Everolimus Treats Underlying Cause of Tuberous Sclerosis Seizures

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MedicalResearch.com Interview with:
Jacqueline French, MD
Professor, Department of Neurology
Director Translational Research& Clinical Trials Epilepsy
NYU Langone Medical Center 

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

Dr. French:  Tuberous sclerosis complex (TSC) is a disease associated with abnormal cell growth, caused by dysfunction of the TSC1 or TSC2 genes and dysruption of the MTOR pathway, which leads to cortical malformations, neuronal hyperexcitability, and seizures. Seizures in patients with TSC often start within the first year of life, and tend not to respond to traditional treatments. Everolimus is a marketed drug that has been used to treat other manifestations of TSC (including giant cell tumors of the brain, renal angiomyolipomas, and angiofibromas of the skin).

This study was a placebo-controlled add-on study of everolimus for the treatment of refractory seizures in children and adults with epilepsy.Following an 8-week baseline phase, patients aged 2-65 years (stratified by age) with TSC and refractory seizures on 1-3 antiepileptic drugs were randomized to EVE LT or HT Cmin target ranges or placebo, and treated in an 18 week Core Phase (6-wk titration + 12-wk maintenance). Primary endpoints were change from baseline in average weekly frequency of TSC-seizures (seizures not previously shown to be generalized in onset by EEG), expressed as response rate (≥50% reduction [RR]), and percentage reduction.

MedicalResearch.com: What are the main findings?

Dr. French:  Overall, 366 patients were randomized to EVE LT (n=117), HT (n=130), or placebo (n=119). The median percentage reduction in TSC-seizures was significantly greater with EVE LT (29.3%, P=0.003) and HT (39.6%, P<0.001) vs placebo (14.9%). RR was also significantly greater with EVE LT (28.2%, P=0.008) and HT (40%, P<0.001) vs placebo (15.1%). The most frequent ≥10% all grade adverse events (AEs) reported with EVE LT/HT vs placebo included stomatitis (28.2%/30.8% vs 3.4%), diarrhea (17.1%/21.5% vs 5%), mouth ulceration (23.9%/21.5% vs 4.2%), nasopharyngitis (13.7%/16.2% vs 16%), upper respiratory tract infection (12.8%/15.4% vs 12.6%), aphthous ulcer (4.3%/14.6% vs 1.7%), and pyrexia (19.7%/13.8% vs 5%). Discontinuations due to AEs (5.1%/3.1% vs 1.7%) were low.

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Monitoring Circulating Tumor Cells May Further Personalized Cancer Treatment

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MedicalResearch.com Interview with:

Dr. Elodie Sollier
Chief Scientific Officer at Vortex Biosciences

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

Response: Circulating Tumor Cell (CTC) burden may be a useful biomarker of response to targeted therapy in PDX (Patient Derived Xenograft) mouse models. Vortex Biosciences’ technology has been proven to enrich CTCs from human blood, but use of the technology with mouse blood had not yet been explored. In this poster, human CTCs are isolated with both high efficiency and purity from xenograft model of breast cancer using Vortex’s technology. Circulating Tumor Cell enumeration increased as the tumor burden increased in the mouse demonstrating its utility as a biomarker for drug treatment response.

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Slight Increase Risk of Alzheimer’s Disease in Patients With Rosacea

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MedicalResearch.com Interview with:

Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital, University of Copenhagen Hellerup, Denmark

Dr. Alexander Egeberg

Alexander Egeberg, MD PhD
National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology
Herlev and Gentofte University Hospital
University of Copenhagen
Hellerup, Denmark 

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

Dr. Egeberg: Certain proteins and inflammatory processes have been found in increased levels in the skin of patients with rosacea, and these have also been linked to dementia, in particular Alzheimer’s disease. While this may be one potential explanation, we cannot say for sure that this is the cause. Our team have recently shown a link between rosacea and other neurological diseases, and single-case reports have previously described a possible association between rosacea and Alzheimers disease.

