2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Market 2019 Global Industry Size, Future Trends, Growth Key Factors, Demand, Business Share, Sales & Income, Manufacture Players, Application, Scope, and Opportunities Analysis by Outlook – 2024
2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Market 2019 research report refines the essential aspects of the industry and presents them in a collective and all-inclusive document format. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Report starts from an overview of the industry chain structure and describes the industry’s environment, then analyzes market size and prediction, applications and areas. In addition, this report includes the 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Market competition scenario in the vendor and company profile, as well as market value analysis and value chain features.
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The global market size of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) is $XX million in 2019 with XX CAGR from 2014 to 2019, and it is expected to reach $XX million by the end of 2024 with a CAGR of XX% from 2019 to 2024.
Geographical Segmentation: For geography segment, regional supply, application-wise and type-wise demand, major players, price is presented from 2014 to 2024. This report covers following regions: North America, South America, Asia & Pacific, Europe, MEA
2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Market Analysis by Major Players:
- Company 1
- Company 2
- Company 3
Application Segment Analysis by Consumption Volume and Market Share 2014-2024; 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) market split into:
- Application 1
- Application 2
- Application 3
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A proficient and organized analysis segments the market by the presence of several diversified local, regional, and multinational vendors in the market as well as by type and application. The manufacturer’s data like price, interview record, shipment, business distribution, gross profit, revenue and are also covered in this report. A regional development status including value, market size and volume in accordance to all the regions and worldwide countries is also added.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Market by Types:
- Type 1
- Type 2
- Type 3
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Detailed TOC of Global 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Market Report 2019 – Market Size, Share, Price, Trend, and Forecast
Chapter 1 Executive Summary
Chapter 2 Abbreviation and Acronyms
Chapter 3 Preface
3.1 Research Scope
3.2 Research Methodology
3.2.1 Primary Sources
3.2.2 Secondary Sources
Chapter 4 Market Landscape
4.1 Market Overview
4.3 Application/End Users
Chapter 5 Market Trend Analysis
Chapter 6 Industry Chain Analysis
6.1 Upstream/Suppliers Analysis
6.2 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Analysis
6.2.1 Technology Analysis
6.2.2 Cost Analysis
6.2.3 Market Channel Analysis
6.3 Downstream Buyers/End Users
Chapter 7 Latest Market Dynamics
7.1 Latest News
7.2 Merger and Acquisition
7.3 Planned/Future Project
7.4 Policy Dynamics
Chapter 8 Trading Analysis
8.1 Export of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) by Region
8.2 Import of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) by Region
8.3 Balance of Trade
Chapter 9 Historical and Current 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) in North America (2013-2018)
9.1 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Supply
9.2 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Demand by End Use
9.3 Competition by Players/Suppliers
9.4 Type Segmentation and Price
9.5 Key Countries Analysis
Chapter 10 Historical and Current 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) in South America (2013-2018)
10.1 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Supply
10.2 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Demand by End Use
10.3 Competition by Players/Suppliers
10.4 Type Segmentation and Price
10.5 Key Countries Analysis
Chapter 11 Historical and Current 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) in Asia & Pacific (2013-2018)
11.1 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Supply
11.2 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Demand by End Use
11.3 Competition by Players/Suppliers
11.4 Type Segmentation and Price
11.5 Key Countries Analysis
Chapter 12 Historical and Current 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) in Europe (2013-2018)
12.1 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Supply
12.2 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Demand by End Use
12.3 Competition by Players/Suppliers
12.4 Type Segmentation and Price
12.5 Key Countries Analysis
Chapter 13 Historical and Current 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) in MEA (2013-2018)
13.1 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Supply
13.2 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Demand by End Use
13.3 Competition by Players/Suppliers
13.4 Type Segmentation and Price
13.5 Key Countries Analysis
Chapter 14 Summary for Global 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) (2013-2018)
14.1 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Supply
14.2 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Demand by End Use
14.3 Competition by Players/Suppliers
14.4 Type Segmentation and Price
Chapter 15 Global 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Forecast (2019-2023)
15.1 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Supply Forecast
15.2 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Demand Forecast
15.3 Competition by Players/Suppliers
15.4 Type Segmentation and Price Forecast
Chapter 16 Analysis of Global Key Vendors
16.1 Company A
16.1.1 Company Profile
16.1.2 Main Business and 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Information
16.1.3 SWOT Analysis of Company A
16.1.4 Company A 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Sales, Revenue, Price and Gross Margin (2014-2019)
16.2 Company B
16.2.1 Company Profile
16.2.2 Main Business and 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Information
16.2.3 SWOT Analysis of Company B
16.2.4 Company B 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS 1746-01-6) Sales, Revenue, Price and Gross Margin (2014-2019)
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Data collection named in spirit of space mission
Clarence Massey (above, left) received treatment for his prostate cancer at the Brooklyn campus of the VA NY Harbor Healthcare System. He is with radiation therapist Nader Girgis, who was part of his treatment team. (Photo by Mitch Mirkin)
As an Air Force mechanic in the 1960s, Clarence Massey worked on bombers and fighter jets in Vietnam.
