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.
VA continues expansion of integrated network system to enable health care staff to share best practice uses of department’s 3D printing capabilities
Today the U.S. Department of Veterans Affairs (VA) announced that it continues to expand its national integrated virtual 3D printing network that began January 2017 at VA’s Puget Sound Healthcare System, growing it from just three hospitals with 3D printing capabilities in early 2017 to 20 at the close of 2018.
This growing network allows VA health care staff to share ideas, solve problems and pool resources on best practice uses of 3D printing for improving Veterans’ care.
Currently, Veterans Health Administration (VHA) innovators across the 20 sites are using 3D printing to solve a wide range of issues, from presurgical planning to manufacturing hand and foot orthotics.
“VA remains at the forefront of innovative work in 3D printing by expanding our expertise across VA,” said VA Secretary Robert Wilkie. “Through this growing virtual network, VA continues to help define how 3D printing technology will be used broadly in medicine for the benefit of patients.”
At the Puget Sound Healthcare System, prints of model kidneys for patients with renal cancer aid in presurgical planning, allowing surgeons to plan their surgical approach to maximize preservation of normal kidney tissue and avoid disturbing unaffected vessels that surround a tumor. This can save doctors up to two hours per surgery, reduce the time patients are under anesthesia, and increase operating room availability.
Occupational therapists are also using 3D printers to manufacture specialized hand orthotics, to provide same-day fitting and delivery, which offers immediate care and reduces the need for multiple visits. The digital blueprint can then be saved, so a replacement can be printed quickly if the orthotic breaks or is damaged.
VA researchers are working with collaborators to create a bioprinting program that uses 3D printing to fabricate replacement tissues that are customized to an individual patient. This would decrease wait times for tissues and organs, reduce the need for grafting surgeries and enable hospital and health care providers to improve the quality and safety of medical procedures. The group is targeting a competitive three-year timeline to have a bioprinted vascular bone implanted into a patient.
The 3D printing virtual Center of Excellence is part of the VHA Innovation Ecosystem. The Ecosystem includes the Diffusion of Excellence Initiative and VHA Innovators Network, two programs that aim to identify and scale innovations and best practices across VA by empowering and enabling employees.
The VA actually spent money — and years — on a scientific study to tell us daily drinking is unhealthy
In 1664, Sir Isaac Newton ascertained that the force drawing objects toward each other was gravity, helping to elucidate why planets orbit around our solar system’s star.
In 1823, Jan Evangelista Purkinje observed that fingerprints are unique to each individual and are left behind on items people touch, thus transforming the efficiency of law enforcement investigations.
In 1928, Alexander Fleming discovered penicillin, drastically altering the medical landscape and how bacterial infections are treated.
And in 2018, a groundbreaking scientific study by the Veterans Affairs Department revealed that daily alcohol use isn’t great for your health.
My name is Ozymandias, King of Kings. Look on my Works, ye Mighty, and despair!
Bravo. Money well spent by the VA, the oft-criticized organization that makes paying Veterans what they’re owed for disabilities, education and housing appear as laborious as Thanos' quest to amass all six Infinity Stones.
Who needs resources directed at such tedious, shoulder-shrugging tasks when, instead, we can be assured that the tens of people in the entire Milky Way Galaxy currently consuming daily booze for the purpose of health benefits have their knowledge checked? But it’s gluten free!
“There has been mounting evidence that finds light drinking isn’t good for your health,” said Dr. Sarah Hartz, principal researcher of the study.
Hartz, an assistant professor at Washington University in St. Louis added that she wasn’t surprised by the results, and that “two large international studies published this year reached similar conclusions,” the VA release said.
An unsurprisingly intelligent researcher and professor not being surprised by unsurprising results should surprise no one.
The predictable findings showed that “downing one to two drinks at least four days per week was linked to a 20 percent increase in the risk of premature death, compared with drinking three times a week or less,” according to the Veterans Affairs blog. “The finding was consistent across the group of more than 400,000 people studied" over a course of seven to 10 years.
Participants ranged in age from 18 to 85 years — Hold on. Four-hundred thousand? It took studying more than 400,000 participants over a period of seven to 10 years to reach that verdict?
The VA could just as easily have saved everyone’s time and paid some poor schmuck named Bobby Joe 10 bucks to stumble down to his local watering hole, take a picture — using his high-tech Motorola Razr — of an all-too-frequent bar-goer who long ago developed aged, leathery skin and a portly stature, and still arrived at the same conclusion.
Never has a single ripped individual graced the cover of a health magazine while flanked by the words, “Shred your gut by slamming beers!” or “Get jacked on jack and cokes!”
