PITS Gene Linked To Rare Neurologic Disorders

MedicalResearch.com Interview with: 

Paul C Marcogliese, Ph.D. Postdoctoral Associate, Laboratory of Dr. Hugo Bellen Department of Molecular and Human Genetics Baylor College of Medicine Houston, Texas 77030

Dr. Marcogliese

Paul C Marcogliese, Ph.D.
Postdoctoral Associate,
Laboratory of Dr. Hugo Bellen
Department of Molecular and Human Genetics
Baylor College of Medicine
Houston, Texas 77030

Loren D. Pena, MD PhD Pediatric Medical Genetics Specialist Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine, Durham, NC

Dr. Peña


Loren D. Pena, MD PhD
Division of Human Genetics
Cincinnati Children’s Hospital Medical Center
Department of Pediatrics
University of Cincinnati
Cincinnati, OH 45229


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

Response: The Undiagnosed Diseases Network (UDN) is a multi-site collaboration across the US that seeks to help diagnose patients with rare disorders that are ill-defined.

Dr. Loren D.M. Pena and Dr. Vandana Shashi at the Duke-Columbia clinical site of the UDN had seen a patient with a severe neurological disorder. While the patient had no symptoms at birth, the patient began falling at about 3 years of age, eventually losing motor coordination and developing seizures. In the interim, the regression has progressed to a severely debilitating state. Re-analysis of the participant’s exome data by our site bioinformatician at Columbia (Nicholas Stong) in Dr. David Goldstein’s laboratory revealed a truncating variant in the single exon gene IRF2BPL that could be the candidate disease-causing gene. The UDN clinicians at Duke then contacted the UDN Model Organism Screening Center (MOSC) led by Dr. Hugo Bellen at Baylor College of Medicine and the Howard Hughes Medical Institute for functional analysis. In parallel, four more patients were found with truncating mutations causing a similar disorder though the UDN and GeneMatcher.org. Additionally, two patients with missense variants in IRF2BPL were identified that displayed seizures and some developmental delay or autism spectrum disorder but no motor regression.

Work in MOSC by Dr. Paul Marcogliese using fruit flies revealed that the IRF2BPL truncating variants are severe loss of function mutations and one of the missense variants was a partial loss of function. Additionally, it was found that the fruit fly IRF2BPL gene, called pits, is expressed in the neurons of the adult fly brain. Lowering the levels of pits by about 50% in fly neurons leads to progressive behavioural abnormalities and neurodegeneration. By combining the human genetics, bioinformatics and model organism data, IRF2BPL was found to be a novel disease-causing gene in humans.

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Cognitive Changes Mapped Over Time in Young Persons at Risk for Psychosis

MedicalResearch.com Interview with:

Richard Keefe PhD Professor in Psychiatry and Behavioral Sciences Duke Institute for Brains Sciences

Dr. Keefe

Richard Keefe PhD
Professor in Psychiatry and Behavioral Sciences
Duke Institute for Brains Sciences

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

Response: A lot of studies have shown that cognitive deficits are present in young people at risk for psychosis. There have been calls for investigations of the idea that cognition declines over time in the young people who are at highest risk, but longitudinal studies are hard to conduct so not much work has been done to address this question.

The main finding from our study is that the cognitive architecture – the way the various aspects of cognitive functioning appear to be organized in each individual’s brain based upon their pattern of performance – changes over time in those young people who are in the midst of developing psychosis. Interestingly, cognitive architecture also becomes more disorganized in those whose high-risk symptoms do not remit over a two year period, and is related to the functional difficulties they may be having. The young people whose high risk symptoms were present at the beginning of the study but remitted later actually improved cognitively over the two year period of the study. Continue reading

Recombinant Polio Vaccine Improved Survival Rate Among Some With Aggressive Recurrent Brain Tumor

MedicalResearch.com Interview with:

Dr. Annick Desjardins, Assistant Professor of Medicine, photographed on October 2, 2013.

Dr. Desjardins

Annick Desjardins, M.D., F.R.C.P.C.
Associate Professor of Neurology
Associate Professor of Neurosurgery
Director of Clinical Research
The Preston Robert Tisch Brain Tumor Center at Duke
Duke University School of Medicine
Durham, NC 27710

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

Response: The poliovirus receptor (CD155) is an onco-fetal cell adhesion molecule with widespread expression in all solid tumors and particularly in primary CNS tumors (adult and pediatric).

Recombinant nonpathogenic polio–rhinovirus chimera (PVSRIPO) was generated by replacing a critical piece of the genetic information from the Sabin type 1 polio vaccine, making PVSRIPO incapable of harming or killing normal brain cells, but toxic/lethal in cancer cells. In preclinical models, it has been demonstrated that the infection of tumor cells, leads to the release of danger signals, which triggers a recruitment of dendritic/CD4/CD8 T cells and a destruction of tumor cells by anti-tumor T cells.

