Ovid Therapeutics Announces Multiple Presentations on the 2020 American Academy of Neurology Science Highlights Platform – GlobeNewswire

NEW YORK, June 08, 2020 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical company committed to developing medicines that transform the lives of people with rare neurological diseases, today announced multiple presentations across its rare neurological disease platform are available on the 2020 American Academy of Neurology (AAN) Science Highlights platform. The presentations were originally slated for discussion at the AAN 72nd Annual Meeting scheduled for April 25-May 1, which was cancelled due to the COVID-19 pandemic. The abstracts were also published in the online supplement to Neurology.

The presentations available on the AAN Science Highlights online platform include the following:

Presentations on OV101 (gaboxadol) in Neurodevelopmental Disorders:

Title: The adaptation and utility of the Clinical Global Impression scale for studying treatment outcomes in neurodevelopmental conditionsTopic: Child Neurology and Developmental Neurology

Title: The pivotal Phase 3 NEPTUNE trial investigating OV101 (gaboxadol) in Angelman syndrome: study overview and rationaleTopic: Child Neurology and Developmental Neurology

Title: Evidence of pharmacodynamic tolerance during repeated daily OV101 (gaboxadol) exposure in individuals with Angelman syndrome Topic: Child Neurology and Developmental Neurology

Title: Physiologically based pharmacokinetic modeling (PBPK) for OV101 (gaboxadol) exposure in children with Angelman syndromeTopic: Child Neurology and Developmental Neurology

Title: Caregiver insight on the core domains in Angelman syndromeTopic: Child Neurology and Developmental Neurology

Title: Quality of life in adolescent and adult individuals with Angelman syndrome: Baseline results from the Phase 2 STARS studyTopic: Child Neurology and Developmental Neurology

Title: Concomitant medication in adolescent and adult individuals with Angelman syndrome: Baseline results from the Phase 2 STARS studyTopic: Child Neurology and Developmental Neurology

Title: The Phase 2a ROCKET trial investigating OV101 (gaboxadol) in adolescents and young adults with Fragile X syndromeTopic: Child Neurology and Developmental Neurology

Presentations on OV935/TAK935 (soticlestat) in Rare Developmental and Epileptic Encephalopathies (DEE):

Title: Initial data from the ongoing ENDYMION open-label extension trial of soticlestat (TAK-935/OV935) in participants with developmental and/or epileptic encephalopathies (DEE)Topic: Epilepsy/Clinical Neurophysiology (EEG)

Title: A phase 1b/2a study of soticlestat (TAK-935/OV935) as adjunctive therapy in patients with developmental and epileptic encephalopathiesTopic: Epilepsy/Clinical Neurophysiology (EEG)

About Ovid TherapeuticsOvid Therapeutics Inc. is a New York-based biopharmaceutical company using its BoldMedicine approach to develop medicines that transform the lives of patients with rare neurological disorders. Ovid has a broad pipeline of potential first-in-class medicines. The Companys most advanced investigational medicine, OV101 (gaboxadol), is currently in clinical development for the treatment of Angelman syndrome and Fragile X syndrome. Ovid is also developing OV935/TAK935 (soticlestat) in collaboration with Takeda Pharmaceutical Company Limited for the potential treatment of rare developmental and epileptic encephalopathies (DEE).

For more information on Ovid, please visit http://www.ovidrx.com/.

Contacts

Investors and Media:Ovid Therapeutics Inc.Investor Relations & Public Relationsirpr@ovidrx.com

Or

Investors: Steve KlassBurns McClellan, Inc.sklass@burnsmc.com (212) 213-0006

Media:Katie Engleman1ABkatie@1abmedia.com(919) 333-7722

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Ovid Therapeutics Announces Multiple Presentations on the 2020 American Academy of Neurology Science Highlights Platform - GlobeNewswire

The Honor Roll of US News Best Children’s Hospitals 2020-21 – WTOP

A photo tour of the 2020-21 Best Childrens Hospitals Which hospitals are best prepared to care for the sickest kids?

A photo tour of the 2020-21 Best Childrens Hospitals

Which hospitals are best prepared to care for the sickest kids? The 2020-21 U.S. News Best Childrens Hospitals rankings identify 88 hospitals with demonstrated expertise in one or more of 10 pediatric specialties. Ten hospitals earned a place on the Best Childrens Hospitals Honor Roll.

Click through the slides to view the Best Childrens Honor Roll hospitals.

10. Lucile Packard Childrens Hospital Stanford

Location: Palo Alto, California

2019-20 Honor Roll rank: Not Ranked

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Neonatology (#3), Pediatric Nephrology (#4), Pediatric Pulmonology & Lung Surgery (#7), Pediatric Neurology & Neurosurgery (#8)

See all of this hospitals rankings.

9. UPMC Childrens Hospital of Pittsburgh

Location: Pittsburgh, Pennsylvania

2019-20 Honor Roll rank: 8

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Pediatric Cardiology & Heart Surgery (#2), Pediatric Diabetes & Endocrinology (#7), Pediatric Gastroenterology & GI Surgery (#9)

See all of this hospitals rankings.

8. Nationwide Childrens Hospital

Location: Columbus, Ohio

2019-20 Honor Roll rank: 7

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Pediatric Neurology & Neurosurgery (#6), Pediatric Pulmonology & Lung Surgery (#6), Pediatric Cancer (#8), Pediatric Orthopedics (#8)

See all of this hospitals rankings.

7. Childrens National Hospital

Location: Washington, D.C.

2019-20 Honor Roll rank: 6

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Neonatology (#1), Pediatric Neurology & Neurosurgery (#3), Pediatric Cancer (#6), Pediatric Nephrology (#7)

See all of this hospitals rankings.

6. Childrens Hospital Colorado

Location: Aurora, Colorado

2019-20 Honor Roll rank: 10 (tie)

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Pediatric Gastroenterology & GI Surgery (#1), Pediatric Diabetes & Endocrinology (#4), Pediatric Pulmonology & Lung Surgery (#5), Pediatric Cardiology & Heart Surgery (#6)

See all of this hospitals rankings.

