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Saturday, January 5, 2019

Detecting depression: Phone apps could monitor teen angst


In this Nov. 1, 2018 photo, Laurel Foster holds her phone in San Francisco. Foster is among teens involved in Stanford University research testing whether smartphones can be used to help detect depression and potential self-harm. (AP Photo/Haven Daley)

Rising suicide rates and depression in U.S. teens and young adults have prompted researchers to ask a provocative question: Could the same devices that some people blame for contributing to tech-age angst also be used to detect it?
The idea has sparked a race to develop apps that warn of impending mental health crises. Call it smartphone psychiatry or child psychology 2.0.
Studies have linked heavy smartphone use with worsening teen mental health. But as teens scroll through Instagram and Snapchat, tap out texts or watch YouTube videos, they also leave digital footprints that might offer clues to their psychological well-being.
Changes in typing speed, voice tone, word choice and how often kids stay home could signal trouble, according to preliminary studies.
There might be as many as 1,000 smartphone “biomarkers” for depression, said Dr. Thomas Insel, former head of the National Institute of Mental Health and now a leader in the smartphone psychiatry movement.
Researchers are testing experimental apps that use artificial intelligence to try to predict depression episodes or potential self-harm.
“We are tracking the equivalent of a heartbeat for the human brain,” said Dr. Alex Leow, an app developer and associate professor of psychiatry and bioengineering at the University of Illinois’ Chicago campus.
At least, that’s the goal. There are technical and ethical kinks to work out — including privacy issues and making sure kids grant permission to be monitored so closely. Developers say proven, commercially available mood-detecting apps are likely years — but not decades — away.
“People often feel that these things are creepy,” because of the tech industry’s surreptitious tracking of online habits for commercial purposes, said University of Oregon psychologist Nick Allen.
Using smartphones as mental illness detectors would require informed consent from users to install an app, “and they could withdraw permission at any time,” said Allen, one of the creators of an app that is being tested on young people who have attempted suicide.
“The biggest hurdle at the moment,” Allen said, “is to learn about what’s the signal and what’s the noise — what is in this enormous amount of data that people accumulate on their phones that is indicative of a mental health crisis.”
Depression affects about 3 million U.S. teens, and rates have climbed in the past decade. Thirteen percent of 12- to 17-year-olds had depression in 2017, up from 8 percent in 2010, U.S. government data show. One in 10 college-aged Americans is affected.
A recent study suggested a parallel rise in smartphone use likely contributed.
People with mental illness typically get treatment “when they’re in crisis and very late in the course of an illness. We want to have a method to identify the earliest signs,” in an objective way, Insel said.
If smartphones prove to be accurate mood predictors, developers say the ultimate goal would be to use them to offer real-time help, perhaps with automated text messages and links to help lines, or digital alerts to parents, doctors or first responders.
Facebook is already doing just that with what it calls “proactive detection.” After a livestreamed suicide, Facebook trained its AI systems to flag certain words or phrases in online posts that could indicate imminent self-harm. Friends’ comments expressing concern about the user’s well-being are part of the equation.
“In the last year, we’ve helped first responders quickly reach around 3,500 people globally who needed help,” Facebook CEO Mark Zuckerberg announced in November. Facebook has not disclosed outcomes of those cases.
The ongoing research includes:
— A Stanford University study involving about 200 teens, including kids at risk for depression because of bullying, family circumstances or other life stresses. As part of the research, teens who have been tracked since grade school get an experimental phone app that surveys them three times daily for two weeks with questions about their mood.
Researchers are combining those answers with passive smartphone data, including how active or sedentary kids are, to identify any changes that might be linked with future depression.
Study participant Laurel Foster, 15, acknowledges feeling stress over academics and “the usual” teen friendship pressures and says depression is rampant at her San Francisco high school. She said using the smartphone app felt a bit like being spied on, but with so many online sites already tracking users’ habits “one more isn’t really a big difference.”
“I feel like it’s good to actually find out what is stressing you,” Laurel said, endorsing the idea of using smartphones to try to answer that question.
— At UCLA, as part of a broader effort to battle campus depression launched in 2017, researchers are offering online counseling and an experimental phone app to students who show signs of at least mild depression on a screening test. About 250 freshmen agreed to use the app in the first year. Personal sensing data collected from the app is being analyzed to see how it correlates with any worsening or improvement in depression symptoms seen in internet therapy.
Sophomore Alyssa Lizarraga, who had the app on her phone for about six months, said it was “a little like the Big Brother thing. Half of me felt that way. The other half felt like I hope it will be useful.”
Lizarraga, 19, has had depression since high school in Whittier, California. She has worried that she’s “addicted” to her phone and spends a lot of time on social media sites. “People need to see the best side of me” there, she said, and comparing herself with others online sometimes gets her down.
But using smartphones in a positive way for mental health might help nudge people to seek early treatment, if they could see how their phone use showed signs of depression, she said.
— At the University of Illinois’ Chicago campus, researchers studying depression and mania in bipolar disorder are using crowdsourcing to test their experimental phone app. Anyone can download the free app, and nearly 2,000 have so far, agreeing to let the researchers continuously track things such as typing speed, number of keystrokes and use of spellcheck. Participants include healthy people, and their data will help researchers zero in on changes in phone use that may signal onset of mood problems, said Leow, the psychiatry and bioengineering expert who helped develop it.
The study is for ages 18 and up, but if proven to work, the technology could be used in kids too, Leow said.
— Mindstrong, a Palo Alto, California, tech health company co-founded by Insel, the former NIH official, is testing a “digital phenotyping” app in several studies. Insel thinks the technology has promise to transform psychiatry, but that the most important question is whether it can be used to improve patient health.
— Verily, a tech health arm of Google parent company Alphabet, is developing a similar app but declined to elaborate beyond a statement from its mental health leader, Menachem Fromer. He cited two key goals: making predictions about someone’s mental health and their symptoms and “discovering new subtypes of disease that may inform treatment decisions.”

