Multiple Myeloma: Phase 3 Study of DARZALEX + VMP Reduced Risk of Disease Progression and Mortality

MedicalResearch.com Interview with:

Dr. Meletios A. Dimopoulos MD Professor and Chairman Department of Clinical Therapeutics University Athens School of Medicine Athens, Greece

Dr. Dimopoulos

DrMeletios A. Dimopoulos MD
Professor and Chairman
Department of Clinical Therapeutics
University Athens School of Medicine
Athens, Greece

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Updated data from the Phase 3 POLLUX trials showed DARZALEX, in combination with lenalidomide and dexamethasone, reduced the risk of disease progression or death by 56 percent, compared to lenalidomide and dexamethasone alone (Hazard Ratio [HR]=0.44; 95 percent CI [0.34-0.55], p<0.0001). After a median follow-up of 32.9 months, the median progression-free survival (PFS) in the DARZALEX arm has not been reached, compared with a median PFS of 17.5 months for patients who received lenalidomide and dexamethasone alone.

DARZALEX in combination with lenalidomide and dexamethasone also significantly increased the overall response rate (ORR) compared to lenalidomide and dexamethasone alone (93 percent vs. 76 percent, p<0.0001), including rates of complete response (CR) or better (55 percent vs. 23 percent, p<0.0001). DARZALEX also showed significantly higher (>3-fold) MRD-negative rates compared to lenalidomide and dexamethasone alone. These data were featured as an oral presentation (Abstract #739) at the 59th American Society of Hematology (ASH) Annual Meeting in early December.

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Clot-Busting Catheter Procedure for DVT May Reduce Symptoms In Some Patients

MedicalResearch.com Interview with:
Suresh Vedantham, M.D
.
Principal Investigator, ATTRACT Trial
Professor of Radiology & Surgery
Mallinckrodt Institute of Radiology
Washington University School of Medicine 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:   About 300,000 Americans each year are diagnosed with a blood clot (deep vein thrombosis, DVT) for the first time.  In total, about 600,000 Americans have a DVT each year, as noted in the 2008 Surgeon General’s Call to Action.

Despite the use of standard treatment (blood thinning drugs and compression stockings), about 40% of DVT patients develop a long-term complication called post-thrombotic syndrome (PTS).  PTS impairs patients’ quality of life and typically causes chronic pain and swelling of the leg that occur on a daily basis. In many patients, this leads to major disability the prevents them from walking, working, or conducting normal daily activities. Some patients develop painful open sores on the leg called “venous ulcers”, that are difficult to heal.

Pharmacomechanical catheter-directed thrombolysis (“PCDT”) is a minimally-invasive treatment that removes blood clots through a tiny (2-3 mm) incision using the clot-busting drug tissue plasminogen activator (TPA) along with catheter-based devices that can chew up the clots. The benefits and risks of PCDT have not before been evaluated for DVT treatment in a rigorous study.

     The final results of the ATTRACT Trial, which was primarily sponsored by the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH), are being published in The New England Journal of Medicine.  ATTRACT, the most rigorous study to date of clot-busting treatment for DVT, was a multicenter randomized controlled trial comparing PCDT and standard therapy versus standard therapy alone in 692 patients with above-knee DVT. This landmark study, conducted in 56 U.S. hospitals, was led by Principal Investigator Dr. Suresh Vedantham, Professor of Radiology & Surgery at the Mallinckrodt Institute of Radiology at Washington University in St. Louis, along with outstanding DVT researchers at McMaster University (Hamilton, Ontario [Canada]), the Massachusetts General Hospital (Boston, MA), and the Mid America Heart Institute (Kansas City, MO).  

The primary study result is that for most patients with DVT, the addition of PCDT to standard therapy does not prevent the development of PTS.  Because the use of PCDT involves a small but significant increase in major bleeding complications, it should not be routinely used as first-line DVT treatment.  However, PCDT did reduce the severity of PTS and appeared likely to provide better relief of DVT-related leg pain and swelling.  Further analyses will determine which DVT patients are most likely to experience these benefits.

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About 20% Increased Risk of Breast Cancer in Women On Oral Contraceptives

MedicalResearch.com Interview with:
“Birth control pills” by lookcatalog is licensed under CC BY 2.0Lina Mørch PhD, MSc

Senior Researcher
Rigshospitalet

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There was a lack of evidence on contemporary hormonal contraception and risk of breast cancer. In particular the knowledge of risk with newer progestins was sparse.

