Proove Opioid Risk Profile Predictive of Opioid Use Disorder

MedicalResearch.com Interview with:

Maneesh Sharma, M.D</strong> Director of Pain Medicine MedStar Good Samaritan Hospital Medical Director of the Interventional Pain Institute Baltimore, Maryland

Dr. Maneesh Sharma

Maneesh Sharma, M.D
Director of Pain Medicine
MedStar Good Samaritan Hospital
Medical Director of the Interventional Pain Institute
Baltimore, Maryland

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

Response: Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Just in the last year alone according to the CDC, synthetic opioid deaths have increased 72%. As a practicing interventional pain specialist, I am confronted with the challenge of assessing patient risk for opioids as I evaluate multi-modal approaches to effective pain management. Existing tools are inadequate, as they either rely on a urine toxicology test to evaluate a patient’s current potential substance abuse as a predictor of future abuse, or on a patient’s honesty to fill out a questionnaire. We know that many patients who are not currently abusing illicit drugs or misusing prescription medications can develop prescription opioid tolerance, dependence, or abuse—especially with prolonged opioid therapy. Furthermore, we know that patients who are looking to abuse medications or divert those prescriptions will obviously lie on questionnaires.
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CRISPR Gene Editing May Lead To Cure For Retinitis Pigmentosa

MedicalResearch.com Interview with:

Kang Zhang, M.D., Ph.D.</strong> Professor of Ophthalmology Chief, Ophthalmic Genetics Founding Director, Institute for Genomic Medicine Co-Director, Biomaterials and Tissue Engineering, Institute for Engineering in Medicine Board Certification in Ophthalmology Fellowship in Vitreoretinal Disease and Surgery Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou China

Dr. Kang Zhang

Kang Zhang, M.D., Ph.D.
Professor of Ophthalmology
Chief, Ophthalmic Genetics
Founding Director, Institute for Genomic Medicine
Co-Director, Biomaterials and Tissue Engineering, Institute for Engineering in Medicine
Board Certification in Ophthalmology
Fellowship in Vitreoretinal Disease and Surgery
Guangzhou Women and Children’s Medical Center
Guangzhou Medical University
Guangzhou China
MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Retinitis pigmentosa is a common blinding condition characterized by mutations in rod photoreceptor specific genes, night blindness and tunnel visual with eventual loss of day vision. Since it can be caused by numerous different mutations in many genes therefore it has been difficult to provide treatment benefits to a majority of patients. Traditional gene therapy has been in a piece-meal fashion, meaning to create a therapy for a particular gene or mutation. In this paper, we describe a universal gene therapy approach using the latest gene editing technology CRISPR/CAS9 to reprogram rod photoreceptors to cone photoreceptors with reversal of RP and restoration of vision.

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Trunk and Branch Drivers Distinguish Early vs Late Mutations in Hepatocellular Carcinoma

MedicalResearch.com Interview with:
Sara Torrecilla Recio

PhD Student
Mount Sinai Liver Cancer Program – Division of Liver Diseases Icahn School of Medicine at Mount Sinai
New York, NY

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

Response: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which represents the second-leading cause of cancer related death worldwide. The landscape of molecular alterations in HCC has been thoroughly explored using next-generation sequencing technologies in single biopsies of tumors. However, in the recent years it has been demonstrated that not all the regions of a tumor harbor the same molecular alterations. This intra-tumor heterogeneity may lead to a misinterpretation of the molecular landscape of the malignancy since not all the molecular alterations would be captured by single-biopsies.

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New Breast Cancer Genes May Identify Women Who Can Benefit From Enhanced Screening

MedicalResearch.com Interview with:

Fergus J. Couch, Ph.D. Zbigniew and Anna M. Scheller Professor of Medical Research Chair, Division of Experimental Pathology Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, MN 55905

Dr. Couch

Fergus J. Couch, Ph.D.
Zbigniew and Anna M. Scheller Professor  of Medical Research
Chair, Division of Experimental Pathology
Department of Laboratory Medicine  and Pathology
Mayo Clinic
Rochester, MN

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

Response: The main finding is that RAD51D, BARD1, and MSH6 can now be included in the list of moderate risk breast cancer genes. In contrast, other genes such as MRE11A and RAD50 do not increase risk of breast cancer. In addition, we provide initial estimates of the level of breast cancer risk associated with mutations in the genes that cause breast cancer. The “new” breast cancer genes may now be useful for identifying women who can benefit from enhanced screening. These new data will need to be considered by the National Comprehensive Cancer Network (NCCN) which provides guidelines for clinical management of individuals with mutations in cancer predisposition genes. These results will also be useful for identifying members of families who are at increased risk of breast cancer.