Was John Basedow pummeling daily boxes of wine while pumping out “Fitness Made Simple” VHS tapes? Doubt it.
Time and resource management skills have seldom been recognized as strengths of the Veterans Affairs, but these Mariana Trench-like depths are hard to fathom.
Byzantine-era computer software creating backlogs of Veteran claims, insufficient manpower to operate said antiquated systems, and now, blinding us with science. It’s poetry in motion.
WASHINGTON — New research linking Veterans’ high blood pressure with wartime exposure to chemical defoliants could dramatically expand federal disability benefits for tens of thousands of Vietnam-era troops.
The findings, from the National Academies of Sciences, Engineering and Medicine, conclude that “sufficient evidence” exists linking hypertension and related illnesses in Veterans to Agent Orange and other defoliants used in Vietnam, Thailand and South Korea in the 1960s and 1970s.
They recommend adding the condition to the list of 14 presumptive diseases associated with Agent Orange exposure, a group that includes Hodgkin’s Disease, prostate cancer and Parkinson’s Disease. That’s an upgrade from past research that showed a possible but not conclusive link between the toxic exposures and high blood pressure problems later in life.
If Veterans Affairs officials follow through with the recommendation, it could open up new or additional disability benefits to thousands of aging Veterans who served in those areas and who are now struggling with heart problems.
Veterans who struggle with high blood pressure issues are eligible for health care at VA facilities. But the illness is eligible for disability benefits in only select cases.
Adding an illness to VA’s presumptive list means that Veterans applying for disability benefits need not prove that their sickness is directly connected to their time in service. Instead, they only need show that they served in areas where the defoliant was used and that they now suffer from the diseases.
That’s a significant difference, since proving direct exposure and clear health links can be nearly impossible for ailing Veterans searching for decades-old paper records.
A change in the designation of hypertension by VA could also add significant new costs to the department’s disability payout expenses.
In 2010, when then Veterans Affairs Secretary Eric Shinseki expanded the list of presumptive illnesses for Agent Orange exposure to include ischemic heart disease and Parkinson's, the department estimated additional costs of more than $42 billion over a decade.
It’s unclear how many Veterans suffer from high blood pressure and would be eligible for disability payments if the change is made. In a statement, VA spokesman Curt Cashour said the department “is in the process of evaluating this report and appreciates the work” of the group.
Regardless the cost, officials from the Veterans of Foreign Wars are already calling for VA officials to move ahead with adding hypertension to the list.
“There is no doubt in anyone’s mind that Agent Orange made Veterans sick, it made their children sick, and it brought pain and suffering and premature death to many,” VFW National Commander B.J. Lawrence said in a statement. “Even though it’s been a half century since they were exposed, the results of that exposure is something they continue to live with daily.”
Over the last year, advocates for “blue water” Navy Veterans — sailors who served in ships off the coastline of Vietnam — have been fighting with department officials over a decision to deny them presumptive status in Agent Orange related claims.
VA officials have insisted that scientific evidence does not exist linking their illnesses to exposure to the defoliant miles away from the Vietnam mainland.
The new study is available at the National Academies Press website.
Los Angeles, CA
Health disparities have persisted over time in the U.S. for a wide range of conditions affecting vulnerable populations. In the VA healthcare system, where financial barriers to receiving care are minimized, disparities are diminished, but still present for many important health outcomes. The Office of Health Equity-QUERI Partnered Evaluation Initiative will use a population health approach to examine the distribution of diagnosed health conditions, mortality, and healthcare quality across the entire VA healthcare system, as defined by Veterans' membership, or not, in vulnerable population groups. Investigators also will evaluate whether characteristics of the healthcare delivery settings (e.g., geography, treatment setting) and of the types of care that individuals use, including new models of care such as Telehealth, influence the quality of care that Veterans receive.
The Office of Health Equity-QUERI Partnered Evaluation Initiative has four specific aims:
- Assess where disparities exist between vulnerable Veteran populations and reference groups for diseases and conditions that are considered the principal causes of disability and mortality, particularly among vulnerable Veteran populations
- Examine gaps and trends in quality of healthcare across treatment settings among vulnerable Veteran populations.
- Determine the extent to which new models of care alter the association between vulnerable population status and gaps in quality of healthcare.
- In partnership with VA's Office of Health Equity, convene an Advisory Board to examine the context for and identify next steps needed to reduce identified disparities for the purpose of informing development of action plans to reduce disparities in VA healthcare.
This evaluation will identify high-priority VA health outcome and quality gaps to address, key organizational and other contextual factors that may impact action plans, and the highest priority next steps to reduce health disparities in VHA.
