Author Interviews, Genetic Research, NEJM, Ophthalmology / 05.05.2015

Professor James Bainbridge, MA, PhD, FRCOphthProfessor of Retinal Studies, UCL Institute of Ophthalmology NIHR Research Professor, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyMedicalResearch.com Interview with: Professor James Bainbridge, MA, PhD, FRCOphth Professor of Retinal Studies, UCL Institute of Ophthalmology NIHR Research Professor, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyConsultant Ophthalmologist, Moorfields Eye Hospital NHS Foundation Trust Medical Research: What is the background for this study? What are the main findings? Prof. Bainbridge : Leber Congenital Amaurosis (LCA) is one of the most common causes of inherited, untreatable blindness in children. There are at least 14 different types of Leber Congenital Amaurosis of which LCA Type 2 (LCA2), caused by defects in the gene RPE65, affects around one in 100,000 people worldwide. Evidence from animal studies support that LCA2 may be amenable to treatment with RPE65 gene replacement therapy. The main findings of this phase I/II clinical trial confirm our preliminary findings (published in NEJM, 2008) that gene therapy can improve night vision. Improvements peak within the first 12 months after treatment but then decline during the three-year follow-up period which is consistent with the published results and interim findings from other studies of RPE65 gene therapy. (more…)
Author Interviews, Cost of Health Care, NEJM, Ophthalmology, UCSF / 16.04.2015

Catherine L. Chen M.D., M.P.H. UCSF Dept of AnesthesiaMedicalResearch.com Interview with: Catherine L. Chen M.D., M.P.H. UCSF Dept of Anesthesia Medical Research: What is the background for this study? What are the main findings? Dr. Chen: Cataract surgery is a very common and safe surgery that most older adults have in their 70's or 80's. It usually happens as a same-day surgery and most patients only need eye drops to numb the eye with little or no intravenous sedation for a procedure that on average is only 18 minutes long. Given their age, these patients typically have other concurrent medical problems, so even though multiple research studies and professional societies have concluded that routine preoperative testing is not necessary before cataract surgery, we found that this testing still frequently occurs in these patients. More than half of the patients in our study had at least one preoperative test performed in the month before their surgery. We hypothesized prior to undertaking this study that the older and sicker patients were the ones who were most likely to get preoperative testing. Instead, what we found was that the most important factor that determined whether or not a patient got tested was the ophthalmologist who operated on the patient. This is an important finding because it shows that most patients are not getting extra testing, but the few that do are getting testing because that's the way their ophthalmologist typically prepares his patients for surgery. Most of the time, this testing is not needed and will not affect how well the patient does during and after surgery. (more…)
Author Interviews, CT Scanning, Duke, Heart Disease, NEJM / 02.04.2015

Pamela S. Douglas, M.D. Duke University School of Medicine Duke University Medical Center Durham, NC 27715MedicalResearch.com Interview with: Pamela S. Douglas, M.D. Duke University School of Medicine Duke University Medical Center Durham, NC 27715 Medical Research: What is the background for this study? Dr. Douglas: The primary objective of the PROMISE study was to compare the health outcomes of people who went to the doctor with new symptoms such as shortness of breath and/or chest pain that were suggestive of coronary artery disease and that required additional evaluation. This was an important investigation because no large research trial has ever been conducted to help guide the care of such patients. Instead, the selection of tests for such patients—which constitutes at least 4 million patients in the United States each year—has been largely left up to physician and patient preference rather than proven results. Medical Research: What are the main findings? Dr. Douglas: 10,003 patients from 193 different medical facilities across the US and Canada agreed to be part of the PROMISE study and  were randomized to a functional stress test or an anatomic test Using CT angiography.  The study found that the clinical outcomes of participants with suspected coronary artery disease were excellent overall, and were similar in terms of death and major cardiac conditions regardless of whether patients had a functional stress test or a computed tomographic scan. However, the CT scan may be better at ruling out the need for subsequent tests and procedures in patients who are free of heart disease, and involved a lower radiation exposure relative to a stress nuclear study. We also found, in a separately reported study, that the costs of the two diagnostic strategies were similar. (more…)
Antibiotic Resistance, Author Interviews, Infections, NEJM / 02.04.2015