More than four decades later, in 2010, he became immersed in another battle. The resident of New York City’s historic Harlem neighborhood underwent nine weeks of radiation therapy for prostate cancer.
The treatment itself wasn’t too bad, he recalls, but the side effects hit him “like a ton of bricks,” says Massey, now 72.
Massey’s outcome was a good one. He’s been in remission. He gives credit to his VA doctors, but, he says, “Mostly I give credit to God. I’m blessed.”
In the years since Massey’s bout with cancer, biomedicine has come a long way—especially when it comes to analyzing genes and proteins. VA and two federal partners—the Department of Defense and the National Cancer Institute—are looking to harness the power of this science through an effort dubbed APOLLO, in the spirit of the famous space mission that landed men on the moon. The research program is described in full detail in an article now online in the journal Clinical Pharmacology & Therapeutics.
The project initially launched in 2016 under the federal Cancer Moonshot, a broader effort likewise inspired by the space theme.
It’s all about precision oncology
The full title of APOLLO sounds complex: Applied Proteogenomics Organizational Learning and Outcomes. But the overarching goal is simple: individualize cancer treatment. That’s what “precision oncology” is all about.
“Each patient is unique, and each tumor is unique,” explains Dr. Craig Shriver, one of the architects of APOLLO. He directs the Murtha Cancer Center Research Program in the department of surgery at the Uniformed Services University of the Health Sciences, in Bethesda, Maryland.
APOLLO, he says, is collecting a wide array of data from patients, on a scale that is largely unprecedented in cancer research. The data will be analyzed with the help of sophisticated technology—including artificial intelligence—and scientists worldwide. Ultimately, the findings will be used to determine the best precision treatment for a given patient.
The main beneficiaries in the short term will be Veterans and active-duty troops, as cancer care at VA and military hospitals increasingly incorporates knowledge gained through APOLLO. The knowledge will eventually filter into medical care at large, so cancer patients everywhere can see better treatment.
Goal is 8,000 patients in five years
APOLLO is starting operations at 10 military hospitals and one VA site (Palo Alto), with additional VA sites likely to be on board by late 2019. There is also one civilian hospital involved, Anne Arundel Medical Center in Maryland. Cancer patients at these facilities can agree to have their information—including molecular results from their tumors—added to the growing APOLLO research database. All information is coded, so patients are not personally identifiable to researchers. The enrollment target is 8,000 patients over five years.
The effort will work hand in hand with VA’s Precision Oncology Program. Through POP, increasing numbers of VA patients with cancer are having their tumors genetically analyzed, so their physicians can prescribe more targeted therapies, or so they can be referred to appropriate clinical trials.
Vietnam Veteran Clarence Massey is thankful his battle with cancer is long behind him. For others his age and younger who are destined to face a similar challenge, APOLLO and its deep dive into the science of cancer is likely to mean better treatment, and added years of life.
In celebration of important medical research conducted by the U.S Department of Veteran Affairs (VA), VA medical centers (VAMCs) nationwide will showcase innovative solutions that VA scientists are developing and bringing into clinical practice with help of university partners and other public and private institutions during VA Research Week, May 13-17.
VAMCs will commemorate VA Research Week with special events such as tours of their research facilities, lectures, poster displays and luncheons to honor the Veterans who voluntarily participate in VA Research studies.
“The Science of Hope,” VA’s 2019 Research Week theme, underscores the promise that the department’s research brings to Veterans and their loved ones coping with post-traumatic stress disorder, traumatic brain injury, limb loss, chronic disease and other serious health challenges.
“One of the most important things we accomplish every day in VA is bringing new hope to Veterans,” said VA Secretary Robert Wilkie. “VA research plays a huge role in that mission. Scientists at VA medical centers across the nation are changing the face of medicine and rehabilitation.”
Examples of current VA Research include advances in prosthetics, such as artificial hands that restore a sense of natural touch; and in precision oncology, which uses molecular analysis of tumors and other individual patient factors to customize cancer treatment.