ViewRay 1st Patient Enrolled in MRI-guided Adaptive Radiation Trial


ViewRay, Inc. (Nasdaq: VRAY) announced today the enrollment of the first patient in the Stereotactic MRI-guided On-table Adaptive Radiation Therapy (SMART) Trial, a multi-center, prospective clinical trial for locally advanced or borderline pancreatic cancer. The trial will explore the clinical benefits of precise, high dose radiation therapy enabled by MR-guidance combined with daily on-table adaptation in the treatment of pancreatic cancer.
Retrospective analysis of precise, high-dose MR-guided radiation therapy delivered using adaptive dose planning has shown promising results with locally advanced pancreatic cancer, suggesting the potential for improving overall survival relative to patients receiving lower radiation doses, without increasing the rate of serious gastrointestinal toxicity. The compelling nature of the retrospective data prompted the SMART trial, aimed at investigating in a controlled, prospective manner, the robustness of this outcome and tracking quality of life over a 5-year trial period.
“High-definition MR and daily treatment plan adaptation allow us to deliver ablative radiation doses safely to pancreatic cancer patients for the first time ever,” said Parag Parikh, M.D., co-PI of the study and Director of GI Radiation Oncology and MR-Guided Radiation Therapy at the Henry Ford Cancer Institute in Detroit. “Through the SMART trial, we will build upon the promising experience from UCLA, Washington University, Amsterdam UMC, University of Miami and University of Wisconsin by further exploring MRIdian`s impact on associated toxicity, local control and patient outcomes in pancreatic cancer at multiple institutions around the world.”
The SMART trial is the first prospective, multi-institutional study to deliver ablative doses of radiation to pancreatic cancer patients. It aims to enroll 133 participants with borderline resectable or inoperable locally advanced pancreatic cancer. In the single-arm study, participants will receive radiation therapy at a dose of 50 Gray in 5 fractions (treatment sessions) using ViewRay`s MRIdian. On-table adaptive re-planning will be used when clinically indicated. In all patients, real-time MRI imaging will be used throughout treatment delivery to monitor the target location and control the radiation beam as necessary.
The trial`s primary outcome measure is grade 3 or higher gastrointestinal toxicity in the first 90 days after treatment, with secondary measures including overall survival at two years, distant progression-free survival at six months, and changes in patient-reported quality of life.
“Early evidence on the use of MRIdian to treat locally advanced pancreatic cancer suggests the potential for significantly prolonged survival and lower toxicity rates. Through this rigorously designed study, we hope to further validate the long-term benefits of treatment on the MRIdian,” said Scott Drake, President and Chief Executive Officer of ViewRay. “We believe MRIdian`s unique combination of real-time visualization, automated beam control, and daily on-table treatment adaptation has the potential to become the standard of care in radiation oncology.”
Along with Parag Parikh, M.D. from Henry Ford Cancer Institute, the trial is led by Percy Lee, M.D. from the University of California Los Angeles.