Henri van Werkhoven PhD student | Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The NetherlandsMedicalResearch.com Interview with: Henri van Werkhoven PhD student and Douwe-PostmaDouwe Postma PhD student Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Community-acquired pneumonia is an important cause of hospitalization and death worldwide. Recommendations for antibiotic treatment in patients hospitalized to a non-ICU ward vary widely between guidelines, because the optimal antibiotic strategy is unknown. Interpretation of the available evidence from clinical studies is complicated by the heterogeneity in designs and findings. In our study, we hypothesized that the most conservative strategy, beta-lactam monotherapy, would be non-inferior to strategies with a broader range of antibiotic coverage. The latter strategies are potentially related to increased antibiotic resistance. For this purpose, we randomized hospitals to follow three different strategies of preferred antibiotic treatment in consecutive periods of four months. Physicians were allowed to deviate from the preferred antibiotic treatment for medical reasons. We found that a strategy with beta-lactam monotherapy (e.g. amoxicillin) as the preferred treatment was non-inferior to the strategies with beta-lactam/macrolide combination therapy or fluoroquinolone monotherapy for 30 and 90-day all-cause mortality. Also there was no difference in length of hospitalization and rate of complications. (more…)
Author Interviews, Heart Disease, NEJM, NYU, UCSD / 20.03.2015

Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI, Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group, The Leon H. Charney Division of Cardiology, Associate Professor of Medicine, New York University School of Medicine, New York, NY 10016.MedicalResearch.com Interview with: Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group, Associate Professor of Medicine, New York University School of Medicine, New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Bangalore: Prior studies have shown a mortality benefit of bypass surgery over stenting. But these studies compared bypass surgery with older generation stents which are no longer used. We used data from the New York state registry of patients who underwent stenting or bypass surgery for 2 or more blockages of coronary arteries. With data from over 18,000 patients we found that there was no difference between stenting and bypass surgery for long term mortality. In addition we found that both procedures have trade offs. Bypass surgery has upfront risk of death and stroke whereas PCI has long term risk of needing a repeat procedure. In addition, in patients who underwent incomplete revascularization, there was increase in myocardial infarction with PCI. (more…)
Author Interviews, MRSA, NEJM / 20.03.2015

 Loren G. Miller, M.D., M.P.H. Los Angeles Biomedical Research Institute (LA BioMed) Infectious Disease SpecialistMedicalResearch.com Interview with: Loren G. Miller, M.D., M.P.H. Los Angeles Biomedical Research Institute (LA BioMed) Infectious Disease Specialist   Medical Research: What is the background for this study? Dr. Miller: Skin and skin structure infections are extremely common reasons for persons to seek medical care in the U.S., accounting for approximately 14.2 million outpatient visits in 2005, the latest year for which statistics are available, and 850,000 hospital admissions. Until this study was completed, the most effective approach to outpatient antibiotic treatment of uncomplicated skin infections in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) was unclear. Prior to this research, there were no data on which antibiotics were best for treatment of these common skin infections. Medical Research: What are the main findings? Dr. Miller: Two antibiotics frequently prescribed to treat serious skin infections - clindamycin and trimethoprim sulfamethoxazole (TMP-SMX) - had similar rates of success in curing uncomplicated infections in outpatients. They also had similar rates of side effects. To conduct the study, we recruited outpatients from emergency departments, clinics and other healthcare facilities associated with Los Angeles County's Harbor-UCLA Medical Center, University of Chicago Medical Center, San Francisco General Hospital and Vanderbilt University Medical Center from May 2009 to August 2011. We studied 524 adults and children with uncomplicated skin infections who had cellulitis, abscesses of 5 centimeters or more or both. In the multicenter, double blind, randomized clinical trial, 264 received clindamycin and 260 received TMP-SMX. We followed the outpatients for a month after their treatment. We found similar outcomes for both groups - 80.3% of the outpatients who received clindamycin and 77.7% of the outpatients in the group that received TMP-SMX were cured within seven to 10 days after the end of their treatment. These are not considered significant differences, so our evaluation is that these two commonly prescribed antibiotics for serious skin infections are similarly effective in treating uncomplicated skin infections in children and adults who have few or no major co-existing conditions. (more…)
Author Interviews, Heart Disease, NEJM, Surgical Research / 15.03.2015