The manuscript reports the results of the phase 1 trial of PVSRSIPO in recurrent WHO grade IV malignant glioma patients. Adult patients with recurrence of a single glioblastoma lesion, 1-5.5cm in dimension, in a non-eloquent area of the brain, were enrolled on study. PVSRIPO is injected slowly over 6.5 hours directly into the tumor via a small catheter inserted via a small bur hole. Once intratumoral injection is completed, the catheter is removed and patients are observed for localized tumor inflammation, followed by tumor contraction. A total of 61 patients were treated on study, 9 patients in a dose escalation phase and 52 in a dose expansion phase. Side effects observed were in relation to the localized inflammation of the tumor and depending on the cerebral functions in close proximity to the tumor: headaches, visual field changes, hemiparesis, etc.

One patient experienced a brain hemorrhage at the time of catheter removal, which triggered right sided weakness and aphasia. The patient remained alive 57.5 months after PVSRIPO infusion at data cutoff of March 20th, 2018. Two on-study death were observed, a patient died from cerebral edema and seizures, which was later found to be due to tumor progression, and one patient died from the complications of an intracranial hemorrhage while receiving anticoagulation and bevacizumab.

The median overall survival among all 61 patients who received PVSRIPO was 12.5 months (95% CI, 9.9 to 15.2), comparatively to 11.3 months (95% CI, 9.8 to 12.5) in a historical control group of patients treated at Duke and who would have met eligibility on trial, would have the trial been available to them.

At 24 months, the survival plateaued in patients treated with PVSRIPO with an overall survival rate of 21% (95% CI, 11 to 33) at 24 months and 36 months in PVSRIPO treated patients, while overall survival in the historical control group continued to decline, with an overall survival rates of 14% (95% CI, 8 to 21) at 24 months and 4% (95% CI, 1 to 9) at 36 months in the historical control group.  Continue reading

African Americans Less Likely To Be Treated With Statins

MedicalResearch.com Interview with:

Michael G. Nanna, MD Fellow, Division of Cardiology Duke University Medical Center Durham, NC

Dr. Nanna

Michael G. Nanna, MD
Fellow, Division of Cardiology
Duke University Medical Center
Durham, NC

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

Response: We know that African Americans are at higher risk for cardiovascular disease than white patients. We also know that African American individuals have been less likely to receive statin therapy compared to white individuals in the past. However, the reasons underlying these racial differences in statin treatment are poorly understood. We set out to determine if African American individuals in contemporary practice are treated less aggressively than whites and, if so, we wanted to investigate potential reasons why this might be the case.

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Female Residents Do Not Perceive Cardiology As Conducive To Work-Family Balance

MedicalResearch.com Interview with:

Pamela S. Douglas, MD, MACC, FASE, FAHA Ursula Geller Professor of Research in Cardiovascular Disease Duke University School of Medicine  Durham, NC 27715   

Dr. Douglas

Pamela S. Douglas, MD, MACC, FASE, FAHA
Ursula Geller Professor of Research in Cardiovascular Disease
Duke University School of Medicine
Durham, NC 27715    

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

Response: For any profession to succeed, it needs to attract top talent. We surveyed internal medicine residents to find out what they valued most in their professional development, how they perceived cardiology as field and how these two areas are associated with  their choosing a career in cardiology or another specialty.

We found that trainees were seeking careers that had stable hours, were family friendly and female friendly, while they perceived cardiology to  have adverse work conditions, interfere with family life and to not be diverse. We were able to predict career choice with 89-97% accuracy from these responses; the predictors are mix of things that attract to cardiology and those that are deterrents.

For men, the attractors outnumber the deterrents, for women its just the opposite.

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Higher Connectivity of Brain Networks Linked to Increased Risk of Psychopathology

MedicalResearch.com Interview with:

Maxwell Elliott Clinical psychology PhD student Working with Ahmad Hariri and the Moffitt & Caspi lab Duke University

Maxwell Elliott

Maxwell Elliott
Clinical psychology PhD student
Working with Ahmad Hariri and the Moffitt & Caspi lab
Duke University

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

Response: The traditional clinical science model identifies individuals who meet specific criteria for mental illness diagnoses (e.g. Depression, Anxiety) and compares them to “healthy” controls to find brain correlates of mental illness.  However, this approach often overlooks the high rates of comorbidity and shared symptamatology across mental illnesses. Emerging research has identified a general factor of psychopathology that accounts for shared risk among internalizing, externalizing, and thought disorders across diverse samples.

This general factor of psychopathology has been called the p-factor. In our study we investigate the brain correlates of the p-factor using a data-driven analysis of resting state functional connectivity. We find that higher p-factor scores and associated risk for common mental illness maps onto hyper-connectivity between visual association cortex and both frontoparietal and default mode networks.

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Cardiovascular Trials Need Better Characterization of Heart Failure in Diabetics

MedicalResearch.com Interview with:

Stephen J. Greene, MD Division of Cardiology Duke University Medical Center Durham, NC

Dr. Greene

Stephen J. Greene, MD
Division of Cardiology
Duke University Medical Center
Durham, NC

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

Response: In 2008, the United States FDA issued an industry guidance specifying that diabetes drugs should routinely be tested in large cardiovascular outcome trials to confirm cardiovascular safety. The guidance specifically mentioned cardiovascular safety in terms of MACE, or major adverse cardiac events, including cardiovascular death, myocardial infarction, and stroke.  Largely because of this, these trials have traditionally had a focus on cardiovascular disease in terms of atherosclerotic events. Heart failure was not mentioned in the FDA document and these trials have had a lesser focus on it.