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Gene Involved in Defective Skin Barrier and Eczema and Ichthyosis Identified

MedicalResearch.com Interview with:

Akio Kihara, PhD. Laboratory of Biochemistry Faculty of Pharmaceutical Sciences, Hokkaido University Sapporo, Japan

Dr. Akio Kihara

Akio Kihara, PhD.
Laboratory of Biochemistry
Faculty of Pharmaceutical Sciences, Hokkaido University
Sapporo, Japan

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

Response: The skin barrier is the most powerful defensive mechanism terrestrial animals possess against pathogens and harmful substances such as allergens and pollutants. Recent studies indicate that lipids play a central role in skin barrier formation. Multi-lamellar structures consisting of lipids are formed extracellularly in the stratum corneum, the outermost layer of epidermis, and their high hydrophobicity prevents the invasion of external pathogens and compounds.

The stratum corneum-specific lipid acylceramide is especially important for skin barrier formation. Decreases in acylceramide levels are associated with cutaneous disorders such as ichthyosis and atopic dermatitis. However, the mechanism behind acylceramide production is poorly understood, especially regarding the last step of acylceramide production: i.e., esterification of ω-hydroxyceramide with linoleic acid. This means that the broader picture of the molecular mechanisms behind skin barrier formation still remained unclear.

Although PNPLA1 has been identified as an ichthyosis-causative gene, its function in skin barrier formation remains unresolved. In the present study, we revealed that PNPLA1 catalyzes the last step of acylceramide synthesis. Our finding completes our knowledge of the entire pathway of the acylceramide production, providing important insights into the molecular mechanisms of skin barrier formation.

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26 Additional Genes Linked to Intellectual Disability Identified

MedicalResearch.com Interview with:
Dr. Muhammad Ayub MBBS, MRCPsych, MSc., MD

Professor of Psychiatry Chair Division of Developmental Disabilities
Department of Psychiatry Queens
University Kingston
Kingston ON Canada

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

Response: Intellectual Disability affects about 1 percent of the population worldwide. Genetics play a major role in its etiology. Better understanding of the genetic causes is a necessary step in development of improved diagnosis and treatment. Recessive inheritance where the affected child inherits a defective copy of a gene from both the parents is an important genetic mechanism for prevalence of the disease in populations where within family marriages are common. These types of marital bonds are common in South Asia and Middle Eastern countries. The families where parents are related are an effective resource to study recessive forms of Intellectual Disability.

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Colorectal Cancer Risk Model Using Environmental and Genetic Factors

MedicalResearch.com Interview with:

Victor Moreno, PhD. Director of Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain Department of Clinical Sciences, Faculty of Medicine University of Barcelona Barcelona, Spain

Dr. Moreno

Victor Moreno, PhD.
Director of Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain
Department of Clinical Sciences, Faculty of Medicine
University of Barcelona
Barcelona, Spain

Gemma Ibáñez-Sanz, MD Gastroenterologist. *Cancer Prevention and Control Unit, Catalan Institute of Oncology. L’Hospitalet deLlobregat, Barcelona, SPAIN *Gastroenterology Department, Bellvitge University Hospital-IDIBELL,  L’Hospitalet de Llobregat, Spain

Dr. Ibáñez-Sanz

Gemma Ibáñez-Sanz, MD
Gastroenterologist.
*Cancer Prevention and Control Unit, Catalan Institute of Oncology. L’Hospitalet deLlobregat, Barcelona, SPAIN
*Gastroenterology Department, Bellvitge University Hospital-IDIBELL,
L’Hospitalet de Llobregat, Spain 

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

Response: Colorectal cancer (CRC) screening by faecal occult blood testing has been demonstrated to reduce CRC incidence and mortality, as well as being a cost-effective strategy compared to no screening. Currently, the target population is defined basically by age (≥50 years old), which has been called a ‘one-size-fits-all’ strategy. This strategy implies performing unnecessary screening tests in low-risk people leading to avoidable risks for patients and extra costs for the healthcare system. On the other hand, high-risk patients may receive non-invasive testing, which is a suboptimal screening technique in their case. Several risk prediction models, either for  colorectal cancer or advanced neoplasia, have been previously developed, all with limited discriminating ability.