A focus of VA Research Week includes VA’s Million Veteran Program (MVP), one of the world’s largest genomic databases. As of mid-April, the program has enrolled nearly 750,000 Veterans. Researchers using MVP data have published important findings on the genetics of hypertension, substance use disorders and other important topics.
In 2019 VA celebrates 94 years of VA Research. To learn more about the work of VA researchers, past and present, visit www.research.va.gov. For more information on local and national events marking National VA Research Week, visit www.research.va.gov/researchweek.
Influenza significantly increased the risk of hospitalization for heart failure, according to a study of more than 450,000 adults, which was published in the March 27 issue of Journal of the American Medical Association (JAMA)/Cardiology, and headed by a Minneapolis Department of Veterans Affairs (VA) researcher.
Senior author Dr. Orly Vardeny, a clinical pharmacist and researcher at the Minneapolis VA Medical Center’s Center for Care Delivery and Outcomes Research and an associate professor of medicine at the University of Minnesota, said this is the largest study to confirm the long-held notion of a connection between influenza, also known as flu, and heart failure.
“The study’s findings support VA’s aggressive effort every year to provide Veterans with influenza vaccine,” said VA Secretary Robert Wilkie. “Although the flu season is winding down, it’s not too late for Veterans, and others, to get a vaccine.”
Vardeny and colleagues reviewed hospitalization data of adults ages 35-84 between October 2010 and September 2014 in four geographically diverse U.S. communities. Researchers correlated this information with reports of influenza activity from the federal Centers for Disease Control Surveillance Network.
“We hypothesized that increased influenza activity would be associated with an increase in hospitalizations for heart failure and myocardial infarction among adults in a community cohort,” Vardeny said.
Indeed, that was the case. Influenza activity was related to an increase in heart-failure hospitalizations across four influenza seasons in the four communities. Communities studied included Jackson, Mississippi; eight suburbs of Minneapolis, Minnesota; and two rural communities, Forsyth County, North Carolina; and Washington County, Maryland.
Researchers found a 5 percent monthly increase in influenza activity was associated with a 24 percent relative increase in heart failure hospitalization rates.
“Our study suggests that influenza may contribute to the risk of heart failure hospitalization in the general population,” Vardeny said. “This is additional strong evidence that adults need to have an annual immunization against influenza to avoid potential complications that lead to hospitalization.”
Study co-authors were from Brigham and Women’s Hospital in Boston, Toronto General Hospital, the University of North Carolina, the University of Wisconsin and the National Heart, Lung and Blood Institute.
A U.S. Department of Veterans Affairs (VA) researcher was recently recognized by the American Academy of Audiology for his work in improving the lives of Veterans and others affected by hearing loss.
Dr. Patrick Feeney was presented the 2019 Jerger Career Award for research in audiology at the American Academy of Audiology’s annual meeting March 29.
The Jerger Award is given annually to an investigator whose research contributions have significantly impacted the practice of audiology. Over the past 30 years, Feeney’s research has focused on peripheral and central auditory function in Veterans and others.
“Hearing loss and tinnitus have long been among the disabilities affecting Veterans,” said VA Secretary Robert Wilkie. “The innovative research conducted by Dr. Feeney and his team is critical in finding ways to address these issues.”
Feeney directs the National Center for Rehabilitative Auditory Research (NCRAR) at the VA Portland Health Care System in Oregon. NCRAR, funded by VA Rehabilitation Research and Development, is the only VA research center dedicated to the discovery and delivery of innovative solutions for Veterans with hearing impairments.
The center educates Veterans and the public about preventing hearing loss and coping with tinnitus — or ringing in the ears. It partners with institutions in the community to promote education, share clinical information, and train auditory researchers and clinicians.
Feeney has worked as a clinical audiologist and served on the faculty at several research institutions. He is a professor at Oregon Health and Science University, is active in several professional organizations and was past president of the American Academy of Audiology from 2008 to 2009. He also has been a faculty member at Ohio State University and the University of Washington.
Feeney has contributed to more than 50 publications in peer-reviewed journals, 11 textbook chapters for the profession of audiology and more than 50 published abstracts.
To learn more about VA research on hearing loss, visit www.research.va.gov/topics/hearing.cfm.
The Department of Veterans Affairs is conducting the most comprehensive study to date of blast injuries on post-Sept. 11 Veterans. Improved battlefield medical care in Iraq and Afghanistan means more troops have survived with traumatic brain injury, or TBI. Researchers are trying to understand the long-term effects of those injuries.
And 800 Veterans from around the country have enrolled to find out what blast exposure has done to them.
Former Army Ranger Chris Riga realized something wasn't right shortly after he had been exposed to several improvised explosive devices.
