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Author Interviews, Brigham & Women's - Harvard, NEJM, Pediatrics, Weight Research / 30.11.2017

MedicalResearch.com Interview with: “Kovalam Beach - Obesity : a rising problem in India” by Miran Rijavec is licensed under CC BY 2.0Mr. Zachary Ward Center for Health Decision Science Harvard T.H. Chan School of Public Health Boston, MA 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although the current obesity epidemic in the US has been well documented in children and adults, less is known about the long-term risks of adult obesity for children given their current age and weight.  As part of the CHOICES project (Childhood Obesity Intervention Cost Effectiveness Study), we developed new methods to simulate height and weight trajectories across the life course based on individual-level data.  We also used a novel statistical approach to account for long-term population-level trends in weight gain, allowing us to make more realistic projections of obesity into the future.  (more…)
Author Interviews, Kidney Disease, Mayo Clinic, NEJM / 06.11.2017

MedicalResearch.com Interview with: Dr. TorresVicente E. Torres, M.D., Ph.D. Director of the Mayo Clinic Translational Polycystic Kidney Disease (PKD) Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Experimental work pioneered by Dr. Jared Grantham showed that cyclic AMP, an intracellular signaling molecule, promotes the development and growth of cysts. Vasopressin, a hormone produced by the pituitary gland, stimulates the production of cyclic AMP in the collecting ducts, from which most cysts derive in autosomal dominant polycystic kidney disease (ADPKD). While this effect of vasopressin is necessary for the kidneys to concentrate and reduce the volume of urine, it promotes the development and growth of cysts in patients with ADPKD. Dr. Vincent Gattone realized that inhibiting the action of vasopressin could be protective in polycystic kidney disease. Work in our and other laboratories confirmed that suppression of vasopressin production, release or action reduces cyst burden, protects kidney function, and prolongs survival in rodent models of the disease. This experimental work provided a strong rationale for clinical trials of tolvaptan, a vasopressin V2 receptor antagonist. Tolvaptan reduced the rate of kidney growth in the TEMPO 3:4 trial, in patients with early ADPKD. It also reduced the rate of decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), from 10.1 to 6.8 mL/min/1.73 m2 over three years. The eGFR benefit was maintained during two additional years when all the patients were treated with tolvaptan in an open label extension of the TEMPO 3:4 trial (TEMPO 4:4). Safety laboratory tests performed every four months showed elevations of liver transaminases in blood in 4.4% of tolvaptan and 1% of placebo-treated patients. Three of 1,271 tolvaptan-treated patients during TEMPO 3:4 and TEMPO 4:4 had evidence of potentially serious drug-induced liver injury. These abnormalities occurred all within the first 18 months of exposure to tolvaptan. Based on the TEMPO 3:4 results, tolvaptan was approved for the treatment of rapidly progressive ADPKD in Japan, Canada, European Union, Switzerland and South Korea. In the United States, the Food and Drug Administration requested additional data to further evaluate the efficacy and safety of this drug. The REPRISE trial was performed to determine the efficacy and safety of tolvaptan in patients with later stage ADPKD. (more…)
Author Interviews, Heart Disease, NEJM, UCLA / 05.11.2017

MedicalResearch.com Interview with: Bruno Péault PhD Professor and Chair, Vascular Regeneration Center For Cardiovascular Science MRC Centre for Regenerative Medicine Scientific Director, BHF Laboratories The University of Edinburgh and Professor, David Geffen School of Medicine at UCLA Orthopaedic Hospital Research Center University of California at Los Angeles Los Angeles, CA 90095-7358 MedicalResearch.com: What is the background for this study? Response: Kidney, lung, liver, muscle, heart are among the many organs which can be severely affected by fibrosis, a natural scarring process whereby healthy tissues are replaced by a fibrous non-functional substitute. For instance, the billions of cardiac muscle cells that die after a heart infarct, consequently to blood supply interruption, are replaced by a fibrotic scar that cannot contract, reducing the capacity of the heart to pump blood, and leading often to heart failure. There is currently no efficient treatment of fibrotic scars, the basic cellular component of which is the myofibroblast, a cell of unremarkable appearance and unclear origin. The transforming growth factor β (TGFβ) molecule triggers fibrosis development after being activated, via the extra-cellular matrix, by αv integrins, which are adhesion molecules present at the surface of the target cells. To gain further insight into the cells that drive fibrosis in the heart and skeletal muscle, and explore ways to control this deleterious process, mice were used in which cells expressing the β receptor for PDGF (platelet derived growth factor) have been genetically tagged with a green fluorescent protein, a system previously used by Prof. Neil Henderson to trace fibrosis in the diseased liver (cells naturally expressing PDGFRβ are, in their vast majority, perivascular cells surrounding small blood vessels, as well as some interstitial fibroblasts). Skeletal muscle was injured by a small incision or with a targeted injection of cardiotoxin, a snake venom compound that locally kills myofibers, while the heart was damaged by prolonged infusion of angiotensin II. In both settings, progression of fibrosis was followed over time and contribution of green fluorescent cells – i.e. those expressing PDGFRβ – was assessed. (more…)
Author Interviews, Diabetes, Lipids, NEJM / 01.11.2017

