Search This Blog

Wednesday, December 11, 2019

Brain training: resilience program helps student-athletes adjust to college life

Imagine the impact on first-year college student-athletes in highly competitive programs if you could teach them resilience – if they learned skills to cope with high expectations, challenging academic courses, rigorous training and physical injuries, homesickness and even the stressors of life beyond college.
In newly published research, a unique and expanding program at the University of Massachusetts Amherst has been shown to improve decision-making and emotional awareness, lower perceived stress and build resilience among diverse and sometimes at-risk college athletes, according to survey data reported by the student participants, compared to a control group of student-athletes. Part of the research was supported by funding in 2017 from the National Collegiate Athletic Association’s (NCAA) Innovations in Research and Practice Grant Program, which is designed to improve the psychosocial well-being and mental health of the student-athlete.
“Participants gained skills key to victory on and off the field, including a sense of belonging, persistence, leadership and the ability to negotiate for the resources they need,” says lead author Genevieve Chandler, a mental health nurse and UMass Amherst nursing professor who developed the innovative program from studying the effects of resilience for two decades.
The new study, published in the Journal of the American Psychiatric Nurses Association, focused on 47 first-year football players and 15 women’s basketball players in Division 1 programs at UMass Amherst between 2016-2018. The participants were 18 or 19 years old; 66% were African American, and the rest were non-Hispanic white, with the exception of one Hispanic participant. The control group consisted of student-athletes who did not receive the training because they arrived later on campus.
Resilience – the ability to persist through challenges and recover from adversity – is no longer considered a character trait by researchers but a “practiced interaction between person and environment,” the study points out.
“Negative thoughts stick to us like Velcro,” Chandler explains. “We have to train our brain to hang on to the positive things. We are experts in stress, so we need to practice building up the calm side of the brain, the focused side.”
Chandler developed the resilience-building workshop as a one-credit academic course called Changing Minds, Changing Lives to address the predictable stresses students face as they adjust to college life – especially those with a history of adverse childhood experiences (ACEs). ACEs emerging from a child’s social experience within the family and community “have a tremendous impact on future violence victimization and perpetration, and lifelong health and opportunity,” according to the Centers for Disease Control and Prevention.
Initially offered to nursing students, Chandler’s class caught the interest of psychiatric social worker Jim Helling, a UMass Center for Counseling and Psychological Health senior clinician who was then working in the Athletic Counseling Office. Helling thought that in a predominantly white university, black student-athletes in particular could benefit from a new kind of support system better suited to helping them cope with chronic stress exposure. “We needed a new approach, a psychological wellness program that would be culturally resonant for students of color,” Helling says. “Ginny’s work focuses on strengths, celebrates resilience and empowers black athletes to express themselves in their own voice. This model has been a game changer for our students.”
Together, they began teaching the course to first-year football student-athletes, who in turn used their newly developed leadership skills to mentor high school football players in nearby Springfield.
In 2018, Chandler and Helling added basketball players, and interest has now spread across campus to target student groups facing particular stress, such as female and minority engineering students in a program traditionally dominated by white males. They have been featured at conferences and conducted resilience course trainings across the country so other educators can teach the curriculum.
Chandler points out that the 50% of study participants who reported ACEs showed greater increments of positive change in emotional awareness scales than participants without ACEs, illustrating the distinctive importance and benefits of resilience training for an at-risk group. An estimated 60% of the U.S. population has at least one ACE.
“I’d hope that it’s a class that everyone could take, honestly,” says Caeleb Washington, a UMass Amherst defensive lineman from Melbourne, Fla., who took the resilience course and later served as a teaching assistant.
The course is interactive and experiential. The content focuses on what Chandler calls the ABCS: active coping, such as exercise or meditation; building strength by focusing on and advancing one’s aptitudes rather than weaknesses; cognitive awareness, which involves being aware of automatic thinking; and garnering social support. To gain the neuroplastic benefits of repetitive practice, each class follows the same format. It begins with each individual describing a “positive practice exercise” they did as homework. Breathing exercises and yoga poses follow. Relevant research is presented and then students, as well as teachers, complete a five-minute, deeply personal writing reflection related to the research. The writing is read aloud, after which class members share feedback about what they found strong in the writing. Class ends with each participant sharing an affirmation, appreciation or appraisal about that day’s class.
“This class has taught me how to breathe. It taught me about leadership and it taught me how to just stay calm,” says UMass Amherst senior Vashnie Perry, a health administration major from the Atlanta area and co-captain of the women’s basketball team. “It’s the best advice I’ve had since I’ve been in college.”

