Lack of Awareness of Cognitive Issues Presages Alzheimer’s Disease

MedicalResearch.com Interview with:
Joseph Therriault

Integrative Program in Neuroscience 

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

Response: Neurologists have known for a long time that Anosognosia, or unawareness of illness, appears in individuals with Alzheimer’s disease. For example, these patients will have diminished awareness of their memory loss, and will also engage in dangerous behaviors, such as leaving the house to go for a walk, without knowing they are at high risk of getting lost.

However, it was not known if decreased awareness of cognitive problems existed in the pre-dementia phase of Alzheimer’s disease. In our study, we compared the ratings of cognitive decline from the patient and their close relative, who also filled out the same questionnaire. When a patient reported having no cognitive problems but the family member reported significant difficulties, the patient was considered to have poor awareness of illness.

We found that patients who are less aware had increased disease pathology, and were nearly three times as likely to progress to dementia within two years, even when taking into account other factors like genetic risk, age, gender and education. The increased progression to dementia was mirrored by increased brain metabolic dysfunction in regions vulnerable to Alzheimer’s disease.

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Aggressive Systolic Blood Pressure Control In Older Patients With HFpEF Should Be Avoided

“Doctors” by Tele Jane is licensed under CC BY 2.0MedicalResearch.com Interview with:
Dr. Apostolos Tsimploulis, Chief Medical Resident
Dr. Phillip H. Lam, Chief Cardiology Fellow
The Washington, DC Veterans Affairs Medical Center, Georgetown University, and
MedStar Washington Hospital Center, Washington, DC 

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

Response: Hypertension is a major risk factor for the development of new heart failure (HF). Findings from multiple randomized controlled trials in hypertension have consistently demonstrated that controlling systolic blood pressure (SBP) to normal levels such as to SBP <120 mm Hg reduces the risk of developing new HF.

However, interestingly, once patients develop heart failure, those with a normal SBP value such as SBP <120 mm Hg tend to have poor outcomes. This paradoxical association – also called reverse epidemiology – although poorly understood – has been described with other HF risk factors such as smoking and obesity. Regarding poor outcomes associated with lower SBP in HF patients with reduced ejection fraction (HFrEF – pronounced Hef-ref), it has been suggested that it may be a marker of weak heart muscle that is unable to pump enough blood. However, less is known about this association in patients with HF and preserved ejection fraction (HFpEF – pronounced Hef-pef) –– the heart muscle is not weak in the traditional sense.

This is an important question for a number of reasons: nearly half of all heart failure patients have HFpEF which accounts for about 2.5 to 3 million Americans. These patients have a high mortality similar to those with HFrEF – but unlike in HFrEF few drugs have been shown to improve their outcomes. Thus, there is a great deal of interest in improving their outcomes. One of those approaches is to control . systolic blood pressure and the 2017 ACC/AHA/HFSA Focused Update of the HF guidelines recommend that SBP “should be controlled in patients with HFpEF in accordance with published clinical practice guidelines to prevent morbidity.”

Thus, our study was designed to answer that simple question: do patients with HFpEF and SBP <120 mmHg, which is considered to be normal SBP, have better outcomes than those with SBP ≥120 mmHg.

Using a sophisticated approach called propensity score matching we assembled two groups of patients with HFpEF – one group with SBP <120 mmHg and the other groups had SBP ≥120 mmHg – and patients in both groups were similar in terms of 58 key baseline characteristics. In this population of balanced patients with HFpEF, those with a normal systolic blood pressure had a higher risk of mortality – starting 30 days post-discharge up to about 6 years. Finding from our restricted cubic spline plots suggest that compared with SBP <120 mm Hg, SBP values ≥120 mm Hg (up to 200 mm Hg) was not associated with a higher risk of death.

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Balovaptan Has Potential to Improve Social Interaction and Communication in Autism Spectrum Disorder

MedicalResearch.com Interview with:

Dr Kevin Sanders, MD Principle Medical Director-Product Development Neuroscience Assistant Professor, Departments of Psychiatry and Pediatrics Vanderbilt University

Dr. Sanders

Dr Kevin Sanders, MD
Principle Medical Director-Product Development Neuroscience
Assistant Professor, Departments of Psychiatry and Pediatrics
Vanderbilt University 

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

Response: The FDA has granted Roche Breakthrough Therapy Designation for its investigational oral medicine balovaptan (previously known as RG7314), a vasopressin 1a (V1a) receptor antagonist for individuals with autism spectrum disorder (ASD).