However, this is the first comprehensive investigation of Alzheimer’s disease in a large population of patients with rosacea. We found a slightly increased risk of dementia, in particular Alzheimer’s disease in patients with rosacea.

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Dilute Apple Juice May Be More Palatable For Rehydration In Children with Mild Gastroenteritis

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MedicalResearch.com Interview with:

Stephen B. Freedman MDCM, MSc, Associate Professor Department of Paediatrics, Sections of Emergency Medicine and Gastroenterology; ACHRI Healthy Outcomes Theme Group Leader Alberta Children’s Hospital, and Alberta Children’s Hospital Research Institute University of Calgary, Calgary, Canada

Dr. Stephen Freedman

Stephen B. Freedman MDCM, MSc,
Associate Professor
Department of Paediatrics, Sections of Emergency Medicine and Gastroenterology;
ACHRI Healthy Outcomes Theme Group Leader
Alberta Children’s Hospital, and Alberta Children’s Hospital Research Institute
University of Calgary,
Calgary, Canada

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

Dr. Freedman: As a pediatric emergency medicine physician I continue to see large numbers of children who are brought for emergency care because of vomiting and diarrhea. In speaking with their caregivers it is clear that many of them try to administer electrolyte maintenance solutions at home but the children either refuse to drink them or they continue to vomit. As a researcher I have noticed that many children continue to receive intravenous rehydration despite not being significantly dehydrated and it appeared that this was often a physician’s response to a failed oral rehydration challenge in the emergency department, either due to refusal to consume the electrolyte maintenance solution supplied or because the children became more nauseous due to the poor palatability of the solution. It appeared that perhaps a less dogmatic approach aimed at providing fluids that children actually like, might overcome these problems leading to improved outcomes.

MedicalResearch.com: What are the main findings?

Dr. Freedman: Children with mild gastroenteritis and minimal dehydration experienced fewer treatment failures when offered dilute apple juice followed by their preferred fluid choice compared with those instructed to drink electrolyte maintenance solution to replace fluid losses. We found the benefit was greatest in those 24 to 60 months of age. The group provided and instructed to take their preferred fluids were administered intravenous rehydration less frequently.

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Aerial Pesticides Linked to Developmental Delay and Autism Spectrum Disorder

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MedicalResearch.com Interview with:

Steven Daniel Hicks, M.D., Ph.D. Penn State Hershey Medical Group Hope Drive, Pediatrics Hershey, PA 17033

Dr. Steven Hicks

Steven Daniel Hicks, M.D., Ph.D.
Penn State Hershey Medical Group Hope Drive, Pediatrics
Hershey, PA 17033 

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

Dr. Hicks:  This research was inspired by results of the CHARGE study (examining environmental influences on autism) which showed that specific pesticides (including pyrethroids) increased the risk of autism and developmental delay, particularly when mothers were exposed in the 3rdtrimester.

We recognized that the department of health sprayed pyrethroids from airplanes in a specific area near our regional medical center every summer to combat mosquito borne illnesses. We asked whether children from those areas had increased rates of autism and developmental delay. We found that they were about 25% more likely to be diagnosed with a developmental disorder at our medical center than children from control regions without aerial spraying of pyrethroids.

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Biomarker Mutations Offer Prognostic Value in Uveal Melanoma

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MedicalResearch.com Interview with:

