Tapeworm Drug May Be Repurposed To Fight Parkinson’s Disease

MedicalResearch.com Interview with:

Dr. Youcef Mehellou PhD Lecturer in Medicinal Chemistry Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University

Dr. Mehellou

Dr. Youcef Mehellou PhD
Lecturer in Medicinal Chemistry
Cardiff School of Pharmacy and Pharmaceutical Sciences
Cardiff University

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

Response: Over the last decade or two, there has been many reports linking genetic mutations to the pathogenesis of Parkinson’s disease (PD). Among the proteins that have been found to be mutated in PD is a protein called PINK1. Indeed, PINK1 mutations that disturb its function in cells were found to be causal of PD in humans. Subsequent studies showed that PINK1 is a major player in maintaining healthy neurons. This is because it is one of the components involved in controlling the quality of the mitochondria, an organelle within the cell, and it does this by triggering the disposal of unhealthy mitochondria. Overall, studies into PINK1 indicated that the activation of PINK1 as a plausible strategy for maintaining health neurons and hence slowing down the development and progress of Parkinson’s disease.

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Atopic Dermatitis: IF Used At All, Systemic Steroids Should Be Short Term Bridge To Other Therapies

MedicalResearch.com Interview with:

Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, Illinois

Dr. Jonathan Silverberg

Dr. Jonathan L. Silverberg MD PhD MPH
Assistant Professor in Dermatology
Medical Social Sciences and Preventive Medicine
Northwestern University, Chicago, Illinois

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

Response: Systemic corticosteroids are commonly used as systemic treatments for atopic dermatitis. However, few studies assessed the efficacy and safety of systemic corticosteroids in atopic dermatitis. This systematic review sought to summarize the available evidence for their use in atopic dermatitis.

Overall, 52 reviews and 12 studies were included in this systematic review. Most studies suffered from small sample size, low quality. In one of the only randomized-controlled trials performed, systemic corticosteroids were less effective than cyclosporine and led to more rebound flares. There were numerous safety and tolerability concerns with both short and long-term treatment with systemic corticosteroids. One study found that even short-term use of systemic corticosteroids was associated with increased sepsis, venous thromboembolism and fractures.

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Database Analyses May Find Supplemental Uses For Established Drugs In Cost-Effective Manner

MedicalResearch.com Interview with:

Michael Fralick, MD FRCPC Research Fellow at the Division of Pharmacoepidemiology and Pharmacoeconomics Harvard University and General Internist at the University of Toronto

Dr. Fralick

Michael Fralick, MD FRCPC
Research Fellow at the Division of Pharmacoepidemiology and Pharmacoeconomics
Harvard University and
General Internist at the University of Toronto

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

Response: Manufacturers of Food and Drug Administration (FDA)-approved prescription drugs often apply for additional indications based on randomized trials. “Real-world” data based on a medication’s actual use and outcomes in routine settings of care might help to inform decision-making regarding such supplemental indications.

MedicalResearch.com: What are the main findings?

Response:  In this non-randomized study we were able to replicate the results of the randomized trial that established the supplemental indication for telmisartan using data from a US healthcare database (insurance claims data) available at the time the randomized trial was completed.

We were also able to confirm the known decreased risk of angioedema with telmisartan compared to ramipril.

MedicalResearch.com: What should readers take away from your report?

Response: If done selectively and with principled methodologies, it might be feasible to use non-randomized real-world data to provide supportive evidence in establishing supplemental drug indications. To improve the validity of the studies, they should ideally be registered prior to them starting.

MedicalResearch.com: Is there anything else you would like to add?

Response: We used real-world data to recreate both the benefits and the harms found in a randomized controlled trial. The randomized trial costed 10s of millions of dollars and took over 7 years to complete. By contrast, our study took a few months to complete and was a small fraction of the cost of the randomized trial.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Michael Fralick, Aaron S. Kesselheim, Jerry Avorn, Sebastian Schneeweiss. Use of Health Care Databases to Support Supplemental Indications of Approved Medications. JAMA Intern Med. Published online November 20, 2017. doi:10.1001/jamainternmed.2017.3919

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

Zoledronic Acid Cost-Effective In Preventing Skeletal Events in Patients With Bone Metatstases

MedicalResearch.com Interview with:

Dr-Charles L Shapiro.jpg

Dr. Shapiro

Charles L.Shapiro MD
Professor of Medicine
Director of Translational Breast Cancer Research
Director of Cancer Survivorship
Division of Hematology/Oncology
Tisch Cancer Institute
New York, NY

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

Response: The new 2017 ASCO guidelines for the use bone-modifying in individuals with bone metastases recently endorsed every 3-month zoledronic, because of high level evidence from three randomized trials, including our trial (published in Jama in Jan 2017, first author Himelstein et al) that giving zoledronic acid every 3-months was non-inferior to the standard of monthly zoledronic. The guidelines also concluded that there was not one preferred bone modifying agent of the other, despite the fact the comparing monthly zoledronic to monthly denosumab in women with bone metastases, denosumab delayed the time to first skeletal-related event (pathological fractures, necessity for radiation or surgery, and spinal cord compression) and subsequent events by 23% (or in absolute terms about 3 months) . Zoledronic acid became generic in 2013, whereas monthly denosumab is still patented until 2022-25.

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Novel PDE4 Inhibitor Improves Symptoms of Autism Disorder Fragile X Syndrome in Animal Model

MedicalResearch.com Interview with:

Dr. Mark E. Gurney, PhD MBA

Dr. Gurney

Dr. Mark E. Gurney, PhD MBA
Chairman & CEO, Tetra Discovery Partners Inc.

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

Response: Fragile X is a genetic condition. Affected patients display a range of behavioral and other symptoms, including seizures, sleep disorders, anxiety, irritability, hyperactivity, autism, mild-to-severe cognitive impairment and intellectual disability.

BPN14770 is a novel therapeutic agent that selectively inhibits phosphodiesterase-4D (PDE4D). Inhibition of PDE4 has been validated as a treatment strategy by many research groups in the Fragile X field, but non-selective PDE4 inhibitors have been associated with significant GI side-effects that have limited those drugs’ use. As a selective inhibitor, such side-effects were not seen for BPN14770 in a Phase 1 clinical trial in healthy young and elderly adults.

In the current study, daily treatment of Fragile X knock-out (FXS) mice with BPN14770 showed a reduction in hyperarousal, improved social interactions and natural behaviors, and changes in nerve structure in the prefrontal cortex of the brain, the portion of that brain associated with cognition. Moreover, the drug’s benefit persisted for two weeks after all drug was cleared from the mice. At the same time, the behavior of normal mice treated with the drug remained unchanged. Examination of neurons from the prefrontal cortex of the treated FXS mice showed an improvement in dendritic spine morphology.

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Oral Semaglutide As Effective As Injectable In Reducing A1C and Weight Loss

MedicalResearch.com Interview with:

Melanie J Davies CBE MB ChB MD FRCP FRCGP Professor of Diabetes Medicine  NIHR Senior Investigator Emeritus Diabetes Research Centre Leicester Diabetes Centre – Bloom University of Leicester

Prof. Davies

Melanie J Davies CBE MB ChB MD FRCP FRCGP
Professor of Diabetes Medicine
NIHR Senior Investigator Emeritus
Diabetes Research Centre
Leicester Diabetes Centre – Bloom
University of Leicester

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

Response:  This was the first study to test the effectiveness of an oral GLP-1 in patients with type 2 diabetes.

The main findings were that compared to both placebo and a GLP-1, Semaglutide, delivered by sub-cutaneous injection weekly, the oral therapy delivered once a day produced better results than placebo and similar results to injectable GLP-1 with regard to reductions in HbA1c and weight loss.

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Antidepressants in Youth Associated With Increased Risk of Type 2 Diabetes

MedicalResearch.com Interview with:
Mehmet Burcu, PhD, MS
Department of Pharmaceutical Health Services Research
University of Maryland, Baltimore 

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

Response: Antidepressants are one of the most commonly used psychotropic medication classes in U.S. youth, with serotonin reuptake inhibitors representing a large majority of total antidepressant use in youth.

The most interesting finding was that the current use of serotonin reuptake inhibitors in youth was associated with an increased risk of type 2 diabetes mellitus, and this increased risk intensified further with the increasing duration of use and with the increasing dose. A secondary analysis also revealed that the risk of incident type 2 diabetes was most apparent in youth who used serotonin reuptake inhibitors for longer durations AND in greater daily doses.