MedicalResearch.com Interview with: M. Loredana Marcovecchio, M.D. Clinical Scientist and Professor David Dunger M.D. Director of Research Professor of Paediatrics University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: The efficacy and safety of ACE Inhibitors and statins in adolescents have been shown in the context of hypertension and familial hypercholesterolemia, respectively. However, there is a lack of data on the long-term use of these drugs in those with type 1 diabetes and, in particular, there is no clear indication for their use in patients with increased albumin excretion. The Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) was a multi-centre, international study, set up by investigators in the UK, Australia and Canada to explore if drugs already used to lower blood pressure (ACE inhibitors) and cholesterol levels (Statins) in adults with diabetes could reduce the risk of kidney, eye and cardiovascular disease in adolescents with Type 1 diabetes. Neither ACE inhibitors nor statins significantly reduced the albumin-creatinine ratio during the 2-4 year trial period. However, some of the secondary outcomes suggest that the drugs may have important benefits. Treatment with the ACE inhibitor resulted in a 43% reduction in the rates of progression to microalbuminuria, which was not statistically significant, but it could have important clinical implications. Preventing even intermittent cases of microalbuminuria is known to reduce the future risk of kidney and cardiovascular complications. Statin therapy led to reduced levels of lipid levels, which could reduce long-term risk for cardiovascular complications. These findings could translate into long-term benefits, but follow-up of this unique cohort will be essential. The essential biological samples and data provided by the participants will continue to inform our future understanding and our options for effective therapies for this vulnerable group of young people with type 1 diabetes. (more…)
Author Interviews, Epilepsy, NEJM, Neurological Disorders, Pediatrics, Surgical Research / 25.10.2017

MedicalResearch.com Interview with: Dr. Manjari Tripathi Professor, Epileptology, Neurology Dr. P Sarat Chandra, Chief epilepsy Neurosurgeon AIIMS, New Delhi MedicalResearch.com: What is the background for this study?:
  1. Surgery for drug resistant epilepsy (DRE) is an accepted procedure for children and there have been multiple surgical series and surgical techniques published in literature. However, till date there are no randomized controlled trials (RCT) available to objectively demonstrate the safety and efficacy of surgical therapy in children with DRE. There are till date only 2 randomized trials for adult patients with drug resistant epilepsy (both for mesial temporal sclerosis only, Wiebe S et al, New Eng J Med, 2001 & Engel J et al, JAMA, 2012).
  2. Children constitute a significant proportion of patients undergoing surgical therapy for DRE (close to 50% in tertiary centers). They have unique problems associated due to uncontrolled epilepsy and some of these include epileptic encephalopathy and status epilepticus. In addition, surgery is also associated with problems like hypothermia, issues related to blood loss etc. Thus the senior author (Manjari Tripathi) and her team felt that a RCT would be very important to objectively assess the role of surgery and hence designed this study.
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Author Interviews, Exercise - Fitness, NEJM, Orthopedics / 04.10.2017

MedicalResearch.com Interview with: Monika Bayer PhD. Institute of Sports Medicine Copenhagen Bispebjerg Hospital Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Acute muscle strain injuries display a major clinical problem with a high incidence rate for both professional and amateur athletes and are associated with substantial risk for recurrence. Common clinical practice advices to follow the RICE (Rest – Ice – Compression – Elevation) principle after strain injuries but it has not been investigated whether patients really benefit from a period of rest or whether an early of loading following the injury would improve recovery. In this study, amateur athletes were divided into two groups: one group started rehabilitation two days after the trauma, the other group waited for one week and began rehabilitation after nine days. All athletes had a clear structural defect of the muscle-connective tissue unit following explosive movements. We found that protraction of rehabilitation onset caused a three-week delay in pain-free recovery. In all athletes included, only one suffered from a re-injury. (more…)
Author Interviews, Diabetes, NEJM, Surgical Research, Weight Research / 20.09.2017

MedicalResearch.com Interview with: Ted Adams PhD Adjunct Professor, Internal Medicine Adjunct Associate Professor, Nutrition & Integrative Physiology The University of Utah  MedicalResearch.com: Why did you decide to conduct this study? Response: The primary aim of the study was to determine the clinical outcomes in patients who underwent gastric bypass surgery. As NIDDK/NIH continued to fund the study, the aim was extended to determining the durability) long-term outcomes) of gastric bypass surgery when compared to non-surgical, severely obese patients. (more…)
Author Interviews, Boehringer Ingelheim, Columbia, Heart Disease, J&J-Janssen, Merck, NEJM / 14.09.2017

