defect. This is pretty amazing! In addition, assuming that GPR101 is the responsible gene (which needs to be confirmed with additional studies) this identifies a new molecular pathway of increasing growth hormone secretion, most likely due to upregulation of GHRH - all of this needs to be confirmed in further human and animal studies. The Xq26 genomic micro-arrangements (which contain the GPR101, but also 3 other genes) is the big news here... (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, NEJM, Nutrition / 26.11.2014

MedicalResearch.com Interview with: Sheila E. Harvey, Ph.D. CTU Manager/Senior Research Fellow ICNARC Napier House London Medical Research: What is the background for this study? Dr. Harvey: The CALORIES trial was set-up in the context of concerns about malnutrition in critically ill patients in NHS hospitals and conflicting evidence as to the optimal route for delivery of early nutritional support to critically ill patients. The enteral route is the mainstay of nutritional support in the critically ill but it is frequently associated with gastrointestinal intolerance and underfeeding. In contrast, the parenteral route, though more invasive and expensive, is more likely to secure delivery of the intended nutrition but has been associated with more risks and complications (e.g. infectious complications) compared with the enteral route. In light of the uncertainty surrounding the most effective route for delivery of early nutritional support and, given recent improvements in the delivery, formulation and monitoring of parenteral nutrition, the UK National Institute of Health Research (NIHR) Health Technology Assessment (HTA) Programme put out a “call” for a large pragmatic randomised controlled trial to be conducted in critically ill patients to determine the optimal route of delivery of early nutritional support. CALORIES was set up to test the hypothesis that early nutritional support delivered via the parenteral route is superior to early nutritional support delivered via the enteral route in adults who had an unplanned admission to an intensive care unit and who could be fed via either route. The primary outcome was all-cause mortality at 30 days. The secondary outcomes included infectious and non-infectious complications (hypoglycaemia, elevated liver enzymes, nausea requiring treatment, abdominal distension, vomiting, new or substantially worsened pressure ulcers). (more…)
Author Interviews, Dartmouth, Lung Cancer, NEJM / 07.11.2014

William C. Black, MD Professor of Radiology Department of Radiology Dartmouth-Hitchcock Medical Center Lebanon, NH 03756MedicalResearch.com Interview with: William C. Black, MD Professor of Radiology Department of Radiology Dartmouth-Hitchcock Medical Center Lebanon, NH 03756 Medical Research: What is the background for this study? What are the main findings? Dr. Black: Lung cancer is the leading cause of cancer related death in the U.S., killing more people than cancers of the colon, breast, and prostate combined. In 2011, the National Lung Screening Trial (NLST) demonstrated that screening for lung cancer with low-dose CT could reduce lung cancer mortality by 20% in adults at high risk for the disease. Since then, several medical organizations have recommended that eligible adults be offered screening. The U.S. Preventive Services Task Force (USPSTF) released a grade B recommendation for low-dose CT screening in December 2012, which means that private insurers must cover the cost of screening by January 1, 2015. The Centers for Medicare and Medicaid (CMS) is expected to issue a final decision on national coverage for CT screening in February 2015 and a preliminary decision for public comment on November 10, 2014. (more…)
Author Interviews, NEJM, Rheumatology / 06.11.2014