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Peppermint Oil Based IBgard® Found Efficacious In Some Patients With Irritable Bowel Syndrome with Mixed Bowel Habits

MedicalResearch.com Interview with:

Brooks D. Cash, M.D., A.G.A.F., F.A.C.G., F.A.S.G.E. Professor of Medicine and Chief of the USA Gastroenterology Division Director, Motility and Physiology Service University of South Alabama Mobile, Alabama

Dr. Cash

Brooks D. Cash, M.D., A.G.A.F., F.A.C.G., F.A.S.G.E.
Professor of Medicine and
Chief of the USA Gastroenterology Division
Director, Motility and Physiology Service
University of South Alabama
Mobile, Alabama 

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

Response: Irritable Bowel Syndrome (IBS) among patients with IBS-M (mixed diarrhea and constipation) is a challenging and difficult to diagnose and treat sub-type of IBS. Patients with IBS-M represent a dissatisfied group of IBS patients due to the lack of proven therapies. It is an area of high unmet medical need.

Among adult patients with IBS, a sizeable proportion suffers from IBS-M with prevalence rates estimated to be between 44 to 66 percent of IBS sufferers[1],[2],[3]. IBS-M patients carry a heavy burden, characterized by bouts of constipation interrupted by diarrhea and vice versa. Physicians find IBS-M challenging to manage because of the difficulty in avoiding ‘overshoots’ when diarrhea management can turn into constipation and vice versa.[4]  Continue reading

Efficacy of SSRIs for Anxiety Influenced By Patient’s Expectations

MedicalResearch.com Interview with:
Vanda Faria PhD
Department of Psychology
Uppsala, Sweden 

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

Response: It has been debated whether selective serotonin reuptake inhibitors (SSRIs), which are commonly prescribed for depression and anxiety, are more effective than placebo. Concerns have been raised that the beneficial effects of SSRIs, as measured in double-blind clinical trials, may be explained by expectancies (a crucial placebo mechanism) rather than the biochemical compound. But no study has tested experimentally the extent to which the SSRI treatment effect can be influenced by expectancies induced by verbal suggestions.

We compared the efficacy of overt vs. covert administration of an SSRI (escitalopram) in patients with social anxiety disorder. Rather than comparing the SSRI with placebo, we compared it with itself while manipulating the patients’ expectations of improvement. This was achieved by informing one group correctly about the SSRI and its effectiveness (overt group) whereas the comparison (covert) group received incorrect information. By use of a cover story, the covert group was led to believe they were treated with a so called “active placebo”, an ineffective neurokinin-1 antagonist yielding similar side effects as the SSRI but lacking anxiety-reducing properties. But the treatment, dosage and duration was in fact identical in both groups.

Results showed that overt outperformed covert SSRI treatment, as the number of treatment responders was more than three times higher on the main clinical outcome measure when correct information was given. Using neuroimaging (fMRI) we also noted differences between the overt and covert SSRI groups on objective brain activity measures. There were differences between the groups e.g. with regard to activation of the posterior cingulate cortex with treatment, and the functional coupling between this region and the amygdala which is a brain region crucially involved in fear and anxiety. The fMRI  results may reflect the interaction between cognition and emotion as the brain changes differently with treatment pending on the expectations of improvement.

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Adulterated Proprietary Chinese Medicines Pose Serious Health Hazards

“Pills” by Victor is licensed under CC BY 2.0MedicalResearch.com Interview with:
Tony Wing Lai Mak , MBChB, MBA, FRCPath, FRCPA, FHKCPath, FHKAM(Path 

Hospital Authority Toxicology Reference Laboratory
Princess Margaret Hospital, Hong Kong

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

Response: Proprietary Chinese medicines (pCMs) and health products are generally believed to be natural and safe. However, the safety of pCMs and health products has been compromised by the illicit practice of adulteration with undeclared drugs. Such adulteration can have serious and even fatal consequences. Previous reports of pCM and health product adulteration were mainly routine surveillance data or case reports/series with a small number of affected patients.

The present study in Hong Kong, to our knowledge, is the largest case series that reports an overview of the use of various adulterated Proprietary Chinese medicine and health products and the resulting adverse effects. From 2005 to 2015, we have identified 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants detected. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue.

The six most common categories of adulterants detected were nonsteroidal ant-inflammatory drugs (18%), anorectics (15%), corticosteroids (14%), diuretics and laxatives (11%), oral antidiabetic agents (10%), and erectile dysfunction drugs (6%). Sibutramine, an anorectic that has been withdrawn from the market owing to its association with increased cardiovascular events and strokes, was the most common adulterant identified. A significant proportion of patients (65.1%) had adverse effects that were attributable to these illicit products, including 14 severe and two fatal cases. These illicit Proprietary Chinese medicine and health products pose severe health hazards to the public.

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IPF: Combination of Nintedanib and Pirfenidone May Have Added Benefit With Manageable Side Effects

MedicalResearch.com Interview with:

Professor Carlo Vancheri Professor of Respiratory Medicine, University of Catania, Italy and Director of the Regional Referral Centre for Rare Lung Diseases and the Laboratory of Experimental Respiratory Medicine.

Prof. Vancheri

Professor Carlo Vancheri
Professor of Respiratory Medicine,
University of Catania, Italy and Director of the Regional Referral Centre for Rare Lung Diseases and the Laboratory of Experimental Respiratory Medicine.

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

Response: The aim of Boehringer Ingelheim’s INJOURNEY trial was to investigate the safety profile of Ofev (nintedanib) in combination with pirfenidone in treating patients with idiopathic pulmonary fibrosis (IPF). Nintedanib and pirfenidone, the only two FDA-approved drugs for the treatment of IPF, are able to slow down the progression of the disease, reducing the forced vital capacity (FVC) decline of about 50%, but this is not a cure. The target for the future is to have even more effective treatments. In the meanwhile, it is necessary to optimize the use of the available drugs. The medical treatment of other pulmonary diseases such as COPD, asthma or pulmonary hypertension is already based on different combinations of drugs.

This 12-week, open-label, randomized study was designed to evaluate the safety, tolerability and pharmacokinetics of nintedanib with add-on pirfenidone, compared with nintedanib alone in patients with IPF. Change in FVC, the established efficacy endpoint in IPF trials, was evaluated as an exploratory endpoint.

The primary endpoint of the INJOURNEY trial was the percentage of patients with on-treatment gastrointestinal adverse events from baseline to week 12 of randomized treatment, and the results showed that the combination of nintedanib and add-on pirfenidone resulted in a manageable safety and tolerability profile, similar to the profile of each drug individually in the majority of patients. Results also indicated there may be a slower decline in FVC in patients treated with pirfenidone along with nintedanib compared with nintedanib alone, suggesting a potential benefit of the combination. However, further research will be necessary to fully evaluate the efficacy of the combination.

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Study Evaluates Pediatric Outcomes of Antidepressant Use During Pregnancy

MedicalResearch.com Interview with:

Xiaoqin Liu, PhD Department of Economics and Business Economics Aarhus University

Dr. Xiaoqin Liu

Xiaoqin Liu, PhD
Department of Economics and Business Economics
Aarhus University 

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

Response: Previous research on the long-term neurodevelopmental outcomes of serotonin-reuptake inhibitor (SSRI) use during pregnancy has primarily focused on offspring risk of autism spectrum disorder. Given SSRIs cross the placental barrier and affect the fetal brain, in-utero SSRI exposure may increase risks of other psychiatric disorders as well as autism spectrum disorder.

We conducted a population-based study to look at a range of diagnostic groups of psychiatric disorders in children whose mothers used antidepressants during pregnancy. This was possible because of the nature of information available in Danish population registers, allowing us to follow children for many years. We found increased risks of various diagnostic groups of psychiatric disorders in children whose mothers continued antidepressant treatment during pregnancy, in comparison to children whose mothers stopped antidepressant treatment before pregnancy.

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Victoza® Receives FDA Approval To Reduce Heart Attack and Stroke in Patients With Type 2 Diabetes and Heart Disease

MedicalResearch.com Interview with:

Todd Hobbs, MD Vice President and Chief Medical Officer Novo Nordisk North America

Dr. Hobbs

Todd Hobbs, MD
Vice President and Chief Medical Officer
Novo Nordisk North America 

MedicalResearch.com: Would you tell us a little about liraglutide? How does it work to control diabetes/blood sugar? 