Barnaby C. Reeves, D.Phil. Professor of Health Services Research, Clinical Trials & Evaluation Unit School of Clinical Sciences, University of Bristol Bristol Royal Infirmary BristolMedicalResearch.com Interview with: Barnaby C. Reeves, D.Phil. Professor of Health Services Research, Clinical Trials & Evaluation Unit School of Clinical Sciences, University of Bristol Bristol Royal Infirmary Bristol Medical Research: What is the background for this study? Response: Variable decisions are made about when to transfuse patients after cardiac surgery. The circumstances of particular patients influence decisions about whether to give a transfusion. Transfusion is a life-saving intervention when a patient is experiencing life-threatening bleeding but most patients have only one or two units of red cells transfused. These transfusions are given at varying levels of anaemia. Some doctors prefer to give a transfusion after cardiac surgery when a patient is only mildly anaemic, believing that the transfusion will promote recovery, while other doctors prefer to wait to transfuse until a patient is substantially anaemic, believing that a transfusion may do more good than harm and is wasteful if it is not needed. Therefore, we carried out a randomized controlled trial comparing restrictive (transfuse when haemoglobin <7.5 g/dL) and liberal transfusion thresholds (transfuse when haemoglobin <9.0 g/dL).* Medical Research: What are the main findings? Response: We obtained written informed consent before surgery but only randomized participants after surgery, in intensive care, if their Hb dropped below 9 g/dL. (Hence, we recruited over 3,500 patients but randomized only 2007.) This design avoids ‘diluting’ any difference between groups by including participants who would not usually be ‘considered’ for transfusion. The primary outcome was the occurrence of one or more serious complications: heart attack, stroke, acute kidney injury, bowel infarction, infection; this included/involved 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group. This slight difference – more in the restrictive group – was not statistically significant. We then compared the percentages of patients who died; these were 4.2% in the restrictive group and 2.6% in the liberal group. The difference in this secondary outcome was of borderline statistical significance. Frequencies of other secondary outcomes (infections, ischaemic events, days in critical care and hospital, pulmonary complications) were not different in the two groups. We also carried out some pre-specified sensitivity analyses for the primary outcome and all-cause mortality. The two most important ones aimed to avoid dilution of the difference between groups as a result of patients having transfusions or outcome events before randomization. Excluding patients who were transfused before randomization shifted the treatment effect to favour the liberal threshold more strongly, for both the primary outcome and mortality. Excluding patients who experienced an outcome event in the first 24 hours after randomization did not change the treatment effect for either outcome. (more…)
Author Interviews, Breast Cancer, NEJM / 10.03.2015

Carla M. Pugh, M.D., Ph.D. FACS Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine and Public Health, Madison, WI MedicalResearch.com Interview with: Carla M. Pugh, M.D., Ph.D. FACS Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine and Public Health, Madison, WI Medical Research: What is the background for this study? What are the main findings? Dr. Pugh: The clinical breast examination is routinely performed on millions of women each year. It is used for screening breast cancer and is also routinely performed on women presenting with symptomatic breast conditions. In this study we assessed the performance of the clinical breast examination among a large sample of practicing physicians. There were two main goals to the study. The first goal was to identify current recommendations for performing the clinical breast examination and investigating how this relates to examination sensitivity or finding a mass. The second and more general goal was to develop a method for objective assessment of clinical skills. Novel clinical breast examination simulators were used in this study; in addition to their ability to present different pathologies and multiple clinical scenarios, they were all integrated with advanced force sensors. These sensors include approximately 2000 discrete sensing elements, measuring force level and distribution thought the breast examination. These sensors provide information at a level of detail that is not possible with observation alone. Four models were used in this study; two models presenting superficial soft masses and two models representing hard chest wall masses. The study was performed from 2013 to 2014 with 553 physicians performing the clinical breast examination on our models. The participants were recruited at three annual clinical meetings: 136 at the American Society of Breast Surgeons, 236 at the American Academy of Family Physicians, and 181 at the American College of Obstetricians and Gynecologists. The study found a significant relationship between the force used during palpation and the accuracy of the assessment of the deep-tissue lesions. More specifically, the study found that some physicians don’t apply enough force during the examination putting them at high risk of missing deep-tissue lesions. Since force can’t be measured by human observation this underscores the added value of integrating sensors into clinical simulators. (more…)
Author Interviews, NEJM / 07.03.2015

