Ketamine Before Stressful Event May Reduce Risk of PTSD

MedicalResearch.com Interview with:

Christine Ann Denny, Ph.D. Assistant Professor Department of Psychiatry Columbia University Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. New York, NY 10032-2695

Dr. Christine Ann Denny

Christine Ann Denny, Ph.D.
Assistant Professor
Department of Psychiatry
Columbia University
Division of Integrative Neuroscience
Research Foundation for Mental Hygiene, Inc.
New York, NY 10032-2695

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

Response: Post-traumatic stress disorder (PTSD) is one of the most common psychiatric illnesses, affecting about 8 million adult Americans, and an annual prevalence of about 3.5% worldwide. At-risk populations such as soldiers and veterans are at a higher risk to develop PTSD. Stress exposure is one of the major risk factors for PTSD and major depressive disorder (MDD), a disorder which is often co-morbid with PTSD.

There are currently very limited treatments for PTSD and MDD. In addition, these disorders are treated in a symptom-suppression approach, which only mitigate symptoms and work in only a small fraction of patients. Prevention is rarely an approach considered except in the form of behavioral intervention. However, pharmacological approaches to preventing psychiatric diseases has not yet been developed.

Our laboratory has previously found that ketamine, a general anesthetic and rapid-acting antidepressant, administered sub-anesthetically prior to stress can prevent against stress-induced depressive-like behaviors. We decided to delve into the literature to determine whether ketamine has any effects on PTSD in the clinic. We found numerous reports linking ketamine to PTSD, but the results were varied. We realized that the main difference in all of these studies was the timing of administration. We decided to systematically test the efficacy of ketamine in mice at various time points relative to a stressor to determine when would be the most effective window to buffer against heightened fear expression.

We found that ketamine administered 1 week, but not 1 month or 1 day, prior to a stressor was the most effective time point to administer the drug to buffer fear. This is critical, as it suggests that a pharmacological approach to enhance resilience can be more effective at protecting against PTSD symptoms than attempting to mitigate symptoms after it has already affected an individual.

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PCSK9 Inhibition with Alirocumab Increases Removal of LDL Cholesterol

MedicalResearch.com Interview with:
Henry N. Ginsberg, MD

Irving Institute for Clinical and Translational Research
Columbia University
Columbia College of Physicians and Surgeons
New York, NY

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

Response: Previous studies in mice and cells have identified increased hepatic low density lipoprotein (LDL) receptors as the basis for LDL lowering by PCSK9 inhibitors, but there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism, particularly effects on very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) or LDL metabolism.

This study in 18 healthy subjects, found that alirocumab decreased the number of IDL and LDL particles in the circulation, and their associated cholesterol and apoB levels by increasing efficiency of the clearance of IDL and LDL. There were not effects on VLDL metabolism. The increased clearance of IDL meant that less LDL was produced from IDL, which is the precursor of LDL. Thus, the dramatic reductions in LDL cholesterol resulted from both less LDL being produced and more efficient clearance of LDL. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.

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AI plus Genetic Database Drives Personalized Cancer Treatment

MedicalResearch.com Interview with:

Dr. Kai Wang Zilkha Neurogenetic Institute, University of Southern California Institute for Genomic Medicine, Columbia University

Dr. Kai Wang

Dr. Kai Wang
Zilkha Neurogenetic Institute, University of Southern California
Institute for Genomic Medicine, Columbia University

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

Response: Cancer is a genetic disease caused by a small number of “driver mutations” in the cancer genome that drive disease initiation and progression. To understand such mechanism, there are increasing community efforts in interrogating cancer genomes, transcriptomes and proteomes by high-throughput technologies, generating huge amounts of data. For example, The Cancer Genome Atlas (TCGA) project has already made public 2.5 petabytes of data describing tumor and normal tissues from more than 11,000 patients. We were interested in using such publicly available genomics data to predict cancer driver genes/variants for individual patients, and design an “electronic brain” called iCAGES that learns from such information to provide personalized cancer diagnosis and treatment.

iCAGES is composed of three consecutive layers, to infer driver variants, driver genes and drug treatment, respectively. Unlike most other existing tools that infer driver genes from a cohort of patients with similar cancer, iCAGES attempts to predict drivers for individual patient based on his/her genomic profile.