"I couldn't keep my balance"
"The first time I noticed, we had been through multiple IED strikes within [the period of] a week ... in Afghanistan, and, unfortunately, I was at a memorial ceremony and I couldn't keep my balance after standing up for about two minutes," Riga says.
Riga served several tours in Afghanistan from 2001 to 2014, eventually commanding all U.S. Special Forces there. During his 29 years in the Army, he served as an Army Ranger in the 82nd Airborne Division as well as in the 3rd and 7th Special Forces Groups in Afghanistan, Africa and Iraq.
"We were always either preparing for combat or deployed in combat," Riga says. "Blasts and exposures were a daily incident."
Researchers are now looking at Veterans with a variety of symptoms, such as PTSD, alcohol abuse, and sleep problems, which tend to co-occur with traumatic brain injuries.
"We don't only look at the military service period," says Regina McGlinchey, one of the co-directors of the VA study. "We look at what happened to these people when they were younger, before they were in the military, so we capture things like rock wars and sledding incidences when they were growing up."
The study's co-director, Bill Milberg, adds that they are also looking at sports injuries and bar fights. "The whole gamut," he says. They're trying to determine if pre-military history affects a person's risk of physical or psychological disorders as a result of military service.
And they're trying to understand the possible impact on a person's emotional well-being.
"We're not trying to understand PTSD, or just TBI," McGlinchey says. "It's like, what does war do to an entire person?"
Researchers found that exposure to blasts resulted in changes to brain function and brain structure. They also learned that Veterans could have suffered a brain injury from blasts even if they never had a concussion. One of the researchers, Laura Grande, found the effects of blast exposure are the same even if a person had no symptoms of concussion.
"It's not the PTSD that's driving this memory deficit," Grande says. "It's not the sleep deprivation. It's not the substance abuse. There is something about blast exposure that is also associated with memory impairment."
Riga lives in western Massachusetts, where he works as a patient advocate at his local VA. A co-worker who works with a lot of recent special operations Veterans told him about the VA study. At 54, Riga has had many concussions and has ongoing problems with short-term memory — so he volunteered. By participating in the VA research, he has been taught how to cope with his memory loss.
"I go through a lot of sticky [notes]," Riga says. "My wallet is full of them. It's a tool. Rather than not only forgetting something and adding the stress of worrying about forgetting something, you can just simply write it down."
Targeting those who may need help
By working with Riga and other Veterans, McGlinchey hopes the VA team can identify combinations of conditions that seem to predict poor outcome.
"So that we can target who it is that are going to need a lot of care; intervene early enough where we can have an effect and have an impact on the rest of their lives rather than letting the horse keep running out of the barn," McGlinchey says. "But first, we have to know who to find, how to target. You can't just bring 3 million people ... who have been deployed in for help. We have to figure out who needs the help."
McGlinchey and her colleagues are trying to identify those at greatest risk for later disability in order to target therapy and other interventions as early as possible.
Veterans interested in participating in the study can contact study recruiter Wally Musto at 617-799-8617.
With the goal of establishing a consensus on medical marijuana use by Parkinson’s patients — which a recent survey co-sponsored by the Parkinson’s Foundation put at 80 percent — the group will host its first conference focused on this compound and the disease.
Set for March 6-7 in Denver, the invitation-only meeting will include a mix of experts from academia, healthcare, government, and the private sector to consider the implications and make recommendations for the use of medical marijuana by patients. Parkinson’s advocates, who are patients, will also attend.
“Now that medical marijuana is legal in 33 states and in many other countries, people are equating access to efficacy,” James Beck, the Foundation’s chief scientific officer, said in a news release. “It is imperative that we address the clinical implications of medical marijuana use among people with PD [Parkinson’s disease].”
Specifically, attendees will discuss both the perceived benefits and hazards of marijuana use in treating Parkinson’s symptoms, in addition to safety issues, potential delivery means, possible sanction as a therapeutic, and areas for more scientific investigation.
Following the meeting, the Foundation will issue suggested practices and highlight areas where more research is needed.
“Having worked as a clinician for the past decade in Colorado, a state at the forefront of medical marijuana use, it is clear that people with PD and their families are intensely interested in the potential of marijuana and cannabinoids in helping manage symptoms and other aspects of their disease,” said Benzi Kluger, associate professor of University of Colorado Hospital and a conference co-chair.
“To date, there is more hype than actual data to provide meaningful clinical information to patients with PD. There is a critical need to analyze existing data on medical marijuana and to set priorities for future research.”
Few clinical studies have evaluated marijuana’s effect on Parkinson’s symptoms in patients. Other than anecdotal evidence that use can help with sleep, pain, appetite, nausea, tremors, and anxiety, definitive scientific research does not back that up.