Michael D Hill, MD MSc FRCPC Calgary Stroke Program Professor, Dept Clinical Neurosciences Hotchkiss Brain Institute University of Calgary, Cumming School of Medicine Foothills Hospital, Calgary, CanadaMedicalResearch.com Interview with: Michael D Hill, MD MSc FRCPC Calgary Stroke Program Professor, Dept Clinical Neurosciences Hotchkiss Brain Institute University of Calgary, Cumming School of Medicine Foothills Hospital, Calgary, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Hill: Major ischemic stroke with blocked proximal arteries results in 60-80% death and disability.  Recent studies of endovascular treatment were neutral.  Evolution of technology has resulted in advances in the devices.  Key features of past trials of endovascular therapy were, underdeveloped imaging paradigms for patient selection, slow treatment times and poor reperfusion rates. Medical Research: What should clinicians and patients take away from your report? Dr. Hill: Simply, endovascular therapy for major ischemic stroke over and above best medical care (ie. IV tPA) is effective . It reduces disability and saves lives.  The NNT is very low 4, making it one of the largest proven effect sizes in all of medicine.  BUT, it applies only under selected conditions. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Cleveland Clinic, NEJM / 04.03.2015

Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195MedicalResearch.com Interview with: Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195 Medical Research: What is the background for this study? What are the main findings? Dr. Moore: Ovarian failure is a common long-term side effect of chemotherapy. Previous studies investigating whether suppressing ovarian function during chemotherapy treatment will preserve ovarian function following chemotherapy have had mixed results. Our study found that suppressing the ovaries with the GnRH analog goserelin during chemotherapy treatment for early stage ER-negative breast cancer resulted in a reduced risk of ovarian failure two years after initiation of treatment. Also, more women who received the goserelin with chemotherapy became pregnant than women who received chemotherapy without goserelin. In addition, there was an apparent improvement in survival among the goserelin group, confirming the safety of this approach in this patient population. (more…)
Author Interviews, Diabetes, Karolinski Institute, NEJM, OBGYNE, Weight Research / 27.02.2015

Kari Johansson, Phd Department of Medicine Solna, Karolinska Institutet Clinical Epidemiology Karolinska University Hospital Stockholm, SwedenMedicalResearch.com Interview with: Kari Johansson, PhD Department of Medicine Solna, Karolinska Institutet Clinical Epidemiology Karolinska University Hospital Stockholm, Sweden   MedicalResearch: What is the background for this study? What are the main findings? Dr. Johannson: The number of women who are obese in early pregnancy has increased dramatically over the last decades. Consequently, there has been a dramatic rise in the number of women becoming pregnant after bariatric surgery. In Sweden the number of births of women with a history of bariatric surgery has increased from 150 (≈0.15%) to more than 500 (0.5%) per year between 2006 and 2011. The positive effects of bariatric surgery on health outcomes, such as diabetes and cardiovascular disease, are reasonably well-studied, but less is known about the effects on pregnancy and perinatal outcomes. We therefore conducted a population-based study, using data from nationwide Swedish registers. The main findings are that women who had a history of bariatric surgery were much less likely to develop gestational diabetes (2% compared to 7%; P<0.001) and give birth to large-for-gestational age babies (9% vs 22%; P<0.001). On the other hand, the operated women were twice as likely to give birth to babies who were small for gestational age (16% vs 8%), and have pregnancies of shorter duration (273 vs 277.5; P<0.001).  (more…)
Author Interviews, CDC, NEJM, Pediatrics, Respiratory / 27.02.2015