Professor Paul Emery Arthritis Research UK Professor of Rheumatology Director - Leeds Musculoskeletal Biomedical Research Unit, LTHT Director – Leeds Institute of Rheumatic and Musculoskeletal Medicine University of LeedsMedicalResearch.com Interview Professor Paul Emery Arthritis Research UK Professor of Rheumatology Director - Leeds Musculoskeletal Biomedical Research Unit, LTHT Director – Leeds Institute of Rheumatic and Musculoskeletal Medicine University of Leeds Medical Research: What is the background for this study? What are the main findings? Professor Emery: Joint damage and functional disability are common in people who suffer from rheumatoid arthritis (RA), even in those with early disease. We know that early aggressive treatment with biologics, such as the anti-TNF agent etanercept, results in rapid remission in many patients with moderate-to-severe rheumatoid arthritis, which can help reduce the risk of joint destruction and disability long term. However, we don’t yet know whether remission achieved with biologic therapy can be maintained after doses are reduced or therapy is withdrawn. The PRIZE trial, a “state-of-the-art” biologic treatment trial conducted in adults with early untreated rheumatoid arthritis, was designed to fill this knowledge gap. The trial included three phases:
  • 1) induction therapy with full-dose combination etanercept-methotrexate therapy;
  • 2) maintenance therapy with a reduced-dose etanercept-methotrexate regimen, methotrexate alone, or no treatment; and
  • 3) complete treatment withdrawal. After clinical remission was induced, remission was shown to be effectively maintained with the reduced-dose combination regimen but not with the biologic-free regimens.Significantly more patients who had received the reduced-dose regimen were in remission after therapy was withdrawn than patients who received no therapy after remission induction. Interestingly, however, after remission was induced with the full-dose combination regimen, no substantial progression of joint damage on x-ray was seen in patients receiving the reduced-dose regimen, methotrexate only, or no treatment.
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Author Interviews, General Medicine, Leukemia, NEJM, Transplantation / 03.11.2014

John E. Wagner, M.D. Principal Investigator Professor Director, Division of Blood and Marrow Transplantation Department of Pediatrics McKnight Presidential Endowed Chair Hageboeck Family / Children's Cancer Research Fund Endowed Chair University of Minnesota Minneapolis, MN 55455MedicalResearch.com Interview with: John E. Wagner, M.D. Principal Investigator Professor Director, Division of Blood and Marrow Transplantation Department of Pediatrics McKnight Presidential Endowed Chair Hageboeck Family / Children's Cancer Research Fund Endowed Chair University of Minnesota Minneapolis, MN 55455 Medical Research: What is the background for this study? What are the main findings? Dr. Wagner: Earlier studies of umbilical cord blood transplantation (UCB) in children with hematological malignancies demonstrated a survival rate of approximately 50%.  While single UCB transplant was very effective despite HLA mismatch, few adults had access to umbilical cord blood as a treatment option due to the cell dose requirement of 2. 5 x 10^6 nucleated cells per kilogram recipient body weight.  For this reason, at the University of Minnesota we explored the co-transplantation of two partially HLA matched umbilical cord blood units in adults as a straightforward strategy to achieving the cell dose requirement.  Early results were remarkable with survival rates higher than that observed in children.  This in turn led to the design of the BMT CTN 0501 study, a randomized trial comparing single versus double umbilical cord blood transplantation in children aged 2-21 years with hematological malignancies.  All patients received a uniform conditioning regimen of fludarabine, cyclophosphamide and total body irradiation and GVHD prophylaxis of cyclosporine A and mycophenylate mofetil.  224 patients were randomized. There were four major findings:
  • 1) survival results overall, regardless of treatment arm, have improved,
  • 2) for children, an adequately dosed single umbilical cord blood unit is sufficient, giving a survival result of 72% at one year,
  • 3) double umbilical cord blood transplant is associated with more GVHD and poorer platelet recovery but survival is comparable to an adequately dosed single unit, and
  • 4) HLA mismatch is well tolerated with potentially better disease free survival in patients transplanted with HLA mismatched umbilical cord blood , a provocative finding that requires further investigation.
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Author Interviews, Colon Cancer, NEJM / 22.10.2014