As the years have gone by, we have learned more and more about the connection between diabetes and heart failure. There is tremendous overlap between the two patient populations. Also, as more and more of the large cardiovascular outcome trials have been completed, we have seen multiple examples of various glucose lowering therapies either increasing or decreasing risk of heart failure events. Given all these data on heart failure/ diabetes interactions, the goal of our research was to carefully examine all of the completed large cardiovascular outcome trials of diabetes therapies to systematically describe the type of heart failure-related data they capture. As an initial step in improving heart failure characterization in these trials, we wanted to first describe what trials have already been doing and where the gaps in understanding heart failure in these trials exist.

Overall, we found major gaps in the amount and quality of the heart failure data capture in these trials. We looked at 21 large trials, including over 150,000 patients. Rates of patients with baseline heart failure were inconsistently provided, and among those trials that did provide it, heart failure patients tended to be underrepresented compared to the general population. Patients with baseline heart failure were also poorly characterized, with minimal data on functional status, ejection fraction, or heart failure medications. Only 6 trials reported rates of new-onset heart failure and the definitions used were non-specific. Most trials tended to report rates of heart failure hospitalization, but did not include data on fatal or other types of heart failure events. Only 2 trials included heart failure events within the primary study endpoint. More details are included in our full manuscript, which was published in the Journal of the American College of Cardiology to coincide with our presentation at the ACC conference.

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Should Digoxin Still Be Used in Patients With Atrial Fibrillation?

MedicalResearch.com Interview with:

Renato D. Lopes MD, MHS, PhD Duke University Medical Center Duke Clinical Research Institute Durham, NC 27705

Dr. Renato Lopes

Renato D. Lopes MD, MHS, PhD
Professor of Medicine, Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute
Terrace Level, Durham, NC 27705

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

1-      Digoxin is used in ≈ 30% of patients with atrial fibrillation (AF) worldwide, despite the lack of randomized clinical trials to assess its efficacy and safety in this setting.
2-      Current AF guidelines recommend digoxin for rate control in patients with AF with and without heart failure (HF).
3-      There are no specific recommendations about serum digoxin concentration monitoring in the atrial fibrillation guidelines.

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Despite Promise, EMRs Have Not Reduced Administrative or Billing Expenses

Barak Richman JD, PhD Bartlett Professor of Law and Business Administration Duke University

Prof. Barak Richman

MedicalResearch.com Interview with:
Barak Richman JD, PhD
Bartlett Professor of Law and Business Administration
Duke University 

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

Response: The US not only has the highest health care costs in the world, we have the highest administrative costs in the world. If we can reduce non-value added costs like the ones we document, we can make substantial changes in the affordability of health care without having to resort to more draconian policy solutions.

Our paper finds that administrative costs remain high, even after the adoption of electronic health records.  Billing costs, for example, constituted 25.2% of professional revenue for ED departments and 14.5% of revenue for primary care visits.  The other numbers are captured below.

Administrative Costs Still High With EHRs

Administrative Costs Still High With EHRs

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Stem Cell Transplantation Offers Hope For Severe Scleroderma

MedicalResearch.com Interview with:

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

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

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

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

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

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Financial Distress Common Among Cancer Patients, Especially Underinsured

MedicalResearch.com Interview with:

Dr. Fumiko Chino, MD Duke Radiation Oncology Duke School of Medicine

Dr. Chino

Dr. Fumiko Chino, MD
Duke Radiation Oncology
Duke School of Medicine

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

Response: The financial burden of cancer treatment is a growing concern. Out-of-pocket expenses are higher for patients with cancer than for those who have other chronic illnesses. Fifty percent of elderly cancer patients spend at least 10% of their income on treatment-related out-of-pocket expenses. Additionally, high financial burden is associated with both increased risk of poor psychological well-being and worse health-related quality of life. A cancer diagnosis has been shown to be an independent risk factor for declaring personal bankruptcy, and cancer patients who declare personal bankruptcy are at greater risk for mortality. These potentially harmful outcomes resulting from financial burden have been recognized as the financial toxicity of cancer therapy, analogous to the more commonly considered physical toxicity.

We conducted an IRB approved study of financial distress and cost expectations among patients with cancer presenting for anti-cancer therapy. In this cross-sectional, survey based study of 300 patients, over one third of patients reported higher than expected financial burden. Cancer patients with highest financial distress are underinsured, paying nearly 1/3 of income in cancer-related costs. In adjusted analysis, experiencing higher than expected financial burden was associated with high/overwhelming financial distress (OR 4.78; 95% CI 2.02-11.32; p<0.01) and with decreased willingness to pay for cancer care (OR 0.48, 95% CI 0.25-0.95, p=0.03).

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Survival Benefit from Primary Prevention Implantable Cardioverter Defibrillators

MedicalResearch.com Interview with:

Daniel J. Friedman, MD Duke University Hospital Duke Clinical Research Institute Durham, NC

Dr. Friedman

Daniel J. Friedman, MD
Duke University Hospital
Duke Clinical Research Institute
Durham, NC

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

Response: Although primary prevention ICDs have saved countless lives among patients with heart failure and a reduced ejection fraction, the use of primary prevention ICDs in patients with more advanced heart failure [defined by New York Heart Association Class (NYHA)] is controversial.