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If Current Trends Continue, Most of Today’s Youth Will Be Obese By Age 35

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.  Continue reading

Vasopressin-Inhibitor Tolvaptan Reduces Kidney Function Decline in Polycystic Kidney Disease

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.

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Anti-Fibrotic Drug May Block Cardiac Scarring That Leads To Heart Failure

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

Dr. Péault

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.

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Study Finds ACE Inhibitors and Statins Can Be Safe In Type I Diabetes

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.

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Early Surgery for Drug Resistant Epilepsy May Limit Cognitive Disabilities

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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Is RICE Best After Injury? Study Suggests Rest Prolongs Recovery

MedicalResearch.com Interview with:

Monika Bayer PhD. Institute of Sports Medicine Copenhagen Bispebjerg Hospital Denmark

Dr. Bayer

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.

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Gastric Bypass: Half of Diabetic Patients In Remission 12 Years After Surgery

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.

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Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation 

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

Dr. Cannon

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.

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New Test for TB Can Detect Antibiotic Resistant Strains

MedicalResearch.com Interview with:

Susan E. Dorman, M.D Associate Professor of Medicine, Division of Infectious Diseases Johns Hopkins University School of Medicine, Baltimore

Dr. Dorman

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.

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Targeted Immunotherapy Can Prevent Some Melanomas From Spreading

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 

Dr. Menzies

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.

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Which Is Better? Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

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 

Prof. Jean Louis MAS

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.

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Tiotropium (Spiriva) Found Beneficial In Early Stages of COPD

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.

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Targeting a Lower Systolic Blood Pressure Likely To Be Well Tolerated, Even In Elderly

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.

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NEJM: On-Pump CABG Should Continue To Be Standard Surgical Treatment

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

Dr. Shroyer

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.

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Nasal Spray Flu Vaccine Ineffective and Not Recommended

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

Dr. Jackson

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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IgG Endopeptidase Has Potential To Reduce Kidney Transplant Rejection

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

Dr. Jordan

Stanley C. Jordan, M.D
DirectorDivision of Nephrology
Medical DirectorKidney 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.

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Healthy Diet Translates Into Longer Life

MedicalResearch.com Interview with:

Mercedes Sotos Prieto PhD Research Fellow Department of Nutrition Harvard T. H. Chan School of Public Health 

Dr. Sotos-Prieto

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.
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20 Year Follow-Up of Surgery vs Active Surveillance for Early Prostate Cancer

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.

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Ozone Air Pollution Linked To US Deaths, Even At Levels Below Current Safety Standards

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.

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Efficacy of Recombinant Flu Vaccine in Adults 50 Years of Age or Older 

MedicalResearch.com Interview with:

Lisa M. Dunkle, M.D. Chief Medical Officer Protein Sciences Corporation 1000 Research Parkway Meriden, CT 

Dr. Dunkle

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

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Does Head Positioning Matter In Acute Stroke?

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

Prof. Anderson

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

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Lithium Use in Pregnancy and Risk of Fetal Cardiac Malformations

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

Dr. Patorno

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.

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Single Tablet Triple Therapy Effective For Refractory Hepatitis C

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.

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Synthetic Human Angiotensin II for the Treatment of Vasodilatory Shock

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

Dr. Khanna

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).

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Rory’s Regulations: Faster Is Better When It Comes To Sepsis Care

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

Dr. Seymour

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.

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Phase 3 Studies Demonstrate Reduce Endometriosis-Associated Pain with Elagolix

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

Dr. Taylor

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.

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Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults?

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

Dr. Villareal

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.

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Bystander CPR Not Only Improves Survival But Reduces Brain Damage

MedicalResearch.com Interview with:

Kristian Kragholm, MD, PhD Departments of Cardiology and Epidemiology/Biostatistics, Aalborg University Hospital, Aalborg, DK

Dr. Kragholm

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.

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Tofacitinib -XELJANZ: Potential New Treatment Option For Moderate To Severe Ulcerative Colitis

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

Dr. Sandborn

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.

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Frequency of Retinal Screening in Diabetes May Be Tailored to Individual

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.