Avadel Reports Resignation of CEO; Appoints COO as Interim CEO


Avadel Pharmaceuticals plc (NASDAQ: AVDL) today announced that Michael S. Anderson has resigned as Chief Executive Officer and as a member the Companys Board of Directors. Gregory J. Divis, Chief Operating Officer of Avadel, has been named Interim Chief Executive Officer of Avadel, effective immediately. The Board of Directors is initiating a search for a permanent Chief Executive Officer.
In conjunction with the management change, Geoffrey M. Glass, President of Clear Sciences, LLC and current member of Avadels Board of Directors, has been named Chairman of the Board. The Honorable Craig Stapleton is stepping down as Chairman but will remain on the Companys Board. In addition, Dr. Eric J. Ende, an experienced biopharmaceutical industry leader, has joined Avadels Board of Directors following consultation with Broadfin Capital, LLC.
On behalf of the entire Board, I would like to thank Mike Anderson for his leadership and service to Avadel and to the Honorable Craig Stapleton for his past and future contributions to the Company as Chairman and member of the Board, said Mr. Glass. I look forward to working closely with Greg and his team as we enter 2019. We will be evaluating all aspects of our existing businesses and corporate strategy to ensure we are best positioned to serve patients and rebuild shareholder value. With four new directors appointed in recent months, I am confident that the Board is fully aligned and focused on these missions.
I am excited to be joining the Board of Directors at this important time, said Dr. Eric Ende. Avadel is a company that delivers value to patients via a strong portfolio of medicines both on market and in development. There is a great opportunity for the Company to re-focus and drive value for shareholders. I look forward to working with my colleagues on the Board to make that happen.
Dr. Ende currently serves as President of Ende BioMedical Consulting Group and as a member of Matinas Biopharmas Board of Directors. Previously he served on the Board of Directors of Genzyme from 2010 until it was acquired by Sanofi-Aventis in 2011 for $20 billion. During his tenure on Genzymes Board of Directors, Dr. Ende was a member of the Audit and Risk Management Committees. From 2002 through 2008, Dr. Ende was the senior biotechnology analyst at Merrill Lynch. From 2000 to 2002, Dr. Ende served as the senior biotechnology analyst at Bank of America Securities and, from 1997 to 2000, he served as a biotechnology analyst at Lehman Brothers.