MedicalResearch.com Interview with: William Harbour, MD Bascom Palmer Eye Institute,  Sylvester Comprehensive Cancer Center  Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine, Miami, Florida    MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Harbour:   Uveal melanoma (UM) is the most common primary cancer of the eye which has the fatal tendency to metastasis to the liver. The molecular landscape of UMs have been well characterized and can be categorized by gene expression profiling (GEP) into two molecular classes associated with metastatic risk: Class 1 (low risk) and Class 2 (high risk). The Class 2 profile is strongly associated with mutations in the tumor suppressor BAP1. This GEP-based test is the only prognostic test for UM to undergo a prospective multicenter validation, an it is available commercially as DecisionDX-UM (Castle Biosciences, Inc).  It is routinely used in many North American centers.  The identification of driver mutations in cancer has become a focus of precision medicine for prognostic and therapeutic decision making in oncology. In UM, thus far, only 5 genes have been reported to be commonly mutated:  BAP1, GNA11, GNAQ, EIF1AX, and SF3B1. In this study, we analyzed the associations between these 5 mutations, and with GEP classification, clinicopathologic features, and patient outcomes. The study showed that GNAQ and GNA11 are mutually exclusive, probably occur early in tumor formation, and are not associated with prognosis.  In contrast, BAP1, SF3B1, and EIF1AX, which are also nearly mutually exclusive, likely occur later in tumor formation and do have prognostic value in UM.  MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Harbour:   These findings suggest that BAP1, SF3B1, and EIF1AX mutations may have clinical value as prognostic markers in UM. Since the GEP remains the most prognostic biomarker in UM, the mutational landscape could supplement the GEP for prognostication.  Several of these markers are also potential therapeutic targets that could guide the selection of a specific treatment on an individual patient basis.   MedicalResearch.com: What recommendations do you have for future research as a result of this study?  Dr. Harbour:   We will be conducting a prospective, 28 center study to evaluate the prognostic value of these mutations as well as another biomarker that we recently reported called PRAME. This could have clinical implications for precision medicine and may aid in the stratification of UM patients for clinical trials.   MedicalResearch.com: Is there anything else you would like to add?  Dr. Harbour:   Mutations in GNAQ and GNA11 occur early in uveal melanoma development and are not prognostically significant.  In contrast, mutations in BAP1, SF3B1 and EIF1AX occur later in tumor progression in a nearly mutually exclusive manner, and they are associated with high, intermediate and low metastatic risk, respectively.     MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.  Citation:  Decatur CL, Ong E, Garg N, et al. Driver Mutations in Uveal Melanoma: Associations With Gene Expression Profile and Patient Outcomes. JAMA Ophthalmol. Published online April 28, 2016. doi:10.1001/jamaophthalmol.2016.0903.   Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions. More Medical Research Interviews on MedicalResearch.com

Dr. J. William Harbour

William Harbour, MD
Bascom Palmer Eye Institute,
Sylvester Comprehensive Cancer Center
Interdisciplinary Stem Cell Institute
University of Miami Miller School of Medicine
Miami, Florida  

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

Dr. Harbour:  Uveal melanoma (UM) is the most common primary cancer of the eye which has the fatal tendency to metastasis to the liver. The molecular landscape of UMs have been well characterized and can be categorized by gene expression profiling (GEP) into two molecular classes associated with metastatic risk: Class 1 (low risk) and Class 2 (high risk). The Class 2 profile is strongly associated with mutations in the tumor suppressor BAP1. This GEP-based test is the only prognostic test for UM to undergo a prospective multicenter validation, an it is available commercially as DecisionDX-UM (Castle Biosciences, Inc).  It is routinely used in many North American centers.

The identification of driver mutations in cancer has become a focus of precision medicine for prognostic and therapeutic decision making in oncology. In UM, thus far, only 5 genes have been reported to be commonly mutated:  BAP1, GNA11, GNAQ, EIF1AX, and SF3B1. In this study, we analyzed the associations between these 5 mutations, and with GEP classification, clinicopathologic features, and patient outcomes. The study showed that GNAQ and GNA11 are mutually exclusive, probably occur early in tumor formation, and are not associated with prognosis.  In contrast, BAP1, SF3B1, and EIF1AX, which are also nearly mutually exclusive, likely occur later in tumor formation and do have prognostic value in UM.

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Racial Disparities in Teen Birth Rate Narrows

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MedicalResearch.com Interview with:

Lisa Romero DrPH, MPH  Division of Reproductive Health National Center for Chronic Disease Prevention and Health Promotion CDC.