Specifically, there are conflicting data from the pivotal primary prevention ICD trials regarding whether primary prevention ICDs reduce all-cause mortality among patients with a severely reduced ejection fraction (≤35%) and NYHA III heart failure.

We performed a patient level meta-analysis using data from 4 pivotal primary prevention ICD trials (MADIT-I, MADIT-II, SCD-HeFT, and DEFINITE) to assess whether primary prevention ICD efficacy varied by NYHA class (II vs. III). Overall, the ICD reduced all-cause mortality among the overall population of patients (NYHA II and III). We subsequently assessed ICD efficacy after stratification by NYHA class.

Among NYHA II patients, the ICD significantly reduced all-cause mortality by reducing sudden cardiac death. Although NYHA III patients randomized to an ICD experienced a significantly lower rate of sudden cardiac death, this did not translate into a reduction in all-cause mortality, due to competing causes of non-sudden death (which an ICD cannot treat). Based on relatively wide confidence intervals associated with the estimate for ICD effect in NYHA III patients, there appears to be substantial heterogeneity in outcomes among these patients. This suggests that many NYHA III patients can benefit from a primary prevention ICD, but further study is necessary to determine which NYHA III patients are poised to benefit.

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Metformin Associated With Lower Mortality in CKD, CHF and Chronic Liver Disease

MedicalResearch.com Interview with:

Matthew J. Crowley, MD, MHS Assistant Professor of Medicine Member in the Duke Clinical Research Institute Duke University Medical Center

Dr. Matthew Crowley

Matthew J. Crowley, MD, MHS
Assistant Professor of Medicine
Member in the Duke Clinical Research Institute
Duke University Medical Center

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

Response: Although metformin is widely considered to be the first-line drug for type 2 diabetes, concerns about lactic acidosis have traditionally limited its use in some populations. However, FDA now indicates that metformin may be used safely for patients with mild-moderate chronic kidney disease and other historical contraindications like congestive heart failure. With the lactic acidosis question addressed for these groups, this review asked “what do we know about how metformin affects mortality and other outcomes for patients with historical contraindications and precautions?”

The main take-home message is that metformin appears associated with lower mortality in patients with mild-moderate chronic kidney disease, congestive heart failure, and chronic liver disease.

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Marital History Linked to Survival After Stroke

MedicalResearch.com Interview with:

Matthew E. Dupre, Ph.D. Associate Professor Department of Community and Family Medicine & Duke Clinical Research Institute (DCRI) Duke University

Dr. Mathew Dupre

Matthew E. Dupre, Ph.D.
Associate Professor
Department of Community and Family Medicine &
Duke Clinical Research Institute (DCRI)
Duke University

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

Response: There have been a handful of recent studies showing how divorce and widowhood increase one’s risk of suffering a serious health event such as a heart attack or stroke. Our research is the first to show that an individual’s marital history can have significant consequences for their prognosis after having a stroke.

We found that people who never married and those with a history of marital loss were significantly more likely to die after suffering a stroke than those who were stably married. We also found that adults who experienced more than one divorce or widowhood in their lifetime were about 50% more likely to die after having a stroke than those in a long-term stable marriage. We were also somewhat surprised to find that remarriage did not seem to reduce the risks from past marital losses.

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Hearing Loss Linked To Increased Depression and Dementia Risk

MedicalResearch.com Interview with:

Dr-Frank-Lin.jpg

Dr. Lin

Frank Robert Lin, M.D., Ph.D.
Associate Professor of Geriatric Medicine, Head and Neck Surgery
Johns Hopkins Medicine

MedicalResearch.com Editor’s note: Dr. Lin discussed his research during Cochlear’s Global Research Symposium, which brought together international experts from the audiology community.

MedicalResearch.com: Is there a link between hearing loss and the risk of developing dementia?

Response: In the last few years, we have investigated the link between hearing loss and dementia in large studies of older adults who have been followed for many years. In these studies, we and others have found that those with greater hearing loss have a higher risk of developing dementia even after we account for factors like age, education, medical comorbidities, etc. We think this is because there are some pathways through which hearing loss can directly affect our thinking and memory abilities

MedicalResearch.com: Is there an association between hearing loss and cognitive decline or premature death?

Response: There is a link between hearing loss and accelerated cognitive decline. There is also external research that links hearing loss and premature death (Friburg 2014, Contrera 2015). Hearing loss can also increase a person’s chance of using medical and social services

MedicalResearch.com: How is hearing loss linked to increased social isolation and depression in the elderly?

Response: Older people with hearing loss are at a greater risk of social isolation due to their difficulty communicating with people. These individuals may be less likely to go out, particularly to settings where listening can be difficult (e.g., restaurants), and even if they do go out, they may feel isolated from the conversation and not able to engage with others.

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

Response: Readers should understand that we’re increasingly understanding that hearing loss can detrimentally impact our thinking and memory abilities, risk of dementia, and our ability to remain engaged with others. Ongoing research is now studying to what extent our current hearing loss therapies can reduce and mitigate these risks and promote healthy aging.