Seema Jain, MD Medical Epidemiologist Epidemiology and Prevention Branch, Influenza Division Centers for Disease Control and Prevention Atlanta, GA 30329MedicalResearch.com Interview with: Seema Jain, MD Medical Epidemiologist Epidemiology and Prevention Branch, Influenza Division Centers for Disease Control and Prevention Atlanta, GA 30329 MedicalResearch: What is the background for this study? What are the main findings? Dr. Jain: Pneumonia is the leading cause of hospitalization among children in the United States with medical costs estimated at almost $1 billion in 2009.  The Centers for Disease Control and Prevention’s Etiology of Pneumonia in the Community (EPIC) study was a multi-center, active population-based surveillance study that aimed to estimate the incidence and etiology of community-acquired pneumonia requiring hospitalization in U.S. children.  Children in the study were enrolled from January 2010 to June 2012 in three U.S. children’s hospitals in Memphis, Nashville, and Salt Lake City. Study staff tested children using a range of laboratory tests for viral and bacterial respiratory pathogen detection. During the study period, the EPIC study team enrolled 2,638 children, of which 2,358 (89 percent) had radiographically-confirmed pneumonia. The median age of children in the study was 2 years old. Intensive care was required for 497 (21 percent) of the children, and three children died.  Among 2,222 children with radiographic pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 1802 (81%).  One or more viruses were detected in 1,472 (66%) of these children.  Bacteria were detected in 175 (8%), and bacterial and viral co-detection occurred in 155 (7%).  The study estimated that annual pneumonia incidence was 15.7/10,000 children during the study period.  The highest incidence was among children younger than 2 years old (62.2/10,000).  Respiratory syncytial virus (RSV) was the most common pathogen detected (28%), and it was associated with the highest incidence among children younger than 2 years old with pneumonia.  Human rhinovirus was detected in 22 percent of cases, but it was also identified in 17 percent of asymptomatic controls who were enrolled, by convenience sample, at the same site during the same time period; thus, making it challenging to interpret the meaning of human rhinovirus detection in children hospitalized with pneumonia.  Other detected pathogens were human metapneumovirus (13%), adenovirus (11%), Mycoplasma pneumoniae (8%), parainfluenza viruses (7%), influenza (7%), coronaviruses (5%), Streptococcus pneumoniae (4%), Staphylococcus aureus (1%), and Streptococcus pyogenes (<1%).  The low prevalence of bacterial detections likely reflects both the effectiveness of bacterial conjugate vaccines and suboptimal sensitivity of bacterial diagnostic tests. (more…)
Author Interviews, Breast Cancer, NEJM / 19.02.2015

  Swain_SandraMedicalResearch.com Interview with: Sandra M Swain, MD, FACP, FASCO Medical Director, Washington Cancer Institute MedStar Washington Hospital Center Washington DC 20010 MedicalResearch: What take-home message would you like the general public to understand about this new analysis from the Cleopatra study? Potential Key Message Options:
  • Updated results from the CLEOPATRA study showed that people treated with the combination of pertuzumab, trastuzumb and chemotherapy lived 15.7 months longer than those who received trastuzumab and chemotherapy alone (median survival of 56.5 months versus 40.8 months).
  • The survival improvement of nearly 16 months observed in CLEOPATRA is unprecedented among studies of metastatic breast cancer. This is the kind of survival improvement that those of us who treat breast cancer strive for, and this data will be incredibly meaningful to patients and their families.
  • Furthermore, the median survival of nearly five years observed in CLEOPATRA patients treated with the pertuzumab regimen is the longest ever observed in a clinical study of people with HER2-positive metastatic breast cancer, once one of the most aggressive forms of breast cancer.
  • Patients who responded with shrinkage of their tumor had a response that was 8 months longer with the pertuzumab regimen compared to the trastuzumab and chemotherapy regimen.
(more…)
Author Interviews, NEJM, Stroke / 12.02.2015