MedicalResearch.com Interview with: Professor Christopher P. Cannon MD Executive Director, Cardiometabolic Trials, Baim Institute Cardiologist Brigham and Women's Hospital Baim Institute for Clinical Research Columbia University College of Physicians and Surgeons MedicalResearch.com: What is the background for this study? What are the main findings? Response: The trial explored whether a dual therapy approach of anticoagulation and P2Y12 antagonist - without aspirin - in non-valvular atrial fibrillation (AF) patients following percutaneous coronary intervention (PCI) and stent placement would be as safe, and still efficacious, as the current standard treatment – triple therapy. For more detailed background on the study, readers may want to review the first paragraph of the article in the New England Journal of Medicine. Results showed significantly lower rates of major or clinically relevant non-major bleeding events for dual therapy with dabigatran, when compared to triple therapy with warfarin. In the study, the risk for the primary safety endpoint (time to major or clinically relevant non-major bleeding event) was 48 percent lower for dabigatran 110 mg dual therapy and 28 percent lower for dabigatran 150 mg dual therapy (relative difference), with similar rates of overall thromboembolic events. (more…)
Author Interviews, Infections, NEJM / 14.09.2017

MedicalResearch.com Interview with: Susan E. Dorman, M.D Associate Professor of Medicine, Division of Infectious Diseases Johns Hopkins University School of Medicine, Baltimore MedicalResearch.com: What is the background for this study? What are the main findings? Response: Tuberculosis, also called “TB” is one of the top 10 causes of death worldwide, according to the World Health Organization.  TB is caused by bacteria called Mycobacterium tuberculosis.  In 2015, over 10 million people became sick from TB and 1.8 million people died from TB.  This is a lot of people – diagnosing and treating TB to improve their health is important.  Because TB usually involves the lungs, it can be passed from person to person through the air, and thus, diagnosing and treating TB is critical to  reduce the spread of TB.   Drug-resistant TB -- TB caused by bacteria that are resistant to commonly used TB antibiotics -- is a serious problem.  In 2015 an estimated 480,000 people had multidrug-resistant TB. We have been working to develop better, faster ways to diagnose TB and drug-resistant TB.  A new test was developed as a partnership between Rutgers University and Cepheid (Sunnyvale, CA), and development was supported by the US National Institutes of Health (NIH).  The new test was designed to detect Mycobacterium tuberculosis bacteria in sputum, and to simultaneously detect whether the bacteria are resistant to several of the main antibiotics (isoniazid, fluoroquinolones, and aminoglycosides) used to treat TB.  The test takes about two hours from sample to result. The NEJM article describes the results of a study that was undertaken in China and South Korea to understand how well the new test works, compared against gold standard tests. (more…)
Author Interviews, Melanoma, NEJM / 14.09.2017

MedicalResearch.com Interview with: Dr Alexander Menzies BSc(Med) MBBS (Hons) FRACP PhD Medical Oncologist and Senior Research Fellow at Melanoma Institute Australia The University of Sydney and Royal North Shore and Mater Hospital  MedicalResearch.com: What is the background for this study? Response: For early-stage melanoma, surgical resection is the standard treatment and is associated with an excellent long-term prognosis. However until now, Stage III melanoma patients (where the disease has spread to the lymph nodes) who have had their tumours surgically removed have simply had to play the waiting game to see if their melanoma would metastasise, with many ultimately dying of the disease. Checkpoint inhibitor immunotherapies and drugs that target the mitogen-activated protein kinase (MAPK) pathway have improved the outcome of patients with metastatic melanoma, but their role as adjuvant therapy is still being actively investigated. Prior Phase III trials (COMBI-D and COMBI-V) have shown improved overall survival in patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. At Melanoma Institute Australia, we were keen to see if this improvement would be seen in the adjuvant setting also. This clinical trial was the first in the world to give targeted therapy to melanoma patients at an earlier stage of the disease to prevent spread and recurrence. (more…)
Author Interviews, Heart Disease, NEJM, Stroke, Surgical Research / 13.09.2017