We have developed a risk stratification model that combines environmental factors with family history and genetic susceptibility. Furthermore, we have assessed the relative contribution of these factors and the utility of the model for risk stratification and public health intervention.

MedicalResearch.com: What are the main findings?

Response: Data from common genetic susceptibility loci could be useful to stratify colorectal cancer screening in average-risk population. Individuals in the top quintile of risk alleles have an 82% increased risk compared to those in the lower quintile. We have estimated the impact of determining an individual environmental and genetic risk score in a Spanish CRC screening population. In our model, although the genetic factors are significant contributors, the modifiable risk factors contribute more strongly. Risk assessment may increase screening participation and adoption of healthier lifestyles.

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

Response: On average, each environmental risk factor increases CRC risk by 35%, while each risk allele only increases it by 7%. This implies that the change of one modifiable risk factor towards healthier lifestyle might offset the effect of 4 risk alleles. Given the fact that environmental factors explain part of the CRC risk, we believe it to be important to give thought to incorporating clinical data to encourage individuals to achieve a healthier lifestyle. As the European Code Against Cancer recommends, and our findings confirm, one should have a healthy diet, a healthy body weight, be physically active and should not smoke or a high consumption of alcohol.

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

Response: Future prospective studies should aim to analyse if stratifying by genetic and lifestyle risk scores is useful and cost-effective to improve screening. Subjects with higher predicted risk should probably start screening earlier and decrease the intervals between tests, while low risk individuals could start later or space more the between test intervals.

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

Response: Population acceptability of genetic tests is not well known. We are currently recruiting subjects from colorectal cancer screening and gastroenterology clinics in a study called COLSCREEN to assess risk perception and attitudes regarding genetic testing to prevent cancer.

No disclosures

Citation:

Sci Rep. 2017 Feb 24;7:43263. doi: 10.1038/srep43263.

Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study.

Ibáñez-Sanz G1, Díez-Villanueva A1, Alonso MH1,2, Rodríguez-Moranta F2,3, Pérez-Gómez B2,4,5, Bustamante M2,6, Martin V2,7, Llorca J2,8, Amiano P2,9, Ardanaz E2,10, Tardón A2,11, Jiménez-Moleón JJ2,12, Peiró R2,13, Alguacil J2,14, Navarro C2,15, Guinó E1,2, Binefa G1,2, Navarro PF2,4,5, Espinosa A2,6, Dávila-Batista V7, Molina AJ2,7, Palazuelos C8, Castaño-Vinyals G2,6,16,17, Aragonés N2,4,5, Kogevinas M2,6,16,17,18, Pollán M2,4,5, Moreno V1,2,19.

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

BRCA Testing Shifts From Cancer Patients to Unaffected Women

MedicalResearch.com Interview with:

Fangjian Guo, MD, PhD Department of Obstetrics and Gynecology Center for Interdisciplinary Research in Women’s Health University of Texas Medical Branch Galveston TX

Dr. Fangjian Guo

Fangjian Guo, MD, PhD
Department of Obstetrics and Gynecology
Center for Interdisciplinary Research in Women’s Health
University of Texas Medical Branch
Galveston TX

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

Response: BRCA testing in patients diagnosed with early-onset breast or ovarian cancer can identify women with high-risk mutations, which can guide treatment. Women who learn they have a high-risk mutation may also want to inform family members that they may also carry a high-risk mutation.

Additionally, BRCA testing can be used to identify high-risk mutation carriers before they develop breast or ovarian cancer. Carriers can then manage their cancer risks with screening (MRI/mammogram), chemoprevention, or prophylactic surgery. Current guidelines recommend BRCA testing for individuals who are considered high-risk for breast or ovarian cancer based on personal or family history.  However, this practice fails to identify most BRCA mutation carriers. It is estimated that more than 90% of mutation carriers have not been identified. One of the issues is that many women who do get tested are actually low-risk and do not have any personal or family history of breast or ovarian cancer.

This study assessed how BRCA testing was used in the US health care system during the past decade. We found that in 2004 most of the tests (75.7%) were performed in patients who had been diagnosed with breast or ovarian cancer. Only 24.3% of tests were performed in unaffected women. However, since 2006, the proportion of BRCA tests performed in unaffected women has increased sharply, with over 60% of the tests performed in unaffected women in 2014.