Response: Victoza® (liraglutide) is a human glucagon-like peptide-1 (GLP-1) analog that was approved by the U.S. Food and Drug Administration (FDA) in 2010 to help lower blood sugar in adults with type 2 diabetes. Victoza® is the #1 prescribed (GLP-1) receptor agonist.

Victoza® is a non-insulin, once-a-day medication that helps lower blood sugar levels in adults with type 2 diabetes by increasing glucose-dependent insulin release, inhibiting glucagon secretion, and slowing gastric emptying.

On August 25, the FDA approved a new indication for Victoza®, making it the only type 2 diabetes treatment approved to reduce the risk of major adverse cardiovascular (CV) events, heart attack, stroke and CV death, in adults with type 2 diabetes and established CV disease.

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New Approach Could Lead To Osteoporosis Drugs With Fewer Side Effects

MedicalResearch.com Interview with:

Dieter Bromme, Ph.D. Professor and Canada Research Chair The University of British Columbia Faculty of Dentistry  Vancouver, BC

Dr. Bromme

Dieter Bromme, Ph.D.
Professor and Canada Research Chair
The University of British Columbia Faculty of Dentistry
Vancouver, BC

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

Response: Every three seconds somebody will fracture a bone because of osteoporosis. Several treatments are available to slow down bone loss but all of them have shortcomings ranging from poor bone quality to various side effects. Thus new treatment strategies and novel drug targets are needed that promise efficacy without significant adverse reactions.

One of the novel promising targets was cathepsin K, a protease solely responsible for the degradation of our organic bone matrix. Major efforts and funds were spent by the pharmaceutical industry to develop potent and selective cathepsin K inhibitors. These inhibitors were highly effective in preserving bone in clinical trials. Despite the good news, cathepsin K inhibitors were never approved because of various non-skeletal side effects. We hypothesized that these side effects are not caused by off-target effects (drugs react with undesired targets) but by on-target effects. Most drugs that target enzymes are active site-directed compounds and thus will stop the entire activity of the target enzyme. If the target is a multifunctional enzyme, safety problems are preprogrammed. Based on our studies to understand the molecular mechanism of collagen degradation by cathepsin K, we developed the concept of ectosteric enzyme inhibition, which allowed us to identify highly selective collagenase inhibitors of this protease.

In our study, we used a red sage-derived small molecule that selectively blocked the collagenase activity of cathepsin K and thus consequently bone degradation in an osteoporosis mouse model without affecting other known functions of the protease. The crucial difference might be that the red sage inhibitor did not block the cathepsin K-mediated degradation of TGF-ß1, a growth factor involved in fibrotic pathologies described in the clinical trials. TGF-ß1 degradation is blocked by these inhibitors and thus accumulates in tissues, causing fibrosis.

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Serotonin Receptors Tied To Weight Gain From Atypical Antipsychotic Medications

MedicalResearch.com Interview with:

Chen Liu, Ph.D. Assistant Professor Departments of Internal Medicine and Neuroscience Division of Hypothalamic Research The University of Texas Southwestern Medical Center Dallas, Texas 75390-9077

Dr. Chen Liu

Chen Liu, Ph.D.
Assistant Professor
Departments of Internal Medicine and Neuroscience
Division of Hypothalamic Research
The University of Texas Southwestern Medical Center
Dallas, Texas 75390-9077 

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

Response: Atypical antipsychotics are second-generation antipsychotics (SGAs) that have been increasingly used to treat a variety of neuropsychiatric conditions such as schizophrenia, depression, and autism. Many patients taking these medications, however, are left in an agonizing dilemma.

On one hand, they rely on these drugs’ psychotropic effect for normal functioning in daily life. On the other, many SGAs, including the most widely prescribed olanzapine and clozapine, can cause a metabolic syndrome that is known for excessive weight gain, dyslipidemia, and type-2 diabetes_ENREF_2. Notably, while full-blown type 2 diabetes and morbid obesity typically take years to unfold in the general population, these conditions progress at a much faster pace (within months) following second-generation antipsychotics treatment. Other factors such as ethnicity, age, and sex can also aggravate SGA-induced metabolic syndrome. Together, these peculiar features strongly suggest a distinct etiology underlying SGA-induced metabolic syndrome that has yet been fully elucidated. Currently, there is no medication specifically targeting SGA-induced metabolic syndrome. For many youths and adults taking second-generation antipsychotics, metabolic complications are difficult to manage as lifestyle changes, nutritional consulting, and commonly used anti-diabetic medications only provide limited relief.

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Evidence Does Not Support Gabapentinoids in Non-Specific Chronic Low Back Pain

MedicalResearch.com Interview with:

Harsha Shanthanna MBBS, MD, MSc Associate Professor, Anesthesiology Chronic Pain Physician St Joseph's Healthcare,McMaster University Hamilton, Canada Diplomate in National Board, Anesthesiology (India) Fellow in Interventional Pain Practice (WIP) European Diplomate in Regional Anesthesia and Pain (ESRA)

Dr. Shanthanna

Harsha Shanthanna MBBS, MD, MSc
Associate Professor, Anesthesiology
Chronic Pain Physician
St Joseph’s Healthcare,McMaster University
Hamilton, Canada
Diplomate in National Board, Anesthesiology (India)
Fellow in Interventional Pain Practice (WIP)
European Diplomate in Regional Anesthesia and Pain

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

Response: Pregabalin (PG) and gabapentin (GB) are increasingly used for nonspecific Chronic Low Back Pain (CLBP) despite a lack of evidence. There have been concerns expressed over their increased prescribing for various non cancer pain indications in recent years. Their use requires slow titration to therapeutic doses and establishing maintenance on a long-term basis. With prolonged treatment, the potential gain over possible adverse effects and risks could become unclear.

We searched Cochrane, MEDLINE and EMBASE databases for randomized control trials reporting the use of gabapentinoids for chronic lower back pain treatment of 3 months or more in adult patients.

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Risk of Suicide Attempts With Methylphenidate Treatment for ADHD

MedicalResearch.com Interview with:
Professor Ian Chi Kei Wong and
Kenneth KC Man, Senior Research Assistant
Department of Social Work and Social Administration, Faculty of Social Science
Department of Pharmacology and Pharmacy, LKS Faculty of Medicine
The University of Hong Kong

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

Response: Patients with attention-deficit/hyperactivity disorder (ADHD) are at higher risk of various mental health problems. Previous studies suggested that individuals with ADHD are having a higher chance of both attempted and completed suicide. Methylphenidate is a psychostimulant that is recommended for the treatment of ADHD. With the increasing usage of methylphenidate over the past decade, there are concerns about the safety of the medication, in particular, psychiatric adverse effects such as suicide attempt.

The current study looked into over 25,000 patients aged 6 to 25 years in Hong Kong who were receiving methylphenidate in 2001 to 2015. Using the self-controlled case series design, in which the patients act as their own control, we found that the risk of suicide attempt was 6.5 fold higher during a 90-day period before methylphenidate was initiated, remained elevated 4-fold during the first 90 days of treatment, and returned to the normal level during ongoing treatment.

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Once-Daily, Fixed-Dose Combination Tablet Containing Doravirine Achieved HIV-1 Viral Suppression

MedicalResearch.com Interview with:

Dr. Kathleen Squires MD Professor and Director of Infectious Diseases Thomas Jefferson University Philadelphia, PA 

Dr. Squires

Dr. Kathleen Squires MD
Professor and Director of Infectious Diseases
Thomas Jefferson University
Philadelphia, PA 

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

  • The pivotal Phase 3 DRIVE-AHEAD study evaluated the safety and efficacy of a once-daily, single tablet, fixed-dose combination containing doravirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection, compared to a fixed-dose combination containing efavirenz.
    • After 48 weeks of treatment, 84 percent of the 364 treatment-naïve patients taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81 percent of the 364 patients taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5 percent.
    • Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1.
    • In addition, comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69 patients in the DOR/3TC/TDF group and 73 patients in the EFV/FTC/TDF group (Observed Failure approach).
      • Of those patients with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81 percent in the DOR/3TC/TDF group and 81 percent in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0 percent.
    • The study also met its primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).