MedicalResearch.com Interview with: Prof. Jean-Louis MAS Université Paris Descartes INSERM UMR S 894 Service de Neurologie et Unité Neurovasculaire Hôpital Sainte-Anne Paris  MedicalResearch.com: What is the background for this study? Response: Stroke is a major cause of death, disability and dementia affecting 17 million people each year worldwide. About 80% of strokes are ischemic strokes due to occlusion of a cerebral artery by a thrombus, itself the consequence of various arterial or heart diseases. In 30 to 40% of cases, no definite cause of ischemic stroke can be identified. Cryptogenic stroke is the term used to refer to these strokes of unknown etiology. The patent foramen ovale (PFO) is a defect between the upper two heart chambers (called atria) though which a thrombus of venous origin may reach the systemic circulation and cause a stroke. This mechanism is called paradoxical embolism. Several case-control studies have shown an association between PFO and cryptogenic ischemic stroke, particularly in patients less than 60 years old, in those who have an atrial septal aneurysm (defined as an abnormal protrusion of the interatrial septum in the right or the left atrium or both) in addition to a PFO, and in those who have a PFO with a large right-to-left shunt. These findings suggested that a PFO might be responsible for stroke and that PFO closure with a device may decrease the risk of stroke recurrence. However, the causative relationship between PFO and stroke and the best strategy to prevent stroke recurrence have long been a hot topic of debate. Three previous randomized clinical trials failed to demonstrate any superiority of PFO closure over antithrombotic therapy. (more…)
Author Interviews, NEJM, Pulmonary Disease / 10.09.2017

MedicalResearch.com Interview with: Dr Prof Nanshan Zhong, MD (Edin), FRCS (Edin), FRCP and Pixin Ran PhD National Center for Respiratory Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response:    According to the latest research, in 2015, 3.2 million people died from COPD globally, with an increase of 11.6% in mortality compared with that in 1990 (GBD 2015 Chronic Respiratory Disease Collaborators. Lancet Respir Med. 2017,5:691-706). COPD has now become the third leading cause of death worldwide and is estimated to become the disease with the seventh greatest burden worldwide in 2030. In China, the prevalence was 8.2% among people aged 40 years or greater, according to our epidemiological survey in 2007. Importantly, current international guidelines have been mainly focusing on the management of moderate-to-severe COPD. However, among this patient cohort, the severely impaired lung function can only be reversed to a very limited extent despite the most potent treatment combinations. Patients with more advanced COPD are frequently associated with a significantly higher mortality and incidence of re-hospitalization and disability, which cause tremendous economic burden for both the families and the society. However, more than 70% of COPD patients are currently categorized as having stage I to early stage II COPD, most of whom have no or very few respiratory symptoms (Zhong NS, et al. Am J Respir Crit Care Med. 2007, 176:753-760; Mapel DW, et al. Int J COPD 2011; 6: 573−581). The vast majority of these patients would have the “COPD assessment Test” (CAT) score of 10 or lower (range: 0 to 40, with higher scores indicating more severe COPD). Admittedly, no medication has been recommended for this patient cohort according to the latest international guidelines. In real-world practice, these patients are almost neglected by physicians and have received virtually no medication. Nonetheless, the annual lung function decline rates among these patients are the most rapid among all COPD patients. (Bhatt SP, et al. Am J Respir Crit Care Med 2015; 191: A2433). An important clinical question has been raised regarding whether an intervention strategy targeting at early stages of COPD can possibly make the airflow limitation more reversible or prevent from further deterioration. (more…)
Author Interviews, Blood Pressure - Hypertension, NEJM / 23.08.2017

MedicalResearch.com Interview with: Dan Berlowitz, MD, MPH Investigator, CHOIR Chief of Staff, Edith Nourse Rogers Memorial VA Hospital Professor, Boston University Schools of Public Health and Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: The main results from the SPRINT study, published in 2015, demonstrated that intensive hypertension therapy targeting a systolic blood pressure (SBP) of 120 mm Hg results in reduced cardiovascular morbidity and mortality when compared to standard therapy targeting a SBP of 140. Yet many have expressed concerns that lowering SBP to 120 may be associated with a variety of symptoms, including dizziness, fatigue, and depression, especially in older and frailer patients. This study using SPRINT data examined patient-reported outcomes including health-related quality of life, depressive symptoms, and satisfaction. The main findings are that there were no differences in patient-reported outcomes among patients receiving intensive therapy compared to standard therapy, even among older SPRINT participants with multiple comorbidities. (more…)
Author Interviews, Heart Disease, NEJM, Surgical Research / 16.08.2017

MedicalResearch.com Interview with: A. Laurie Shroyer, Ph.D., M.S.H.A. WOC Health Science Officer Northport VAMC Research and Development Office (151) Northport, NY 11768 Professor and Vice Chair for Research, Department of Surgery Stony Brook University, School of Medicine Stony Brook, NY  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Since the 1990’s, two different approaches have been commonly used by cardiac surgeons to perform an adult coronary artery bypass graft (CABG) procedure, these approaches have been referred to as  “on-pump” (with cardiopulmonary bypass) or “off-pump” (without cardiopulmonary bypass) procedures. The Department of Veterans Affairs (VA) Randomized On/Off Bypass Follow-up Study” (ROOBY-FS) compared the relative performance of off-pump versus on-pump approaches upon 5-year patients’ clinical outcomes including mortality and major adverse cardiovascular events. (more…)
Author Interviews, Flu - Influenza, Kaiser Permanente, Merck, NEJM, Vaccine Studies / 10.08.2017