Investigators will use a population health approach to examine the distribution of diagnosed health conditions, mortality, and healthcare quality across the entire VA healthcare user population, as defined by their membership or not in vulnerable population groups. These vulnerable groups are defined by: race/ethnicity, sex, socioeconomic status, rurality of residence, service-connected disability status, serious mental illness, and age group. Secondary VA administrative data sources will be used to build on an existing database containing a complete multi-year cohort of VA patients.
The key partner is VA's Office of Health Equity, which "strives to advance health equity and reduce health disparities for all, especially vulnerable populations based on racial or ethnic group, religion, socioeconomic status, gender, age, mental health, cognitive, sensory, or physical disability, sexual orientation, geographic location, or other characteristics historically linked to discrimination or exclusion."
Each year, tuberculosis (TB) kills more people than any other single infectious disease. Although tuberculosis can often be treated through a long and grueling course of antibiotics, not everyone is completely cured. Even among patients who are infected with Mycobacterium tuberculosis (Mtb) strains that are considered to be susceptible to the standard treatment regimen, 5 percent of patients relapse within six months of completing standard treatment. Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and through NIAID’s Tuberculosis Research Units Network (TBRU-N), found that a more refined analysis of TB strains collected from volunteers before treatment could accurately predict whether those volunteers would be likely to relapse after standard treatment was completed.
The consequences of TB relapse can reach beyond an individual patient, as any bacteria that remain in the patient after treatment has ended are more likely to be resistant to antibiotics. Multidrug-resistant tuberculosis is often much more difficult to treat, and its spread is a serious concern.
If health professionals could know whether a patient might relapse after standard treatment, they could decide to prescribe a different, or longer, treatment regimen. However, predicting whether a patient will relapse can be difficult. Research published in the New England Journal of Medicine in August sought to determine if identifying the level of drug required to kill the Mtb strains in a new patient’s sputum, a viscous mucus, could predict whether the patient would relapse later, once treatment was complete.
The researchers used data and samples from volunteers who had participated in a prior study run by the Tuberculosis Trial Consortium of the Centers for Disease Control and Prevention. Roughly 1,000 adult volunteers from the United States and Canada, all of whom tested positive to drug-susceptible TB, enrolled in the study between April 1995 and February 2001. Before the study began, volunteers gave samples of sputum, which were stored for later testing. Volunteers then underwent both eight weeks of standard antibiotic therapy and an additional 16 weeks of either once-per-week rifapentine and isoniazid treatments, or twice-weekly rifampicin and isoniazid treatments. For two years after treatment completion, researchers followed the volunteers, noting who relapsed.
In this current study, researchers analyzed the TB strains in the volunteers’ stored sputum. They studied Mtb strains collected from all 57 volunteers who relapsed after completion of treatment and whose sputum bacteria could be cultured, and from 68 randomly selected volunteers who were cured as controls. The researchers cultured the bacteria isolated from the sputum of the 125 volunteers before they started TB treatment and tested for the bacteria’s susceptibility to isoniazid and rifampicin at different concentrations. The researchers found that strains collected from volunteers who relapsed required higher concentrations of isoniazid and rifampicin to halt their growth, on average, as compared to strains collected from patients who were cured. Based on these results, researchers developed a model to predict how likely a patient with drug-susceptible TB will relapse.
The researchers then conducted a follow-up study to validate their model using a group of volunteers enrolled in a different study led by NIAID’s Division of Microbiology and Infectious Diseases at sites in Brazil, the Philippines, and Uganda. These volunteers, who had also been diagnosed with drug-susceptible TB, also provided sputum samples prior to undergoing standard treatment with isoniazid, rifampin, ethambutol, and pyrazinamide, followed by two months of isoniazid and rifampin. Some volunteers were randomly assigned to an additional two months of isoniazid and rifampin. Using the model developed in the first study, researchers demonstrated that bacteria in pre-treatment sputum samples from 11 volunteers who experienced a relapse required higher concentrations of drugs to be killed in culture, as compared to bacteria cultured from pre-treatment sputum from 14 volunteers who did not relapse.
The results of this study provide a first step in identifying which patients are likely to relapse after completion of TB standard therapy. This has the potential to improve TB treatment success rates and decrease the development of drug-resistant Mtb.
VA scientists elected as National Academy of Medicine members for outstanding professional achievement, commitment to service
Four senior U.S. Department of Veterans Affairs (VA) researchers were recently elected as new members of the National Academy of Medicine (NAM), one of the highest honors in the fields of health and medicine.