VistaGen gets nod for first Fast Track tag for treatment of social anxiety disorder

VistaGen Therapeutics, Inc. (NASDAQ: VTGN), a clinical-stage biopharmaceutical company developing new generation medicines for central nervous system (CNS) diseases and disorders with high unmet need, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for development of the Company’s PH94B neuroactive nasal spray for on-demand treatment of social anxiety disorder (SAD).

The FDA’s Fast Track process is designed to facilitate the development and review of new treatments for serious conditions with unmet medical need, such as SAD, with the purpose of getting innovative new treatment options to patients sooner. After successful Phase 2 development, VistaGen is preparing PH94B for Phase 3 development. PH94B has potential to be the first fast-acting, non-sedating, as-needed treatment for as many as 20 million individuals in the U.S. suffering from SAD.
“The FDA’s grant of Fast Track designation for development of PH94B for SAD, which to our knowledge is the FDA’s first Fast Track designation for a SAD drug candidate, is another important regulatory milestone for VistaGen and a key step forward in our development program for PH94B as a new generation anxiolytic. With a high global prevalence of anxiety disorders, including SAD, and alarming increases in dependency, addiction and even deaths associated with misuse of benzodiazepines, the urgency for a new non-addictive, non-sedating, fast-acting, as-needed treatment for SAD and other anxiety disorders is more important now than ever before. Based on clinical studies to date, PH94B, at non-systemic microgram doses, has strong potential to fill the large current treatment gap,” said Shawn Singh, Chief Executive Officer of VistaGen.