MedicalResearch.com Interview with: Michael Jackson  PhD, MPH Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network  MedicalResearch.com: What is the background for this study?
  • Response: Each year, Kaiser Permanente Washington is one of five sites across the country that participate in the United States Influenza Vaccine Effectiveness Network. The Network reports its early interim results in the MMWRand presents additional interim results to the Advisory Committee on Immunization Practices (ACIP). This New England Journal of Medicine publication is an update of those interim results.
  • The findings in this New England Journal of Medicine are special because prior randomized controlled trials indicated that the nasal spray vaccine (FluMist)—also called live attenuated influenza vaccine (LAIV)—would work well to protect children and teens from the flu, whereas in actual practice we found that the flu shot worked much better, particularly against the predominant strain, A(H1N1)pdm09.
  • The nasal spray vaccine was first seen to be less effective for young children than the flu shot in 2013-2014 for the A(H1N1)pdm09 virus strain. In response, the A(H1N1)pdm09 virus strain used in the nasal spray vaccine was changed for the 2015-2016 influenza season. The 2016/17 season was the first since 2015-2016 to be dominated by the A(H1N1)pdm09 virus, making this our first opportunity to evaluate the updated nasal spray vaccine.
  • The Influenza Vaccine Effectiveness Network evaluated the impact of this change as part of our estimates of influenza vaccine effectiveness in 2015-2016. Preliminary findings from this study were presented to the ACIP in June 2016, which led to the nasal spray vaccine not being recommended in 2016-2017 in the US, although the nasal spray vaccine remains licensed in the US. In 2016-2017, the LAIV A(H1N1)pdm09 vaccine strain was unchanged from 2015-2016.
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Author Interviews, Kidney Disease, NEJM, Transplantation / 04.08.2017

MedicalResearch.com Interview with: Stanley C. Jordan, M.D Director, Division of Nephrology Medical Director, Kidney Transplant Program Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory Cedars-Sinai, Los Angeles, CA  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background for this study is as follows: Patients who are highly HLA sensitized have antibodies to transplant targets create an immunologic barrier to transplant. Currently, there are no approved therapies for elimination of these antibodies. Desensitization is available but is not always successful and most desensitized patients are still transplanted with a positive crossmatch. Thus, many patients are not able to receive life-saving kidney transplants unless newer therapies to remove antibodies are found. The findings of our study published in the New England Journal of Medicine revealed that the use of the enzyme from streptococcal pyogenes called IdeS® (IgG endopeptidase) is very effective in eliminating donor specific antibodies and allowing transplantation to occur. Antibodies were eliminated from one week up to two months after one treatment with Ides® allowing a safe environment for the transplant to occur. Rejections episodes did occur in some of the patients but were generally mild and easily treatable. Only one patient of 25 lost his allograft during the study. Thus, the study shows promising results for a new approach for elimination of pathogenic antibodies that did not exist before. (more…)
Author Interviews, Brigham & Women's - Harvard, Lifestyle & Health, NEJM, Nutrition / 13.07.2017

MedicalResearch.com Interview with: Mercedes Sotos Prieto PhD Research Fellow Department of Nutrition Harvard T. H. Chan School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous research have found that adherence to the 2010 Alternate Heathy Eating Index, the Mediterranean Diet pattern, and DASH pattern is associated with health benefits, but none of those studies have examined dynamic changes in diet quality over time and subsequent risk of mortality. This is the first study to demonstrate that improvement in these three diet scores over time is associated with reduced risk of total and cardiovascular mortality. In contrast, worsening diet quality over 12-years was associated with 6%-12% increased mortality. In addition, not only improvement in diet quality but maintaining a high adherence to any of the three dietary patterns over 12 years was significantly associated with 9%-14% lower total mortality. (more…)
Author Interviews, NEJM, Prostate Cancer / 13.07.2017

MedicalResearch.com Interview with: Dr. Timothy Wilt, MD MPH Core Investigator: Minneapolis VA Center for Chronic Disease Outcomes Research Staff Physician: Section of General Internal Medicine, Minneapolis VA Health Care System Professor: Medicine, University of Minnesota School of Medicine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer is common and potentially serious. However, the comparative benefits and harms of surgery versus observation in men with localized prostate cancer are not known. After nearly 20 years, surgery did not significantly reduce all-cause or prostate cancer mortality compared to observation, particularly in men with low risk disease. Surgery was associated with more harms than observation, causing complications within 30 days in about 20% of men and large long term increases in urinary incontinence, sexual dysfunction and dissatisfaction, as well as treatment related bother and reductions in daily functioning. (more…)
Author Interviews, Brigham & Women's - Harvard, Environmental Risks, NEJM, Race/Ethnic Diversity / 29.06.2017