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ONCEMRK Study: Once Daily Raltegravir In Combination With Other Antivirals Effective For Some HIV Patients

MedicalResearch.com Interview with:

Dr. Pedro Cahn Chief of the infectious disease unit at Juan A. Fernandez Hospital Buenos Aires, Argentina, and ONCEMRK lead study investigator

Dr. Pedro Cah

Dr. Pedro Cahn
Chief of the infectious disease unit at Juan A. Fernandez Hospital
Buenos Aires, Argentina, and
ONCEMRK lead study investigator

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

The ONCEMRK Phase 3 study was conducted to evaluate the efficacy and safety of once-daily ISENTRESS (raltegravir) HD 1200 mg (given as two 600 mg oral tablets) compared to twice daily raltegravir 400 mg, each in combination therapy with emtricitabine plus tenofovir disoproxil fumarate in previously untreated adults with HIV-1 infection with levels of HIV-1 RNA ≥ 1,000 copies/mL.

  • Week 96 data showed:
    • 5 percent of the 531 patients taking once-daily raltegravir 1200 mg (2 x 600 mg) achieved viral suppression of less than 40 copies/mL of HIV-1 RNA, compared to 80.1 percent of the 266 patients taking twice-daily raltegravir 400 mg, both in combination therapy with emtricitabine plus tenofovir disoproxil fumarate, with a treatment difference of 1.4 percent.
    • Increases in CD4+T-cell counts from baseline were comparable for the two treatment regimens, with an average increase of 261.6 cells/mm3 for once-daily raltegravir (1200 mg) and 262.2 cells/mm3 for twice-daily raltegravir (400 mg).
    • Efficacy was consistent across a variety of patient populations, including those with high viral load at baseline (HIV-1 RNA >100,000 copies/mL).
    • Treatment-emergent viral mutations leading to any drug resistance were detected in less than 1 percent of patients in both treatment arms, with 4/531 (0.8 percent) in the once-daily raltegravir (1200 mg) treatment arm, and 2/266 (0.8 percent) in the twice-daily raltegravir (400 mg) treatment arm through 96 weeks.
    • The rate of discontinuation of therapy due to adverse events through 96 weeks was low (1.3 percent in patients receiving once-daily raltegravir (1200 mg) and 2.3 percent in patients receiving twice-daily raltegravir (400 mg).

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Trying Statins Again After Adverse Effect Linked To Lower Risk of Heart Attack

MedicalResearch.com Interview with:

Alexander Turchin, MD,MS Director of Quality in Diabetes Associate Professor, Harvard Medical School Brigham and Women's Hospital Boston, MA

Dr. Turchin

Alexander TurchinMD,MS
Director of Quality in Diabetes
Associate Professor, Harvard Medical School
Brigham and Women’s Hospital
Boston, MA

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

Response: Cardiovascular disease is the # 1 cause of death in the U.S. and worldwide. Statins are some of the most effective medications available for prevention of cardiovascular events.

However, many patients stop statins, frequently because of adverse reactions. In our study we aimed to assess the risk-benefit balance of trying a statin again after experiencing an adverse reaction.

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Optimistic Results From Phase 3 Study of RBP-6000 Buprenorphine Monthly Depot for Treatment of Opioid Use Disorder

Medical Research.com Interview with:

Dr. Christian Heidbreder, PhD Chief Scientific Officer Indivior Inc. Richmond, VA 23235, USA

Dr. Heidbreder

Dr. Christian Heidbreder, PhD
Chief Scientific Officer
Indivior Inc.
Richmond, VA 23235, USA

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

Response: This pivotal Phase 3 clinical trial (RB-US-13-0001) evaluated the efficacy and safety of RBP-6000, an investigational once-monthly injectable buprenorphine in the ATRIGEL® delivery system for the treatment of adults with moderate-to-severe opioid use disorder (OUD) as part of a complete treatment plan to include counseling and psychosocial support1.

The 24-week Phase 3 study met its primary and key secondary endpoints, demonstrating statistically significant differences in percentage abstinence and treatment success across both dosage regimens of RBP-6000 versus placebo1.

The findings also showed that outcomes with RBP-6000 are consistent across other secondary clinical endpoints, including control of craving and withdrawal symptoms, as compared to placebo. These outcomes were associated with buprenorphine plasma concentrations ≥ 2 ng/mL and predicted whole brain mu-opioid receptor occupancy of ≥ 70%, and were also maintained for the one-month dosing intervals and for the entire treatment duration1.

The results were confirmed by exposure-response analyses demonstrating a relationship between buprenorphine plasma concentrations, abstinence, withdrawal symptoms and opioid craving1.

RBP-6000 was generally well tolerated and had a safety profile consistent with that of transmucosal buprenorphine. Injection site reactions were not treatment-limiting. The most common (reported in ≥ 5% of subjects) treatment-emergent adverse events (TEAEs) reported in the active total group were constipation, headache, nausea, injection site pruritus, vomiting, increased hepatic enzyme, fatigue and injection site pain1.

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Newer Insulin Formulation Reduces Risk of Hypoglycemia

MedicalResearch.com Interview with:

Wendy Lane MD Director of Clinical Research Mountain Diabetes and Endocrine Center Asheville, NC 

Dr. Lane

Wendy Lane MD
Director of Clinical Research
Mountain Diabetes and Endocrine Center
Asheville, NC

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

Response: The SWITCH1 trial was the first double blinded insulin trial to compare the rate of severe, nocturnal severe and symptomatic blood glucose-confirmed hypoglycemia between two basal insulins, insulin glargine U100 and insulin degludec U100, in patients with type 1 diabetes.

The trial design (double blinded crossover treat-to-target) eliminated any bias in the results, which showed clear-cut reductions in all categories of hypoglycemia with insulin degludec compared to insulin glargine.

Severe hypoglycemia has dangerous and greatly feared consequences including cognitive impairment, seizures, coma and death, and it is the main barrier to effective use of insulin in the treatment of type 1 diabetes. Insulin degludec, which was shown to reduce the risk of hypoglycemia compared to insulin glargine in the SWITCH1 trial, should be viewed by clinicians as an advancement in insulin therapy which will increase its safety and improve the quality of life of our patients with type 1 diabetes.

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Optimization of Medication Use Critical to Success of ACOs

MedicalResearch.com Interview with:
Kimberly Westrich, MA
Vice President, Health Services Research, National Pharmaceutical Council, and
Kristina Lunner
Principal, Leavitt Partners

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

Response: With the advent of accountable care organizations (ACOs) following passage of the Affordable Care Act in 2010, it became important to understand how success in an ACO world is different from success in a capitated environment, where the focus is only on managing costs. In an ACO, providers are responsible for the quality of care they provide for a defined population in addition to having at least some financial responsibility. We wanted to explore how an ACO can succeed in this environment of dual responsibility for costs and quality, and more specifically, how pharmaceuticals fit into this success.

To address these questions, the National Pharmaceutical Council worked with the American Medical Group Association (AMGA), Premier, Inc., and a group of seven leading ACOs to develop a conceptual framework for considering the role of pharmaceuticals in ACOs. This framework shows how optimizing medication use in a value-based healthcare environment, such as an ACO, can help the organization achieve its cost and quality benchmarks.

We evaluated ACO readiness to optimize medication use in 2014 and again with our most recent study, published in June 2017 online ahead of print in the Journal of Managed Care & Specialty Pharmacy. For our 2017 study, we worked with Leavitt Partners to survey and interview ACOs to understand how they optimize medication use, determine if there is an association between efforts to optimize medication use and achievement on financial and quality metrics, ascertain organizational factors that correlate with optimized medication use, and identify barriers to optimized medication use.
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Brexanolone Shows Promise in PostPartum Depression

MedicalResearch.com Interview with:

Samantha Meltzer-Brody, MD, MPH Associate Professor and Associate Chair for Faculty Development Director, Perinatal Psychiatry Program Director, Taking Care of Our Own Program Department of Psychiatry Chapel Hill, NC 2759

Dr. Meltzer-Brody

Samantha Meltzer-Brody, MD, MPH
Associate Professor and Associate Chair for Faculty Development
Director, Perinatal Psychiatry Program
Director, Taking Care of Our Own Program
Department of Psychiatry
Chapel Hill, NC 2759 

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

Response: The Lancet published results from a randomized, placebo-controlled, phase 2 clinical trial with the investigational medication, brexanolone, for women with severe postpartum depression (PPD). During the study, which was conducted at multiple sites across the country, physician researchers administered brexanolone in 21 women, 10 of whom were administered a 60-hour infusion of brexanolone. The other 11 women were given a placebo. Results from the trial showed that 70 percent of participants who received the drug saw remission of their PPD symptoms within 60 hours of treatment, an effect that was maintained until the 30-day follow up.