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

Response: Readers should know that hearing loss is a growing public health issue. It has been estimated that by 2050 1.2 billion people will suffer from hearing loss, underscoring the need for us to address it and recognize the burden of hearing loss on wider health. To learn more visit,www.linresearch.org and www.nas.edu/hearing

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

Citation:

Cochlear’s Global Research Symposium October 2016

Disclosure:  Symposium supported by Cochlear Limited (ASX: COH), together with Macquarie University and the Australian Hearing Hub

www.cochlear.com

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

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Do People Wearing Activity Trackers Really Exercise More?

MedicalResearch.com Interview with:
Aarti Sahasranaman, PhD
Duke-NUS Gradaute Medical School
Singapore

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

Response: More than half of adults in developed countries do not achieve recommended levels of physical activity. Despite the popularity of activity trackers as a tool for motivating and monitoring activity levels, little research exists on whether they can help people lead healthier lives, or if financial incentives could encourage people to wear them for longer and achieve higher fitness levels. One in ten US adults owns an activity tracker but research suggests that about a third of people abandon them within 6 months of purchase.

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Brain Scans Can Predict Specific Spontaneous Emotions

MedicalResearch.com Interview with:

Kevin S. LaBar, Ph.D. Professor and Head, Cognition & Cognitive Neuroscience Program Co-Director of Undergraduate Studies in Neuroscience Center for Cognitive Neuroscience Duke University Durham, NC

Dr. Kevin LaBar

Kevin S. LaBar, Ph.D.
Professor and Head, Cognition & Cognitive Neuroscience Program
Co-Director of Undergraduate Studies in Neuroscience
Center for Cognitive Neuroscience
Duke University
Durham, NC

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

Response: Emotion research is limited by a lack of objective markers of emotional states. Most human research relies on self-report, but individuals may not have good insight into their own emotions. We have developed a new way to identify emotional states using brain imaging and machine learning tools. First, we induced emotional states using film and music clips while individuals were in an MRI scanner. We trained a computer algorithm to identify the brain areas that distinguished 7 emotions from each other (fear, anger, surprise, sadness, amusement, contentment, and a neutral state). This procedure created a brain map for each of the 7 emotions. Then, a new group of participants self-reported their emotional state every 30 seconds in an MRI scanner while no stimuli were presented. We could predict which emotion was spontaneously reported by the subjects by comparing their brain scans to each of the 7 emotion maps. Finally, in a large group of 499 subjects, we found that the presence of the fear map during rest predicted state and trait anxiety while the presence of the sadness map predicted state and trait depression.

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Most Gastric Bypass Patients Keep Weight Off After Surgery

MedicalResearch.com Interview with:

Matthew Leonard Maciejewski, PhD Professor in the Division of General Internal Medicine Department of Medicine Duke University School of Medicine Research Career Scientist and Director of the Health Economics and Policy Unit in the Center for Health Services Research in Primary Care Durham VA Medical Center

Dr. Matt Maciejewski

Matthew Leonard Maciejewski, PhD
Professor in the Division of General Internal Medicine
Department of Medicine
Duke University School of Medicine
Research Career Scientist and Director of the Health Economics and Policy Unit in the Center for Health Services Research in Primary Care
Durham VA Medical Center

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

Response: No study based on a US cohort undergoing current procedures has examined weight change comparing surgical patients and nonsurgical patients for as long as we have. This is the first study to report 10-year outcomes on gastric bypass patients and compare them to matched patients who did not get surgery. At 1 year, gastric bypass patients lost 31% of their baseline weight compared controls who only lost 1.1% of their baseline weight. At 10 years, gastric bypass had lost 28% of their baseline weight.

We also compared weight loss at 4 years for Veterans who received the 3 most common procedures (gastric bypass, sleeve gastrectomy, and adjustable gastric banding). At 4 years, patients undergoing gastric bypass lost more weight than patients undergoing sleeve gastrectomy or gastric banding. Given that few high quality studies have examined sleeve gastrectomy to 4 years, the 4-year sleeve outcomes contribute to filling this important evidence gap as the sleeve gastrectomy is now the most commonly performed bariatric procedure worldwide.

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Persistent Postpartum Pain Linked To Higher Risk of Depression

MedicalResearch.com Interview with:
MS WEI DU, First author
Third Year Medical Student
DUKE-NUS Medical School and
DR BAN LEONG SNG, Senior Author
Senior Consultant Department of Women’s Anesthesia KK
Women’s and Children’s Hospital

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

MS WEI DU: We performed a cohort study involving 200 healthy women who received epidural pain relief during the deliveries of their firstborns to investigate the relationship between persistent childbirth pain, psychological and pain vulnerability with postnatal depression. Postnatal depression was evaluated using the Edinburgh Postnatal Depression Score (EPDS).

Patients with persistent pain (>4 weeks postpartum) had significantly higher EPDS scores as compared to patients whose pain resolved by 4 weeks by a difference of 2.44 mean score, and compared to patients who never had pain postpartum by a difference of 4.07 mean score. Other significant factors that were associated with higher EDPS score included higher levels of stress, greater pain vulnerability during the intrapartum period and higher anxiety level at 6 to 8 weeks postpartum.