5. Childrens Hospital Los Angeles

Location: Los Angeles, California

2019-20 Honor Roll rank: 5

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Neonatology (#2), Pediatric Cardiology & Heart Surgery (#3), Pediatric Orthopedics (#4), Pediatric Cancer (#5), Pediatric Gastroenterology & GI Surgery (#6)

See all of this hospitals rankings.

4. Texas Childrens Hospital

Location: Houston, Texas

2019-20 Honor Roll rank: 3 (tie)

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Pediatric Cardiology & Heart Surgery (#1), Pediatric Nephrology (#2), Pediatric Neurology & Neurosurgery (#2), Pediatric Pulmonology & Lung Surgery (#3)

See all of this hospitals rankings.

3. Cincinnati Childrens Hospital Medical Center

Location: Cincinnati, Ohio

2019-20 Honor Roll rank: 3 (tie)

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Pediatric Cancer (#3), Pediatric Diabetes & Endocrinology (#3), Pediatric Nephrology (#3), Pediatric Orthopedics (#3)

See all of this hospitals rankings.

2. Childrens Hospital of Philadelphia

Location: Philadelphia, Pennsylvania

2019-20 Honor Roll rank: 2

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Pediatric Cancer (#1), Pediatric Diabetes & Endocrinology (#1), Pediatric Orthopedics (#1), Pediatric Pulmonology & Lung Surgery (#2)

See all of this hospitals rankings.

1. Boston Childrens Hospital

Location: Boston, Massachusetts

2019-20 Honor Roll rank: 1

Number of 2020-21 Honor Roll specialties: 10

Highest-ranking specialties: Pediatric Nephrology (#1), Pediatric Neurology & Neurosurgery (#1), Pediatric Pulmonology & Lung Surgery (#1), Pediatric Urology (#1)

See all of this hospitals rankings.

More from U.S. News

10 Concerns Parents Have About Their Kids Health

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COVID-19: Racing the Clock to Treat a New Mystery Syndrome

The Honor Roll of U.S. News Best Childrens Hospitals 2020-21 originally appeared on usnews.com

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The Honor Roll of US News Best Children's Hospitals 2020-21 - WTOP

Roche’s Ocrevus Continues to Impress in the EU with Strong Uptake in New Start and Switch Multiple Sclerosis Patient Segments, but Novartis’ Mayzent…

In the wake of the Mayzent EMA approval, neurologists expect to diagnose more patients with active secondary progressive multiple sclerosis to broaden the pool of patients eligible for the second-to-market S1P receptor modulator, according to Spherix Global Insights

EXTON, Pa., April 9, 2020 /PRNewswire/ --Driven by expanded access to and uptake of disease-modifying therapies (DMTs) to treat advanced stages of relapsing multiple sclerosis (MS), the MS market in Europe shows signs of continued expansion of the number of patients treated with DMTs. Spherix collected data from 247 EU5 neurologists surveyed between February 5th and March 3rd for the most recent semiannual report included in Spherix's RealTime Dynamix: Multiple Sclerosis (EU) service. Findings confirm that the introductions of Roche's Ocrevus, Merck KGaA's Mavenclad, and (most recently) Novartis' Mayzent have contributed to the growth in treatment rates for relapsing remitting MS (RRMS), active secondary progressive MS (SPMS), and primary progressive MS (PPMS). Ocrevus has shown tremendous ability to usurp historical mainstays just two years after its initial launches in Europe, the anti-CD20 monoclonal antibody (mAb) has replaced glatiramer acetate (GA) as one of the most preferred DMTs on the market. Generic alternatives to Copaxone could have cut back on the erosion of the GA class, but Teva's success in patent litigation and continued Copaxone brand loyalty have minimized generic disruption. Indeed, steady declines in overall GA share reveal that the first generics in the MS market have struggled to establish a foothold capable of buoying the class back to its historical level of popularity.

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Increasing use of Ocrevus in patients starting on a DMT for the first time, as well as patients switching to a different brand, are both driving Ocrevus' quickly rising reported share in MS. Within the segment of new start patients, Biogen's Tecfidera and Sanofi's Aubagio are currently the share leaders, as neurologists have become accustomed to relying on the convenience of oral DMTs for their MS patients initiating DMT treatmentespecially in France. However, with many neurologists favoring induction treatment, in which new patients are initiated on an aggressive approach with a high efficacy agent, Ocrevus is an increasingly popular option for patients starting on DMT treatment. In the UK, where induction treatment is especially common, the rise of Ocrevus use in new start patients accompanies a corresponding drop in Tecfidera use among the same group, threatening the latter DMT's dominance in early lines of therapy.

Among switch patients, Ocrevus is now the most prescribed therapy, besting Novartis' Gilenya and Biogen's Tysabri. With European Medicines Agency (EMA) restrictions placed on use of Sanofi's Lemtrada beginning in November 2019, prescribing of Lemtrada as a switch-to agent has dropped significantly, and overall preference for and reported share of the DMT have fallen. Neurologists now appear to be replacing prior use of Lemtrada with more prescribing of Ocrevus, especially in Germany, Italy, and Spain. Tecfidera, the second most frequently prescribed switch-to agent just one year ago, has also experienced a substantial contraction of reported share in France and Germany.

Story continues

Ocrevus' growth trajectory has been impressive and sustained over the past two years, but new and emerging agents are poised to abate its increasing dominance. Approved by the EMA on January 13th, just weeks before survey fielding, Novartis' Mayzent is now the only therapy, besides Bayer's Betaferon, indicated specifically for the treatment of active SPMS. Given the decline of interferon shares and the desire to use high-efficacy treatments for patients with advanced disease, neurologists expect that Mayzent's true competition will be with Ocrevus. Indeed, audit data from 1,266 charts of EU patients recently switched to a new DMT, analyzed as part of Spherix's RealWorld Dynamix: DMT Switching in Multiple Sclerosis (EU) service, showed that Ocrevus was the active SPMS switch segment leader. Early perceptions among neurologists suggest that Mayzent could become a key option for active SPMS. More than half of EU neurologists are extremely willing to prescribe Mayzent to a patient with active SPMS, and diagnosis of active SPMS is expected to increase considerably over the next two years indicating that neurologists plan to reclassify a proportion of their RRMS patients as having active SPMS in order to make them eligible for Mayzent treatment.