Preclinical findings, however, suggest a correlation between cannabinoids — marijuana’s active compound — and a reduction of Parkinson’s symptoms such as slowness and excessive movement.
Cannabinoid receptors that make up the brain’s endocannabinoid system are linked to neurons that regulate thinking and various body functions. Some researchers believe that cannabis may be neuroprotective, easing the damage caused by Parkinson’s to brain cells, the Foundation notes on its website.
Still, possible adverse effects include impaired cognition, dizziness, blurred vision, mood and behavioral changes, balance loss, and hallucinations.
A. Jon Stoessl, a conference co-chair and co-director of the Djavad Mowafaghian Centre for Brain Health at the University of British Columbia, said the field needs a clearer understanding and determination regarding which cannabinoids are likely to help or harm, what symptoms could be affected, and how to go about clinical trials.
A survey conducted by the Foundation and Northwestern University found that 80 percent of Parkinson’s patients have used cannabis, 23 percent of physicians have been formally educated about medical marijuana use, and 95 percent of neurologists have gotten requests to prescribe the medicine.
The Foundation also notes that “[s]ince cannabis has been approved through legislation rather than regulation, there are no labels, dosage recommendations or timing instructions that physicians can reference.”
Visit this site for more information on medical marijuana and Parkinson’s, or call the Foundation’s helpline at 800-473-4636.
A large, international genetic study using Million Veteran Program data has identified more than 200 gene variants that could contribute to high blood pressure. The study also identified over 200 drugs currently used to treat other diseases that could potentially be repurposed to treat high blood pressure.
Dr. Todd Edwards of the VA Tennessee Valley Healthcare System—one of the senior authors on the study and himself a Veteran—explained the significance of the findings. “We’re redrawing the map of blood pressure genetics,” he said in a Vanderbilt University press release.
Nearly 100 researchers from around the world collaborated on the study, including 24 VA researchers. The results appeared in the January 2019 issue of the journal Nature Genetics.
Study group included more than 300,000 Veterans
Each person has different variations of genes at specific locations on their genome. These variations are mostly inherited. The idea behind genome-wide association studies such as this one is that people who share the same gene variants could have similar risks for diseases.
While lifestyle choices—such as smoking, diet, and alcohol use—influence the risk of high blood pressure, doctors have known for some time that a significant part of a person’s risk comes from the genes inherited from parents.
Previous genome studies reported more than 250 genome locations that affect blood pressure. In this study, the researchers identified 201 new locations on the genome that affect blood pressure. They also identified 304 locations that had been identified by previous studies.
They found these new gene associations by looking at the genomes and blood pressure data of more than 300,000 Veterans who participate in MVP, along with more than 140,000 participants from the UK Biobank. By comparing genomes across this large participant group, the researchers identified the gene variants shared by those with high blood pressure.
Once they had identified the new gene locations, the researchers compared their results with the genomes of more than 300,000 participants from the International Consortium for Blood Pressure and Vanderbilt University’s BioVU. The comparison confirmed the findings from the MVP data.
Findings may lead to new drug treatments
Beyond identifying new gene locations affecting blood pressure, the study yielded several other interesting results. Once the researchers had identified genome locations related to blood pressure, they cross-checked those genes against a list of genes targeted by drugs used to treat diseases other than hypertension. This analysis pointed to over 200 drugs that interact with the identified genes, meaning that those drugs could potentially be repurposed for treatment of high blood pressure. The study also identified 40 new genes that could be the focus of new drug development to treat high blood pressure.
The researchers also compared the genetic effects on blood pressure between black, white, and Hispanic Veterans in the MVP database. They found that the effects of gene variations were similar among ethnic groups.
Another phase of the study focused on the genetic underpinning of kidney function. The kidney is an important organ for blood pressure regulation. The researchers looked at gene expression in mouse kidney cells to identify which cell types are most involved in regulating blood pressure. They found that structures in the kidney called tubules are the most important for blood pressure. Genes identified by the study were most expressed in tubule cells.
Developing a hypertension risk score
Finally, the researchers used the new genomic data obtained in the study to create a score for predicting high blood pressure in patients. The score counts the number of gene variants related to high blood pressure that are present in an individual patient’s genome. The higher the score, the greater the genetically predicted burden of high blood pressure for a given individual. The researchers checked these scores against the electronic medical records of over 250,000 Veterans. On average, individuals with higher scores were more likely to have high blood pressure, as well as kidney disease, stroke, complications related to diabetes, and aortic aneurysms, as well as a number of other conditions.