What we have found is that iCAGES outperforms other tools in identifying driver variants and driver genes for individual patients. More importantly, a retrospective analysis on TCGA data shows that iCAGES predicts whether patients respond to drug treatment and predicts long-term survival. For example, we analyzed two groups of patients and found that using iCAGES recommend drugs can increase patients’ survival probability by 66%. These results suggest that whole-genome information, together with transcriptome and proteome information, may benefit patients in getting optimal and precise treatment. Continue reading

Fetal Structural Defects Detected Later in Pregnancy Than Chromosomal Abnormalities

MedicalResearch.com Interview with:
Sarah Horvath, MD
Paula M. Castaño, MD, MPH
Anne R. Davis, MD, MPH

Columbia University Medical Center

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

Response: Approximately 3% of pregnant women in the United States will receive a prenatal diagnosis of fetal aneuploidy (such as trisomy 21) or fetal structural abnormality (such as cardiac or CNS malformations). Many of these women will undergo abortion. Advances in screening over the past few decades have allowed earlier diagnosis of aneuploidy, but most structural abnormalities cannot be diagnosed until the anatomy ultrasound at 18-20 weeks gestational age because of fixed patterns of fetal development. Our analysis examines gestational age at time of abortion for these two types of fetal diagnosis from 2004-2014.

Our main finding was that median gestational age at time of abortion for fetal aneuploidy decreased from 19 weeks to 14 weeks. However, over the same 11 year period, median gestational age at time of abortion for fetal structural abnormalities remained unchanged and at or above 20 weeks gestation.

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Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis

MedicalResearch.com Interview with:

Dr. Jeri Nieves PhD Director of bone density testing New York's Helen Hayes Hospital

Dr. Jeri Nieves

Dr. Jeri Nieves PhD
Director of bone density testing
New York’s Helen Hayes Hospital

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

Response: Amyotrophic lateral sclerosis (ALS) is a devastating severe neurodegenerative disorder that causes progressive muscle atrophy, paralyses, and eventual respiratory failure.

Our objective was to evaluate the associations between nutrition and severity of ALS around the time of diagnosis. This was a cross-sectional analysis of data from a multicenter cohort of 302 patients with ALS. We assessed nutrient intake using a modified Block Food Frequency Questionnaire. The outcomes were respiratory function (measured using percentage forced vital capacity; FVC%) and functional performance measured by ALS Functional Rating Scale–Revised (ALSFRS-R), both considered important indicators of the severity of ALS. Results of the regression analysis were that higher intakes of antioxidants and carotenes from vegetable intake were associated with higher ALSFRS-R scores or better %FVC.

We used a novel analysis to evaluate the diet as a whole and found that higher intakes of antioxidants, fiber from grains, vegetables, fruit, eggs, fish, and poultry were all associated with higher function in patients with ALS. However, milk and lunch meats were associated with lower measures of function. These consistent results from two different statistical analyses indicate that diet may help minimize the severity of ALS. Perhaps these findings point to the role of oxidative stress in ALS severity.

In summary, increased consumption of antioxidant nutrients, foods high in carotenoids and fiber, vegetables and fruits, poultry and fish are associated with better function around the time of ALS diagnosis.

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Risk of Pregnancy-Associated Stroke Across Age Groups

MedicalResearch.com Interview with:
Eliza Miller, M.D
.
Vascular Neurology Fellow
New York-Presbyterian Hospital/Columbia University Medical Center
We collaborated with researchers at the Massachusetts General Hospital and with the New York State Department of Health.