VA Drs. Ann McKee, Albert Siu, Lucila Ohno-Machado and Rachel Werner were selected on Oct. 15 by current NAM members for their contributions to medical sciences, health care and public health.
“VA is extremely proud to have Drs. McKee, Siu, Ohno-Machado and Werner on our health care team,” said VA Secretary Robert Wilkie. “Their accomplishments and the tremendous work they do each day to improve the health and lives of our Veterans exemplifies the level of excellence we aspire to achieve as an agency.”
McKee, chief of Neuropathology at the VA Boston Healthcare System and professor of neurology and pathology at Boston University School of Medicine, was elected for her groundbreaking work on chronic traumatic encephalopathy (CTE), Alzheimer’s disease, aging, and vascular neuropathology. Her research in those areas has revolutionized medicine’s understanding of the clinicopathological and molecular features of CTE in athletes and Veterans exposed to neurotrauma or blast injury, and changed the public dialogue on sports-related risks.
Siu, who directs the Geriatric Research, Education and Clinical Center at the James J. Peters VA Medical Center in New York, is a professor of geriatrics and palliative medicine at Icahn School of Medicine at Mount Sinai, New York. He was elected for his seminal contributions to evidence-based practice in health-services research and in pioneering programs that intersect geriatrics and palliative care.
Ohno-Machado, a research scientist at the VA San Diego Healthcare System and chair of biomedical informatics at UC San Diego Health, was elected for creating an algorithm that allows sharing access to clinical data while respecting the privacy of individuals and institutions.
Werner, a core investigator at the Center for Health Equity Research and Promotion at the Philadelphia VA Medical Center, is a professor of medicine and director of Health Policy and Outcomes Research at the Perelman School of Medicine, University of Pennsylvania. She was elected for advancing the understanding of how health care provider performance measurement and incentives often bring unintended and undesired equity consequences that compete with efficiency goals.
For more information on VA Research, visit www.research.va.gov.
Energy drinks like Rip-It and Wild Tiger may be essential fuel for hard-charging U.S. service members, but they’re only exacerbating mental health issues and behavioral issues, according to a new study in Military Medicine.
- The research found that soldiers who consumed at least two energy drinks a day were far more prone to “mental health problems, aggressive behaviors, and fatigue,” with high consumption reported in one out of every six soldiers months after the end of a high-stress deployment.
- Most alarmingly, however, is the assertion that ongoing energy drink consumption and the resulting aggressive behaviors “are associated with being less responsive to evidence-based treatments for PTSD” — a conclusion that suggests soldiers are mortgaging their long-term health for their short-term performance downrange.
- This conclusion was based on a survey of 627 male infantry soldiers, mostly junior enlisted between the ages of 18 and 24, seven months after the end of an unnamed combat deployment in order to gauge long-term impact.
- The problematic behaviors recorded in Military Medicine include extreme irritability (66%), sleep issues (35%), alcohol abuse (29.8%) and depression (9.6%), as well as a higher rate of post-traumatic stress disorder (11.2%), following the end of a deployment.
- It’s important to note that most of these behaviors aren’t a product of the energy drinks themselves, but a long-term impact of an abnormal sleep cycle: “Interestingly, energy drink use was associated with fatigue,” the authors note. “This relationship suggests that energy drink use may potentially exacerbate, rather than alleviate, fatigue.”
In Richmond, Virginia, experiments include implanting pacemakers in dogs, then inducing abnormal heart rhythms and running the animals on treadmills to test cardiac function before euthanizing them by injection or draining their blood.
VA spokesman Curt Cashour said former secretary David Shulkin approved the continuation of the experiments on March 28, the same day he was fired by President Donald Trump.
But Shulkin told USA TODAY on Monday that he “wasn’t asked, nor did I request a review for an approval,” of the ongoing dog experiments. He said he delegated that responsibility to the agency’s research specialists.
Whether he – or his successor – signed off on them is important because a law Trump signed on March 23 requires that dog experiments be “directly approved” by the VA secretary to receive agency funding. It doesn’t specify written permission. Cashour said Shulkin gave the go-ahead orally in an early-afternoon meeting March 28 with five other top VA executives.
Revelations that the tests are set to continue under new VA Secretary Robert Wilkie are sure to trigger a fresh round of debate. The records reviewed by USA TODAY show there are nine active experiments at four VA facilities, and more are likely in the future.
An investigation uncovering surgery failures and deaths in VA experiments on dogs has led to more scrutiny from the agency's chiefs and Congress, but that's not stopping tests involving pain for dogs. USA TODAY
VA: ‘Ethically sound’
VA officials contend the research could lead to discoveries that may help Veterans with heart conditions or breathing problems, which can accompany paralysis. Cashour said researchers use dogs “only when no other species would provide meaningful results and the work is ethically sound.” The VA says more than 99 percent of agency studies involve rats or mice.