DR BAN LEONG SNG: Patients with persistent pain (>4 weeks postpartum) had significantly higher EPDS scores as compared to patients whose pain resolved by 4 weeks by a difference of 2.44 mean score, and compared to patients who never had pain postpartum by a difference of 4.07 mean score. Other significant factors that were associated with higher EDPS score included higher levels of stress, greater pain vulnerability during the intrapartum period and higher anxiety level at 6 to 8 weeks postpartum.

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

MS WEI DU: We concluded that greater pain vulnerability and stress during intrapartum period, and presence of persistent pain or higher anxiety during postpartum period are positively associated with higher scores on postnatal depression tests.

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

DR BAN LEONG SNG: The research findings support the need to address pain comprehensively to lessen the risk of developing postnatal depression. We are currently conducting a larger study to evaluate the impact of pain and postnatal depression in pregnant women.

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

DR BAN LEONG SNG: Postnatal evaluation and management of childbirth pain and postnatal depression is important in our care of mothers and their newborns.

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

Citation:

World Congress of Anaesthesiologists abstract discussing:

Persistent childbirth pain increases risk of postnatal depression

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

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Same Genes Predict Educational Attainment and Socioeconomic Success

MedicalResearch.com Interview with:

Daniel Belsky, PhD Assistant Professor of Medicine Duke University School of Medicine Durham, NC 27708

Dr. Daniel Belsky

Daniel Belsky, PhD
Assistant Professor of Medicine
Duke University School of Medicine
Durham, NC 27708

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

Dr. Belsky: The genome-wide association study
(GWAS) of educational attainment by the Social Science Genetic Association Consortium was the first large-scale genetic investigation of a human social/behavioral trait. Follow-up studies, including studies some of us were involved in, established that the genetic signature uncovered by this GWAS was highly reproducible; people who carried more education-associated alleles completed more schooling—and this was true even when studies compared siblings in the same family. Because getting a good education requires many of the same skills and abilities needed to get ahead in life more generally, we hypothesized that the same genetics that predicted success in schooling would predict success in life.

To ask this question, we designed a study to do three things.
• First, we wanted to test if the genetics of success in schooling would predict social and economic success through midlife (better jobs, salaries, and credit scores, fewer financial problems, etc.).
• Second, if the genetics of educational success did predict broader economic outcomes, we wanted to test how this came about:
o When and how did differences develop between children whose genomes predicted more educational success and children whose genomes predicted less success?
o The goal of this analysis was to try and learn something about pathways to success – pathways that any child could take advantage of, regardless of their genetics.
• Third, we wanted to know what kinds of psychological characteristics linked genetics with behavior. The goal of this analysis was to begin building a bridge between statistical models of the genome and the biological mechanisms that connect DNA sequence with behavior.

MedicalResearch.com: What are the main findings?

Dr. Belsky: There are four major take home points:
(1) Genetic discoveries for educational attainment are not discoveries for education only. The same genetics predict socioeconomic success well beyond the completion of schooling.
(2) Genetic discoveries were associated with social mobility — children with higher polygenic scores tended to achieve more socioeconomic success even if they were born poor.
(3) The psychological characteristics that mediated genetic associations with life outcomes included intelligence, but also self-control and interpersonal skills, for example being friendly.
(4) The pattern of characteristics and behaviors that connects DNA sequence with life outcomes begins early in life and extends through adulthood. Kids with higher polygenic scores started talking and reading earlier, and they had higher IQ scores, more self-control, and were more skilled interpersonally. As they grew into adolescence and adulthood, they were more ambitious, more willing to move away from home in search of opportunity, more successful in attracting better educated and higher earning spouses, and better at managing their money.

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

Dr. Belsky: Our research speaks to three audiences. To scientists — behavioral/social and genetic — our results highlight the need for interdisciplinary collaborations to untangle genetic influences on human outcomes. We found that children’s genes shaped the environments they grew up in, suggesting that social and behavioral scientists may need to pay more attention to genetics. We also found that genes influenced life outcomes through patterns of behavior that are also affected by environmental circumstances, suggesting that geneticists may need to pay more attention to the social and behavioral sciences.
To policy makers, our research highlights the importance of developing regulations for the use of genetic information. “Precision education” or other tailoring of environments to children’s genomes is not possible with the data we have in hand today. But our findings suggest that such data may someday become available. It is vital to have the conversation about what that might mean and how we will deal with it BEFORE it happens.
Finally, to the general public, our research emphasizes the small effects of known-genetics on important human outcomes. Our findings provide a provocative window into how our genes may shape our lives. But we can make only very weak predictions about how far a child can go in life based on their genes.

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

Dr. Belsky: Two big questions are “How do children’s environments affect the relationship between their genomes and their outcomes as adults?” and “How may genetics linked to educational success affect adult health and aging?”

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

Dr. Belsky: I was most surprised to find the very same genetics that predicted better cognitive and social functioning in children were unrelated to their physical health. When we tested if the polygenic score predicted children’s physical health – measured from repeated clinical exams across childhood – we found no association whatsoever.

