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.
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.
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.
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.
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.
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). 
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.
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.
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.
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.
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.
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?
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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...
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).
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.
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.
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.