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Mortality From Cardiovascular Disease in Type 1 and Type 2 Diabetes Drops, But Still Exceeds General Population

MedicalResearch.com Interview with:

Aidin Rawshani, MD, PhD student Sahlgrenska Academy University of Gothenburg

Dr. Rawshani

Aidin Rawshani, MD, PhD student
Sahlgrenska Academy
University of Gothenburg

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Management of diabetes has improved in the past decades, studies have shown that mortality and cardiovascular disease among patients with diabetes has decreased, but these studies have not compared the trends among persons with type 1 diabetes and type 2 diabetes to those of the general population, where there have also been reductions in cardiovascular morbidity and mortality.

We observed marked reductions in incidence for cardiovascular disease and mortality among individuals with diabetes, however, similar trends were observed for the general population. We observed a 43% (HR 1.43, 95% CI 1.25–1.62) greater event rate reduction for cardiovascular disease among individuals with type 1 diabetes compared to matched controls. The reduction in the rate of fatal outcomes did not differ significantly between patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had a 13% (HR 0.87, 95% CI 0.85–0.89) lesser event rate reduction compared with matched controls.

There was a 27% (HR 1.27, 95% CI 1.22–1.32) greater event rate reduction for cardiovascular disease among individuals with type 2 diabetes, compared with matched controls. Nevertheless, there remains a substantial excess overall rate of all outcomes analysed among persons with type 1 diabetes and type 2 diabetes, as compared with the general population.

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Quadrivalent HPV Vaccination and the Risk of Adverse Pregnancy Outcomes

MedicalResearch.com Interview with:
Anders Hviid

Senior Investigator, M.Sc.,Dr.Med.Sci.
Department of Epidemiology Research
Division of National Health Surveillance & Research

MedicalResearch.com: What is the background for this study?

Response: HPV vaccination targeting girls and young women has been introduced in many countries throughout the world. HPV vaccines are not recommended for use in pregnancy, but given the target group, inadvertent exposure will occur in early unrecognized pregnancies. However, data on the safety of HPV vaccination in pregnancy is lacking.
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Instantaneous Wave-free Ratio vs Fractional Flow Reserve to Guide PCI

MedicalResearch.com Interview with:

Dr. Matthias Götberg MD PhD Department of Cardiology, Clinical Sciences Lund University, Skåne University Hospital Lund, Sweden

Dr. Matthias Götberg

Dr. Matthias Götberg MD PhD
Department of Cardiology, Clinical Sciences
Lund University, Skåne University Hospital
Lund, Sweden

MedicalResearch.com: What is the background for this study?

Response: Cardiologists encounter patients with narrowing of the coronary arteries on a daily basis. They typically use visual estimation of the severity of narrowing when performing coronary angiography, but it is difficult to accurately assess, based on a visual estimation alone, whether a stent is needed to widen the artery and allow the blood to more freely.

FFR (Fractional Flow Reserve) is more precise tool and results in better outcomes than using angiography alone to assess narrowing of the coronary arteries. With FFR, the doctor threads a thin wire through the coronary artery and measures the loss of blood pressure across the narrowed area. To acquire an accurate measurement, the patient must be given adenosine, which is a drug that dilates the blood vessels during the procedure. This drug causes discomfort; patients describe having difficulty breathing or feeling as if someone is sitting on their chest. The drug also adds to the cost of the procedure and can have other rare but serious side effects.

iFR (Instantaneous Wave-Free Ratio) is also based on coronary blood pressure measurements using a thin wire, but unlike FFR, it uses a mathematical algorithm to measure the pressure in the coronary artery only when the heart is relaxed and the coronary blood flow is high. As a result, a vasodilator drug is not needed.

iFR has been validated in smaller trials and have been found to be equally good as FFR to detect ischemia, but larger randomized outcome trials are lacking.

iFR-Swedeheart is a Scandinavian Registry-based Randomized Clinical Trial (RRCT) in which 2000 patients were randomized between iFR and FFR as strategies for performing assessment of narrowed coronary vessels. The primary composite endpoint at 12 months was all-cause death, non-fatal myocardial infarction, and unplanned revascularization.