Allena Names Louis Brenner, M.D. as CEO, Confirms Key Milestones for 2019


Allena Pharmaceuticals, Inc. (NASDAQ:ALNA), a late-stage, biopharmaceutical company dedicated to developing and commercializing first-in-class, oral enzyme therapeutics to treat patients with rare and severe metabolic and kidney disorders, today announced that Louis Brenner, M.D., President and Chief Operating Officer at Allena, will be promoted to Chief Executive Officer and appointed to the Board of Directors effective February 1, 2019. Dr. Brenner will succeed Alexey Margolin, Ph.D. as Chief Executive Officer. Dr. Margolin, who co-founded Allena in 2011, will transition to Chairman of the Board effective February 1, 2019. He will continue advising the company in this new role.
I am honored to succeed Alex as the CEO of Allena. Since the companys founding, Alex has played a key role in shaping our vision and cementing our position as a leader in the development of novel medicines for people living with rare and severe metabolic and kidney disorders. We are grateful for his many contributions, said Louis Brenner, M.D., Chief Executive Officer designate of Allena Pharmaceuticals. 2019 promises to be a transformational year for Allena, following our recent alignment with the FDA on the design of our Phase 3 program for reloxaliase in patients with enteric hyperoxaluria, including our strategy to seek approval using the accelerated approval regulatory pathway, and we anticipate numerous milestones across our broader pipeline throughout the year. I look forward to working with the entire Allena team as we build on our strong foundation and advance our pipeline of first-in-class non-absorbed, oral enzyme therapeutics.
Louis Brenner, M.D. has served as Chief Operating Officer of Allena since April 2015and as President since February 2017. Dr. Brenner has more than a decade of industry leadership experience, including pharmaceutical development strategy, regulatory affairs, business development and commercialization. Prior to joining Allena, Dr. Brenner served as Chief Medical Officer at Idera Pharmaceuticals, Chief Medical Officer at Radius Health, and Senior Vice President at AMAG Pharmaceuticals. He began his industry career at Genzyme Corporation. In these roles, he led successful product development programs for medicines that are currently marketed in the renal and metabolic areas. He holds an M.D. from Duke University, an M.B.A. from Harvard Business School and a B.S. from Yale University. He completed his residency in internal medicine at Brigham and Womens Hospital and his fellowship in nephrology at Brigham and Womens Hospital and Massachusetts General Hospital. Dr. Brenner holds a clinical appointment at Brigham and Womens Hospital.
I have worked together with Lou for several years, and cannot think of a better candidate to lead Allena through its next stage of growth. Lous extensive experience in late-stage clinical development and the pursuit of new regulatory approvals uniquely fits the needs of Allena as we approach our ultimate goal bringing to patients the first ever drug for enteric hyperoxaluria, said Alexey Margolin, Ph.D., outgoing Chief Executive Officer of Allena Pharmaceuticals. I feel privileged to have had the opportunity to help build our Companys platform, and I am deeply thankful to all of the stakeholders including patients, clinicians, investors, business partners, and especially Allena employees who have enabled this progress to-date.
I am encouraged by Allenas progress in developing its pipeline of oral enzyme therapies, including the successful advancement of reloxaliase from preclinical studies into the ongoing Phase 3 program in patients with enteric hyperoxaluria, said Gino Santini, who will become Lead Independent Director of Allena Pharmaceuticals in connection with the leadership transition. I have enjoyed working with Alex since the early days of the Company and look forward to his continued contributions as our new Chairman. I am also eager to work more closely with Lou. Given his expertise in nephrology, his experience in late-stage drug development, and, most importantly, his passion for helping patients, Lou is the ideal choice to lead Allena as it advances its pipeline toward the market.
2019 Corporate Strategy and Milestones
Reloxaliase: Reloxaliase is a first-in-class, non-absorbed, orally-administered enzyme for the treatment of severe hyperoxaluria. Allena is currently evaluating reloxaliase in two ongoing pivotal Phase 3 trials, URIROX-1 and URIROX-2, which are designed to evaluate the safety and efficacy of reloxaliase in patients with enteric hyperoxaluria. Allena recently announced that it had reached alignment with the FDA on both the design of URIROX-2 and its strategy to pursue a Biologics License Application submission for reloxaliase using the accelerated approval regulatory pathway. URIROX-1 is currently enrolling patients, and Allena initiated URIROX-2 in the fourth quarter of 2018.
Allena is also evaluating reloxaliase in Study 206, a multi-center, open-label, single arm Phase 2 basket study of reloxaliase in adults and adolescents with primary hyperoxaluria or enteric hyperoxaluria with advanced chronic kidney disease (CKD) and elevated plasma oxalate.
Allena expects to achieve the following key milestones for reloxaliase:
Report interim clinical data from Study 206 in the first half of 2019;
Report topline data from the URIROX-1 Phase 3 clinical trial in the second half of 2019; and
Report topline data from Study 206 in the second half of 2019.