Along with Mayzent's ability to establish a niche in active SPMS, the other threat to Ocrevus further along the horizon may again come from Novartis, with the company's subcutaneous anti-CD20 mAb, ofatumumab. Although the agent is approximately a year away from an EMA decision, EU neurologists have high hopes for its efficacy (expected to be comparable to that of Ocrevus given its mechanistic similarities) and convenient route of administration allowing it to be administered at home. One German neurologist considers ofatumumab a "highly effective therapy concept with better controllability than [Ocrevus]."

Although optimism is high for ofatumumab's at-home administration capabilities, neurologists are accustomed to the built-in opportunities for patient monitoring that come with infusion mAbs; in reality, candidacy for ofatumumab may depend heavily on likelihood of good patient compliance and adherence. In the upcoming EU RealWorld Dynamix audit, Spherix will evaluate the impact of DMT dosing profile on brand selection during a switch. The audit will also gauge Mayzent's early performance in the active SPMS market and the brand's success in competing with current preferred DMTs for that patient segment.

About RealTime Dynamix RealTime Dynamix: Multiple Sclerosis (EU)is an independent service providing strategic guidance through rapid and comprehensive twice-yearly reports, which include market trending, launch tracking, and a fresh infusion of unique content with each wave. The 7th wave of research will publish in April 2020.

About RealWorld Dynamix RealWorld Dynamix: DMT Switching in Multiple Sclerosis (EU) is an independent, data-driven service unmasking real patient management patterns through annual reports based on chart audits of ~1,250 patients switched to a new DMT within the previous three months. The report uncovers the "why" behind treatment decisions, includes year over year trending to quantify key aspects of market evolution, and integrates specialists' attitudinal & demographic data to highlight differences between stated and actual treatment patterns. The second annual report will publish in July 2020.

About Spherix Global InsightsSpherix Global Insights is a hyper-focused market intelligence firm that leverages our own independent data and expertise to provide strategic guidance, so biopharma stakeholders make decisions with confidence. We specialize in select immunology, nephrology, and neurology markets.

Spherix was recently recognized by Philadelphia Business Journal as a 2019 Soaring 76 recipient for the fastest growing companies in the Greater Philadelphia area and by The Philadelphia Inquirer as an Entrepreneurs' Forum 2019 Philadelphia 100 Winner for the fastest growing privately-held companies in the Greater Philadelphia area.

All company, brand or product names in this document are trademarks of their respective holders.

For more information contact:Meg Stabb, Neurology Insights DirectorEmail:info@spherixglobalinsights.comwww.spherixglobalinsights.com

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Roche's Ocrevus Continues to Impress in the EU with Strong Uptake in New Start and Switch Multiple Sclerosis Patient Segments, but Novartis' Mayzent...

Prior Head Injury Associated With Severe Parkinson’s Phenotype – Medscape

FROM AAN 2020

Head injury before the onset of Parkinson's disease is associated with more severe motor and nonmotor phenotypes,according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.

Neurologists have identified various phenotypes among patients with Parkinson's disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood.Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson's disease, would be associated with a more severe phenotype.

"Head injury is a risk factor for other conditions that involve cognitive impairment," said Dr. Brown. "The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson's disease."

The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson's disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in theParkinson's Progression Markers Initiative(PPMI) and theFox Insight(FI) study.

Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.

In all, 267 participants with Parkinson's disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson's disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury.

Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was 0.60 for patients with severe head injury and 0.76 in those with no head injury.

"The improvement from baseline in the participants with Parkinson's disease but without head injury was small and not statistically significant," said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. "We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population."

In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).

"The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results," said Dr. Brown. "Subjective cognitive impairment...is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson's disease."

Clarifying whether the relationship between head injury and Parkinson's disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. "We would like to further characterize the differences between people with Parkinson's disease with and without a history of head injury," said Dr. Brown. "More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role."

The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.

SOURCE:Brown EG et al. AAN 2020,Abstract S17.002.

This article originally appeared on MDedge.com.

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Prior Head Injury Associated With Severe Parkinson's Phenotype - Medscape

Is There a Case for Cognitive Testing for Senior… : Neurology Today – LWW Journals

Article In Brief

The article revisits the controversy around policies at some academic medical centers that require older neurologists to undergo cognitive testing for recredentialing.

Aging is known to be associated with cognitive decline. Is that reason enough to test more senior neurologists and other physicians for potential cognitive deficits that might cause a patient-care problem?

A growing number of health systems say yes and are implementing policies that require cognitive and other screenings when physicians reach a certain age. But the policies are controversial: One state passed legislation prohibiting the practice, although the ban was reversed the next year; most recently, the Equal Employment Opportunity Commission (EEOC) filed a lawsuit that argues one health system's mandatory-examination policy is illegal.

Physician demographics suggest the controversy will not go away soon. There are currently about 150,000 practicing physicians age 65 and older in the US, up from about 95,000 in 2013, according to the American Medical Association.

Proponents of age-based screenings say evidence shows they are needed. At Yale New Haven Hospital, the teaching hospital for Yale School of Medicine, physicians age 70 or older must complete a neuropsychological assessment; of the first 141 to undergo the assessment, nearly 13 percent demonstrated cognitive deficits that were likely to impair their ability to practice independently, according to a January 14 report in JAMA.

Meanwhile, about 70 older physicians from across the country have undergone a late-career health screening through the University of California-San Diego (UCSD) Physician Assessment and Clinical Education program and roughly 20 percent have been referred for further evaluation, said David Bazzo, MD, director of the UCSD Fitness for Duty program.

Opponents disagree with the idea of age-based screening. Scott E. Hirsch, MD, a neuropsychiatristboard-certified in neurology and psychiatryat NYU Langone Health, who evaluates physicians on behalf of the New York State Office of Professional Medical Conduct, is one of them. Dr. Hirsch pointed out that maintenance of certification exams require physicians to demonstrate mastery of the knowledge needed to practice.