RRCT is a new trial design originating from Scandinavia using existing web-based national quality registries for online data entry, randomization and tracking of events. This allows for a very high inclusion rate and low costs to run clinical trials while ensuring robust data quality.  Continue reading

Study Fails To Support Routine Screening For Subclinical Hypothyroidism During Pregnancy

MedicalResearch.com Interview with:

Professor, Brian Casey, M.D. Gillette Professorship of Obstetrics and Gynecology UT Southwestern Medical Center

Dr. Casey

Professor Brian Casey, M.D.
Gillette Professorship of Obstetrics and Gynecology
UT Southwestern Medical Center 

MedicalResearch.com: What is the background for this study?
Response: For several decades now, subclinical thyroid disease, variously defined, has been associated with adverse pregnancy outcomes.  In 1999, two studies are responsible for increasing interest in subclinical thyroid disease during pregnancy because it was associated with impaired neuropsychological development in the fetus.  One study showed that children born to women with the highest TSH levels had lower IQ levels.  The other showed that children of women with isolated low free thyroid hormone levels performed worse on early psychomotor developmental tests. Together, these findings led several experts and professional organizations to recommend routine screening for and treatment of subclinical thyroid disease during pregnancy.

Our study was designed to determine whether screening for either of these two diagnoses and treatment with thyroid hormone replacement during pregnancy actually improved IQ in children at 5 years of age.

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Can Patients With A Pacemaker or Defibrillator Get An MRI?

MedicalResearch.com Interview with:

Robert Russo, MD, PhD, FACC The Scripps Research Institute The La Jolla Cardiovascular Research Institute

Dr. Robert Russo

Robert Russo, MD, PhD, FACC
The Scripps Research Institute
The La Jolla Cardiovascular Research Institute 

MedicalResearch.com: What is the background for this study?

Response: For an estimated 2 million people in the United States and an additional 6 million people worldwide, the presence of a non-MRI-conditional pacemaker or implantable cardioverter defibrillator (ICD) is considered a contraindication to magnetic resonance imaging. This creates a dilemma for at least half of these patients, who are predicted to require an MRI scan during their lifetime after a cardiac device has been implanted. Safety concerns for patients with an implanted cardiac device undergoing MRI are related to the potential for magnetic field-induced cardiac lead heating resulting in myocardial thermal injury, and a detrimental change in pacing properties. As a result, patients with an implanted device have long been denied access to MRI, although it may have been the most appropriate diagnostic imaging modality for their clinical care. Despite the development of MRI-conditional cardiac devices, a strategy for mitigating risks for patients with non MRI-conditional devices and leads will remain an enduring problem for the foreseeable future due to an ever increasing demand for MRI and the large number of previously and currently implanted non-MRI-conditional devices.

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Survival Rates Improving For Very Preterm Infants

MedicalResearch.com Interview with:

Carla M. Bann, Ph.D. Division of Statistical and Data Sciences RTI International Research Triangle Park, NC

Dr. Carla Bann

Carla M. Bann, Ph.D.
Division of Statistical and Data Sciences
RTI International
Research Triangle Park, NC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Several medical advances have been made over the past two decades to improve the care and survival of infants born pre-term. However, approaches to care differ greatly among providers for infants born at the limits of viability (22 to 24 weeks gestation), far earlier than the 40 weeks generally expected for a pregnancy to reach full-term. Little is known about the outcomes of these infants, particularly whether those who survive experience significant neurodevelopmental impairments.

RTI served as the data coordinating center for this research that examined the survival and neurodevelopmental impairment at 18-22 months corrected age of over 4,000 infants born at 22 to 24 weeks gestation during 2000 to 2011 at medical centers participating in a national research network funded by the NIH. In this group of babies, infant survival improved over time from survival rates of 30 percent in 2000-2003 to 36 percent in 2008-2011. The proportion of infants who survived without a neurodevelopmental impairment also increased from 16 percent in 2000-2003 to 20 percent in 2008-2011.

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Persistence of Zika Virus in Body Fluids — Preliminary Report

MedicalResearch.com Interview with:
Gabriela Paz-Bailey MD PhD

Senior Epidemiologist
Centers for Disease Control and Prevention 

MedicalResearch.com: What is the background for this study?

Response: Zika virus is recognized as a cause of microcephaly and other severe birth defects when a woman is infected during pregnancy. Additionally, it has been associated with potentially fatal complications, such as Guillain-Barré syndrome. It is not well understood how often Zika virus particles can be detected in semen and other body fluids and for how long they remain detectable. Existing evidence is based on case reports and cross-sectional observations, primarily from returning travelers. A more comprehensive description of the dynamics of the early stages of Zika virus infection, observed within infected people over time, is needed to inform diagnostic testing as well as prevention recommendations and interventions.
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Therapeutic Hypothermia After In-Hospital Cardiac Arrest in Children

MedicalResearch.com Interview with:

Victoria Pemberton, RNC, MS, CCRC Program Officer Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute, NIH Bethesda, Maryland

Victoria Pemberton

Victoria Pemberton, RNC, MS, CCRC
Program Officer
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute, NIH
Bethesda, Maryland

MedicalResearch.com: What is the background for this study? What are the main findings?