MedicalResearch.com Interview with: Dr Bruce Campbell MBBS(Hons), BMedSc, PhD, FRACP Consultant Neurologist, Head of Hyperacute Stroke Department of Neurology     Royal Melbourne Hospital NHMRC Early Career Research Fellow Melbourne Brain Centre @ RMH Department of Medicine University of Melbourne Australia MedicalResearch: What is the background for this study? What are the main findings? Dr. Campbell: EXTEND-IA was a randomised trial comparing standard thrombolysis with tPA plus endovascular stent-thrombectomy versus tPA alone in ischemic stroke patients selected for the presence of major vessel occlusion and salvageable brain tissue using CT perfusion imaging. It was designed in 2011 at a time when there was uncertainty about the effectiveness of endovascular therapy which deepened in 2013 with the publication of 3 neutral trials. The recent publication of the Dutch MR-CLEAN study showing improved outcomes with stent-thrombectomy was a major advance and prompted a data safety and monitoring committee review of the EXTEND-IA data leading to early termination of the trial for efficacy.
The key findings from EXTEND-IA were that the addition of stent-thrombectomy to tPA led to a dramatic increase in restoration of blood flow to the brain from 34% to 89%. This translated to markedly improved outcomes at 3 months with 71% of stent-thrombectomy patients compared with 40% of tPA-only patients regaining independence. The 3 trials released today were remarkably consistent in their outcomes and this provides a solid evidence base to recommend stent-thrombectomy as the new standard of care for patients with large vessel ischemic stroke.
Patients who were treated with stent-thrombectomy in EXTEND-IA had more than double the rate of reperfusion (restoration of blood flow to the brain) compared to the standard tPA patients and this translated to a 31% absolute increase in the proportion of patients living independently at 3 months. (more…)
HIV, Kidney Disease, NEJM, Transplantation / 11.02.2015

Elmi Muller, M.B., Ch.B., M.Med. University of Cape Town–Surgery Groote Schuur Hospital Observatory Cape Town Cape Town, South Africa MedicalResearch.com Interview with: Elmi Muller, M.B., Ch.B., M.Med. University of Cape Town–Surgery Groote Schuur Hospital Observatory Cape Town Cape Town, South Africa Medical Research: What is the background for this study? Dr. Muller: South Africa currently offers dialysis and transplantation as a treatment option for patients with End Stage Renal Disease (ESRD). However, dialysis is not freely available to everyone, but severely limited and only available to a selected group of patients. This means that patients get assessed when they present with ESRD and they only get accepted onto a dialysis programme if they fulfill certain criteria. These criteria are criteria to assess the patient’s medical fitness in general as well as social criteria to assess whether the patient will be compliant with follow-up.  In most state hospitals, patients will only be accepted onto a dialysis program if they are also fit to receive a transplant in the long run.  The idea is that dialysis programs should naturally feed into transplant programs. Therefore a patient who is not a suitable transplant candidate will normally be turned down for dialysis. In 2008, when the HIV positive-to-positive program started, patients with ESRD and HIV would be turned down for dialysis. The reason was that they were seen as unfit for transplantation and therefore not suitable dialysis patients. This meant that anybody with HIV and ESRD was doomed to die. This situation remained unchallenged for a number of years, especially as the rollout of antiretroviral therapy was quite slow in the state sector. Because of very high HIV rates in the country, more and more HIV positive brain-dead donors presented to the Groote Schuur Hospital Transplant team. These donors were mostly braindead people who were worked up for organ donation (after consent was obtained from the family) and who then turned out to be HIV positive. In 2008 it made sense to try and marry this supply of donors with the group of HIV positive patients without any treatment options in the country. (more…)
Author Interviews, Genetic Research, Leukemia, NEJM, Personalized Medicine / 11.02.2015