Edwards acknowledges that more research is needed to understand how genes affect blood pressure, but he asserts these findings may help advance treatment. “We can’t accurately say what your blood pressure’s going to be at age 65 by looking at your genotype, but we might be able to tailor your treatment a little more accurately with some of the results we have from this study,” he says.
High blood pressure is the leading cause of death and disability in the United States and around the world. According to the National Institute of Aging, more than 60 percent of people over 65 have high blood pressure, and the number of people with high blood pressure is increasing. High blood pressure is the largest inheritable factor for stroke and coronary artery disease. It is responsible for 13 percent of deaths worldwide.
MVP is a national, voluntary research program funded by VA’s Office of Research and Development. MVP partners with Veterans receiving care in the Veterans Health Administration to study how genes affect health. As of January 2019, MVP had enrolled more than 725,000 Veterans. It is already one of the world’s largest databases of health and genomic information.
Researchers at the VA San Diego Healthcare System aim to see whether cannabidiol, or CBD—a compound derived from cannabis plants—can help ease PTSD. The study will give CBD as an add-on to prolonged exposure therapy, a proven psychotherapy for PTSD.
The $1.3 million VA-funded study will enroll 136 Veterans, from all service eras.
Dr. Mallory Loflin, a research scientist with VA and assistant professor of psychiatry at the University of California, San Diego, is leading the study. Loflin, with VA’s Center of Excellence for Stress and Mental Health, specializes in studying new mental health treatments that target the body’s endocannabinoid system. CBD and related compounds from cannabis bind with receptors—proteins on the surface of cells—that are part of this system.
Loflin says past research suggests that CBD can increase extinction learning in PTSD. This has to do with people “unlearning” unhelpful responses and behaviors they’ve developed in the wake of trauma. This, she says, could boost the speed and effectiveness of prolonged exposure therapy, which helps patients gradually work through their traumatic memories. She says CBD could also ease insomnia and over-arousal. Those types of effects are beneficial on their own, but they could also further boost Veterans’ engagement and retention in treatment.
VA Research Currents interviewed Loflin to learn more about the trial, which plans to start recruiting patients by March 2019.
It seems there is a lot of confusion and misinformation floating around on the internet about CBD, and cannabis in general. Does that present special challenges for this study?
I certainly get more questions from prospective participants! In particular, folks have a lot of questions about whether it’s legal for them to participate in the study, and whether they could get in trouble with their work. Because I have a Schedule 1 license, under the Controlled Substances Act our participants are 100-percent legally allowed to receive the study drug. The challenge, though, is with the work question. Just because something is legal doesn’t mean that one’s workplace allows it, so we do have to advise them to do their homework to find out if their employer prohibits use of cannabidiol, even in the context of a research study and for medical treatment. That’s obviously something we wouldn’t have to think about with other medication trials.
While there has been legitimate research showing health benefits from CBD, there’s also been hype about how it’s good for virtually anything that ails a person. Is there a concern that this might lead to a stronger-than-usual placebo effect?
Yes, and this isn’t just an issue for CBD either. This is a common problem for cannabinoid research in general. Folks talk about cannabis and cannabinoids being cure-alls for everything from Alzheimer’s to warts, which creates a huge demand on participants to see improvement when they’re in a “cannabinoid research study.” Unfortunately, what we then see is that even folks in the placebo condition in these trials tend to see greater benefit from the inactive treatment than folks would usually see from an active treatment outside the study! This strong placebo effect creates headaches for researchers because it makes it very difficult for our experimental condition (the study drug) to outperform the placebo, increasing the likelihood that the trial will fail.
We’ve obviously thought a great deal about this issue and will attempt to measure folks’ expectations about the study drug and attempt to control for that when we analyze the data. Also, I designed this study as an adjunct to psychotherapy because I wanted to test whether the addition of CBD to one of our current frontline treatments for PTSD (prolonged exposure) helps with the process of treatment. But it’s also possible it could impair treatment.
I’m equally interested in finding out whether taking CBD at the same time as psychotherapy disrupts treatment gains. This is a major question I get from therapists whose patients are self-treating themselves with a cannabinoid during psychotherapy, whether it helps, hurts, or makes no difference. So even if the study “fails” and doesn’t find that CBD outperforms placebo because of too strong of a placebo effect, we should at least be able to see if those in the CBD condition fared worse, which is a very important question.
Tell me about the CBD product you are using in the study.