When asked to cite the most recent breakthroughs credited to the VA dog research, Cashour pointed to the invention of an implantable cardiac pacemaker and procedures that led to the first successful liver transplant. Those experiments date to the 1960s, according to the VA’s website.
Lawmakers who have been pushing to end invasive dog experiments at the VA say they are disappointed the agency’s new leadership is moving forward with the testing.
“Why there’s this commitment to it, I don’t know because it doesn’t yield any results,” said Rep. Dina Titus, D-Nev., lead co-sponsor of a bill with Rep. Dave Brat, R-Va., that would stop the experiments. “It’s not economically sound, they could be looking at new technologies, and morally people just don’t support testing on puppies.”
Although they were glad Trump signed the legislation in March requiring the VA secretary's approval to fund the experiments, Titus, Brat and Rep. Brian Mast, R-Fla., said they will continue pushing to stop them altogether.
“We haven’t executed what we wanted as intent, which was to bring this to an end in its entirety,” said Mast, a Veteran who lost both his legs in Afghanistan and is now a member of the House VA Committee.
The issue started gaining traction with lawmakers in spring 2017, when an advocacy group, White Coat Waste Project, released documents showing VA researchers in Richmond had botched surgeries on dogs.
Within months, the House unanimously passed legislation to defund the experiments, but the measure stalled in the Senate after VA officials launched a public campaign to stop it.
That campaign included getting support from Veterans’ groups, such as The American Legion and Paralyzed Veterans of America. It also included an op-ed by Shulkin, the now-former VA secretary, published in USA TODAY outlining the need for the canine testing.
Before he was fired, Shulkin said his views on the subject had changed, and he put a moratorium on new experiments beginning without his permission. In March, he ordered that all ongoing studies be reviewed by VA research executives.
Cashour, the VA spokesman, said that review concluded dogs are “the only viable models" for nine experiments.
In a letter to lawmakers obtained by USA TODAY, the VA said they include the tests on spinal cords in Cleveland, brains in Milwaukee, the five heart experiments in Richmond and another cardiac study in St. Louis.
Four studies were discontinued or paused after the review. Researchers determined mice could be used instead of dogs for a Los Angeles experiment on narcolepsy, and pigs could be used for a Milwaukee study on blood flow. Another brain experiment in Milwaukee was put on hold for further review, and a second Los Angeles experiment was closed out.
When asked what the new secretary’s views are on dog experiments, Cashour pointed to Shulkin’s op-ed from last summer and said the VA’s position is unchanged under Wilkie.
Still, the VA recently commissioned a $1.3 million study overseen by the National Academy of Sciences to evaluate the need for dogs as research subjects.
“This is important to ensure that the debate surrounding this issue is grounded in careful analysis that takes into account the full context of the issue,” Cashour said.
Call to suspend experiments
White Coat Waste Project, the group that started the campaign to end the experiments, says they should be suspended until the study is completed.
“I think it calls into question the integrity of the VA’s intentions if it is going to continue funding and conducting dog experiments that it has just paid an organization over a million dollars to scrutinize,” said Justin Goodman, the vice president of advocacy and public policy for the organization.
Some Veterans’ groups that supported the experiments last year did not return messages seeking confirmation of their continued support, including The American Legion and Vietnam Veterans of America.
Paul Rieckhoff, CEO and founder of Iraq and Afghanistan Veterans of America, said his group still backs the experiments as long as they are done the right way.
"We’re not advocating all dog research per se, but when done ethically, it can lead to medical breakthroughs," he said.
But Paralyzed Veterans of America, which initially expressed support for continuing dog testing, told USA TODAY its position has since evolved.
“We no longer oppose efforts to end VA fatal medical research on dogs,” spokeswoman Liz Deakin said.
The group’s former executive director, a Marine Veteran who was paralyzed in a vehicle accident as he prepared to deploy to Afghanistan after the 9/11 attacks, also has rescinded his support.
Sherman Gillums Jr., who is now chief strategy officer at American Veterans, said after reviewing the science and speaking to experts at the VA and elsewhere, he concluded the dog experiments haven’t translated to human medical advances for decades.
“It’s time for us to look at better ways and spend money smarter than we’ve done it in the past – especially if it’s going to involve causing pain to the same animals that most Veterans need as service dogs,” he told USA TODAY. “To imagine them in cages being tested on with no real outcome that gives anybody hope, it just seems cruel.”