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

Response: Prior research has found that older women of childbearing age are at higher risk of stroke during pregnancy and postpartum than younger women. We hypothesized that their increased stroke risk might not be due to pregnancy-related factors, but just due to the fact that stroke risk increases with age for all people. We used billing data from New York State hospitals to calculate incidence risk ratios for four age groups: 12-24, 25-34, 35-44 and 45-55. In each age group, we compared the incidence of stroke in women who were pregnant or postpartum to the incidence of stroke in women of the same age who were not pregnant.

As in prior studies, we found that the incidence of pregnancy-associated stroke was higher in older women compared to younger women (about 47/100,000 deliveries in the oldest group, versus 14/100,000 deliveries in the youngest group). However, the incidence ratios showed that pregnancy increased stroke risk significantly in women under 35, but did not appear to increase stroke risk in women over 35. In the youngest group (age 12-24), pregnancy more than doubled the risk of stroke, and in the 25-34 age group, pregnancy increased stroke risk by 60%. In women aged 35 and older, pregnancy did not increase stroke risk. Women who had pregnancy-related strokes tended to have fewer traditional vascular risk factors like hypertension and diabetes, compared to same-aged women with non-pregnancy related strokes.

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Maternal Use of SSRIs May Be Related to Speech and Language Disorders in Offspring

MedicalResearch.com Interview with:

Alan S. Brown, M.D., M.P.H. Professor of Psychiatry and Epidemiology Columbia University Medical Center Director, Program in Birth Cohort Studies, Division of Epidemiology New York State Psychiatric Institute

Dr. Alan Brown

Alan S. Brown, M.D., M.P.H.
Professor of Psychiatry and Epidemiology
Columbia University Medical Center
Director, Program in Birth Cohort Studies, Division of Epidemiology
New York State Psychiatric Institute 

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

Response: Maternal use of antidepressants during pregnancy has been increasing.  A previous study from a team that I led in a national birth cohort in Finland showed that mother’s use of a serotonin reuptake inhibitor antidepressant is related to an increased risk of depression in offspring.  We sought to evaluate whether these medications also increased risk of speech/language, scholastic, and motor outcomes in offspring.  We found an increased risk (37% higher risk) of speech/language disorders in offspring of mothers exposed to SSRIs in pregnancy compared to mothers who were depressed during pregnancy but did not take an SSRI during pregnancy.

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Antibiotics Encourage Spread of C.diff To Subsequent Patients Who Occupy the Same Bed and Haven’t Received Antibiotics

MedicalResearch.com Interview with:

Dr. Daniel E. Freedberg MD M

Dr. Daniel E. Freedberg

Dr. Daniel E. Freedberg MD MS
Division of Digestive and Liver Diseases
Columbia University Medical Center
New York, New York

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

Response: We conducted this study because previous studies indicate that the gastrointestinal microbiome is easily shared between people who co-occupy a given space (such as a hospital room).  We wondered if antibiotics might exert an effect on the local microbial environment.

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Sharp Rise in Heroin Use Among Young Adults Who Use Nonmedical Prescription Opioids

MedicalResearch.com Interview with:

Silvia S. Martins, MD, PHD Associate Professor of Epidemiology  Department of Epidemiology Mailman School Of Public Health Columbia University New York, NY 10032

Dr. Silvia Martins

Silvia S. Martins, MD, PHD
Associate Professor of Epidemiology
Department of Epidemiology
Mailman School Of Public Health
Columbia University
New York, NY 10032

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

Response: Given the high probability of nonmedical use among adolescents and young adults, the potential development of prescription opioid use disorder secondary to nonmedical use among youth represents an important and growing public health concern. Still, no study had investigated time trends, specifically if prescription opioid use disorder has increased in the past decade among adolescents, emerging adults and young adults who are nonmedical users of prescription opioids.