Dr. Lisa Romero

Lisa Romero DrPH, MPH 
Division of Reproductive Health
National Center for Chronic Disease Prevention and Health Promotion
CDC

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

Dr. Romero: Since 2006, teen birth rates have fallen almost half among Hispanic and black teens; dropping the national teen birth rate to an all-time low. While dramatic declines among Hispanic and black teens have helped reduce gaps, birth rates remain twice as high for these teens nationally compared to white teens, and more than three times as high in some states. Data also highlight the role socioeconomic conditions play, finding that higher unemployment and lower income and education are more common in communities with the highest teen birth rates, regardless of race.

This research highlights the importance of teen pregnancy prevention interventions that address socioeconomic conditions like unemployment and lower education levels, for reducing disparities in teen births rates. State and community leaders can use local data to better understand teen pregnancy in their communities and to direct programs and resources to areas with the greatest need. 

To generate these findings, we analyzed national- and state-level data from the National Vital Statistics System (NVSS) to examine trends in births to American teens aged 15 to 19 years between 2006 and 2014. County-level NVSS data for 2013 and 2014 offer a point-in-time picture of local birth rates. To better understand the relationship between key social and economic factors and teen birth rates, researchers examined data from the American Community Survey between 2010 and 2014.
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Scientists Rejuvenate Old Stem Cells With Common Vitamin

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MedicalResearch.com Interview with:

Keir Menzies PhD Assistant Professor  University of Ottawa Brain and Mind Research Institute University of Ottawa

Dr. Keir Menzies

Keir Menzies PhD
Assistant Professor
University of Ottawa Brain and Mind Research Institute
University of Ottawa 

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

Dr. Menzies: Currently there is significant amount of research identifying the power of stem cells to regenerate damaged or aging tissue. Our research discovered that reduced stem cell health was linked to unusually low levels of a small molecule called NAD, one of the most important cellular molecules to maintain the performance of mitochondria, the engine of the cell. Then by boosting NAD levels, using a special form of vitamin B3 called nicotinamide riboside, stem cells could be rejuvenated during aging by improving mitochondrial function.  We then go on to show that by improving stem cell function we could prolong the lifespan of mice, even when the treatment began at a relatively old age.

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Within the Umbrella of Schizophrenia Are Separate Diseases For Which Specific Treatments Can Be Developed

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MedicalResearch.com Interview with:

Dolores Malaspina, MD, MPH The Anita and Joseph Steckler Professor, Department of Psychiatry and Professor, Department of Child & Adolescent Psychiatry NYU Langone Medical Center

Dr. Dolores Malaspina

Dolores Malaspina, MD, MPH
The Anita and Joseph Steckler Professor, Department of Psychiatry
and Professor, Department of Child & Adolescent Psychiatry
NYU Langone Medical Center 

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

Dr. Malaspina: Although over one hundred single nucleotide variations in the human genetic code are associated with schizophrenia, using big data these account for a small portion of schizophrenia risk and most of them overlap with risks for other mental conditions.

In a completely different hypothesis generated approach, we focused on identifying rare or novel variations in genes that we earlier found had brand new disrupting mutations for cases with no family history compared to healthy parents.

Four or 5 cases were found with other rare sequences in 4 such influential genes. The respective groups of cases markedly differed in clinical presentations.  

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Malaspina: Within the umbrella diagnosis of Schizophrenia are separate diseases for which specific treatments can be developed. For these genes we identified groups with a developmental condition, early adult deterioration, one with specific working memory dysfunction and one with slow processing speed.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Malaspina: Removing the 30% of cases harboring one of these genes from the patient mix will allow faster progress on the other cases for person specific treatments.

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

Dr. Malaspina: In humans as in other mammals, most new gene disruptions arise in the paternal germ line and are transmitted to young in association with paternal age. This replenishes psychosis genes into the population since persons with the disease have fewer offspring. Once these genes arise the can then be inherited and produce inherited forms of the disease.

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

Citation:

Thorsten M. Kranz, Adam Berns, Jerry Shields, Karen Rothman, Julie Walsh-Messinger, Raymond R. Goetz, Moses V. Chao, Dolores Malaspina.