The tests are fairly challenging and I don't think you can do well on them if you have an underlying cognitive problem, he said. We are already doing so much to stay credentialed. I don't see how cognitive screening adds anything.

A number of neurology leaders contacted for this story declined to be interviewed, but those who did agree to be interviewed had mixed opinions about mandated cognitive screening.

Policies mandating routine age-based screening started emerging about a decade ago, Dr. Bazzo said. In 2011, his UCSD program and the Coalition for Physician Enhancement convened a range of professionalsphysician-evaluators conducting assessments on behalf of state medical boards investigating complaints; geriatricians; administrative law judges who preside over physicians' disciplinary hearings; and prosecutors and defense attorneys involved in physician disciplinary casesto discuss the aging physician workforce.

In addition to educational sessions and a review of age-based physician screening commonly conducted in Canada, conference participants were surveyed on the issue. The majority favored age-based screening for physicians, starting at age 70, that includes assessments of physical and mental health and a cognitive screen, according to a report in the Journal of Medical Regulation.

That sort of started the ball rolling, Dr. Bazzo said.

Since then, many organizationsranging from huge systems like Scripps Health to community hospitals like Sinai Hospital in Baltimorehave implemented age-based screening policies. In 2014, the University of Pittsburgh Medical Center (UPMC) became one of the first to implement a policy to assess physical and cognitive abilities, said Donald M. Yealy, MD, senior medical director of the system's health services division.

Dr. Yealy and colleagues drafted the policy for two reasons. First, they recognized that some other fieldscommercial aviation, for examplehave age-related thresholds that trigger a professional re-evaluation or practice change to optimize safety.

At the same time, we also realized that we had some reported safety concerns in which we wondered, but were never certain, if a more scheduled and proactive approach might have helped us avert a patient care issue, Dr. Yealy said.

The UPMC policy applies to advanced practice providers as well as physicians. The UPMC medical staff accepted the policy, which follows steps similar to those used with other physicians when a concern arises, without much controversy.

We learned that having a set policy creates a natural and non-threatening opportunity for any physician to personally re-evaluate, he said. We have had many who, at their 70th birthday, have altered what privileges they request or shifted into a different type of practice.

By contrast, Intermountain Healthcare, a large system based in Utah, had a very different experience. That system had a mandatory retirement age of 72 for medical staff in 2013, when neuropsychologist Kelly Garrett, PhD, was asked to help plan a late-career physician program.

Our credentialing committees were giving exemptions, allowing physicians to practice beyond age 72, but they felt that they did not have enough data in order to be able to grant these extensions with much degree of confidence, Dr. Garrett said.

In 2014, Intermountain's medical staff approved a policy that required late-career physicians to complete a history and physical, including sensory and cognitive screenings. Four years later, the Utah State Legislature prohibited mandatory age-based screenings for physicians. In 2019, the ban was reversed but the new law dictates some principles that must be followed.

Intermountain has been reticent to return to business as usual and is now exploring reorganizing the program such that at least the cognitive screening part would be a voluntary program available to physicians regardless of age, Dr. Garrett said.

In February, the EEOC filed suit against Yale New Haven Hospital saying its policy requiring neuropsychological and eye examinations before physicians can obtain or renew staff privileges violates the Age Discrimination in Employment Act.

For some neurology leaders, age-based screening smacks of ageism. The idea of screening to make sure a physician's cognitive skills are adequate for the job does not alarm S. Andrew Josephson, MD, FAAN, professor and chair of neurology at the UCSF Weill Institute for Neurosciences. But age-based screening bothers him.

I would worry that, if we set some arbitrary age cutoff, we are not really focusing on the problem we should be concerned about, which is identifying physicians who have cognitive impairment from a variety of issues, whether it be a neurodegenerative process, substance abuse issues, or some other problem, he said.

Richard P. Mayeux, MD, MSc, FAAN, professor of neurology, psychiatry and epidemiology and chair of neurology at Columbia University College of Physicians and Surgeons, also gives age-based screening a thumbs-down.

It's illegal to do it as part of job credentialing based on age, said Dr. Mayeux, co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center. Our strategy is to single out and test only people who have demonstrated some impairment of some sort. Impaired physicians, I have no problem evaluatingbut evaluating people simply because they're old, I think is inappropriate.

Neil A. Busis, MD, FAAN, associate chair for technology and innovation in the neurology department at New York University Grossman School of Medicine, said it's important to balance the twin goals of maintaining a robust neurology workforce and protecting patients. Screening for potential impairment might be a way of striking that balance, he said. Commercial airline pilots older than 40 years must have a first-class medical certificate renewed every six months.

I think well thought-out processes from other industries can be applicable to medicine, he said. Certain kinds of health screening seem like a reasonable thing to do.

That said, if protecting patient safety is the reason for screening, singling out physicians might not be justified. If you're going to mandate screening for physicians, how about nurses and everybody else who works at the hospital? Dr. Busis said.

There is no standard approach to age-based screening or assessment programs, which vary considerably on at least three variables.

There is no cut-off score that determines that a provider is competent to practice independently, Dr. Bazzo said. Rather, neuropsychologist (and AAN member) William Perry, PhD, vice chair of the UCSD department of psychiatry, reviews and interprets each neurocognitive screening report to determine whether more in-depth testing for diagnostic purposes is recommended.

At UPMC, by contrast, physicians and advanced practice practitioners covered by the age-based screening policy must notify the credentialing committee who will be conducting the physical examination and cognitive assessment they obtain on their own. Obviously, that would give us an opportunity to make sure that the person who is going to do any part of the assessment was qualified and did not have any conflicts, Dr. Yealy said.

The credentialing committee requires a specific tool for the cognitive assessment. The physical examination must look for physical impairment that might impact an ability to function in whatever type of physician you are, whether it's a cognitive specialty and/or procedural specialty, Dr. Yealy said.

Dr. Perry and other neuropsychologists who are most active in late-career physician screening convened last year to discuss the tools available and agreed that the MicroCog is the best option because it has been normed on physicians. Acknowledging that the instrument has some limitations, Dr. Perry said it is not used to diagnose a specific condition, but rather to determine whether a more in-depth evaluation is needed.