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Romosozumab Has Potential To Reduce New Vertebral Fractures at 12 Months

MedicalResearch.com Interview with:

MedicalResearch.com Interview with: Felicia Cosman, M.D.

Dr. Felicia Cosman

Felicia Cosman, M.D.
Medical Director of the Clinical Research Center
Helen Hayes Hospital
Professor of Medicine
Columbia University College of Physician and Surgeons
New York
Editor-in-Chief, Osteoporosis International

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

Response: Amgen and UCB presented detailed data from the Phase 3 FRAME study in an oral session at ASBMR 2016, and the data were also published in the New England Journal of Medicine. Additionally, the FRAME abstract has been awarded the 2016 ASBMR Most Outstanding Clinical Abstract Award. The FRAME data show significant reductions in both new vertebral and clinical fractures in postmenopausal women with osteoporosis.

Patients receiving a monthly subcutaneous 210 mg dose of romosozumab experienced a statistically significant 73 percent reduction in the relative risk of a vertebral (spine) fracture through 12 months, the co-primary endpoint, compared to those receiving placebo (fracture incidence 0.5 percent vs. 1.8 percent, respectively [p<0.001]). By six months, new vertebral fractures occurred in 14 romosozumab and 26 placebo patients; between six to 12 months, fractures occurred in two versus 33 additional patients in each group, respectively.

Patients receiving romosozumab experienced a statistically significant 36 percent reduction in the relative risk of a clinical fracture, a secondary endpoint, through 12 months compared to those receiving placebo (fracture incidence 1.6 percent vs. 2.5 percent, respectively [p=0.008]).

In patients who received romosozumab in year one, fracture risk reduction continued through month 24 after both groups transitioned to denosumab treatment through the second year of the study: there was a statistically significant 75 percent reduction in the risk of vertebral fracture at month 24 (the other co-primary endpoint) in patients who received romosozumab followed by denosumab vs. placebo followed by denosumab (fracture incidence 0.6 percent vs. 2.5 percent, respectively [p<0.001]).

Clinical fractures encompass all symptomatic fractures (both non-vertebral and painful vertebral fractures; all clinical fractures assessed in the FRAME study were symptomatic fragility fractures. A 33 percent reduction in relative risk of clinical fracture was observed through 24 months after patients transitioned from romosozumab to denosumab compared to patients transitioning from placebo to denosumab (nominal p=0.002, adjusted p=0.096).

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Medical Marijuana Laws Linked To Lower Opioid-Related Traffic Deaths

MedicalResearch.com Interview with:

June H. Kim Doctoral candidate,Department of Epidemiology Mailman School Public Health Columbia University

June Kim

June H. Kim
Doctoral candidate,Department of Epidemiology
Mailman School Public Health
Columbia University

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

Response: A previous study indicated that states with medical marijuana laws had a reduced rate of opioid overdoses. If this is true, we’d expect to see similar reductions in opioid use associated with these laws. For this study, we used data from the FARS, a national surveillance system that records any crash events on US public roads that result in a fatality. Some states provide uniform testing of the majority of their deceased drivers, year to year. Among these states, we found that there was a lower prevalence of positive opioid toxicology tests among drivers crashing in states with an operational medical marijuana versus drivers crashing in states before a future medical marijuana law is implemented, particularly among drivers aged 21-40.

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Earned Income Tax Credits Linked To Improved Health Parameters

MedicalResearch.com Interview with:

Peter Muennig, MD, MPH Associate Professor Mailman School of Public Health Columbia University New York, NY 10032

Dr. Peter Muennig

Peter Muennig, MD, MPH
Associate Professor
Mailman School of Public Health
Columbia University
New York, NY 10032

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

Response: We looked that the supplemental Earned Income Tax Credit
( EITC ) programs offered by states to determine whether they have health impacts or not.

We found that, on average, folks who live in states that offer supplemental EITC showed improvements in health after EITC was implemented.

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