Phenotypically distinct subtypes of psychosis accompany novel or rare variants in four different signaling genes. EBioMedicine, 2016; DOI: 10.1016/j.ebiom.2016.03.008

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

More Medical Research Interviews on MedicalResearch.com

 

 

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All Preterm Children At Risk of Emotional and Behavioral Problems Upon School Entry

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MedicalResearch.com Interview with:
Jorijn Hornman, BSc (MD PhD student)
Departments of Health Sciences
University Medical Center Groningen
University of Groningen, Netherlands

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

Response: Preterm children are at increased risk of emotional and behavioral problems compared to full-term children. Prevalences vary with degree of prematurity and assessment age. Unknown was whether stability of these problems upon school entry differs between preterm and full-term children.

MedicalResearch.com: What are the main findings?

Response: We found that preterm children had higher rates than full-term children of persistent (7.2% versus 3.6%), emerging (4.3% versus 2.3%), and resolving (7.5% versus 3.6%) emotional and behavioral problems. Early preterm children –born at <32 weeks gestation- had the highest rates of persistent (8.2%) and emerging (5.2%) problems, and moderately preterm children –born at 32-35 weeks gestation- the highest rates of resolving problems (8.7%).

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Many Fragile Neonates Still Receive Acid-Suppressing Medications

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MedicalResearch.com Interview with:

Jonathan Slaughter, MD, MPH Assistant Professor of Pediatrics Center for Perinatal Research Nationwide Children's Hospital/The Ohio State University Columbus, OH 43205

Dr. Jonathan Slaughter

Jonathan Slaughter, MD, MPH
Assistant Professor of Pediatrics
Center for Perinatal Research
Nationwide Children’s Hospital/The Ohio State University
Columbus, OH 43205 

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

Dr. Slaughter:   Increasing data has emerged over the last decade showing potential harm following acid suppression use in newborns, older children, and adults.  There are virtually no published data that show acid suppression via histamine-2-receptor antagonists (H2RAs) or proton-pump inhibitors (PPIs) is effective for gastroesophageal reflux disease (GERD) treatment or for other indications (stress ulcer prophylaxis, post-operative acid suppression) in healthy or sick newborns. Given the potentially limited effectiveness of these medications and increasing safety concerns following H2RA/PPI use in infants, we wanted to evaluate the frequency and duration of H2RA/PPI use among infants hospitalized within US children’s hospital neonatal intensive care units (NICUs) to determine if these drugs appeared to be overused and if use appears to have changed over time.  We also evaluated neonatal diagnoses associated with acid suppression to identify targets for future studies that may evaluate the usefulness of acid suppression in neonates following a given diagnosis.
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Still A Lot Of Work To Do To Reverse Childhood Obesity

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MedicalResearch.com Interview with:

Ashley Wendell Kranjac, PhD Department of Sociology and Kinder Institute for Urban Research Rice University Houston, Texas

Dr. Ashley Kranjac

Ashley Wendell Kranjac, PhD
Department of Sociology and
Kinder Institute for Urban Research
Rice University
Houston, Texas and

Robert L. Wagmiller, Jr. Associate Professor Department of Sociology Temple University Philadelphia, PA 19122

Dr. Robert Wagmiller

Robert L. Wagmiller, Jr.
Associate Professor
Department of Sociology
Temple University
Philadelphia, PA 19122

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

Response: The Center for Disease Control recently reported a decline in child obesity amongst 2-to5-year old children between 2003/4 and 2011/12 (see, Ogden et al. 2014). We aimed to identify the sources of this decline because this change occurred in a relatively short period of time. What we found is that the decline in obesity did not occur due to the things that you might expect like changes in physical activity or dietary practices (although there were some differences in these factors across years). But, rather, what we found is that because there were differences in obesity rates for the youngest and oldest children in this age range in 2003/4, but not in 2011/12, that the decline in obesity exists. In other words, because the oldest children in 2003/4 had significantly higher obesity rates than the youngest children in this time period, but this effect is not observable in 2011/12, we see a decline in obesity.

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