MedicalResearch.com Interview with: Qian Di, M.S, Doctoral Student Department of Environmental Health and Francesca Dominici, Ph.D. Principal Investigator of this study Professor of Biostatistics co-Director of the Harvard Data Science Initiative Harvard T.H. Chan School of Public Health Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Clean Air Act requires Environmental Protection Agency to set National Ambient Air Quality Standard (NAAQS). Currently the annual NAAQS for PM2.5 is 12 microgram per cubic meter; and there is no annual or seasonal ozone standard. However, is current air quality standard stringent enough to protect human health? This is our main motivation. We conducted the largest attainable cohort study, including over 60 million Medicare participants, to investigate the association between long-term exposure to ozone/PM2.5 and all-cause mortality. We found significant harmful effect of PM2.5 even below current NAAQS. Each 10 microgram per cubic meter increase in PM2.5 is associated with 13.6% (95% CI: 13.1%~14.1%) increase in all-cause mortality. For ozone, 10 ppb increase in ozone exposure is associated with 1.1% (95% CI: 1.0%~1.2%) increase in mortality. Also, there is no appreciable level below which mortality risk tapered off. In other words, there is no “safe” level for PM2.5 and ozone. In other words, if we would reduce the annual average of PM2.5 by just 1 microgram per cubic meter nationwide, we should save 12,000 lives among elder Americans every year; 5 microgram --- 63,817 lives every year. Similarly, if we would reduce the annual summer average of ozone by just 1 ppb nationwide, we would save 1,900 lives every year; 5 ppb --- 9537 lives. Besides, we found black people, males and people of low SES are more vulnerable to air pollution. (more…)
Author Interviews, Flu - Influenza, NEJM, Vaccine Studies / 22.06.2017

MedicalResearch.com Interview with: Lisa M. Dunkle, M.D. Chief Medical Officer Protein Sciences Corporation 1000 Research Parkway Meriden, CT MedicalResearch.com: What is the background for this study? What are the main findings? Response: The first and only recombinant protein influenza vaccine (RIV, Flublok) was approved in 2013 as a trivalent formulation for use in adults 18 years of age and older. This approval was based on demonstration of clinical efficacy (full approval) in adults 18-49 years of age and accelerated approval was granted for adults 50 years of age and older. Two clinical trials were conducted in 2014-2015 with RIV4 (Flublok Quadrivalent), of which the trial reported in the current NEJM is one. These studies supported full approval of Flublok in adults 50 years of age and older and approval of Flublok Quadrivalent in all adults 18 years of age and older. The second trial of immunogenicity of Flublok Quadrivalent in adults 18-49 years of age will be the subject of another publication in the near future. The main findings of the current trial are well summarized in the Conclusion of the Abstract: “RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness in older adults.” Additionally, the recombinant vaccine (RIV4, Flublok Quadrivalent) demonstrated significantly less injection site pain and tenderness following vaccination. Based on the characteristics of the study participants, one can conclude that RIV4 is safe and effective in most individuals with underlying chronic diseases (more…)
Author Interviews, NEJM, Stroke / 22.06.2017

MedicalResearch.com Interview with: Craig Anderson | MD PhD FRACP Executive Director Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney Neurologist, Neurology Department, Royal Prince Alfred Hospital The George Institute for Global Health at Peking University Health Science Center Haidian District | Beijing, 100088 P.R. China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Preliminary small studies indicate that lying flat increases blood flow and oxygenation to the brain.  Thus, patients with acute ischemic stroke may benefit from lying flat in bed.  Conversely, sitting up in bed, with the head elevated to at least 30 degrees, may reduce swelling in the brain for patients who have large ischemic or hemorrhagic forms of stroke.  The optimal head position to produce the best outcome from acute stroke, and avoid potential risks, such as aspiration pneumonia, is unknown.  We undertook a large scale multicentre randomized controlled trial where 114 hospitals were randomised to sequentially apply lying flat or sitting up head positioning as a policy of care to a consecutive series of patients, that overall totalled over 11000 patients, presenting with acute stroke.  The study showed there was no difference in the chance of good physical recovery for patients between the two head positions but also that there were no excessive harms for either. In other words, head positioning alone didn’t produce any benefits or harms in patients with acute stroke (more…)
Author Interviews, Brigham & Women's - Harvard, NEJM, Ophthalmology / 08.06.2017