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

Citation:

D. W. Belsky, T. E. Moffitt, D. L. Corcoran, B. Domingue, H. Harrington, S. Hogan, R. Houts, S. Ramrakha, K. Sugden, B. S. Williams, R. Poulton, A. Caspi. The Genetics of Success: How Single-Nucleotide Polymorphisms Associated With Educational Attainment Relate to Life-Course Development. Psychological Science, 2016; DOI:10.1177/0956797616643070

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.

Epigenetic Changes Link Environmental Deprivation to Depression

MedicalResearch.com Interview with:
Dr. Johnna Swartz, PhD
Postdoctoral researcher in the lab of Ahmad Hariri
Duke postdoctoral researcher in the lab of Ahmad Hariri

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

Dr. Swartz: Prior research has shown that low socioeconomic status is a risk factor for the development of depression. In this study, we examined whether this risk factor was associated with changes in an epigenetic tag near the gene coding for the serotonin transporter, which has previously been linked to depression. We found that adolescents growing up in families with lower socioeconomic status accumulated more of these tags over time, which may lead to decreased gene expression. Moreover, we found that more of these tags were associated with increased activity in the amygdala, a brain region that plays an important role in the stress response.

Finally, we found that adolescents with increased activity in the amygdala were more likely to develop depression symptoms a year later, particularly if they had a close relative with a history of depression. This is some of the first research to draw a link from an environmental risk factor to changes in depression symptoms through changes in epigenetic markers and brain function.

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Medicare Patients May Have Better Outcomes with Carotid Endarterectomy Than Stenting

MedicalResearch.com Interview with:
Jessica J. Jalbert PhD
From the Division of Pharmacoepidemiology and Pharmacoeconomics
Department of Medicine, Brigham and Women’s Hospital
Harvard Medical School, Boston, MA
LASER Analytica
New York, NY

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

Dr. Jalbert: Landmark clinical trials have demonstrated that carotid artery stenting (CAS) is a safe and efficacious alternative to carotid endarterectomy (CEA) for the treatment of carotid artery stenosis. Clinical trials, however, tend to enroll patients that are younger and healthier than the average Medicare patient. We therefore sought to compare outcomes following CAS and CEA among Medicare patients.

MedicalResearch.com: What are the main findings?

Dr. Jalbert: We found that outcomes among real-world Medicare patients undergoing CAS and CEA were similar. While our results were inconclusive due to small sample size, we also found some evidence suggesting that patients over the age of 80 and those with symptomatic carotid stenosis may have better outcomes following carotid endarterectomy than CAS.

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PCSK9 Antibody May Revolutionize Treatment of Atherosclerosis and Acute Coronary Syndrome

MedicalResearch.com Interview with:

Paul A. Gurbel, M.D. Director, Inova Center for Thrombosis Research and Drug Development Director, Cardiovascular Medicine Research Director, Interventional Cardiology Inova Heart and Vascular Institute Falls Church, VA Professor of Medicine, Johns Hopkins University School of Medicine Adjunct Professor of Medicine, Duke University School of Medicine

Dr. Paul Gurbel

Paul A. Gurbel, M.D.
Director, Inova Center for Thrombosis Research and Drug Development
Director, Cardiovascular Medicine Research
Director, Interventional Cardiology
Inova Heart and Vascular Institute
Falls Church, VA
Professor of Medicine,
Johns Hopkins University School of Medicine
Adjunct Professor of Medicine,
Duke University School of Medicine 

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

Dr. Gurbel: In current practice, treatment with statins and antiplatelet agents is the primary strategy to reduce death and ischemic cardiovascular events following ACS (acute coronary syndrome)/PCI. Immediately following ACS, many patients are incompletely responsive to potent current therapy and remain at high risk for recurrent thrombotic events. Treatment with monoclonal antibodies that target proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new potent lipid lowering therapy. Recent studies have shown that PCSK9 antibodies combined with statins provided marked additional benefits in reducing atherogenic lipid fractions. In a recent meta-analysis, PCSK9 antibody therapy was also associated with a reduction in mortality and no increase in serious adverse events. In the current Narrative Review, we focused on novel pathways affected by PCSK9 antibodies that may make them appropriate for immediate treatment in patients with acute coronary syndrome.

MedicalResearch.com: What are the main findings?

Dr. Gurbel: PCSK9 antibodies, in addition to markedly reducing LDL levels, may also reduce pro-inflammatory oxidized LDL levels and platelet function. The latter properties, in addition to plaque stabilization, may provide antithrombotic properties favorably influencing clinical outcomes following acute administration at the time of  acute coronary syndrome.

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

Dr. Gurbel: In addition to a potent lipid lowering effect, PCSK9 antibody therapy when administered immediately at the time of acute coronary syndrome in addition to standard statin and antiplatelet therapy may provide additional antithrombotic effects. The latter novel properties of PCSK9 antibodies may be associated with improved patient outcomes. However, at this time there is no direct evidence for recommending PCSK9 antibody therapy in patients at the time of presentation with acute coronary syndrome .

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

Dr. Gurbel: A large scale randomized study assessing the clinical effects of PCSK9 antibody therapy on top of current statin and antiplatelet therapy is needed. In addition, mechanistic studies to further delineate anti-inflammatory and antithrombotic effects of PCSK9 antibody therapy are also needed.