David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of CambridgeMedicalResearch.com Interview with: David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of Cambridge Medical Research: What is the background for this study? What are the main findings? Dr. Kent: Cancers are the result of the sequential acquisition of errors in the genetic code.  Most studies have focused on the sum of these mutations (e.g., A+B+C = cancer) but no study in patients has asked the question of whether or not the order of genetic mutations impacts the disease (e.g., does A to AB equal B to BA).  We studied patients with chronic blood disorders (known as myeloproliferative neoplasms, or MPNs) that are precursors to cancer to access the earliest stages of tumour development and studied whether or not the order of mutation acquisition impacted disease.  We studied patients with mutations in two genes (JAK2 and TET2) and showed that the order of acquisition of these mutations impacted timing of clinical presentation, disease subtype, frequency of thrombotic events, and differed in their response to targeted therapy in the lab. (more…)
Author Interviews, Cancer Research, NEJM, Thyroid / 11.02.2015

Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, FranceMedicalResearch.com Interview with: Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, France   Medical Research: What is the background for this study? What are the main findings? Dr. Schlumberger: Patients with advanced refractory thyroid cancer is rare (4-5 patients/million population) but portends a poor prognosis with a median overall survival of 3-5 years from the diagnosis of metastases. Before the availability of kinase inhibitors there was no effective treatment, and for this reason placebo was used as control in SELECT trial. This trial showed an improvement of PFS lenvatinib vs placebo (hazard ratio: 0.21; 99% CI: 0.14–0.31, P<0.001; median PFS: 18.3 vs 3.6 months, respectively) and objective response rate of 65% with some complete responses. Time to response was short (2 months). Similar benefits were observed in naive patients and in patients who had been treated with another tyrosine kinase inhibitor, demonstrating the absence of cross resistance. Toxicity was significant and could be controlled with dose reduction and symptomatic treatment. Medical Research: What should clinicians and patients take away from your report? (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, HIV, NEJM / 30.01.2015

Douglas B. Jacobs B.S., MD/MPH Candidate Harvard T.H. Chan School of Public HealthMedicalResearch.com Interview with: Douglas B. Jacobs B.S., MD/MPH Candidate Harvard T.H. Chan School of Public Health Medical Research: What is the background for this study? Response: In May 2014, a formal complaint submitted to the Department of Health and Human Services contended that four Florida insurers were structuring their formularies in a way that discouraged enrollment from HIV positive beneficiaries. These insurers placed all HIV drugs, including generics, on the highest cost-sharing tiers. This formal complaint served as the impetus for this research. We wanted to discover if this was a phenomenon that was isolated to Florida, or if it was national in scope, and what the implications would be for HIV positive beneficiaries. As such, we analyzed what we called “adverse tiering”—in which all drugs for certain conditions are placed in the highest cost sharing tiers—in 12 states in the federal marketplace. We compared cost-sharing for a commonly prescribed class of HIV medication, called Nucleoside Reverse Transcriptase Inhibitors, or NRTIs. (more…)
Author Interviews, Blood Pressure - Hypertension, Cost of Health Care, NEJM / 29.01.2015

Andrew Moran, MD, MPH Herbert Irving Assistant Professor of Medicine Columbia University Division of General Medicine Presbyterian Hospital 9th floor East room 105 New York, NY 10032MedicalResearch.com Interview with: Andrew Moran, MD, MPH Herbert Irving Assistant Professor of Medicine Columbia University Division of General Medicine Presbyterian Hospital  New York, NY 10032 Medical Research: What is the background for this study? What are the main findings? Response: In 2014, a panel appointed by the Eighth Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure (JNC 8) recommended new guidelines for high blood pressure (hypertension ) treatment in U.S. adults.  The guidelines made sweeping changes to the prior guidelines and stirred up controversy among hypertension and public health experts.  Essentially, the panel recommended more conservative treatment targets that narrowed the population eligible for treatment with blood pressure-lowering medications.  Nonetheless, about 28 million U.S. adults have uncontrolled hypertension even under the new more conservative guidelines.  We asked the question:  are the new guidelines cost-effective? That is, does treating this common condition with the available medicines add more health and reduce medical costs?  It is surprising that this question has rarely been answered before. (more…)
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 tamoxifen, 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…)