FDA Breakthrough Therapy Designation for balovaptan is primarily based on efficacy findings in the VANILLA (Vasopressin ANtagonist to Improve sociaL communication in Autism) study, a Phase II trial of balovaptan in adults with ASD. Trial results were first presented at the International Congress for Autism Research (IMFAR) in May 2017. Treatment effects were observed on the Vineland-II (secondary endpoint) and also demonstrated that balovaptan was safe and well tolerated by the subjects in the study. The Vineland-II is a scale that measures socialization, communication and daily living skills. This data was presented to the FDA and is part of the basis of the Breakthrough Designation.  Continue reading

ZIKA: Mouse Study Finds Antioxidant Ebselen Reduces Risk of Sexual Transmission

MedicalResearch.com Interview with:

Image of a baby with microcephaly (left) compared to a normal baby (right). This is one of the potential effects of Zika virus. Signs of microcephaly may develop a few months after birth. Wikipedia image

Image of a baby with microcephaly (left) compared to a normal baby (right). This is one of the potential effects of Zika virus. Signs of microcephaly may develop a few months after birth.
Wikipedia image

Yogy Simanjuntak PhD
Postdoctoral Research Fellow
Institute of Biomedical Sciences
Academia Sinica, Taiwan 

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

Response: Despite the low case fatality, Zika virus infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Primarily transmitted by Aedes species mosquitoes, Zika also can be sexually transmitted in humans. By August 2016, the sexual transmission of Zika had been documented in 11 countries worldwide and most of the cases were from male to female. Infectious Zika in semen has been reported. Moreover, unlike in serum or urine samples, Zika RNA can still be detected in semen up to 188 days after the onset of symptoms. In the absence of approved antiviral drugs or vaccines for Zika infection, preventing the disease transmission is critical.

We observed Zika progressively damaged testes by gaining access to testicular cells including sperm. Notably, Zika caused signs of increased testicular oxidative stress and inflammation, characterized by high levels of reactive oxygen species and pro-inflammatory cytokines. Our data indicate that these factors may contribute to testicular damage as well as successful sexual transmission of Zika; thus, we speculate antioxidants might display beneficial effects to alleviate these disease outcomes.

We found that antioxidant ebselen both alleviated testicular damage and prevented sexual transmission of Zika via sperm from infected male mice to uninfected female mice.

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Genetic Pathways Determine Susceptibility to Dengue Shock Syndrome

MedicalResearch.com Interview with:

CDC/ Frederick Murphy

This transmission electron microscopic (TEM) image depicts a number of round, Dengue virus particles that were revealed in this tissue specimen. CDC image

Luisa Pereira PhD
Institute for Research and Innovation in Health
University of Porto 

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

Response: By using admixture mapping along the genome in Thai cohorts, we were able to identify new candidate genes conferring protection/susceptibility to dengue fever. A very interesting result was that the set of genes differed with the dengue phenotype: genes coding proteins that may link to the virus, conditioning its entrance in the host cells and mobility therein were associated with the less severe phenotype; genes related with blood vessels permeability were associated with the dengue shock syndrome.  Continue reading

Combination Axitinib + Pembrolizumab Active Against Renal Cell Carcinoma

MedicalResearch.com Interview with:

Prof. Michael B. Atkins, MD Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center William M. Scholl Professor and Vice-Chair Department of Oncology and  Professor of Medicine Georgetown University Medical Cente

Prof. Atkins

Prof. Michael B. Atkins, MD
Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center
William M. Scholl Professor and Vice-Chair Department of Oncology and
Professor of Medicine
Georgetown University Medical Center 

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

Response: Prior studies combining programmed death-1 (PD-1) checkpoint inhibitors with tyrosine kinase inhibitors of the vascular endothelial growth factor (VEGF)-pathway have been characterized by excess toxicity precluding further development. We hypothesized that axitinib, a more selective VEGF inhibitor would combine safely with pembrolizumab (anti-PD-1) and yield antitumour activity in treatment-naïve patients with advanced renal cell carcinoma.