Rhythm to Update on Milestones, Data at JP Morgan


Rhythm Pharmaceuticals, Inc. (NASDAQ:RYTM), a biopharmaceutical company focused on the development and commercialization of therapeutics for the treatment of rare genetic disorders of obesity, today announced that the company will outline expected 2019 milestones and review updated clinical data from its Phase 2 basket studies of setmelanotide in patients with BBS in a presentation at the 37th Annual J.P. Morgan Healthcare Conference on Thursday, January 10, 2019. Setmelanotide is a first-in-class melanocortin-4 receptor (MC4R) agonist.
We expect 2019 to be an important year for Rhythm, marked by key advancements across our clinical development program for setmelanotide and culminating in preparations for the submission of our first NDA for POMC and LEPR deficiency obesity, said Keith Gottesdiener, M.D., Chief Executive Officer of Rhythm. Our significant achievements in 2018, including completing pivotal enrollment in our Phase 3 trials in POMC and LEPR deficiency obesity, initiating an additional pivotal trial in BBS and Alstrm Syndrome, and beginning to build an integrated patient community, have brought us closer to providing a first-in-class therapeutic option for people living with rare genetic disorders of obesity who have no approved treatments for reducing body weight and hunger.

Pfizer begins phase 2b/3 trial of PF-06651600 to treat alopecia


Pfizer has started a phase 2b/3 clinical trial of PF-06651600, an oral JAK3 inhibitor to treat patients with moderate to severe alopecia areata.
Alopecia areata is a chronic autoimmune skin disease, which makes hair loss on the scalp, face and body. At present, there are no approved therapies for this autoimmune skin disease.
The PF-06651600 has achieved the primary efficacy endpoint in Phase 2a study, which showed that it improved hair regrowth on the scalp relative to baseline at week 24 as measured by the Severity of Alopecia Tool (SALT) score.
The investigational candidate also reached all secondary endpoints in the study, in addition to meeting the primary efficacy endpoint.
Last September, the company secured breakthrough therapy designation from the US Food and Drug Administration (FDA) to treat alopecia areata. The approval was based on the totality of the data and the emerging clinical profile.
The PF-06651600 is also being assessed for rheumatoid arthritis, Crohns disease and ulcerative colitis.
Pfizer will enroll up to 660 patients in the double-blind, placebo-controlled and dose-ranging phase 2b/3 clinical trial to assess the safety and effectiveness of PF-06651600 in adults and adolescents aged 12 years and older with 50% or greater scalp hair loss.
The company has multiple kinase inhibitors in clinical trials across multiple indications, including the PF-04965842 investigational selective JAK1 inhibitor in phase 3 clinical trial to treat atopic dermatitis and the PF-0670084 investigational tyrosine kinase 2(TYK2)/JAK1 inhibitor to treat soriasis, Crohns disease, ulcerative colitis and alopecia areata.
Pfizer global product development inflammation and immunology chief development officer Michael Corbo said: We are proud to start this global pivotal Phase 2b/3 trial for PF-06651600 in patients with alopecia areata. We hope this potential treatment will be able to help patients who currently have limited treatment options.
Including our JAK3 program, Pfizer has several selective kinase programs in the clinic with studies spanning across rheumatology, gastrointestinal disorders, and medical dermatology, where we aspire to deliver potentially transformative medicines to those living with chronic autoimmune and inflammatory conditions.

Many Doctors Eager to Get Rid of ObamaCare


Is This the End of the Affordable Care Act?