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Letermovir Found Highly Effective In Preventing CMV Infection

MedicalResearch.com Interview with:

Roy F Chemaly, M.D., M.P.H., F.A.C.P., F.I.D.S.A Professor, Department of Infectious Diseases, Director, Infection Control and Employee Health, Division of Internal Medicine Director of the clinical virology research program,Department of infectious diseases Infection control and employee health The University of Texas MD Anderson

Dr. Chemaly

Roy F Chemaly, M.D., M.P.H., F.A.C.P., F.I.D.S.A
Professor, Department of Infectious Diseases,
Director, Infection Control and Employee Health, Division of Internal Medicine
Director of the clinical virology research program,Department of infectious diseases
Infection control and employee health
The University of Texas MD Anderson

MedicalResearch.com: Would you briefly explain the significance of CMV infections? What is the background for this study?

Response: Cytomegalovirus (CMV) is one of the most important causes of infectious complications following organ transplantation and is a significant cause of illness and death in patients who have undergone allogeneic hematopoietic cell transplantation (allo-HCT). For more than 20 years, we have been managing this infection and trying to develop effective strategies to control it, but to no one’s satisfaction; CMV infection is still associated with significant morbidity and mortality in this high-risk population.

Most transplant centers have adopted preemptive antiviral therapy as the strategy of choice for HCT patients.1 While anti-CMV drugs have decreased the incidence of CMV diseases, their use for prophylaxis has not been associated with improved outcomes.1

Demographic and transplant trends heighten the need for new anti-CMV agents. In the U.S, 83% of people aged 60 and older are CMV seropositive. These older patients received 8% of all hematopoietic-cell transplants in 2000-2006, a figure that jumped to 22% in 2007-2013. As Baby Boomers age, many more allogeneic transplant patients will be CMV seropositive.

Therefore, prophylactic antiviral compounds that could effectively control viral replication, and restrict some pathologic processes of CMV diseases, could potentially lessen the complications associated with CMV infection and possibly reduce all-cause mortality.

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Drugs Receiving Accelerated FDA Approval Often Have Flaws In Their Evidence Base

MedicalResearch.com Interview with:

Huseyin Naci, PhD Assistant Professor of Health Policy LSE Health Department of Social Policy London School of Economics and Political Science London, United Kingdom

Dr. Naci

Huseyin Naci, PhD
Assistant Professor of Health Policy
LSE Health
Department of Social Policy
London School of Economics and Political Science
London, United Kingdom 

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

Response: An increasing proportion of novel therapeutic agents are entering the market on the basis of expedited development and approval programs. The Food and Drug Administration’s (FDA) Accelerated Approval pathway is one such expedited approval program. In our study, we examined the dynamics of research on drugs receiving accelerated approvals. We were particularly interested in the timing and characteristics of research studies including drugs with accelerated approvals.

Our primary findings are the following:

  • First, there is an abundance of research on drugs receiving accelerated approvals. Yet, the majority of this research (about 70%) is of poor quality. Ideally, these drugs are evaluated in so-called randomised controlled trials to establish their efficacy and safety. However, only about a third of all existing studies are randomised controlled trials.
  • Second, a substantial share (about 30%) of the existing research on these drugs is in areas not approved by the FDA. This may be indicative of industry research practices in trying to prioritise identification of new uses for drugs receiving accelerated approvals instead of strengthening their evidence base.
  • Third, when focusing on well-designed studies, only about a half actually evaluate the effectiveness of the accelerated approval drugs. The rest appears to use the accelerated approval drug as background therapy. Interestingly, these two types of studies are conducted concurrently. In other words, while one research group is trying to find out if an accelerated approval drug is effective, other research groups are already using it as part of a background regimen when testing the effectiveness of another, potentially newer drug

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New Simultaneous Antidepressant and Benzodiazepine Use Relatively Common

MedicalResearch.com Interview with:

Greta A Bushnell, MSPH Doctoral Candidate, Department of Epidemiology UNC, Gillings School of Global Public Health

Greta Bushnell

Greta A Bushnell, MSPH
Doctoral Candidate, Department of Epidemiology
UNC, Gillings School of Global Public Health

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

Response: Patients with depression may be co-prescribed a benzodiazepine at antidepressant initiation for a short period for a variety of reasons. Reasons include reducing concurrent anxiety and insomnia, reducing depression severity more quickly, and improved antidepressant continuation. However, there are concerns with benzodiazepines including dependency. As such, benzodiazepines are usually recommended for only short-term treatment.

Prior to our study, little was known about a) how often new simultaneous antidepressant and benzodiazepine prescribing occurred among patients initiating antidepressant treatment for depression or b) whether new simultaneous users became long-term benzodiazepine users.

In a large commercial insurance database, we identified adults aged 18-64 years with depression who initiated an antidepressant from 2001 to 2014. We found that 11% of adults simultaneously initiated benzodiazepine treatment, which increased from 6% in 2001 to a peak at 12% in 2012. We observed similar antidepressant treatment length at six months in simultaneous new users and among patients initiating antidepressants only. The majority of simultaneous new users had only one benzodiazepine prescription fill before benzodiazepine discontinuation; however, 12% were identified as long-term benzodiazepine users.

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Long-acting Injectable Medications Reduce Relapse and Rehospitalizations in Schizophrenia

MedicalResearch.com Interview with:

Jari Tiihonen, MD, PhD Professor, Department of Clinical Neuroscience Karolinska Institutet Stockholm, Sweden

Prof. Tiihonen

Jari Tiihonen, MD, PhD
Professor, Department of Clinical Neuroscience
Karolinska Institutet
Stockholm, Sweden 

MedicalResearch.com: What are the limitations of existing analyses of the comparative effectiveness of antipsychotics?

Response: It has remained unclear if there are clinically meaningful differences between antipsychotic treatments in relapse prevention of schizophrenia, due to the impossibility of including large unselected patient populations in randomized controlled trials, and due to residual confounding from selection biases in observational studies.

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IPF Patients Treated With Nintedanib (Ofev) More Likely To Have Stable Lung Function

MedicalResearch.com Interview with:

Kevin R. Flaherty

Dr. Flaherty

Kevin R. Flaherty, M.D., M.S.
Professor, Department of Internal Medicine
Associate Director, T32 Multidisciplinary Training Program in Lung Diseases
Chair, Pulmonary Fibrosis Foundation Clinical Care Network Steering Committee
University of Michigan Medicine 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This is a new post-hoc analysis, recently presented at the 2017 American Thoracic Society (ATS) conference, which sought to further assess the efficacy of Ofev (nintedanib), an FDA-approved drug treatment for idiopathic pulmonary fibrosis (IPF), and its effect on lung function in those with this disease.

IPF is a rare and serious lung disease that causes permanent scarring of the lungs and affects as many as 132,000 Americans.

The analysis examined pooled data from the two placebo-controlled, global Phase III INPULSIS trials, which evaluated the efficacy and safety of 52 weeks’ treatment with nintedanib in people with IPF. In both trials, a higher proportion of people treated with placebo than nintedanib had disease progression from baseline to week 52, as defined by the proportions of patients with ≥5% or ≥10% declines in lung function, as measured by forced vital capacity (FVC) % predicted. Additionally, a lower proportion of patients treated with placebo than nintedanib had no decline or an improvement in FVC % predicted.

These data support the initial findings from the Phase III INPULSIS trials which found that more patients treated with nintedanib versus placebo had an absolute decline in FVC of less than 5%.

In this subgroup analysis, we assessed the proportions of patients from the two INPULSIS trials treated with nintedanib and placebo who had no decline or an improvement in lung function from baseline to week 52 using pooled data for this post-hoc analysis. In terms of those who participated, a total of 864 patients were included (519 treated with nintedanib, 345 treated with placebo). Baseline characteristics including age, gender and FVC were similar between the subgroups of patients who had no decline or an improvement in FVC and those whose FVC declined, and between the nintedanib and placebo groups within each subgroup.

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FDgard® Demonstrated Rapid Relief of Symptoms in Functional Dyspepsia

MedicalResearch.com Interview with:

William D. Chey, M.D., F.A.C.G.</strong> Director, Division of Gastroenterology Michigan Medicine Gastroenterology Clinic Ann Arbor, Michigan

Dr. Chey

William D. Chey, M.D., F.A.C.G.
Director, Division of Gastroenterology
Michigan Medicine Gastroenterology Clinic
Ann Arbor, Michigan

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

Response: Functional Dyspepsia (FD), which is persistent or recurring upper abdominal pain, burning, or fullness with no known organic cause, is a relatively common and often frustrating condition. The precise causes of this condition are unknown, but problems with mild inflammation, leakiness of the lining of the gut, overactive sensation, and abnormal contractions of the upper digestive tract are thought to play a role in many patients. FD often reoccurs over time and it is an area of high unmet medical need.