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

Dr. Gurbel: PCSK9 antibody therapy provides marked lowering of LDL. The latter property may revolutionize the treatment of patients with atherosclerosis. The potential antithrombotic effects of PCSK9 antibody therapy, in turn, may revolutionize acute therapy of ACS. 

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

Citation:

Navarese EP, Kołodziejczak M, Kereiakes DJ, Tantry US, O’Connor C, Gurbel PA. Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies for Acute Coronary Syndrome: A Narrative Review. Ann Intern Med. [Epub ahead of print 22 March 2016] doi:10.7326/M15-2994

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. Paul Gurbel (2016). PCSK9 Antibody May Revolutionize Treatment of Atherosclerosis and Acute Coronary Syndrome MedicalResearch.com

Risk/Benefits of Sildenafil For Swimming-Induced Pulmonary Edema

MedicalResearch.com Interview with:

Richard Moon, MD, CM, MSc, FRCP(C), FACP, FCC Medical Director, Hyperbaric Center Professor of Anesthesiology Department / Division Anesthesiology / GVTU Division Medicine / Pulmonary Duke University School of Medicine

Dr. Richard Moon

Richard Moon, MD, CM, MSc,
FRCP(C), FACP, FCCP

Medical Director, Hyperbaric Center
Professor of Anesthesiology
Department / Division
Anesthesiology / GVTU Division
Medicine / Pulmonary
Duke University School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Moon: This study was performed to investigate the reason why young, fit individuals develop a condition usually associated with severe heart disease: pulmonary edema. Immersion pulmonary edema (also known as swimming-induced pulmonary edema, SIPE) develops in certain susceptible individuals while swimming or scuba diving, usually in cold water. Some SIPE-susceptible people include highly conditioned triathletes and Navy SEAL trainees. The prevalence of SIPE in triathletes is around 1.5%, and in open sea swimming trials in naval special forces trainees has been reported to be 1.8-60%. SIPE often requires hospitalization and has caused death.

Medical Research: What should clinicians and patients take away from your report?

Dr. Moon: We directly measured arterial pressure, pulmonary artery pressure (PAP) and PA wedge pressure (PAWP) during submersed exercise in cold water. We found that both PAP and PAWP were higher in swimming-induced pulmonary edema-susceptible individuals compared with a group of volunteers of similar age who had never experienced SIPE. This confirmed that SIPE is a form of hemodynamic pulmonary edema, which is curious since all of the people we studied had normal hearts. We hypothesized that the cause could be differences between the groups in venous tone or LV diastolic compliance. When we retested the SIPE-susceptibles under the same conditions after a dose of sildenafil, pulmonary artery pressures were decreased, with no adverse effects on hemodynamics. We concluded that by dilating pulmonary vessels and systemic venous sildenafil could be an effective prophylaxis against SIPE.  Continue reading

Meditation May Improve Experience with Imaging-Guided Needle Breast Biopsy

MedicalResearch.com Interview with:

Mary Scott Soo, M.D. FACR Associate professor of Radiology Duke Cancer Institute

Dr. Mary Scott Soo

Mary Scott Soo, M.D. FACR
Associate professor of Radiology
Duke Cancer Institute

Medical Research: What is the background for this study?

Dr. Soo: Imaging-guided needle breast biopsies for diagnosing suspicious breast lesions have been performed for many years and have definite advantages as a diagnostic tool over surgical biopsies. These biopsies are performed in outpatient settings, which decrease costs and reduce delays, and are highly accurate and less invasive than surgical procedures, requiring only local anesthesia. However, performing biopsies in this outpatient setting limits the use of intravenous sedation and pain medication that could address commonly experienced patient anxiety and occasional associated pain. Anxiety and pain can negatively impact the patient’s experience and could possibly affect the biopsy outcome due to patient movement, and could potentially even alter patients’ adherence to follow-up recommendations. Prior studies have explored methods to reduce anxiety, using interventions such as music, hypnosis and anxiolytics. Although hypnosis and anxiolytics are effective, these are a little more complicated to implement due to training costs for administering hypnotherapy, and costs, potential side effects, and need for an adult driver to take the patients home when anxiolytics are used. Other research has shown that meditation-based interventions can lead to positive psychological and physical outcomes, and may be helpful for decreasing anxiety, pain and fatigue.

Loving-kindness mediation is a type of mediation that focuses on relaxation and developing positive emotions, by silently repeating phrases encouraging compassion and goodwill towards oneself and others, while also reducing negative emotions. Previous studies have shown that even a 7-minute loving-kindness meditation can be effective for increasing positive emotions, so my co-authors Rebecca Shelby PhD, a clinical psychologist at Duke’s Pain Prevention and Treatment Research Program,clinical psychologist Anava Wrenn PhDwho has used loving-kindness meditation in a different practice setting, and breast imaging radiologist Jennifer Jarosz MD and I put together a team to study whether an audio-recorded, lovingkindness meditation could reduce anxiety, fatigue and pain during the imaging-guided breast biopsy time frame.  We consulted with Mary Brantley, MA, LMFT, who teaches loving-kindness meditation at Duke’s Integrative Medicine, to develop an audio-recorded loving-kindness mediation used specifically in the breast biopsy setting, and compared this to using music during biopsies or standard care (supportive dialogue) from the technologist and radiologist performing the biopsy.

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