The idea is not to use the MicroCog to remove people from practice, he said. The idea is to catch something before it's extreme and problematic because then a physician is able to make changes to their practice.

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Is There a Case for Cognitive Testing for Senior... : Neurology Today - LWW Journals

Neurologic Symptoms and COVID-19: What’s Known, What Isn’t – Medscape

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Since the Centers for Disease Control and Prevention (CDC) confirmed the first US case of novel coronavirus infection on January 20, much of the clinical focus has naturally centered on the virus' prodromal symptoms and severe respiratory effects.

However, US neurologists are now reporting that COVID-19 symptoms may also could include encephalopathy, ataxia, and other neurologic signs.

"I am hearing about strokes, ataxia, myelitis, etc," Stephan Mayer, MD, a neurointensivist in Troy, Michigan, posted on Twitter on March 26.

Other possible signs and symptoms include subtle neurologic deficits, severe fatigue, trigeminal neuralgia, complete/severe anosmia, and myalgia as reported by clinicians who responded to the tweet.

Last week, as reported by by Medscape Medical News, the first presumptive case of encephalitis linked to COVID-19 was documented in a 58-year-old woman treated at Henry Ford Health System in Detroit.

Physicians who reported the acute necrotizing hemorrhagic encephalopathy case in the journal Radiology counseled neurologists to suspect the virus in patients presenting with altered levels of consciousness.

Researchers in China also reported the first presumptive case of Guillain-Barre syndrome associated with COVID-19. A 61-year-old woman initially presented with signs of the autoimmune neuropathy GBS, including leg weakness, and severe fatigue after returning from Wuhan, China. She did not initially present with the common COVID-19 symptoms of fever, cough, or chest pain.

Her muscle weakness and distal areflexia progressed over time. On day 8, the patient developed more characteristic COVID-19 signs, including 'ground glass' lung opacities, dry cough, and fever. She was treated with antivirals, immunoglobulins, and supportive care, recovering slowly until discharge on day 30.

"Our single-case reportonly suggests a possible associationbetween GBS andSARS-CoV-2 infection. It may or may not havecausal relationship. More caseswith epidemiological data are necessary," senior author Sheng Chen, MD, PhD, told Medscape Medical News.

However, "we still suggest physicians who encounter acute GBS patients from pandemic areas protect themselves carefully and test for the virus on admission. If the results are positive, the patient needs to be isolated," added Chen, a neurologist at Shanghai Ruijin Hospital and Shanghai Jiao Tong University School of Medicine in China.

Neurologic presentations ofCOVID-19 "are not common, but could happen," Chen added. Headache, muscle weakness and myalgias have been documented in other patients in China, he said.

We know almost nothing about the potential interactions between COVID-19 and the nervous system. Dr Robert Stevens, Johns Hopkins School of Medicine, Baltimore

Despite this growing number of anecdotal reports and observational data documenting neurologic effects, the majority of patients with COVID-19 do not present with such symptoms.

"Most COVID-19 patients we have seen have a normal neurological presentation. Abnormal neurological findings we have seen include loss of smell and taste sensation, and states of altered mental status including confusion, lethargy, and coma," Robert Stevens, MD, who focuses on neuroscience critical care at the Johns Hopkins School of Medicine in Baltimore, Maryland, told Medscape Medical News.

Other groups are reporting seizures, spinal cord disease, and brain stem disease. It has been suggested that brain stem dysfunction may account for the loss of hypoxic respiratory drive seen in a subset of patients with severe COVID-19 disease, he added.

However, Stevens, who plans to track neurologic outcomes in COVID-19 patients, also cautioned that it's still early and these case reports are preliminary.

"An important caveat is that our knowledge of the different neurological presentations reported in association with COVID-19 is purely descriptive. We know almost nothing about the potential interactions between COVID-19 and the nervous system," he noted.

He added it's likely that some of the neurologic phenomena in COVID-19 are not causally related to the virus.

"This is why we have decided to establish a multisite neuro-COVID-19 data registry, so that we can gain epidemiological and mechanistic insight on these phenomena," he said.

Nevertheless, in an online report February 27 in the Journal of Medical Virology, Yan-Chao Li, MD, and colleagues write that "increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system, inducing neurological diseases."

Li is affiliated with the Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine, Jilin University, Changchun, China.

Scientists observed SARS-CoV in the brains of infected people and animals, particularly the brainstem, they note. Given the similarity of SARS-CoV to SARS-CoV2, also known as COVID-19, the researchers suggest a similar invasive mechanism could be occurring in some patients.

Although it hasn't been proven, Li and colleagues suggest COVID-19 could act beyond receptors in the lungs, traveling via "a synapseconnected route to the medullary cardiorespiratory center" in the brain. This action, in turn, could add to the acute respiratory failure observed in many people with COVID-19.

Other neurologists tracking and monitoring case reports of neurologic symptoms potentially related to COVID-19 include Mayer and Amelia Boehme, PhD, MSPH, an epidemiologist at Columbia University specializing in stroke and cardiovascular disease.

Boehme suggested on Twitter that the neurology community conduct a multicenter study to examine the relationship between the virus and neurologic symptoms/sequelae.

Medscape Medical News interviewed Michel Dib, MD, a neurologist at the Piti Salptrire hospital in Paris, who said primary neurologic presentations of COVID-19 occur rarely and primarily in older adults. As other clinicians note, these include confusion and disorientation. He also reports cases of encephalitis and one patient who initially presented with epilepsy.

Initial reports also came from neurologists in countries where COVID-19 struck first. For example, stroke, delirium, epileptic seizures and more are being treated by neurologists at the University of Brescia in Italy in a dedicated unit designed to treat both COVID-19 and neurologic syndromes, Alessandro Pezzini, MD, reported in Neurology Today, a publication of the American Academy of Neurology.

Pezzini notes that the mechanisms behind the observed increase in vascular complications warrant further investigation. He and colleagues are planning a multicenter study in Italy to dive deeper into the central nervous system effects of COVID-19 infection.

