For Most Patients Balanced IV Fluids Better Than Saline

MedicalResearch.com Interview with:

Wesley H. Self, MD, MPH Associate Professor Department of Emergency Medicine Vanderbilt University Medical Center Nashville, TN 

Dr. Self

Wesley H. Self, MD, MPH
Associate Professor
Department of Emergency Medicine
Vanderbilt University Medical Center
Nashville, TN  

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

Response: Doctors have been giving IV fluids to patients for more than 100 years. The most common IV fluid during this time has been saline; it has high levels of sodium and chloride in it (similar to table salt).  Balanced fluids are an alternative type of IV fluid that has lower levels of sodium and chloride that are more similar to human blood.

Our studies were designed to see if treating patients with these balanced fluids resulted in better outcomes than saline.  We found that patients treated with balanced fluids had lower rates of death and kidney damage than patients treated with saline.

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Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty?

MedicalResearch.com Interview with:

Dr. David R. Anderson, MD, FRCPC, FACP Faculty of Medicine Dean, Professor Dean, Faculty of Medicine Division of Hematology, Department of Medicine  & Nova Scotia Health Authority

Dr. Anderson

Dr. David R. Anderson, MD, FRCPC, FACP
Faculty of Medicine Dean, Professor
Dean, Faculty of Medicine
Division of Hematology, Department of Medicine
& Nova Scotia Health Authority

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

Response: Blood clots in the lungs (pulmonary embolism) and veins of the legs (deep vein thrombosis) are well recognized complications following total hip and knee arthroplasty surgeries.  Prior to the routine use of antithrombotic prophylaxis, pulmonary embolism was the most common cause of death following these procedures.  Oral anticoagulants such as rivaroxaban are commonly prescribed for the indication of preventing blood clots following total hip or knee arthroplasty.  For maximal benefit these agents are continued following surgery for up to five weeks following total hip arthroplasty and for two weeks following total knee arthroplasty.

There is evidence that aspirin has some benefit for the prevention of deep vein thrombosis and pulmonary embolism following total hip or knee arthroplasty.  However there is less evidence for its benefit than for oral anticoagulants.  We reasoned that aspirin would potentially be an attractive alternative for extended out of hospital prophylaxis following total hip or knee arthroplasty for patients who received a short course (5 days )of rivaroxaban following surgery.  Aspirin would be attractive for this indication because of its low cost, ease of use, and low rates of side effects.

Our study demonstrated that in a randomized controlled trial involving a large group (over 3400) of patients undergoing total hip or knee arthroplasty that extended therapy with aspirin was comparable to rivaroxaban for the prevention of deep vein thrombosis and pulmonary embolism following surgery.  Low rates of complications (< 1%) were observed with both treatment arms.  We also found that rates of clinically important bleeding complications (the most common side effect with antithrombotic drugs) were uncommon and similar with the two agents.

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Hepatitis: 8 Weeks of Once Daily, Combination Pill Found Effective in HCV 1 and 3

MedicalResearch.com Interview with:

In the United States, hepatitis A, hepatitis B and hepatitis C are the most common types, but also included are hepatitis D and E. CDC/ E.H. Cook, Jr.

In the United States, hepatitis A, hepatitis B and hepatitis C are the most common types, but also included are hepatitis D and E.
CDC/ E.H. Cook, Jr.

Stefan Zeuzem, M.D.
Professor of Medicine
Chief Internal Medicine
Goethe University Hospital
Frankfurt, Germany

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

Response: Chronic hepatitis C virus (HCV) infection is a major global public health problem with more than 71 million people infected worldwide, and can result in significant morbidity and mortality, including liver cirrhosis, hepatocellular carcinoma, and death.1

This publication describes the efficacy and safety results from two Phase 3 clinical trials, ENDURANCE-1 and ENDURANCE-3, in patients with chronic HCV genotypes (GT) 1 or 3 infection who were treated with an all-oral, once-daily combination regimen of direct-acting antiviral agents (DAA) glecaprevir (GLE) at 300 mg and pibrentasvir (PIB) at 120 mg.

The findings from ENDURANCE-1 trial show that the GLE/PIB combination regimen (G/P) given for 8 weeks to HCV GT1 chronically infected non-cirrhotic treatment-naïve or treatment-experienced (with sofosbuvir and/or interferon with ribavirin) patients was safe and well-tolerated, achieved high efficacy with a sustained virologic response at post-treatment week 12 (SVR12) rate >99% and was non-inferior to 12-week treatment with G/P.

The trial also included subjects who were co-infected with human immunodeficiency virus (HIV), and all of these subjects achieved SVR12 while maintaining HIV suppression throughout the study. ENDURANCE-3 trial results show that the G/P regimen given for 8 weeks to HCV GT3 chronically infected non-cirrhotic treatment-naïve patients was safe and well-tolerated, achieved high efficacy in this historically difficult to cure GT with an SVR12 rate >94%, and was non-inferior to 12-week treatment with G/P, which in turn was non-inferior to the treatment with 12-week DAA regimen of sofosbivir and daclatasvir.  Continue reading

Stem Cell Transplantation Offers Hope For Severe Scleroderma

MedicalResearch.com Interview with:

“Breastfeeding welcome here” by Newtown grafitti is licensed under CC BY 2.0

Picture of a female patient’s left arm, showing skin lesions caused by Scleroderma
Wikipedia image

Keith M. Sullivan, M.D.
James B. Wyngaarden Professor Of Medicine
Division of Cellular Therapy
Duke University Medical Center
Durham, North Carolina 27710, USA 

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

  • Scleroderma with internal organ involvement is a devastating  autoimmune disorder with considerable morbidity and high mortality which have not changed in 40 years of reporting. Effective new therapies are needed.
  • Despite 2 prior randomized trials showing benefit for reduced-intensity stem cell transplant vs. conventional cyclophosphamide immune suppression, clinical practice in the US did not change due in part due to concern about patient safety and durability of response (attached).
  • The current randomized trial compares 12 monthly infusions of cyclophosphamide with high-dose chemotherapy plus whole-body irradiation designed to wipe-out (myeloablate) the defective, self-reactive immune system and replace with the patients own stem cells which had been treated to remove self-reacting lymphocytes. This was the first study to test if myeloablative autologous could re-establish a normal functioning immune system in patients with scleroderma.

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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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