Functional Dyspepsia can have a significant impact on quality of life. Currently, off-label medications are used to treat FD, as there is no U.S. Food and Drug Administration (FDA)-approved pharmaceutical product for the condition.

An estimated 62 percent of FD patients suffer from Epigastric Pain Syndrome (EPS, which is epigastric pain or burning), while an estimated 73 percent of FD patients suffer from Postprandial Distress Syndrome (PDS, which is early fullness, pressure and heaviness); 35 percent suffer from both.

In this study, we compared the efficacy of a unique encapsulated formulation of caraway oil and l-Menthol, the primary component in peppermint oil), (COLM-SST) to placebo in patients taking their usual Functional Dyspepsia medications. Caraway oil contains carvone and d-limonene, which have gastroprotective and prokinetic effects; l-Menthol has anti-inflammatory, prokinetic, analgesic and gastroprotective effects.

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Injectable Cabotegravir Holds Promise as HIV Prevention Stategy

MedicalResearch.com Interview with:

Martin Markowitz MD Clinical Director and Staff Investigator Aaron Diamond AIDS Research Center Aaron Diamond Professor at The Rockefeller University

Dr. Markowitz

Martin Markowitz MD
Clinical Director and Staff Investigator
Aaron Diamond AIDS Research Center
Aaron Diamond Professor at The Rockefeller University

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

Response: Cabotegravir ((CAB) is an inhibitor of HIV-1 integrase and is amenable to formulation in both oral and long acting injectable forms. In preclinical studies injectable CAB protected against low dose intrarectal challenge using an HIV-like virus in the rhesus macaque model.

These results support the clinical development of CAB as prevention. This study was a first attempt to establish a dosing regimen and evaluate safety and acceptability of intramuscular injections of CAB. The study was a placebo controlled blinded study of approximately 120 subjects with a 5:1 randomization active/placebo. Subjects received 800mg CAB given as 2 2mL injections or placebo every 12 weeks for 3 injections after a 4 week safety lead in of oral therapy. Safety acceptability and PK were assessed.

The main findings were that injections were associated with injection site reactions in the vast majority of participants that were mild to moderate and of short duration. Only 4 subjects who entered the injection phase discontinued due to injection intolerance. There were no additional safety signals and the participants considered the injections acceptable when asked to complete questionnaires. PK analysis found that despite modeling that suggested that the 800mg q 12 week dose would be adequate, this was not the case. More rapid uptake and release from the depot resulted in lower than anticipated drug levels at trough. Alternate dosing regimens are under study.

Another finding is that there were participants (14%) who had detectable drug in plasma detected at 52 weeks after last injection suggesting the presence of a tail in some individuals.

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All NSAIDS Raise Risk of Heart Attack, Even When Taken For Short Period of Time

MedicalResearch.com Interview with:
Michèle Bally, BPharm, MSc, PhD

Epidemiologist, Department of Pharmacy, CHUM
Researcher, Health Innovation and Evaluation Hub, CRCHUM

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

Response: The objective of this study was to better understand the risk of heart attack associated with using oral prescription non-steroidal anti-inflammatory drugs or NSAIDs (ibuprofen, diclofenac, celecoxib, and naproxen) the way people usually do to treat pain and inflammation in real life circumstances.

In clinical trials, NSAIDs were typically taken on a continuous basis in high standardized doses, as assigned by the trial protocol. However, the dosages and the treatment durations studied in trials may not represent the reality of many patients who use NSAIDs in low or varying doses, use these drugs on and off, or switch between NSAID medications.

We were particularly interested in determining the onset of the risk, that is how soon does the risk of heart attack start increasing? Also, we wanted to investigate the effect of dose and duration of treatment. To do this, we studied the use of a low or high dose level of NSAIDs over certain set periods of time, including taking these medications only for 1 to 7 days.

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Restrictions on Pharmaceutical Detailing Linked To Increase in Generic Drug Prescription

MedicalResearch.com Interview with:

Ian Larkin, PhD</strong> Assistant Professor of Strategy UCLA Anderson School of Management

Dr. Ian Larkin

Ian Larkin, PhD
Assistant Professor of Strategy
UCLA Anderson School of Management

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

Response: The study examined whether restrictions put in by medical centers on salesperson visits to physicians, known as “detailing,” affected subsequent physician prescribing behavior. Detailing represents the most prominent form of pharmaceutical marketing. Detailing visits allow the sharing of scientific information, but they also often involve small gifts for physicians and their staff, such as meals.

Pharmaceutical companies incur far greater expenditures on detailing visits than they do on direct-to-consumer marketing, or even on research and development of new drugs. Specifically, the study examined detailing restrictions put into place by 19 academic medical centers (AMCs) in five states in the U.S. It compared changes in prescribing by thousands of AMC physicians whose practices limited typical elements of detailing visits, such as provisions of meals and educational gifts, to a carefully matched control group of similar physicians practicing in the same geographic regions but not subject to such detailing restrictions.

The study, which included more than 25,000 physicians and all 262 drugs in eight major drug classes — from statins to sleep aids to antidepressants, representing more than $60 billion in aggregate sales in the United States — was, to date, by far the most comprehensive to examine the impact of detailing restrictions. The comprehensive and quasi-experimental methodology, which compared prescribing behavior before and after implementation of policies, and which included a large matched control group of physicians not subject to policy changes, was an important innovation relative to prior research. The study used prescription data from CVS Caremark, one of the largest pharmacy benefit managers in the United States.

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Statins Users May Have Higher Likelihood of Back Disorders

MedicalResearch.com Interview with:

Una Makris MD, MSc Clinical Investigator at the VA North Texas Health System Assistant Professor at UT Southwestern Medical Center Departments on Internal Medicine and Clinical Sciences

Dr. Makris

Una Makris MD, MSc
Clinical Investigator at the VA North Texas Health System
VA North Texas Health Care System
Assistant Professor at UT Southwestern Medical Center
Departments on Internal Medicine and Clinical Sciences
Dr. Makris is a Rheumatologist, clinically, and spends the majority of time focused on clinical research investigating how to improve outcomes for adults with back pain.

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

Response: Back pain is the most common type of musculoskeletal (MSK) pain. We know that expenditures for back pain exceed $100 billion each year (and this was in 2005). Back pain results in tremendous disability (including reduced mobility) and impaired quality of life (not exclusive to physical consequences, but also including important psychosocial repercussions). We also know that statins are prescribed very often, and frequently in younger populations who are active. Some reports suggest that statins may have a protective effect on  musculoskeletal conditions such as back pain.

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Animal Study Suggests Lorcaserin (Belviq®) May be Useful to Reduce Opioid Intake

MedicalResearch.com Interview with:
Christina R. Merritt and Kathryn A. Cunningham
Center for Addiction Research
University of Texas Medical Branch
Galveston, TX 77555

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

Response: Opioid use disorder (OUD) is one of the top public health problems in the United States. Overdoses on prescription opioids, heroin and fentanyl accounted for 33,091 deaths in the U.S. in 2015 (https://www.cdc.gov/mmwr/volumes/65/wr/mm655051e1.htm); each day, 91 Americans die from an opioid overdose (https://www.cdc.gov/drugoverdose/epidemic/). The first-ever Surgeon General’s Report on Alcohol, Drugs and Health (https://addiction.surgeongeneral.gov/ ) observed that more people used prescription opioids than tobacco in 2015. Furthermore, individuals with OUD, the most problematic pattern of opioid abuse, often relapse, particularly in environments associated with past drug use, and new means to help maintain abstinence are needed.

Serotonin (5-hydroxytryptamine; 5-HT) function in the brain, particularly through its cognate 5-HT2C receptor, is an important regulator of the abuse liability of cocaine and other psychostimulants. Previous studies suggested that the weight loss medication and selective 5-HT2C receptor agonist lorcaserin (Belviq®) can curb cocaine- and nicotine-seeking in preclinical models, even when tested in tempting environments. We administered lorcaserin to rats who were trained to take the powerful painkiller oxycodone (OxyContin®), a prescription opioid currently approved for treatment of acute and chronic pain with characteristically high abuse potential. Lorcaserin suppressed oxycodone intake as well as the drug-seeking behaviors observed when rats were exposed to cues such as the lights and sounds previously associated with drug intake. Taken together, these findings highlights the therapeutic potential for lorcaserin to extend abstinence and enhance recovery from OUD.