Alfredo Falcone MD Chiara Cremolini Fotios Loupakis University of Pisa and Azienda-Ospedaliero Universitaria Pisana ItalyMedicalResearch.com Interview with: Alfredo Falcone MD Chiara Cremolini Fotios Loupakis University of Pisa and Azienda-Ospedaliero Universitaria Pisana Italy Medical Research: What are the main findings of the study? Dr. Falcone: In the TRIBE study the main findings are that the use of an initial more intensive therapy with a triplet of cytotoxics (FOLFOXIRI) plus bevacizumab vs a doublet (FOLFIRI) + bevacizumab improves the outcome of metastatic colorectal cancer patients with unresectable metastases. In particular FOLFOXIRI + bevacizumab vs FOLFIRI+bevacizumab improved RECIST response-rate (65% vs 53%, p=0.006), progression-free survival which was the primary endpoint (median 12,1 vs 9,7 months, HR=0,75, p=0.003) and overall survival (median 31,0 vs 25,8 months, HR=0.79, p=0.054). These results, also compared to those reported in previous phase III studies in molecularly unselected patients, represent an important advance in the treatment of this disease. (more…)
Author Interviews, Cost of Health Care, Emergency Care, NEJM, UCLA / 16.10.2014

Daniel A. Waxman, MD, PhD Department of Emergency Medicine David Geffen School of Medicine University of California, Los Angeles RAND Corporation Santa Monica, CaliforniaMedicalResearch.com Interview with: Daniel A. Waxman, MD, PhD Department of Emergency Medicine David Geffen School of Medicine University of California, Los Angeles RAND Corporation Santa Monica, California Medical Research: What are the main findings of the study? Dr. Waxman: About 10 years ago, three states (Texas, Georgia, and South Carolina) passed laws which made it much harder for doctors to be sued for malpractice related to emergency room care.   The goal of our research was to determine whether the lower risk of being sued translated into less costly care by emergency physicians.  To figure this out, we looked at the billing records of nearly 4 million Medicare patients and compared care before and after the laws took effect, and between states that passed reform and neighboring states that didn’t change their laws.   We found that these substantial legal protections didn’t cause ER doctors to admit fewer patients to the hospital, to order fewer CT or MRI scans, or to spend less for the overall ER visit. (more…)
Author Interviews, Infections, NEJM / 08.10.2014

Anders Perner, MD, PhD Overlæge / Senior staff specialist Professor / Professor in Intensive Care Dept of Intensive Care Rigshospitalet Copenhagen DenmarkMedicalResearch.com Interview with: Anders Perner, MD, PhD Overlæge / Senior staff specialist Professor / Professor in Intensive Care Dept of Intensive Care Rigshospitalet Copenhagen Denmark Medical Research: What are the main findings of the study? Dr. Perner: In the large international randomised trial, we showed similar outcomes in patients with septic shock with anemia transfused at a lower vs. a higher hemoglobin threshold. The lower threshold group received 50 % fewer transfusions and one-third of these patients were never transfused in ICU. (more…)
Author Interviews, NEJM, OBGYNE / 03.10.2014

Dr. Jeff Peipert MD, PhD Institute for Public Health Robert J. Terry Professor, Department of Obstetrics & Gynecology, School of Medicine Washington University in St. LouisMedicalResearch.com Interview with: Dr. Jeff Peipert MD, PhD Institute for Public Health Robert J. Terry Professor, Department of Obstetrics & Gynecology, School of Medicine Washington University in St. Louis Medical Research: What are the main findings of this study? Dr. Peipert: In the Contraceptive CHOICE Project, over 70% of teenage girls and women who were provided no-cost contraception and were educated about the effectiveness and benefits of long-acting reversible contraceptive (LARC) methods selected the intrauterine device (IUD) or contraceptive implant.  This group of over 1400 young women aged 15-19 years had rates of pregnancy, birth, and abortion that were far below national rates for sexually experienced teens. (more…)
Author Interviews, Melanoma, NEJM / 30.09.2014