MedicalResearch.com Interview with: Elisabetta Patorno, MD, DrPH Assistant Professor of Medicine, Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital MedicalResearch.com: What is the background for this study? Response: Lithium, a widely used medicine to treat bipolar disorder, has been associated with a 400 fold increased risk of Ebstein’s anomaly, a congenital malformation of the heart, and a 5 fold increased risk of cardiac defects overall in infants when taken early in pregnancy, based on the results from the International Register of Lithium Babies in the 1970’s. Beyond this data, most of the information on the safety of lithium during pregnancy accumulated in the last 40 years is based on case reports and small studies with conflicting results. Despite these concerns and the limited information, lithium remains a first-line treatment for the 1% of women of reproductive age with bipolar disorder in the U.S. population, due to its recognized efficacy during pregnancy and the postpartum period, and due to the presence of a larger body of evidence showing increased risk of congenital malformations for other mood stabilizers, such as valproate. (more…)
Author Interviews, Hepatitis - Liver Disease, NEJM / 31.05.2017

MedicalResearch.com Interview with: Dr Marc Bourlière Professeur Associé CHP (Associate Professor PHC) Chef de service (Head of Department) Hôpital Saint Joseph Hépato-Gastroentérologie MedicalResearch.com: What is the background for this study? What are the main findings? Response: The majority of HCV patients can be cured with combinations of direct-acting antivirals (DAAs); however, there is still 5 to 10% of patients who relapse after treatment with DAAs for whom there are currently no approved therapeutic options available. In these two international phase 3 studies, we have demonstrated that a single tablet triple regimen combining sofosbuvir, velpastasvir and voxilaprevir (a pangenotypic protease inhibitor) for 12 weeks cured 96% of the patients who had relapsed following prior treatment with DAA regimens including NS5A inhibitors and 98% of the patients who had relapsed following prior treatment with DAA regimens without an NS5A inhibitor. These two studies demonstrate that a pangenotypic retreatment option for this patient population could be soon available. (more…)
Author Interviews, Blood Pressure - Hypertension, Cleveland Clinic, Critical Care - Intensive Care - ICUs, Infections, NEJM / 22.05.2017

MedicalResearch.com Interview with: Ashish Khanna, MD, FCCP Assistant Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine Staff Intensivist Center for Critical Care and Department of Outcomes Research Cleveland Clinic, Cleveland MedicalResearch.com: How did you become interested in this topic? Response: Anesthesia forms the basis of my training but I also completed a fellowship in critical care and, at the present time, I do more work in critical care than anesthesia. About 75% of my time is spent in the Cleveland Clinic critical care units, including the Medical and surgical ICUs (Intensive Care Units). (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Emergency Care, Infections, NEJM, University of Pittsburgh / 21.05.2017

MedicalResearch.com Interview with: Christopher W. Seymour, M.D., M.Sc. Assistant professor of Critical Care Medicine and Emergency Medicine, and member of Clinical Research Investigation and Systems Modeling of Acute Illness University of Pittsburgh MedicalResearch.com: What is the background for this study? What are the main findings? Response: Following the tragic and widely publicized death of Rory Staunton, 12, from undiagnosed sepsis in 2012, New York became the first state to require that hospitals follow a protocol to quickly identify and treat the condition. The mandate led to widespread controversy in the medical community as to whether such steps would have saved Rory or anyone else’s life. Rory’s Regulations require hospitals to follow protocols for early identification and treatment of sepsis, and submit data on compliance and outcomes. The hospitals can tailor how they implement the protocols, but must include a blood culture to test for infection, measurement of blood lactate (a sign of tissue stress) and administration of antibiotics within three hours of diagnosis—collectively known as the “three-hour bundle.” We analyzed data from nearly 50,000 patients from 149 New York hospitals to scientifically determine if  Rory’s Regulations worked. We found that they did - 83 percent of the hospitals completed the bundle within the required three hours, overall averaging 1.3 hours for completion. For every hour that it took clinicians to complete the bundle, the odds of the patient dying increased by 4 percent. (more…)
Author Interviews, NEJM, OBGYNE, Yale / 21.05.2017