Clinicians in China also report neurologic symptoms in some patients. A study of 221 consecutive COVID-19 patients in Wuhan revealed 11 patients developed acute ischemic stroke, one experienced cerebral venous sinus thrombosis, and another experienced cerebral hemorrhage.

Older age and more severe disease were associated with a greater likelihood for cerebrovascular disease, the authors report.

Chen and Li have disclosed no relevant financial relationships.

Follow Damian McNamara on Twitter: @MedReporter. For more Medscape Neurology news, join us on Facebook and Twitter.

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Neurologic Symptoms and COVID-19: What's Known, What Isn't - Medscape

His Patients Inspired His Songwriting In and Out of the… : Neurology Today – LWW Journals

Article In Brief

Working with neurology patients has inspired William Baek, MD, to write and produce songs for two albums. This lifelong musician discusses the added value music brings to his life and how that passion prevents him from feeling burnout.

William Baek, MD, is a clinical associate professor at University of California Riverside; a Fellow of the American Association of Neuromuscular and Electrodiagnostic Medicine; and diplomate of the American Board of Disability Analysts. But when he's not working as a general neurologist in private practice in Upland, CA, you can find him in a music studio, writing and recording songs.

A passionate musician since childhood, he has found inspiration for his songwriting from his patients' experiences. His first album, released in 2018, can be found on YouTube and Spotify. His second album is due out in 2020.

Dr. Baek spoke to Neurology Today about the role music-writing has played in his practice and life. His comments are edited and excerpted below.

I started playing the piano at age 10. Initially the lessons were my mom's ideashe plays the piano wellbut I loved music and really took to it. I was born in the United States, but my family moved to Seoul, Korea, when I was nine and then returned to the States when I was 26, and it was in Korea where I learned to play the piano.

As a pre-medical student, I also took up the trombone. I had always wanted to play a brass instrument, and initially I thought about the trumpet, but I found the trombone interesting because it's almost like singing. You have to have a good sense of pitch because you can play multiple notes in the same position.

I loved music so much that while I was in college, I thought that I wanted to become a singer and a rock star, but back where I come from in Korea, if you want to go into the entertainment business, you say goodbye to college. I was already a pre-med student, so I thought I should finish that. But I played lead trombone in our medical school orchestra, and while I was taking the bus home at midnight after studying in the medical school library, I would write songs.

There wasn't a lot of time for that, but I did do one fun project. My uncle was a producer with a record label, and he had a song that they wanted to be sung in many different languages. Since I'm bilingual in Korean and English, I translated the song into Korean. Translating lyrics isn't as easy as it soundsyou can't just do a direct translation. You have to make the translation work as a song. I had listened to enough Korean music that I could do that. Then one of my co-residents and I recorded the song in Korean for my uncle's label. It was a typical love song, but my uncle put a good pop-catchy spin on the arrangement that was totally amazing. I still have that CD at home.

But other than that, during my residency and fellowship my musical interests went on the back burner. I got married and we had children, and while I took a couple of voice lessons, there wasn't much time.

In 2012, I had gone into private practice and had a little more room to breathe. Recording an album of my own was my dream, but I wanted to learn how to sing more professionally first. So every Thursday at lunchtime I'd rush out of clinic, grab a sandwich, and drive to a 30-minute voice lesson. After I had been doing that for several years, all the time writing songs, one of the ICU nurses at a hospital where I work, who sings semi-professionally, introduced me to Stephan de Reine, a producer with GRA music group. Once I met him I realized that my dream could come true. I began working with himI write the melody and the lyrics, and he does all the arranging. In January 2018 I released my first album on his label.

During my rotations, I often hear very poignant stories that aren't really something I could put into scientific papers. I want other people to hear our patients' stories about their life experiences, so that maybe I can raise awareness and also maybe reach out to people who are experiencing these conditions so that they can be comforted.

Nowadays I listen to a lot of music that is a bit superficial, and I want to talk about more serious topics. The songs on my first album are about Alzheimer's and Parkinson's, there's a song about myasthenia, and a song about multiple sclerosis, Walk Again. Another song, Chained to a Dream, is about stroke. My father experienced a stroke back in 1996 and I wanted to write about what that was like. The songs don't have medical terminology or lingo, I've kept them abstract so that people who don't have these medical conditions can relate to them as well. I can't compete with Ariana Grande or Taylor Swift, but I could find my own niche, and I think this is a good niche for me.

I clearly remember when this first occurred to me. It was 2005, and I was a neuromuscular fellow at the University of California, San Diego. My mentor and I were treating patients with amyotrophic lateral sclerosis (ALS), and I thought, Maybe I could write a song that could express musically some of what they are experiencing. That song is also on my album, and it was my first song inspired by a patient.

They're always very interestedthey want to follow my YouTube channel and find out where they can get the album. Naturally, the patients gravitate toward the songs that describe their illness in particular. I recently heard from one patient and it was particularly heartwarming. She is a full-time pharmacist who has MS. She's a wonderful patient advocate and an example of how people can overcome illness. She told me, When I have a bad day, I listen to your song and it makes me feel so much better. That made me feel that I've already achieved what I wanted to do.

He's a man of few words, so it was hard for me to try to get into his brain and describe the illness. But when my mom heard it, she was like Aha! She thought it really described the struggle of the person, and their relationship to their caregiver. Some people might find it depressing, but for others, it's cathartic. I wrote the album to help heal my patients, but I think it's healed me.

The second album was completed at the end of December 2019, but there have been problems with releasing it. I went to record in France with my producer last June, but then there were strikes and some delays. It should be coming out this year, and it will include some more songs inspired by medical conditions. I see a significant pediatric population, and I wrote a song about life with ADHD called Free Wheeling. Although I don't have ADHD, I did feel a lot of stress under the school system in Korea to conform. I had to fit the norm and the social structure, but I had my ideas and my own person. The school wouldn't budge, and they wanted to treat each child uniformly in a mechanical way, which is something like the way society seems to want to control people with ADHD.

Back in 2018, I sang Walk Again at the MS Walk in Fontana, CA. That was just an amazing experience. I also sang it at a family practice conference held at Disneyland. I'm hoping to sing at another MS Walk this year, and someday I would love to share my songs at the AAN conference.