It’s manufactured in a lab to replicate plant-derived CBD. It’s isometrically identical but doesn’t come from cannabis. There was a lot of back and forth on which source to use, but we decided to go with lab-derived for consistency of the drug product. This also helps us test just the effects of CBD alone. Most plant-derived CBD products contain other potentially active compounds that will vary from plant to plant and product type to product type. We could have used plant-derived pure CBD, but at that point it’s just a single molecule. It’s easier to get to that molecule from a synthetic lab-made product than from a plant.
Would it be correct to use the term “medical marijuana” or “medical cannabis” for this trial?
Neither is technically correct, since our CBD product doesn’t come from cannabis, although I’d argue that the term medical marijuana isn’t precise in any context, since the scientific term for all is cannabis and “marijuana” is really just a colloquial term, and one with quite a racialized history, too. I guess you’d call our study a “cannabinoid trial.”
Do naturally derived CBD products contain various other compounds, even in very small amounts, that may contribute to the therapeutic effect? By using a synthetic and “pure” CBD product, are you possibly sacrificing some therapeutic benefit and effectiveness?
It’s important to point out that it might not even be CBD that’s responsible for therapeutic effects. It could very well be one of its metabolites [substances that are created when a compound is broken down in the body]. It’s also very likely that a lot of those other compounds in the cannabis plant have therapeutic benefit. However, it’s equally likely that a lot of them also interact with and suppress the effects of CBD, as well. The problem is that we haven’t categorized most of those other compounds in a systematic way, and we know very little about their bioavailability, metabolism, actions, and effects. By studying just one molecule we can at least parse out the direct effect of CBD by itself. We have a very long way to go to understand the effects of everything in the cannabis plant.
Participants in the trial will receive capsules that contain either CBD or a lookalike placebo. Why use capsules as opposed to other forms of CBD?
It came down to regulatory process more than anything else. Encapsulating a pharmaceutical product is considered standard pharmacy procedures, but mixing it with sesame oil (for sublingual) or another solid (for inhalation) would be changing the formulary. In the eyes of the Food and Drug Administration (FDA), this would then be considered a different drug product, not pure CBD. We would have had to do all kinds of preliminary studies to demonstrate safety with that new “mixture” before obtaining FDA approval to proceed with the study. Since we don’t have enough data yet to know which method of delivery produces the most consistent effect, oral seemed like a good first start.
What legal and regulatory processes did your team have to go through to do this trial?
First, we applied to VA Clinical Science Research and Development for funding. That application was reviewed by a scientific panel of researchers who scored it based on merit of the study design and potential for impact on Veterans’ health. After receiving notice that the study would be funded, we applied for and received approval from the FDA to test oral CBD as an investigational new drug product for the treatment of PTSD. We also received approval from the California Department of Justice to recruit state residents as participants in a controlled-substance research study.
I also applied for and was granted a Schedule 1 researcher registration, which required a site visit from the federal Drug Enforcement Administration to ensure that we had appropriate facilities and procedures in place to store and administer the drug. Because we decided to purchase CBD as an active pharmaceutical ingredient and encapsulate it in our pharmacy, we did not need National Institute of Drug Abuse approval, though this would be a typical first step for a cannabis-based study. But we did need to get approvals from federal VA contracting for sourcing the drug product from a chemical manufacturer.
The trial will enroll 136 Vets. Will that be a large enough sample to enable you to stratify the results based on factors like service era, duration of PTSD, gender, or race? In other words, will you be able to learn which subgroups of Veterans with PTSD can potentially benefit most from CBD?
We’ll certainly investigate whether those factors impacted outcomes as a secondary follow-up to the study, but you’re correct that the sample size isn’t large enough to test this as a primary outcome.
Is this the first randomized, controlled trial of CBD for PTSD in the U.S. or worldwide? Are there any—even small pilot studies—that show up in the medical literature?
Not at all! Two other cross-over trials that compare different combinations of THC and CBD with placebo for PTSD are underway in British Columbia and Arizona. To my knowledge, though, this is the first cannabinoid trial primarily funded by VA. There is also a double-blind clinical trial preparing to launch at New York University that would test CBD alone as a potential treatment for comorbid PTSD and alcohol use disorder.
CBD at a glance
CBD is short for cannabidiol (pronounced kan-a-bih-die-ole). CBD is one of hundreds of chemical compounds found in cannabis plants. One large group of these compounds is known as cannabinoids. Scientists have identified more than 100 cannabinoids, including CBD.
Besides CBD, another compound found in cannabis is THC, short for tetrahydrocannabinol. THC is “pscychoactive,” meaning it produces a high, a feeling of euphoria. CBD does not have this property.
Studies and anecdotal experience suggest a variety of possible health benefits from cannabinoids such as CBD and THC—for example, easing chronic pain and anxiety—but researchers are still learning exactly which compound produces which effects, and what the risks are.