MedicalResearch.com Interview with: Hugh S. Taylor, M.D. Anitta O’keeffe Young Professor and Chair Departemnt of Obstetrics, Gynecology and Reproductive Sciences Yale School of Medicine Chief of Obstetrics and Gynecology Yale-New Haven Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Elagolix is an investigational, oral gonadotropin-releasing hormone (GnRH) receptor antagonist that blocks endogenous GnRH signaling by binding competitively to GnRH receptors. Administration results in rapid, reversible, dose-dependent inhibition of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, leading to reduced ovarian production of the sex hormones, estradiol and progesterone, while on therapy. Data from two replicate Phase 3 studies evaluating the efficacy and safety of elagolix were published in the New England Journal of Medicine. Elagolix demonstrated dose-dependent superiority in reducing daily menstrual and non-menstrual pelvic pain associated with endometriosis compared to placebo. At month three and month six, patients treated with elagolix reported statistically significant reductions in scores for menstrual pain (dysmenorrhea, DYS) and non-menstrual pelvic pain (NMPP) associated with endometriosis as measured by the Daily Assessment of Endometriosis Pain scale. The safety profile of elagolix was consistent across both Phase 3 trials and also consistent with prior elagolix studies. Ultimately, the studies showed that both elagolix doses (150 mg QD and 200 mg BID) were effective in improving dysmenorrhea, non-menstrual pelvic pain and quality of life over 6 months in women with endometriosis-associated pain. The elagolix safety/tolerability profile was consistent with the mechanism of action. (more…)
Author Interviews, Exercise - Fitness, Geriatrics, NEJM, Weight Research / 17.05.2017

MedicalResearch.com Interview with: Dennis T. Villareal, MD Professor of Medicine Division of Endocrinology, Diabetes & Metabolism Baylor College of Medicine Staff Physician, Michael E DeBakey VA Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The prevalence of obesity in the elderly is rapidly increasing, given that the baby boomers are becoming senior citizens, but we do not know how best to manage obesity in the elderly population. Weight loss is the cornerstone of management for obesity but weight loss in the elderly is controversial because weight loss could cause not only fat loss but also muscle mass and bone mass losses, that could worsen rather than improve frailty. We tested the hypothesis that weight loss plus exercise training, especially resistance training, would improve physical function the most compared to other types of exercise (aerobic training or combined aerobic and resistance training added to diet-induced weight loss). Previous studies especially in younger adults have shown that combining aerobic with resistance exercise could lead to interference to the specific adaptations to each exercise, and thus less gain in strength with combined exercise compared to resistance training alone. On the other hand, contrary to our hypothesis, we found that there was no interference between aerobic and resistance exercise, and the most effective mode to improve physical function and thus reverse frailty was in fact weight loss plus the combination of aerobic and resistance exercise, which was also associated with some preservation of muscle and bone mass. (more…)
Author Interviews, Heart Disease, NEJM / 05.05.2017

MedicalResearch.com Interview with: Kristian Kragholm, MD, PhD Departments of Cardiology and Epidemiology/Biostatistics, Aalborg University Hospital, Aalborg, DK MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is well known that early help from bystanders including cardiopulmonary resuscitation (CPR) before arrival of the emergency medical services can increase chances of 30-day survival by three to four times compared to situations where no bystander resuscitation was initiated. The main and novel finding of our study is that bystander interventions, in addition to increasing survival, also lowers the risk of damage to the brain and nursing home admission in 30-day survivors during the first year following out-of-hospital cardiac arrest. (more…)
Author Interviews, Gastrointestinal Disease, Immunotherapy, NEJM, UCSD / 04.05.2017

MedicalResearch.com Interview with: William J. Sandborn, MD Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Vice Chair for Clinical Operations, Department of Medicine Director, UCSD IBD Center University of California San Diego and UC San Diego Health System MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is still a substantial unmet need for new treatments for patients with ulcerative colitis. A previous Phase II study had suggested that tofacitinib might be effective for short term therapy of ulcerative colitis. The patients in that study for the most part had not failed anti-TNF therapy. Now we report the findings from 3 large Phase III trials, two short term trials and one long term trial, demonstrating that tofacitinib 10 mg twice daily is effective for short term therapy, and that both 5 mg and 10 mg twice daily is effective for long term therapy. We also demonstrated that tofacitinib is effective both in patients who have not failed anti-TNF therapy and patients who have failed anti-TNF therapy. The study demonstrated induction of clinical remission, clinical response and mucosal healing (flexible sigmoidoscopy improvement) over the short term, and maintenance of clinical remission, clinical response, and mucosal healing over the long term. (more…)
Author Interviews, Diabetes, NEJM, Ophthalmology, Personalized Medicine / 20.04.2017

MedicalResearch.com Interview with: John M. Lachin, Sc.D. Research Professor of Biostatistics and of Epidemiology, and of Statistics The George Washington University Biostatistics Center and David Matthew Nathan, M.D. Professor of Medicine, Diabetes Unit Massachusetts General Hospital  MedicalResearch.com: What is the background for this study? Response: Traditional guidelines for screening for retinopathy, based on indirect evidence, call for annual examinations. The automatic annual screening for retinopathy, without considering potential risk factors for progression,  appears excessive based on the slow rate of progression through sub-clinical states of retinopathy. (more…)