If you're always invested 100 percent of your waking time in patient care, it's exhausting and monochromatic. We need this variety and variability in our lives, in order to appreciate different things. So many of my friends who are doctors have other talents too, and they should take time for them. We see a lot of burnout, and I tell my colleagues: You were somebody before you became a doctor, and I'm sure you still have other non-medical aspects to your life. People need to explore these other sides of themselves and cultivate them in order to avoid burnout. The more involved I am in music, the happier I am.

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Biomarkers of Senescence and Inflammation Linked to Risk of… : Neurology Today – LWW Journals

Article In Brief

Scores on a set of five markers of inflammation predicted the cognitive scores of patients with Parkinson's disease at 36 months. Two measures of cellular senescence likewise predicted cognitive outcomes.

Blood-derived biomarkers of senescence and inflammation look promising as predictors of cognitive decline in Parkinson's disease (PD), according to a January 13 study in the Journal of Parkinson's Disease.

At diagnosis, patients' summary scores on a set of five markers of inflammation predicted their cognitive scores at 36 months. Two measures of cellular senescence likewise predicted cognitive outcomes.

While significant, the results from the Incidence of Cognitive Impairments in Cohorts with Longitudinal Evaluation-Parkinson's Disease (ICICLE-PD) study were not strong enough to be of immediate clinical utility. They add, however, to the existing literature on risk factors observable at diagnosis that should one day enable neurologists to offer patients a reliable prognosis of cognitive outcomes, said the study's senior author and independent commentators.

The findings look robust, commented David K. Simon, MD, PhD, professor of neurology at Harvard Medical School and director of the Parkinson's Disease and Movement Disorders Center at Beth Israel Deaconess Medical Center, who was not involved with the study.

This is a very well organized, well conducted study. But we see a lot of studies about biomarkers like this, and we're not using them in the clinic yet. I'd want to see the results validated in a larger cohort before I use these biomarkers to tell a patient that they're likely to develop dementia.

The ongoing ICICLE-PD study, based in Newcastle upon Tyne and Gateshead, United Kingdom, includes154 newly diagnosed PD patients and 99 healthy, age-matched controls from the Newcastle area.

The inflammatory markers used in the study were C-reactive protein, TNF alpha, IL-6, IL-10, and IFN-gamma. For markers of senescence, the investigators used p21 and p16cell-cycle regulators known to suppress tumorsas well as telomere length in blood cells. Found at the end of every chromosome, telomeres serve as protective caps. Because their length has previously been shown to shorten with age, stress and illness, the study sought to determine if a shorter length at baseline would distinguish patients from controls and predict worse cognitive outcomes at 18 and 36 months.

As expected, the study found that PD patients as a group had shorter average telomeres in blood cells at baseline and 18 months compared to age-matched healthy controls. Shorter telomere length among the PD patients was also correlated with an increased risk of PD dementia (PDD) at 36 months.

Results from measurements of p21 and p16 were not as clear. Overall, the best predictor of cognitive score over the 36 months of the study was a summary score of the five markers of inflammation, while the development of dementia best correlated with short telomeres.

We think these different components might be related, said the senior author of the paper, Gabriele Saretzki, PhD, a lecturer in aging research at the Biosciences Institute of Newcastle University.

As more patients in the ICICLE-PD cohort progress to dementia, she said, results should strengthen.

For now we could only go to 36 months, Dr. Saretzki said. At 72 months, we should have three to four times more dementia cases, and that will allow us to make much better statistical associations.

A spate of recent studies has sought to tease out which clinical and biological markers might be predictive of PDD. Last November, another paper in the journal Movement Disorders based on the ICICLE-PD cohort reported that pro-saccades appear to be a useful non-invasive biomarker for long-term PD cognitive decline.

For the new study, Dr. Saretzki and colleagues sought to use ICICLE-PD blood and serum samples in hopes of bringing clarity to contradictory data regarding telomeres. Some prior studies had found no evidence that their length in leukocytes or other cellular chromosomes held any value for predicting PDD. Other studies had found significant effects, although one, published in PLoS One in 2014, found the opposite of the expected direction: longer, rather than shorter, telomeres were associated with increased risk of dementia progression.

The whole telomere field is very difficult, said Dr. Saretzki. I tell students, be very careful when you read papers in this area. Results can depend on not just genetics but on lifestyle factors, psychological or physical stress and inflammation. It's really complex.

After correcting for multiple comparisons, Dr. Saretzki's group found that PD subjects had significantly shorter telomere length at baseline compared with controls (p< 0.001) as well as significantly faster shortening of their telomeres over the first 18 month period (p=0.002).Even so, the telomere lengths of some PD patients overlapped with those of controls. Importantly, however, they also found shorter telomeres at baseline in those PD patients who went on to develop an early dementia.

Even so, because only 11 of the PD patients developed dementia within 36 months, as measured by the Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA), the small numbers precluded a meaningful regression analysis of the predictive power of telomere length for PDD, the paper concluded.

Contrary to expectations, PD participants displayed significantly lower levels of p21 gene expression than controls at baseline (p< 0.001), but there was no difference in change with time. For p16 expression, the differences between PD and controls at baseline or the rate of change per month of p16 expression levels did not reach statistical significance. Dr. Saretzki speculated that perhaps the gene expression measures her group conducted on p16 and p21 are less informative than the measures of protein levels previously published.

The baseline composite inflammatory score was only predictive of MoCA score (p=0.037) at 36 months, independently of age, gender, body mass index, and levodopa equivalent doses. Thus, the composite inflammatory score at baseline was best associated with cognitive score, but not with rate of change for any other clinical indicators over the follow-up period. What's more, none of the baseline biomarkers of senescence or inflammation significantly predicted motor function at 36 months or their rate of change.

Connie Marras, MD, PhD, associate professor of neurology at the University of Toronto and a neurologist at the Toronto Western Hospital Movement Disorders Centre, said that the study provides the basis for further investigations. But, she said, Because they only had 11 people who developed dementia at 36 months, we have to consider these findings quite preliminary.