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Based on Genetic Profile, Longer Adjuvant Treatment Recommended for Some GIST Tumors

MedicalResearch.com Interview with:
Heikki Joensuu, MD

Department of Oncology
Helsinki University Hospital
University of Helsinki
Helsinki, Finland 

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

Response: The randomized Scandinavian Sarcoma Group (SSG) XVIII trial compared three years of adjuvant imatinib to one year of adjuvant imatinib as adjuvant treatments of patients who had undergone macroscopically complete surgery for a GIST with a high risk for tumor recurrence. In this trial, patients treated with 3 years of imatinib had improved overall survival as compared to those who were allocated to one year of adjuvant imatinib. In 2 other randomized trials that compared either 1 year of adjuvant imatinib to one year or placebo, or 2 years of adjuvant imatinib to observation, no improvement in overall survival was found, although in all three trials adjuvant imatinib improved recurrence-free survival (RFS). The reasons for the discrepant findings with respect of overall survival in the 3 trials have been unclear.

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Discovery of New Gene That Causes Sudden Death in Young Athletes

MedicalResearch.com Interview with:
Lia Crotti, MD, PhD

Department of Cardiovascular, Neural and Metabolic Sciences
San Luca Hospital
IRCCS Istituto Auxologico Italiano

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

Response: Sudden cardiac death in one of the major cause of death in Western Countries and among the causes of these deaths in young people under the age of 35, inherited forms of cardiomyopathy have a prominent role. Among these cardiomyopathies, Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) plays a major role. In ARVC, the heart tissue is replaced by fatty and fibrous tissue. This process encourages the development of life-threatening arrhythmias, such as ventricular fibrillation, that causes a cardiac arrest and sudden death in few minutes without a ready device to shock the heart. Intense physical activity favors the progression of the disease and arrhythmias are frequently triggered by adrenergic activation: those are the reason why young athletes with this disease are at high risk.

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70-Gene Signature Changes 50% of Breast Cancer Chemotherapy Advice

MedicalResearch.com Interview with:
Anne Kuijer, MD

Departments of Surgery and Radiology
University Medical Center Utrecht and
Thijs van Dalen, PhD
Department of Surgery
Netherlands Cancer Institute, Amsterdam

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

Response: In recent years it has become evident that clinicopathological factors fail to accurately determine prognosis in hormone receptor positive early stage breast cancer patients at intermediate risk of developing metastases. Gene-expression profiles, such as the 70-gene signature (MammaPrint) are therefore increasingly used for chemotherapy decision-making. In the current multicentre study we assessed the impact of 70-gene signature use on chemotherapy decisions in these patients. We demonstrated that, without the use of the 70-gene signature, half of patients was advised chemotherapy, which reflects the current controversy regarding chemotherapy benefit. Use of the 70-gene signature changed the chemotherapy advice in half of all patients and adherence to the 70-gene signature result was high.

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Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy

MedicalResearch.com Interview with:

Sara Saberi, MD Assistant Professor Inherited Cardiomyopathy Program Frankel Cardiovascular Center University of Michigan Hospital and Health Systems

Dr. Sara Saberi

Sara Saberi, MD
Assistant Professor
Inherited Cardiomyopathy Program
Frankel Cardiovascular Center
University of Michigan Hospital and Health Systems 

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

Response: Patients with hypertrophic cardiomyopathy are often told not to exercise or to significantly curb their exercise due to concern over the potential risk of increased ventricular arrhythmias and sudden cardiac death. There is no data regarding risks/benefits of exercise in HCM though. There is, however, data that shows that patients with HCM are less active and more obese than the general population AND a majority feel that exercise restrictions negatively impact their emotional well-being.

So, we devised a randomized clinical trial of a 16-week moderate-intensity aerobic exercise program versus usual activity with the primary outcome being change in peak VO2 (oxygen consumption). This exercise intervention resulted in a 1.27 mL/kg/min improvement in peak VO2 over the usual activity group, a statistically significant finding. There were no major adverse events (no death, aborted sudden cardiac death, appropriate ICD therapies, or sustained ventricular tachycardia). There was also a 10% improvement in quality of life as measured by the Physical Functioning scale of the SF-36v2.

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