Hospital leaders increasingly open to negotiated price caps

With Democrats debating Medicare for All and public-option health plans, healthcare CEOs have become surprisingly open to the idea of negotiated caps on provider payment rates, according to Modern Healthcare’s latest Power Panel survey.
While expressing strong misgivings about those Democratic reform proposals, 75% of CEOs responding to the survey last month said their organization could live with some form of price caps as long as their industry had the opportunity to negotiate reasonable levels.
“There has been a change in thinking about payment caps over the last five years,” said Howard Kern, CEO of Sentara Healthcare. “The industry can’t be out there setting outrageous prices. We have to be prepared to set rates that are reasonable. But all the players, including pharma, have to be playing under the same rules.”
Price caps are only one of a number of major policy challenges and opportunities the CEOs anticipate facing depending on the outcome of the 2020 presidential and congressional elections.
The survey was based on a small sample size, with 12 healthcare CEOs responding. Those surveyed overwhelmingly see federal health policy currently moving in the wrong direction.
In contrast, after the election they want to see action on expanding and strengthening the Affordable Care Act, controlling prescription drug prices, and boosting funding for mental health and addiction treatment. About 42% of those responding said the election will have a major impact on their industry. “This may be one of the most significant elections for healthcare in a very long time,” said Chris Van Gorder, CEO of Scripps Health, citing the possibility of victorious Democrats establishing a single-payer government health insurance system, which he opposes.
Half of respondents said the election outcome will have only a modest impact, though some said that with the expectation that voters are unlikely to give either party commanding control of Congress and the ability to pass ambitious legislation.
“Drug prices have got to be addressed, but there will have to be some alignment between the Senate and the House to get that done,” Kern said.
Van Gorder agreed that curbing drug prices is critical, particularly as value-based payment grows. “Some drugs are so expensive that they could destroy the value-based plan with just a few patients needing that therapy,” he said. “We need some frames around those costs.”
The healthcare executives are deeply worried about what will happen if the courts strike down the ACA as unconstitutional, in response to a lawsuit filed by Republican attorneys general and backed by the Trump administration. A ruling in that case is expected soon from the conservative-dominated 5th U.S. Circuit Court of Appeals, after which an appeal to the U.S. Supreme Court is likely no matter the decision.
Difficult to fathom
Still, the CEOs have a hard time imagining either the courts or federal elected officials erasing the most popular provisions of the law, such as expanding Medicaid to low-income adults. Most predicted that if the courts topple the ACA, Congress will reenact it with slight changes to pass constitutional muster.
“If the ACA is struck down without a plan to replace it, we’re in deep trouble in this country,” said Dr. Gary Kaplan, CEO of Virginia Mason Health System. “All those provisions for coverage, pre-existing condition protections, and keeping children on their parents’ health plan have become norms. We have to be prepared to reenact legislation.”
CEOs interviewed for this article had different views of Democratic proposals to establish cheaper public-option health plans to compete with private insurers, which some experts consider a more politically viable approach than Medicare for All.
Peter Fine, CEO of Banner Health, warned that public-option plans likely would underpay providers and disrupt the healthcare system. “We have to make big investments on a long-term horizon,” he said. “When we see a significant level of disruption, does that make us nervous? You bet it does.”
In contrast, Kaplan sees some form of a public-option plan that pays reasonable rates and moves the U.S. toward universal coverage as desirable. In Washington state, where his system operates, public-option plans administered by private insurers and paying hospitals about 160% of Medicare rates are slated to hit the market in 2021, under a state law passed this year.
Still, he cautions that the public-option plans have to pay more than Medicare, and that rates need to be set through a collaborative effort between government, health plans and providers.
“There are huge disparities in commercial rates and there could be some advantages if those payments are leveled out, particularly for those who don’t have pricing power in the market,” he said.
Billing legislation expected to hurt
Half of CEOs surveyed said current bipartisan congressional efforts to protect patients from surprise, out-of-network bills would have a negative impact on their organizations.
While they support the idea of shielding patients from such bills, they oppose the idea of capping out-of-network rates. They’d prefer an arbitration process between providers and payers.
“If you set the price cap for out-of-network care in the emergency room at 150% of Medicare, we would lose millions,” said Van Gorder, whose state already caps out-of-network rates but not for self-insured plans. “And it would take away the incentive of insurers to negotiate a fair rate. That’s why insurers are advocating for this.”
Shifting Medicaid financing to a capped federal payment model, which the Trump administration and congressional Republicans strongly support, is another proposal that 75% of CEOs said would have a negative effect on their organizations. That’s a direction Republicans are likely to go if they win the elections.
But one CEO said much depends on the complex details of how a Medicaid block grant or per-capita cap model is designed.
“We could be very receptive to a block-grant approach giving us more flexibility to manage Medicaid patients,” said Kern, whose organization offers health plans serving people dually eligible for Medicaid and Medicare. “But I am worried the feds will look for the states to pick up a bigger share of the costs of seniors on Medicaid.”
ACA backup plan TBD
Meanwhile, the CEOs said they are not making any contingency plans for the ACA being thrown out or for the next Congress to pass a major healthcare overhaul like Medicare for All. Instead, they are focusing on delivering high-quality care and innovating to increase the value of the care they provide.
“We won’t react to every fear or piece of legislation,” Van Gorder said. “If we did that, we would drive the organization absolutely nuts. I get up every day worrying about whether we’re going to deliver good care to the patient in the trauma room. I worry less about what legislators are doing in Washington or Sacramento.”
The CEOs interviewed all lamented the partisan-driven reversals in health policy over the past decade. They guardedly hope that Republicans and Democrats after the 2020 elections will move forward together on the nation’s health goals.
“Had Republicans and Democrats worked together to fix the ACA, we wouldn’t be talking now about radical approaches that I don’t think will work,” Van Gorder said. “After the election I’m highly skeptical that will happen. But I’d like to think it will.”

SABCS 2019 – Astrazeneca and Daiichi join the Her2 resistance

New data confirms that trastuzumab deruxtecan has an exciting destiny, but the antibody-drug conjugate’s impressive efficacy in late-stage breast cancer comes at a price.