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Thyroid Hormone Medication Should Not Be Taken With Cow’s Milk

MedicalResearch.com Interview with:
Deborah Chon MD
Endocrinology fellow
UCLA David Geffen School of Medicine 

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

Response: Our study shows that drinking cow’s milk concurrently with oral levothyroxine significantly reduces the absorption of the medication.

Levothyroxine is used for the physiologic replacement of thyroid hormone in patients with hypothyroidism and for serum TSH suppression in patients with thyroid cancer. It is the mostly commonly prescribed medication in the United States as of 2014. Frequent dose adjustments of levothyroxine have been shown to be a costly burden to the national healthcare system.

Previous studies have shown that certain foods and medication, such as calcium supplements, can interfere with levothyroxine absorption. However, this is the first study to demonstrate that ingesting cow?s milk, a common breakfast staple, affects oral levothyroxine absorption.

To determine the possible effect of cow’s milk ingestion, we measured levothyroxine absorption in humans with and without concurrent milk consumption. Pharmacokinetic studies were conducted in healthy adults without allergies to milk or levothyroxine, and who were not pregnant nor using oral contraceptives. All subjects had no history of known thyroid disease and normal thyroid hormone function at baseline. Following an overnight fast, serum total thyroxine T4 (TT4) concentrations were measured at baseline and at 1, 2, 4, and 6 hours after ingestion of 1,000 ?g of oral levothyroxine alone or when co-administered with 12 oz. of milk (2% fat). There was a four-week washout period between the two study visits.

Ten subjects (mean age 33.7?10.2 years, 60% male) completed the study. The serum total T4 absorption over six hours, calculated as area under the curve (AUC), was significantly lower when taking cow?s milk concurrently with levothyroxine compared levothyroxine alone (mean?SD: 67.26?12.13 vs. 73.48?16.96; p = 0.02). Also, peak serum TT4 concentrations were significantly lower in those who ingested levothyroxine concurrently with milk, compared to taking levothyroxine alone (p=0.04).
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NSAIDS Diclofenac and Ibuprofen Associated with Increased Risk of Cardiac Arrest

MedicalResearch.com Interview with:

Kathrine Bach Søndergaard MD, Research Fellow Gentofte University Hospital Department of Cardiology Hellerup

Dr. Søndergaard

Kathrine Bach Søndergaard MD, Research Fellow
Gentofte University Hospital
Department of Cardiology
Hellerup 

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

Response: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have in previous studies been associated with an increased risk of cardiovascular adverse events, such as myocardial infarction and heart failure. Cardiac arrest is the ultimate adverse event; however, no research exists of the association between cardiac arrest and use of NSAIDs, which we aimed to assess in this study.

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Psoriasis: Efficacy and Safety of Guselkumab vs Humira for Moderate to Severe Disease

MedicalResearch.com Interview with:

Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center

Dr. Blauvelt

Andrew Blauvelt, M.D., M.B.A.
President and Investigator
Oregon Medical Research Center

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

Response: Findings from the Phase 3 VOYAGE 1 study showed that patients with moderate to severe plaque psoriasis receiving guselkumab, an human anti-interleukin (IL)-23 monoclonal antibody, achieved significant improvement in skin clearance and in comparison with Humira® (adalimumab), a TNF blocker.  The Phase 3 study and head-to-head analysis of guselkumab vs. adalimumab showed the significant and durable efficacy of guselkumab as maintained through one year when compared with adalimumab, and the robust efficacy of this novel IL-23 targeted therapy in meeting all primary and major secondary endpoints.

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Regional Variation in Chemotherapy Prescriptions For Metastatic Prostate Cancer

MedicalResearch.com Interview with:

Megan Elizabeth Veresh Caram MD Clinical Lecturer Internal Medicine, Hematology & Oncology University of Michigan

Dr. Caram

Megan Elizabeth Veresh Caram MD
Clinical Lecturer
Internal Medicine, Hematology & Oncology
University of Michigan

 

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

Response: Abiraterone and enzalutamide are oral medications that were approved by the Food & Drug Administration in 2011 and 2012 to treat men with metastatic castration-resistant prostate cancer. Most men with advanced prostate cancer are over age 65 and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D and Dartmouth Atlas data.

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Flu Treatment With Neuraminidase Inhibitors During Pregnancy Not Linked To Birth Defects

MedicalResearch.com Interview with:

Dr. Sophie Graner Department of Women's and Childrens Health Karolinska Institute, Stockholm, Sweden

Dr. Graner

Dr. Sophie Graner
Department of Women’s and Childrens Health
Karolinska Institute, Stockholm, Sweden

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

Response: Pregnant women are at increased risks of severe disease and death due to influensa infection, as well as hospitalization. Also influenza and fever increase the risk of adverse pregnancy outcomes for their infants such as intrauterine death and preterm birth. Due to this, the regulatory agencies in Europe and the US recommended post exposure prophylaxis and treatment for pregnant women with neuraminidase inhibitors during the last influenza pandemic 2009-10. Despite the recommendations, the knowledge on the effect of neuraminidase inhibitors on the infant has been limited. Previously published studies have not shown any increased risk, but they have had limited power to assess specific neonatal outcomes such as stillbirth, neonatal mortality, preterm birth, low Agar score, neonatal morbidity and congenital malformations.
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mGlu2 receptor Agonist ADX71149 Plus Levetiracetam May Reduce Seizures With Fewer Side Effects

MedicalResearch.com Interview with:

Robert Lutjens, PhD Head of Discovery at Addex Therapeutics Geneva, Switzerland

Dr. Lutjens

Robert Lutjens, PhD
Head of Discovery at Addex Therapeutics
Geneva, Switzerland

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

Response: Metabotropic glutamate receptors represent an attractive therapeutic target for various neurologic conditions. In particular, the metabotropic glutamate receptor subtype 2 (mGlu2) can affect excitatory synaptic transmission by decreasing glutamate release. As excess gluatamate is observed in epilepsy, targeting mGlu2 could lead to new avenues of therapy. Positive allosteric modulators (PAMs) of mGlu2 could be valuable candidate drugs as they do not directly activate receptors. Therefore, they may avoid tachyphylaxis and side effects emerging from direct receptor agonism. 

The publication summarizes the effects obtained when the mGlu2 receptor is activated using an agonist or PAM, such as ADX71149, in the 6Hz psychomotor seizure test, considered to be the most relevant model of pharmacoresistant limbic seizures. The data show that while seizures are reduced when mGlu2-acting compounds are administered alone, their combination with the antiseizure drug levetiracetam (LEV) result in a potent reduction of doses required to produce full efficacy, which is important because higher doses of LEV are associated with dose-limiting side effects, such as aggression, nervousness/anxiety, somnolence and fatigue. In this study, a fixed dose of ADX71149 was seen to increase the potency of LEV, leading to an approximate 35-fold increase in its potency. Conversely, using a fixed dose of LEV with varying doses of ADX71149 resulted in an approximate 14-fold increase in ADX71149 potency.

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Guselkumab Potentially Increases Treatment Choices For Psoriasis

MedicalResearch.com Interview with:

Prof. Dr. med. Kristian Reich Dermatologie, Allergologie Psoriasis- und Neurodermitis-Trainer Hamburg

Prof.  Kristian Reich

Prof. Dr. med. Kristian Reich
Dermatologie, Allergologie
Psoriasis- und Neurodermitis-Trainer
Hamburg

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

Response: Ustekinumab is an antibody against the p40 molecule shared by IL-12 and IL-23. The antibody shows a favorable benfit-risk profile in the treatment of psoriasis. IL-23 is regarded a key driver in psoriasis pathology. It is speculated that antibodies against the IL-23-specific subunit p19 may produce even higher levels of clinical response than ustekinumab or the anti-TNF antagonist adalimumab. Guselkumab is the first IL-23p19 antibody to publish phase III data in psoriasis.   
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Antidepressants Have Variable Effects On Symptom Clusters

MedicalResearch.com Interview with:

Adam Chekroud PhD Candidate Human Neuroscience Lab

Adam Chekroud

Adam Chekroud
PhD Candidate
Human Neuroscience Lab
Department of Psychology
Yale University

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

Response: We know that depression includes a wide range of symptoms, from low mood and feeling worthless, to problems sleeping, slowed thinking, and suicidal ideation.