As thousands of Americans finalized their health insurance plans for 2019 last week, a new ruling has put the future of the Affordable Care Act (ACA) in jeopardy.
On December 14, US District Judge Reed O’Connor sided with a group of 20 states with Republican governors and legislatures in deeming Obamacare unconstitutional in requiring Americans to secure health insurance. This, he said, was due to Congress stripping the tax penalty for the uninsured in 2017.
The US Supreme Court had ruled the ACA constitutional based on that individual mandate, but with the mandate gone, O’Connor wrote, so was the constitutionality of the law itself.
This does not mean that the law disappears right away—or perhaps ever. While the Trump Administration’s Department of Justice previously announced it would not defend the “individual mandate” to secure health insurance, others are likely to challenge the ruling. Numerous states with Democratic leadership intend to appeal O’Connor’s ruling, and the matter could head back to the Supreme Court.
In the meantime, those seeking coverage through state-based exchanges created by the law will continue to have coverage.

Doctors’ Passionate Pleas for Better Patient Care

Upon hearing the decision, more than 300 physicians made their voices heard in a post on Medscape.
The majority of comments expressed satisfaction at O’Connor’s decision to do away with Obamacare.
A number of physicians pointed out that, while good in theory, the ACA ran into problems when it became a reality after 2010. Said one neurologist:
Many ideas with noble goals have been failures when put into practice. The ACA is one.
Some self-employed physicians commented on the high premiums the law created, not only for patients, but for business owners.
One optometrist said:
The ACA forgot about small businesses, individuals, and others who are not living off the government dole. Our premiums have skyrocketed along with extremely high deductibles. There are parts of the plan that are good, but there are many aspects of this plan that need to [be] changed in a big way. If we are going to have a national health plan then EVERYONE needs to contribute; none of this only the middle class and rich will pay.
A number of physicians took exception to the American Medical Association’s (AMA’s) backing of an appeal as representative of the nation’s physicians. Said one internist:
I’m so glad the ACA was declared unconstitutional! Thank God! The medical organizations that oppose this latest Texas ruling are in my opinion no friend of mine, or [of] physicians in general, or [of] patients.
Added another physician:
The AMA is not speaking for most of us. The ACA is a disaster and until the AMA gets behind a fair market-based solution to health insurance, nothing good will happen.
If there was anything positive seen in the ACA by physicians it is protection for those with pre-existing conditions. However, as one ophthalmologist noted, the law was also flawed in that regard as well:
…[I]t put the companies that invented pre-existing conditions in charge of the system. Probably not a good idea except that lobbyists write the bill. We need a system where people like me can buy into Medicare and subsidize that system, with an adjunct not-for-profit insurance industry for those who can afford to pay more. This has to be done as a coordinated transition over time, not by simply terminating the ACA and trying to implement another system.
Another ophthalmologist summed up a number of comments, pointing out the high cost of the law for Americans and that rejection of the ACA as a law does not equate to support for insurers denying coverage due to pre-existing conditions:
In the past, there was agreement amongst both Democrats and Republicans that insurance carriers should not be able to hold these against potential members. So don’t make it seem as if a vote against the ACA is a vote against the pre-existing condition clause.

Despite Peer Objection, Some Support Remains

While many physicians commenting to Medscape were in favor of doing away with the ACA, there were still physicians who felt the law has helped US healthcare in the last several years.
Said one cardiologist:
Many of us are outraged by the exorbitant cost of health insurance: 18% of our GDP; 27% of our premiums going to insurers’ “administration” and bonuses. Yet, 22 million Americans can’t afford to see a doctor or health professional without the ACA. Something is wrong here—and it ain’t Obamacare…. Resist this ridiculous and un-American move to scuttle the ACA. Fix it but don’t let these politicians silence our voice. We are the stewards of healthcare.
Many who noted their objection to O’Connor’s decision felt similarly: not 100% behind Obamacare, but in favor of finding a solution before tearing it down.
One nephrologist said:
The law has problems no doubt. However before advocating to throw it out please give a solution to how pre-existing coverage problem can be resolved. You talk about people making bad health choices, but what about the person who gets lymphoma out of no fault of their own. Do they need to be penalized as having [a] pre-existing condition and not be able to get health insurance anymore or at unaffordable prices?
A fellow nephrologist added:
I’m embarrassed that there are physicians in this country who would do away with universal health care. The last thing we need is to increase the number of uninsured patients in this country. We should keep ACA and make changes to it that would decrease premiums and improve coverage.