Trastuzumab deruxtecan, the antibody-drug conjugate being developed for breast cancer by Astrazeneca and Daiichi, is forecast to be one of the biggest launches of 2020. The strength of today’s data from the phase II Destiny-Breast01 trial, unveiled at the San Antonio Breast Cancer Symposium, suggest that the substantial expectations are justified.
This sting in the tail is safety, however. The results confirm that the ADC can cause serious toxicities, with 14% of patients in the study suffering interstitial lung disease, four whom died of the complication, with their deaths deemed treatment-related. But with an impressive 61% of heavily pre-treated patients responding to the therapy, this issue seems unlikely to derail the project’s approval chances.
This is impressive in a population that had had a median six prior lines of cancer therapy including Roche’s ADC Kadcyla. As a single-arm study there are limitations to this data, but investigators noted that the results stand out in a very crowded field.
“To put it in context, progression-free survival of 16 months [and] response rate of 60% – those are roughly double or triple what typically we’ve seen in other studies of this third- and later-line population,” Dr Ian Krop of the Dana-Farber Cancer Institute said in a press conference. Overall survival was not reached.
PHASE II TRIAL (DESTINY-BREAST01)PHASE I TRIAL (DS8201-A-J101)
Response rateN
(184 in study)
Response rateN
(118 in study)
Confirmed ORR (primary endpoint)60.9%11259.5%66
     Complete response6.0%11
     Partial response54.9%101
Disease control rate (CR+PR+SD)97.3%93.7%
Median progression-free survival16.4 months22.1 months
Median duration of response14.8 months20.7 months
Median prior lines of cancer therapy6 (range 2-27)7
Rate of interstitial lung disease*13.6%2516.9%20
* in phase I trial this includes ILD, pneumonitis or organising pneumonia. Source: Ian Krop & SABCS; NEJM, The Lancet.
In an earlier phase I study trastuzumab deruxtecan managed an objective response rate of 60% in Her2-positive breast cancer patients previously treated with an average of seven therapies including Kadcyla. At the time, Astra called that achievement “unprecedented”, and this larger trial has largely replicated the findings of that work (Astra and Daiichi lay out their plan for a better Herceptin, May 8, 2019).
The current treatment sequence for metastatic Her2-positive disease is dominated by three Roche products. First-line treatment with a taxane plus Herceptin plus Perjeta; second-line treatment is generally Kadcyla. There is no consensus on the best therapy for the third-line setting.
The response rate to trastuzumab deruxtecan in Destiny-Breast01 was particularly notable among patients previously treated with Perjeta: 64.5% of these responded compared with 54% who had never received Roche’s drug.

Waterfall graph of change in tumour size with trastuzumab deruxtecan
Source: Ian Krop & SABCS.
Trastuzumab deruxtecan’s Achilles heel is its side-effect of interstitial lung disease. This was seen in 13.6% of the Destiny-Breast01 patients, a slight improvement from the rate in phase I, but still a drawback that could lead to a black box warning on any future label. Dr Krop conceded that the rates of interstitial lung disease were higher than seen in studies of other drugs, including Herceptin and Kadcyla. He added that the investigators could not explain this, particularly since ADCs are supposed to allow the specific targeting of tumours. This side-effect will require careful monitoring.
The project is due a US decision on its BLA for third-line breast cancer in the first quarter of next year. The sellside has already pencilled in some huge sales numbers that make the ADC one of the sector’s most valuable oncology assets currently in development. EvaluatePharma‘s consensus has sales topping $2bn by 2024 and some analysts have mooted peak sales of $7bn, though this all relies on trastuzumab deruxtecan proving its worth in earlier settings. Presumably these are the kind of revenues Astra was anticipating when it paid $1.4bn up front to license the drug (Astra shakes hands with Daiichi to take on Roche, March 29, 2019).
Moreover, there are plenty of other next-gen Her2s following behind. Data on Seattle Genetics’ TKI tucatinib and Macrogenics’ margetuximab are also expected at SABCS, and there are plenty of others working on a “better Herceptin” (SITC 2019 preview – Pieris joins the quest for a better Herceptin, November 4, 2019).
If one of these competing agents can come close to trastuzumab deruxtecan’s efficacy without its safety signal, expectations might have to be reined in. But for now, this is the project to beat.

FDA Panel Friday for Horizon’s teprotumumab for thyroid eye disease

The FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee will meet on Friday, December 13, to review and discuss Horizon Therapeutics’ (HZNP +0.8%) marketing application for lead drug teprotumumab for thyroid eye disease.

Twist Bioscience EPS misses by $0.11, beats on revenue

Twist Bioscience (NASDAQ:TWST): Q4 GAAP EPS of -$0.96 misses by $0.11.
Revenue of $15.74M (+87.2% Y/Y) beats by $1.69M.

Tonix Pharma nabs European patent covering TNX-102 SL

Nano cap Tonix Pharmaceuticals (NASDAQ:TNXP) is up 22% after hours in reaction to its receipt of a new composition of matter patent in Europe covering TNX-102 SL.