  • Previous studies have examined cardiac arrest when it occurs outside of the hospital in both children and adults, with current guidelines recommending hypothermia (body cooling) or normothermia (maintenance of normal body temperature) after such an arrest.   This trial addresses pediatric cardiac arrest in a hospital setting, for which no previous data existed. Because children who experience an in-hospital cardiac arrest differ significantly from children who arrest outside of the hospital, it is important to test these treatments in this population.
  • The trial found no significant differences in survival and neurobehavioral functioning a year after cardiac arrest between children assigned to the hypothermia arm and those assigned to normothermia.

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Cigarette Smoking Remains A Huge Public Health Problem

MedicalResearch.com Interview with:
Andrew Hyland, PhD

Chair of the Department of Health Behavior at Roswell Park Cancer Institute and
Karin Kasza, MA
Senior Research Specialist in the Department of Health Behavior
Roswell Park Cancer Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The PATH Study is unique because it is a large, nationally representative study of more than 45,000 youth and adults who are interviewed at multiple points over time and asked about their use of a wide array of tobacco products. The data reported in this study are from the baseline wave, and we find that while cigarettes are by far the most commonly used product for both youth and adults, we see a lot of use of non-cigarette products. E-cigarettes trailed only cigarettes in popularity for youth and water pipe smoking was high among 18-24 year olds. However, we see different patterns of use for different products with cigarettes being used much more frequently that other products like e-cigarettes. Another surprising finding was that about 4 in 10 youth and adult tobacco users were currently using two or more tobacco products.

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Cancer Killed While Preserving A Kidney Transplant

MedicalResearch.com Interview with:

Kenar D. Jhaveri, MD Professor of Medicine Division of Kidney Diseases and Hypertension Hofstra Northwell School of Medicine, 100 Community Drive, Great Neck, NY 11021

Dr. Kenar Jhaveri,

Kenar D. Jhaveri, MD
Professor of Medicine
Division of Kidney Diseases and Hypertension
Hofstra Northwell School of Medicine,
100 Community Drive, Great Neck, NY 11021

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The immune check point inhibitors are novel anti cancer agents being used rapidly in various cancers. Many cancers don’t allow our natural immune system to attack the cancer. These immunotherapy agents “activate” the immune system to attack the cancer. These agents have been reported to cause multiple end organ side effects as noted by this recent NYT article. We also recently reported the known renal effects of immunotherapy.

In the kidney transplant patient who is on immunosuppressive agents, the physicians need to keep the immune system suppressed to preserve the kidney. When one of these agents are used for a cancer in a kidney transplant patient, prior reports have suggested severe rejection episodes and loss of the transplanted kidney. Our case in the NEJM is the first report of a preventive strategy used to allow for simultaneous treatment of cancer and preventive rejection of the kidney. We used a regimen of steroids and sirolimus( an anti-proliferative agent that is used to treat cancer and also is an immunosuppresant) along with the immunotherapy. The cancer started regressing and the kidney did not reject.

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Improved Resolution of Disease Phenotypes With Multilocus Genomic Variation

MedicalResearch.com Interview with:
Jennifer E Posey MD, PhD

Assistant Professor
Department of Molecular and Human Genetics
Baylor College of Medicine

Tamar Harel MD, PhD
Clinical Genetics Academic Research Fellow
Department of Molecular and Human Genetics
Baylor College of Medicine

Current affiliation:
Department of Genetic and Metabolic Diseases
Hadassah-Hebrew University Medical Center
Jerusalem, Israel

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: As physician scientists and geneticists, our goal is to understand how genetic variation in each of us can impact health and disease. Physicians are often taught that the simplest explanation for a medical condition is the most correct explanation, and have historically searched for a single unifying diagnosis. However, in our own practice, we have met – and learned from – individuals who have more than one genetic condition affecting their health.