We wanted to know whether antidepressants work well in treating all of these symptoms, or whether they are primarily effective on certain kinds of symptoms.

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SWORD Study Demonstrates Two-Drug Control of HIV

MedicalResearch.com Interview with:

Kati Vandermeulen Senior Director, Global Regulatory Leader and Compound Development Team Lead IDV Janssen

Kati Vandermeulen

Kati Vandermeulen
Senior Director, Global Regulatory Leader and Compound Development Team Lead
IDV Janssen

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

Response:  SWORD is the first large trial program specifically conducted to look at the combination of dolutegravir and rilpivirine as a complete, two-drug antiretroviral regimen. Results of the two identical Phase III SWORD studies have been positive and demonstrate that the two-drug regimen of dolutegravir and rilpivirine is as effective, with comparable tolerability, to traditional three- or four-drug (integrase inhibitor-, non-nucleoside reverse transcriptase inhibitor-, or boosted protease inhibitor-based) antiretroviral regimens for the maintenance treatment of HIV.
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5-alpha reductase inhibitors For BPH Linked to Higher, Not Lower, PSA Levels

MedicalResearch.com Interview with:
Teemu J Murtola, MD, PhD, adjunct professor
University of Tampere, Faculty of Medicine and Life Sciences
Tampere University Hospital, Department of Urology
Tampere, Finland

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

Response: A previous study called Prostate Cancer Prevention Trial
(PCPT) showed that finasteride, which belongs to a drug group called
5alpha-reductase inhibitors lowers serum PSA and increases sensitivity
of PSA to detect high-grade prostate cancer in men who had little or
no symptoms of the lower urinary tract. We postulated that this effect
would increase the accuracy and benefits of PSA-based prostate cancer
screening.

Finnish Randomized Study of Screening for Prostate Cancer was a large
trial of over 80,000 men randomized either to be screened for prostate
cancer with a PSA test at 4-year intervals or to be followed for
prostate cancer incidence and mortality via national registries. Three
consecutive screening rounds were commenced between 1996-2008. In the
current study we compared the effects of PSA-based screening on
prostate cancer risk and mortality separately among men who were using
5alpha-reductase inhibitors finasteride or dutasteride and among men
who were not.

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Roles of Angiotensin Peptides and Recombinant Human ACE2 in Heart Failure

MedicalResearch.com Interview with:

Gavin Y Oudit, MD, PhD, FRCPC Associate Professor, Department of Medicine, University of Alberta Clinician-Scientist, Mazankowski Alberta Heart Institute Canada Research Chair in Heart Failure Division of Cardiology, 2C2 Walter Mackenzie Health Sciences Centre Edmonton, Alberta

Dr. Gavin Oudit

Gavin Y Oudit, MD, PhD, FRCPC
Associate Professor, Department of Medicine, University of Alberta
Clinician-Scientist
Mazankowski Alberta Heart Institute
Canada Research Chair in Heart Failure
Division of Cardiology
Edmonton, Alberta

Heart specialist Gavin Oudit and his research team discovered a molecule — angiotensin converting enzyme 2 (ACE2)—that works to restore balance to the pathways responsible for chronic and acute heart failure, including in hearts from patients with advanced heart failure who underwent heart transplants.

In developing the new drug, Oudit and his team discovered to an extent not seen before how the renin-angiotensin system (RAS), which regulates the body’s sodium balance, fluid volume, and blood pressure, is at play in both acute and chronic heart failure. In collaboration with Dr. Oudit, recombinant human ACE2 was made by Apeiron Biologics, purchased by GlaxoSmithKline, and has recently completed phase II clinical trial.

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Multiple Treatment Options Now Available for Multiple Sclerosis

MedicalResearch.com Interview with:

Tomas Kalincik, MD, PhD, PGCertBiostat Neurologist and Senior Research Fellow Melbourne Brain Centre | Department of Medicine | University of Melbourne Department of Neurology | Royal Melbourne Hospital Melbourne | Victoria | Australia

Dr. Tomas Kalincik

Tomas Kalincik, MD, PhD, PGCertBiostat
Neurologist and Senior Research Fellow
Melbourne Brain Centre | Department of Medicine | University of Melbourne
Department of Neurology | Royal Melbourne Hospital
Melbourne | Victoria | Australia

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

Response: Multiple sclerosis is a disease predominantly of young adults, with the peak of incidence in the 3rd and 4th decades. It is the most common cause of neurological disability in young adults. Only in Australia, 23,000 people are living with MS, with MS representing an annual cost of almost 1 billion $AU to the Australian society. It is a disease that presents with broad range of neurological symptoms and signs, which are typically temporary (these are called relapses) that with time can lead to permanent neurological disability. While there is currently no cure for MS, with appropriate therapy, its symptoms can be controlled and the disability progression slowed down.

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Aspirin Promotes Growth of Staph aureus in Nose

MedicalResearch.com Interview with:
Dr. Fernanda Buzzola

IMPaM, UBA-CONICET

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

Response: Staphylococcus aureus represents a serious problem to public health due to methicillin-resistance and the bacterial persistence over a long period of time in the host. Approximately the 20% of the human population is at risk to acquire an endogenous infection by S. aureus as a consequence of its asymptomatic nasal colonization.

Aspirin, the main source of salicylic acid in the human host, is currently taken by millions of human beings worldwide without medical prescription and widely indicated for defined purposes, including prevention of coronary thrombosis. Salicylic acid is a plant hormone known too for its use as a key ingredient in anti-acne preparations and medications for skin conditions. We also consume mild doses of salicylic acid when we eat fruits and vegetables. Iron is an important trace element for the human body and plays an essential role in blood formation. The metabolism of many bacteria, including S. aureus, also depends on the availability of iron molecules. Salicylic acid forms complexes with iron ions in the blood and so deprives not only us but also the staphylococcal bacteria of this element. S. aureus modifies its metabolism if the iron content is insufficient. The microorganism reacts to the changed – from its perspective, negative – conditions through the intensified formation of a biofilm, a sort of layer of slime formed by the aggregation of individual bacteria. The enhanced biofilm production allows the bacteria to survive for an even longer period under unfavourable living conditions.

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NSAIDS Have Minimal Effect On Back Pain and Risk GI Side Effects

MedicalResearch.com Interview with:

Dr. Gustavo Machado BPhty (Hons) Cert.MDT The George Institute for Global Health Sydney Medical School, University of Sydney Sydney, New South Wales, Australia

Dr. Gustavo Machado

Dr. Gustavo Machado BPhty (Hons) Cert.MDT
The George Institute for Global Health
Sydney Medical School, University of Sydney
Sydney, New South Wales, Australia

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

Response: People with back pain are usually told by their health care practitioners to take analgesic medications to relieve their pain. But our previous research published in the BMJ showed that paracetamol does not have a measurable impact on patient’s symptoms. This resulted in recent changes in guidelines’ recommendations. The 2017 National Institute for Health and Care Excellence (NICE) guidelines/UK no longer recommend paracetamol as a stand-alone intervention for back pain.

So now non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as the analgesic of first choice. However, our results show that compared to placebo, commonly used NSAIDs, such as Ibuprofen (e.g. Nurofen) and Diclofenac (e.g. Voltaren), provide only small benefits for people with back pain while increasing the risk of gastrointestinal adverse effects by 2.5 times.

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Treatment With Liraglutide (Victoza) Reduces Fat Around the Heart

MedicalResearch.com Interview with:

Gianluca Iacobellis MD PhD Professor of Clinical Medicine Division of Endocrinology, Diabetes and Metabolism Department of Medicine University of Miami, FL

Dr. Gianluca Iacobellis

Gianluca Iacobellis MD PhD
Professor of Clinical Medicine
Division of Endocrinology, Diabetes and Metabolism
Department of Medicine
University of Miami, FL

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

Response: We know that epicardial fat, the visceral fat of the heart, is associated with coronary artery disease, diabetes and obesity. My studies have shown that epicardial fat can be easily measured with non invasive imaging procedures. Remarkably, epicardial fat has recently emerged as therapeutic target responding to medications targeting the fat. Liraglutide, a GLP-1 analog has shown to provide modest weight loss and beneficial cardiovascular effects beyond its glucose lowering action. So , we sought to evaluate the effects of liraglutide on epicardial fat.

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