Georgina Long BSc PhD MBBS FRACP Associate Professor of Melanoma Biology and Translational Research Melanoma Institute Australia and the University of Sydney MedicalResearch.com Interview with: Georgina Long BSc PhD MBBS FRACP Associate Professor of Melanoma Biology and Translational Research Melanoma Institute Australia and the University of Sydney Medical Research: Could you provide some background on this project? Why did you decide to do this research project? What prior work led up to this latest paper? Dr. Long: Pre-clinically, we had data that showed that the combination of BRAF inhibitor + MEK inhibitor
  • Decreased skin proliferative toxicity seen with BRAF inhibitors alone (seen as hyperproliferative lesions in rats)
  • and delayed the emergence of resistance I.e. The tumours in the mice reduced in size more, and stayed reduced for longer.We then confirmed this concept in a randomised phase 2 study, although it was not powered for a definitive progression free survival (PFS_ difference like a phase 3 trial is, we saw a strong difference in response rate and in PFS, yet there were only 54 patients per arm.
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Author Interviews, Kidney Stones, NEJM, Radiology, UCSF / 17.09.2014

Rebecca Smith-Bindman, MD Professor in the Departments of Radiology; Epidemiology and Biostatistics; and Obstetrics, Gynecology and Reproductive Medicine UCSF San Francisco Calif.MedicalResearch.com Interview with: Rebecca Smith-Bindman, MD Professor in the Departments of Radiology; Epidemiology and Biostatistics; and Obstetrics, Gynecology and Reproductive Medicine UCSF San Francisco Calif. Medical Research: What are the main findings of the study? Dr. Smith-Bindman: New technology is rapidly developed in medicine, and its important to understand how that technology should be used to improve patient health outcomes. Sometimes the technology is far better than existing technology and it should replace the earlier technology, and sometimes it is not and therefore should not be used. In this clinical scenario – I e. patients who present to an emergency department with abdomen or back pain thought to possibly reflect kidney stones, ultrasound is a simpler, less expensive , and more readily available test in the emergency department setting and therefore if it is equal to CT with respect to patient outcomes, it should be used as the first test in these patients. Currently, CT is the test widely used for patients with suspected kidney stones. We assessed a large number of patients with suspected kidney stones seen at one of 15 large academic emergency medicine departments across the country. Patients were assigned to point of care ultrasound performed by an ED physician, radiology ultrasound or radiology CT. We assessed a broad range of patient centered outcomes and found each of the three tests we studied were equivalent in terms of these outcomes including complications related to missed diagnoses, related serious adverse events, time spent in the emergency department and repeated ED visits and hospitalizations. However, the exposure to ionizing radiation was around half as high in patients who underwent ultrasound as their first test, and thus ultrasound should be used as the first imaging test in patients with suspected nephrolithiasis. (more…)
Author Interviews, Cancer Research, NEJM / 12.09.2014

MedicalResearch.com Interview with: Dr. Charles Mullighan, M.D., MBBS(Hons), MSc Department of Pathology St. Jude Children's Research Hospital Memphis, TN 38105 MedicalResearch: What are the most important take home points from this study for practicing clinicians and their patients? Dr. Mullighan: Acute lymphoblastic leukemia (ALL) remains a leading cause of cancer death in children, and the prognosis worsens with increasing age. Current therapies are inadequate for many patients. This study has defined the genetic basis of a recently described subtype of Acute lymphoblastic leukemia called Ph-like ALL. We show that the prevalence increases with rising age, and that in both children and young adults the disease is driven by a diverse range of genetic changes that activate kinase signaling, which fuels the growth of leukemia cells. Ph-like Acute lymphoblastic leukemia currently has a poor outcome. The activated kinases may be inhibited by currently approved tyrosine kinase inhibitors (TKIs). We have shown efficacy of these inhibitors in cell lines and experimental models, and in a series of patients with Ph-like Acute lymphoblastic leukemia treated with TKIs. (more…)
Author Interviews, Infections, NEJM / 08.09.2014