In the past, it was difficult for physicians to diagnose such individuals. Genetic testing required a physician to recognize the potential for more than one genetic diagnosis in an individual. Single-gene and gene panel testing provided an additional barrier to accurate diagnoses, as they are more narrow in scope, and more than one molecular test was often needed to identify all conditions. Targeted testing also required a physician to accurately pre-suppose which combination of genetic conditions was most likely, and choose the correct targeted tests.

The clinical availability of whole exome sequencing (WES) has removed these barriers: WES is a broad-based, unbiased analysis of an individual’s genetic variation that does not pre-suppose a specific genetic cause. If analysis is pursued systematically, WES can identify more than one genetic diagnosis in an individual, even when not suspected.
In our study, we have been able to assess the frequency with which individuals can have more than one genetic diagnosis, and have begun to understand how genetic variation at more than one place in the genome can affect how a condition may present. We found that among 7,374 individuals referred for WES, 2,076 (28%) had a molecular diagnosis. Of these 2,076, 5% had two, three, or four molecular diagnoses. In our analyses of the clinical features that may be observed in an individual with two genetic conditions, we found that pairs of diagnoses with overlapping clinical features may be incompletely diagnosed as having one or the other condition, and pairs of diagnoses with very distinct clinical features may be erroneously diagnosed in the clinic as having an entirely new condition.
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Economic Effects of Medicaid Expansion in Michigan

MedicalResearch.com Interview with:

John Z. Ayanian, MD, MPP</strong> Director of the Institute for Healthcare Policy and Innovation and Alice Hamilton Professor of Medicine University of Michigan

Dr. John Z. Ayanian

John Z. Ayanian, MD, MPP
Director of the Institute for Healthcare Policy and Innovation and
Alice Hamilton Professor of Medicine
University of Michigan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our study assessed the broad economic impact of Medicaid expansion in Michigan – one of several Republican-led states that have chosen to expand Medicaid under the Affordable Care Act. About 600,000 low-income adults in Michigan are covered through the program, known as the Healthy Michigan Plan, which began in April 2014.

Using an economic modeling tool that is also used to advise the state government for fiscal planning, we found that federal funding for the Healthy Michigan Plan is associated with over 30,000 additional jobs, about $2.3 billion in increased personal income in Michigan, and about $150 million in additional state tax revenue annually. One third of the new jobs are in health care, and 85 percent are in the private sector. The state is also saving $235 million annually that it would have spent on other safety net programs if Medicaid had not been expanded.

Thus, the total economic impact of the Healthy Michigan Plan is generating more than enough funds for the state budget to cover the state’s cost of the program from 2017 through 2021. Beginning in 2017, states are required to cover 5 percent of the costs of care for Medicaid expansion enrollees, and the state share of these costs will rise to 10 percent in 2020. The remaining costs are covered by federal funding.

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Fish Oil Fatty Acids in Pregnancy May Reduce Wheeze and Asthma in Offspring

MedicalResearch.com Interview with:

Hans Bisgaard, M.D., D.M.Sc. COPSAC, Herlev and Gentofte Hospital University of Copenhagen Copenhagen, Denmark

Dr. Hans Bisgaard

Hans Bisgaard, M.D., D.M.Sc.
COPSAC, Herlev and Gentofte Hospital
University of Copenhagen
Copenhagen, Denmark

MedicalResearch.com: What is the background for this study?

Response: Asthma and lower respiratory infections are leading causes of morbidity and mortality in pediatric populations. Thus, having low cost, effective, safe options for prevention could have important implications for both clinical practice and public health.

The increased use of vegetable oils in cooking and of grain in the feeding of livestock has resulted in an increase in the intake of n−6 polyunsaturated fatty acids and a decrease in the intake of n−3 polyunsaturated fatty acids, especially the long-chain poly-unsaturated fatty acids (LCPUFAs) — eicosapentaenoic acid (20:5n–3, EPA) and docosahexaenoic acid (22:6n–3, DHA) — found in cold-water fish. N3-LCPUFAs are known to have immune-modulatory effects, and observational studies have suggested an association between a diet that is deficient in n−3 LCPUFA during pregnancy and an increased risk of asthma and wheezing disorders in offspring. Only a few randomized, controlled trials of n−3 LCPUFA supplementation during pregnancy have been performed and these have generally been underpowered and produced ambiguous results.

Therefore, we conducted a double-blind, randomized, controlled trial of n−3 LCPUFA supplementation during the third trimester of pregnancy in a total of 736 Danish women to assess the effect on the risk of persistent wheeze and asthma in offspring.