The terms hemp and marijuana are associated with CBD, and there is much confusion as to their precise definitions. See this blog post from the National Institute on Drug Abuse for an explanation.
What’s important to know is that varieties of the cannabis plant that would be considered marijuana contain far more THC than do varieties that are grown as hemp. According to the 2018 Farm Bill, hemp that is grown legally in the U.S. can contain no more than 0.3 percent of THC.
CBD products can be derived from either “marijuana” or “hemp” varieties of cannabis—or they can be made synthetically in a lab. CBD can be used in various forms, such as oils, sprays, creams, gummies, and capsules.
Although CBD does not produce a high, until recently it was considered a Schedule 1 drug—in all its forms—and was subject to tight regulation. The 2018 Farm Bill loosened restrictions on CBD derived directly from hemp, as part of the bill’s legalizing of commercial production of hemp. However, there are currently no hemp-derived CBD products that meet FDA criteria for research. The synthetic version being used in the VA trial and other forms of CBD being used in research are still classified as Schedule 1 drugs. As such, approvals for the research must be obtained from several agencies, including the Drug Enforcement Administration and the FDA.
Vaccinations have begun in a Phase 1 human clinical trial testing a freeze-dried, temperature-stable formulation of an experimental tuberculosis (TB) vaccine candidate. The trial is being conducted at the Saint Louis University School of Medicine Center for Vaccine Development and will enroll as many as 48 healthy adult volunteers aged 18 to 55 years. The experimental vaccine, called ID93, was developed by scientists at the Infectious Disease Research Institute (IDRI) in Seattle. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is supporting the trial through a contract to IDRI.
ID93 is a recombinant vaccine candidate made from four proteins of Mycobacterium tuberculosis (the bacterium that causes TB). Many vaccines require a temperature-controlled system during transport, which can be costly and logistically challenging. Freeze-dried powder vaccines can be distributed at a cheaper cost to remote, low-resource settings. The powder formulations are mixed with sterile water for administering with a needle and syringe. Investigators are examining if a powder formulation combining ID93 and the adjuvant GLA-SE (an immune response-stimulating protein) in a single vial, reconstituted with sterile water, is as effective at inducing an immune response in participants as the previously tested two-vial combination of powdered ID93 and liquid GLA-SE.
“Tuberculosis remains the leading infectious cause of death worldwide, and a highly effective vaccine would be a crucial tool in ending this pandemic,” said NIAID Director Anthony S. Fauci, M.D. “A vaccine that did not require a cold chain could be much more easily distributed to communities in need.”
Currently, Bacillus Calmette–Guérin (BCG) is the only Food and Drug Administration approved TB vaccine. It is commonly given to babies in TB-endemic regions to protect children against meningitis and disseminated disease. However, the vaccine does not adequately prevent TB disease in adolescents and adults.
ID93 + GLA-SE is being developed as a vaccine candidate that could be administered to people who have already received the BCG vaccine or have already been exposed to TB, to prevent reactivation or reinfection. The vaccine was recently shown to be safe and immunogenic in a Phase 2a clinical trial that enrolled adults in South Africa who had recently been cured of TB with standard therapy. Other early-stage clinical trials showed ID93 + GLA-SE is safe and immunogenic in healthy adults in the United States and in BCG-vaccinated adults in South Africa.
“To our knowledge, the freeze-dried formulation of ID93 + GLA-SE represents the first time a thermostable vaccine candidate containing a modern immune-boosting substance has reached clinical testing,” said Christopher Fox, Ph.D., vice president of Formulations at IDRI and principal investigator of the NIAID contract. “Implementing technologies designed for low-resource settings early in product development could help accelerate vaccine rollout in hard-to-reach areas.”
Daniel Hoft, M.D., Ph.D., director of the Division of Infectious Diseases, Allergy and Immunology at the Saint Louis University School of Medicine, is the principal investigator for the clinical trial. All participants will receive two vaccinations 56 days apart. Half of those enrolled (24 people) will receive the single-vial formulation of ID93 and GLA-SE, and the remaining participants will receive the previously tested two-vial presentation of powdered ID93 and liquid GLA-SE.
Participants will be monitored for any possible reactions to the vaccine and will be asked to provide blood samples at specified time points over approximately seven months. Investigators will examine the samples to determine if participants have generated an immune response. To ensure the safety of participants, a safety monitoring committee composed of an independent group of experts will review safety data throughout the trial, which is expected to end in November 2020. For more information, visit ClinicalTrials.gov and search identifier NCT03722472.