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Hemophilia B: Rebinyn® Now Available To Treat Acute Bleeds and Surgical Bleeding

MedicalResearch.com Interview with:

Stephanie Seremetis, M.D. Corporate Vice President and Chief Medical Officer Biopharmaceuticals at Novo Nordisk

Dr. Stephanie Seremetis

Stephanie Seremetis, M.D.
Corporate Vice President and Chief Medical Officer
Biopharmaceuticals at Novo Nordisk


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

Response: We’re proud and excited to make Rebinyn® (Coagulation Factor IX (Recombinant), GlycoPEGylated) available as a new extended half-life treatment for hemophilia B management.

Rebinyn® is an injectable medicine used to treat and control bleeding in adults and children with hemophilia B. It can be used to treat bleeds when they occur and to manage bleeding during surgery. Rebinyn® is not used for routine prophylaxis or for immune tolerance induction in patients with hemophilia B.

Hemophilia B is a serious, chronic, inherited bleeding disease that affects about 5,000 people in the U.S. People living with hemophilia B have low levels of clotting Factor IX protein in the blood, often resulting in prolonged or spontaneous bleeding, especially into the muscles, joints or internal organs.  Continue reading

Endocrine Disrupter PFAS Chemicals Linked To Weight Regain, Especially in Women

MedicalResearch.com Interview with:

Gang Liu, PhD Postdoctoral Research Fellow Department of Nutrition Harvard T.H. Chan School of Public Health

Dr. Gang Liu

Gang Liu, PhD
Postdoctoral Research Fellow
Department of Nutrition
Harvard T.H. Chan School of Public Health 

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

Response: Although many approaches can be used to achieve a short-term weight loss, maintenance of weight loss has become a key challenge for sustaining long-term benefits of weight loss. Accumulating evidence has suggested that certain environmental compounds may play an important role in weight gain and obesity development.

The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs), which are extensively used in many industrial and consumer products including food packaging, paper and textile coatings, and non-stick cookware, have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown.

In a 2-year POUNDS Lost randomized clinical trial that examined energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants aged 30-70 years. Body weight was measured at baseline, 6, 12, 18, and 24 months. Resting metabolic rate (RMR) and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline, 6, and 24 months.

We found that higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. On average, women in the highest tertile of PFASs regained 1.7-2.2 kg more body weight than women in the lowest tertile. In addition, higher baseline plasma PFAS concentrations, especially perfluorooctanesulfonic acid (PFOS) and perfluorononanoic acid (PFNA), were significantly associated with greater decline in RMR during the first 6 months and less increase in RMR during weight regain period.  Continue reading

Intake of Sugar-Sweetened Beverages By Both Partners Appears To Harm Fertility

MedicalResearch.com Interview with:

Dr-Elizabeth-Hatch

Dr. Hatch

Dr. Elizabeth E. Hatch, PhD
Professor, Epidemiology
School of Public Health
Boston University

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

Response: We are conducting a large, ongoing, preconception cohort study, PREgnancy STudy Online or PRESTO http://sites.bu.edu/presto/   in the U.S. and Canada of couples who are planning a pregnancy.  The overall goal of the study is to identify factors that affect fertility, measured by the time taken to conceive, and factors that affect the risk of miscarriage.  Since many women are postponing pregnancy until the later reproductive years, we would like to help find behavioral and environmental factors that might either help or harm fertility so that couples can avoid the stress and expense of infertility workups and treatment.  As part of the larger study, we looked at consumption of sugar-sweetened beverages (SSBs) by both the male and female partner, since some previous research suggested that sugar-sweetened beverages might harm semen quality and ovulation.

For this analysis, we included 3,828 women aged 21 to 45 and 1,045 of their male partners. We asked both males and females (in separate baseline questionnaires) about their usual consumption of SSBs over the last month, and we had a drop-down menu with names of individual sodas (both sugar-sweetened and diet) and energy drinks.  We also asked general questions about the frequency of fruit juice and ‘sports drink’ consumption.   In our analysis, we controlled for multiple factors that might ‘confound’ the associations, such as body mass index, education, caffeine, smoking and alcohol consumption, as well as a measure of overall diet quality.

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