The clinical follow-up rate among children was 96% (N=664) by the end of the 3 years double-blind period and 93% (N=647) after an additional follow-up to age 5 years.
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Mutliple Sclerosis: Ocrelizumab Lowers Rate of Disease Progression and Disability

MedicalResearch.com Interview with:

Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School part of UTHealth | The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030

Dr. Jerry Wolinsky,

Jerry S. Wolinsky, MD
Emeritus Professor in Neurology
McGovern Medical School
The University of Texas Health Science Center at Houston
Houston’s Health University
Department of Neurology
Houston, Texas 77030

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses.

However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval.

The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis.

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Only High Risk Patients May Require Anticoagulation After Arthroscopic Knee Surgery

MedicalResearch.com Interview with:

Suzanne C. Cannegieter, M.D., Ph.D. Einthoven Laboratory  Leiden University Medical Center  The Netherlands

Dr. Suzanne Cannegieter,

Suzanne C. Cannegieter, M.D., Ph.D.
Einthoven Laboratory
Leiden University Medical Center
The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Patients who undergo arthroscopic knee surgery and patients who are treated with casting of the lower leg are at increased risk for venous thromboembolism (VTE). It is uncertain whether thromboprophylaxis is effective in these situations to prevent VTE. For both indications, several trials have been performed to evaluate the effectiveness of anticoagulant prophylaxis. However, an overall risk–benefit balance could not be established because of methodologic shortcomings; hence, there has been reluctance to establish international guidelines regarding the use of anticoagulant therapy for either of these indications.

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Dapivirine Vaginal Ring Helps Prevent HIV Infection in Women

MedicalResearch.com Interview with:
Ms. Neliëtte Van Niekerk M.Com
and Dr. Annalene Nel M.B., Ch.B., Ph.D.
From International Partnership for Microbicides
Silver Spring, MD

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Existing prevention methods have not done enough to stop the alarming rates of infection among women and girls, especially in sub-Saharan Africa, where young women are at least twice as likely to have HIV as young men. Rates of new infections among women aged 15-24 were more than four times greater than that of men the same age, and this age group accounted for 25 percent of new infections in South Africa. To provide women with more prevention options, the nonprofit International Partnership for Microbicides (IPM) developed a vaginal ring that contains an antiretroviral drug called dapivirine. Women insert the ring themselves and replace it every month.

The Ring Study was a Phase III clinical trial that assessed the safety and long-term efficacy of the monthly dapivirine ring among nearly 2,000 women in South Africa and Uganda. We found that the ring reduced the risk of HIV-1 infection in about one-third of the women in the trial, and it was safe, with no difference in adverse effects between the active and placebo ring groups.

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Cardioprotective Effect of PCSK9 Inhibitors Should Outweigh Potential Harm of Diabetes Risk

MedicalResearch.com Interview with:
Brian A. Ference, M.D
Division of Cardiovascular Medicine
Wayne State University School of Medicine
Detroit, MI

MedicalResearch.com: What are the main findings?

Response: Lifelong exposure to modestly lower plasma LDL-C levels caused by rare loss-of-function mutations in the PCSK9 gene is associated with a substantially lower lifetime risk of developing cardiovascular disease. This discovery motivated the development of monoclonal antibodies directed against PCSK9 which have now been shown to reduce plasma LDL-C levels by 50-60%. The cardiovascular medicine community is early anticipating the results of two large cardiovascular outcome trials that will determine if lowering LDL-C levels by inhibiting PCSK9 will reduce the risk of cardiovascular events.

Because monoclonal antibodies and other therapies directed against PCSK9 are designed to recapitulate the phenotype of PCSK9 loss-of-function mutations, we reasoned that it may be possible to anticipate the efficacy and safety results of the ongoing cardiovascular outcome studies by more precisely characterizing the effect of genetic variants in the PCSK9 gene on the risk of both cardiovascular events and new onset diabetes.

To do this, we a constructed genetic score consisting of multiple independently inherited variants in the PCK9 gene to create an instrument that mimics the effect of PCSK9 inhibitors. We then compared the effect of genetic variants that mimic the effect of PCSK9 inhibitors with the effect of genetic variants in the HMGCR gene that mimic the effect of statins to make inferences about the likely effect of PCSK9 inhibitors on the risk of cardiovascular events and new onset diabetes as compared to treatment with a statin.

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