MedicalResearch.com Interview with: Stephen H. Gillespie, M.D., D.Sc University of St. Andrews Medical School, St. Andrews Stephen H. Gillespie, M.D., D.Sc University of St. Andrews Medical School, St. Andrews Medical Research: What are the main findings of the study? Dr. Gillespie: REMox TB was a pioneering trial that has shown that a large-scale trial can be run efficiently in resource-poor settings with a high TB burden, adhere to the highest standards of good clinical trial practices, and deliver a clear, unequivocal result. REMoxTB was among the most rigorous Tuberculosis drug trials ever conducted in the modern era of TB treatment and among the largest ever conducted for a new TB treatment. It enrolled 1,931 patients at 50 sites in nine countries, mostly in Africa and Asia. Previously, there were thought to be regional differences in way in which patients' response to treatment across the world but we showed that a rigorous approach to trial conduct there was no evidence for that difference. The study confirmed that daily moxifloxacin was safe over four months of therapy and the moxifloxacin containing arms were more bactericidal initially. Despite its substantial anti-TB activity it did not prove possible to shorten therapy to four months.  . These findings, with the safety of moxifloxacin, and its activity against TB, support the continued clinical testing of moxifloxacin as a component of other novel regimens. (more…)
Author Interviews, HIV, Infections, NEJM / 04.09.2014

Bongani M. Mayosi, M.B., Ch.B., D.Phil. Department of Medicine, Old Groote Schuur Hospital Cape Town, South AfricaMedicalResearch.com Interview with: Bongani M. Mayosi, M.B., Ch.B., D.Phil. Department of Medicine, Old Groote Schuur Hospital Cape Town, South Africa Medical Research: What are the main findings of this study? Dr. Mayosi: In those with definite or probable tuberculous pericardial effusion: (1)       Prednisolone for 6 weeks and Mycibacterium indicus pranii  for three months had no significant effect on the combined outcome of death from all causes, cardiac tamponade requiring pericardiocentesis or constrictive pericarditis. (2)      Both therapies were associated with an increased risk of HIV-associated malignancy. (3)       However, use of prednisolone reduced the incidence of constrictive pericarditis and hospitalization. (4)       The beneficial effects of prednisolone on constriction and hospitalization were similar in HIV-positive and HIV-negative patients (more…)
Author Interviews, Heart Disease, NEJM / 01.09.2014

Gilles Montalescot M.D., Ph.D. Professor of Cardiology University of Paris VI; Director, Cardiac Care Unit Institute of Cardiology, Pitié-Salpêtrière University Hospital Paris, FranceMedicalResearch.com Interview with: Gilles Montalescot M.D., Ph.D. Professor of Cardiology University of Paris VI; Director, Cardiac Care Unit Institute of Cardiology, Pitié-Salpêtrière University Hospital Paris, France Medical Research: What are the main findings of the study? Dr. Montalescot : Among the 1862 patients with ongoing STEMI who were enrolled in the ATLANTIC study, we found no difference between those randomized to pre-hospital (in-ambulance) ticagrelor 180 mg and those randomized to in-hospital (in-catheterization laboratory) ticagrelor 180 mg in terms of either pre-PCI ST-segment elevation resolution (≥70%) or pre-PCI TIMI 3 flow in the culprit artery, which were the co-primary endpoints. There was also no difference between the groups in terms of major adverse cardiovascular events at 30 days, with the exception that rates of definite stent thrombosis were lower in the pre-hospital ticagrelor group than in the in-hospital group, both in the first 24 hours (0% versus 0.8%, p= 0.008) and at 30 days (0.2% versus 1.2%, p = 0.02). The safety of pre-hospital ticagrelor did not appear to be an issue, since the incidence of non-CABG-related major bleeding was low and similar in both treatment groups, whichever bleeding definition was used (PLATO, TIMI, STEEPLE, GUSTO, ISTH or BARC). (more…)
Author Interviews, Heart Disease, NEJM / 30.08.2014

MedicalResearch.com Interview with: John J.V. McMurray, M.D Professor of Medical Cardiology British Heart Foundation, Cardiovascular Research Centre University of Glasgow, Glasgow, United Kingdom MedicalResearch.com Interview with: John J.V. McMurray, M.D Professor of Medical Cardiology British Heart Foundation, Cardiovascular Research Centre University of Glasgow, Glasgow, United Kingdom Medical Research: What are the main findings of the study? Dr. McMurray: That compared to an evidence-based dose of an evidence-based ACE inhibitor (enalapril 10 mg bid), LCZ696 reduced the primary composite outcome of cardiovascular death or heart failure hospitalization by 20%, both the components of that composite and all-cause mortality (the latter by 16%) - all reductions are highly statistically significant and clinically important. LCZ696 treated patients also reported fewer symptoms and physical limitations due to heart failure. We think this is a remarkable finding - to beat what has been the gold-standard, cornerstone, therapy for around 25 years. The findings show conclusively that adding neprilysin inhibition to renin-angiotensin system blockade is superior to renin-angiotensin system blockade alone in patients with heart failure and reduced ejection fraction . (more…)
Author Interviews, Infections, NEJM / 27.08.2014

MedicalResearch.com Interview with: Ziad A. Memish, M.D. Alfaisal University Riyadh Saudi Arabia Medical Research: What are the main findings of the study? Dr. Memish:  This is an important study as we looked at the secondary transmission of MERS-CoV among household/family contacts.  Of the total study population of 280 contacts from 26 clusters collected over 6 months period last year, only 12 family contacts were positive for MERS-CoV. Knowing that 7 (2.5%) were positive by PCR, only additional 5 probable secondary transmission were identified by serology which is a very small fraction missed by PCR. (more…)
Author Interviews, Genetic Research, Hematology, Johns Hopkins, NEJM / 27.08.2014

Jerry Spivak, M.D Professor of Medicine and Oncology Director, Center for the Chronic Myeloproliferative Disorders John Hopkins MedicineMedicalResearch.com Interview with: Jerry Spivak, M.D Professor of Medicine and Oncology Director, Center for the Chronic Myeloproliferative Disorders John Hopkins Medicine Medical Research: What are the main findings of the study? Dr. Spivak: The main findings of this study are that polycythemia vera occurs in two clinical forms: an indolent form in which only phlebotomy may be necessary and a more aggressive form requiring myelosuppressive therapy and that these two forms of the disease can be distinguished genetically. (more…)
Author Interviews, General Medicine, Infections, NEJM / 26.08.2014

Medical Research Interview with: Brian Dannemann, MD, FACP Senior Director, JNJ Pharmaceutical Research and Development Titusville, NJ 08560 MedicalResearch: What are the main findings of the study? Dr. Dannemann : The final investigational 120-week results from the TMC207-C208 Phase 2 study demonstrated that bedaquiline (SIRTURO®) showed nearly twice an many patients in the bedaquiline group as in the placebo group were cured on the basis of the World Health Organization (WHO) outcome definitions for Multidrug-Resistant Tuberculosis which was statistically significant (38 of 66 patients  [58%] and 21 of 66 patients [32%] respectively; p = 0.003). (more…)
Author Interviews, NEJM, Respiratory / 22.08.2014

John DeVincenzo, M.D. Professor of Pediatrics Division of Infectious Diseases Professor of Microbiology, Immunology and Biochemistry University of Tennessee School of Medicine. University of Tennessee. Medical Director, Molecular Diagnostics and Virology Laboratories Le Bonheur Children's Hospital Memphis, TennesseeMedicalResearch.com Interview with: John DeVincenzo, M.D. Professor of Pediatrics Division of Infectious Diseases Professor of Microbiology, Immunology and Biochemistry University of Tennessee School of Medicine. Le Bonheur Children's Hospital Memphis, Tennessee Medical Research: What are the main findings of the study? Dr. DeVincenzo: The main findings are
  • a) This is the first time that anyone has shown that the infection caused by the RSV virus can be effectively reduced in a human after the infection has already started.
  •  b) We also show for the first time that once we reduce the amount of virus in the patient, that very quickly, they start to feel better. This clinical improvement was not expected to occur so rapidly.
  • c) The antiviral appeared safe and it was easy to give.
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