Even so, she applauded the effort, given the importance to patients of a reasonably accurate prognosis of their cognitive status.

Cognitive slowing is a big deal for patients, she said. My patients ask what they can expect. It affects their planning for their lives and their careers. We need better ways to predict who will progress faster in terms of cognitive decline.

Elizabeth Bradshaw, PhD, the Adler assistant professor in neurological sciences at Columbia University's department of neurology, said she was excited to see the results on senescence. In particular, the findings regarding telomeres look straightforward and quite exciting.

But, she said, the findings for p16 and p21, as well as for the inflammatory markers, puzzled her.

The p16 and p21 didn't go in the direction you might expect based on the telomere results, Dr. Bradshaw said. But they examined total blood. If they had been able to break it out into specific cell types, like monocytes or memory T cells, perhaps that would explain what was driving the reduction of p21. If it turned out to be in a memory T population, that would be consistent with data suggesting that there is a potentially pathogenic role for memory T cells.

Dr. Simon agreed that the study's finding that increased risk of dementia was linked to lower, rather than higher, levels of p16 and p21 was the opposite of what was expected.

The authors acknowledge in the paper that some of the results were paradoxical, he said. The bottom line is I wouldn't discount their findings, but I would like to see the results replicated in other studies.

Dr. Marras has received fees for consulting for Acorda Therapeutics, serving on the advisory board of Denali Therapeutics, an honorarium for teaching from EMD Serono, and research contracts from Grey Matter Technologies.

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Biomarkers of Senescence and Inflammation Linked to Risk of... : Neurology Today - LWW Journals

A Blood Test for Tau Is Consistent with PET and CSF… : Neurology Today – LWW Journals

Article In Brief

Researchers found in two different studies that blood tests, which indicated abnormally high levels of a tau protein closely linked to dementia due to Alzheimer's disease (AD), distinguished AD from frontotemporal lobar degeneration. In one study, it also predicted which patients who were cognitively normal or had mild cognitive impairment upon initial evaluation would later develop Alzheimer's dementia.

A blood test for Alzheimer's disease (AD) pathology appears to be as accurate as more invasive measures and equally well correlated with AD dementia, according to two studies published simultaneously in the March issue of Nature Medicine.

The studies measured plasma phosphorylated-tau-181 (p-tau181), a form of the tau protein, and found that abnormally high levels are as closely linked to dementia due to AD as are PET scans of amyloid protein and measures of p-tau181 in cerebrospinal fluid.

Not only did a high level of plasma p-tau181 distinguish AD from frontotemporal lobar degeneration, but in one of the studies it also predicted which patients who were cognitively normal or had mild cognitive impairment (MCI) upon initial evaluation would later develop Alzheimer's dementia.

While neurologists and officials at the National Institutes of Health (NIH) applauded the findings, they emphasized that the results need to be replicated and the p-tau181 test further investigated before it can be made available in the neurology clinic.

I think we are still a few years away from having this sort of test available to the general neurologist in a clinic setting or in their office, said Eliezer Masliah, MD, director of the neuroscience at NIH's National Institute on Aging. But they and their patients should know that these less expensive, less invasive tests are coming. We are hopeful that they will be approved in the near future by the FDA.

A longtime AD researcher called the findings a triumph.

I've been in this field since 1980 and having a blood test for Alzheimer's has been one of the holy grails, said Steven T. DeKosky, MD, FAAN, the Aerts-Cosper Professor of Alzheimer's Research at the University of Florida College of Medicine, and associate director of the Florida Alzheimer's Disease Research Center. This is a remarkable accomplishment. Right now, I'm sure all of us who do PET scan studies would love to be able to use this plasma test as a screen.

The principal investigator of one of the two studies told Neurology Today that his group is already working to validate plasma p-tau181 in a primary-care setting and to develop a clinical-grade test that could be used in any laboratory.

The test could be used in patients with either dementia or MCI to improve the diagnostic work-up, especially at specialized clinics and in patients where lumbar puncture or amyloid PET imaging cannot be done, said Oskar Hansson, MD, PhD, professor in the department of clinical memory research at Lund University in Sweden.

Dr. Hansson's group measured plasma p-tau181 levels in three cohorts comprising a total of 589 individuals. The first group included 64 participants who were cognitively unimpaired (with or without a positive amyloid-beta scan), 28 who had MCI, 38 who had AD dementia, and 52 with non-AD neurodegenerative disease. The second cohort, which was followed up for eight years to track conversion to AD dementia, included 219 cognitively unimpaired participants (42 percent of whom were positive for amyloid-beta), and 125 with MCI (65 percent of whom were amyloid-beta positive). A third cohort included pathology from post-mortem tests on 33 individuals:16 had confirmed AD dementia and 47 were non-AD.

The study found a clear association between plasma and CSF levels of p-tau181 in both cohorts one and two (p<0.001). In 174 participants from cohort one, plasma P-tau181 levels predicted positive tau PET scans (area under the curve (AUC) = 0.87-0.91 for different brain regions). Increased plasma p-tau181 was also associated with increased amyloid-beta PET (using a global cortical composite measure) in both cohort one and two (p< 0.001).

In the autopsy-confirmed cohort three, plasma p-tau181 distinguished AD dementia from non-AD neurodegenerative diseases as accurately as did tau PET and CSF p-tau181 (AUC = 0.94-0.98).

The results show that plasma p-tau181 may be increased early in AD, potentially even in some A+ cognitively unimpaired individuals (preclinical AD), the paper reported. Plasma p-tau181 then increased further during the symptomatic (prodromal and dementia) stages of AD. In contrast, plasma p-tau181 was not increased in non-AD. These characteristics mark out plasma p-tau181 as a promising biomarker to track disease progression in AD and to differentiate AD from non-AD conditions, with utility for patient management in clinical practice, research and trials.

In cognitively unimpaired and MCI subjects, a level of p-tau181 above 1.81 pg mL1 at baseline was associated with a dramatically increased risk of future AD dementia (p< 0.001). None of the other plasma biomarkers analyzed in the study, including total tau, amyloid-beta42/amyloid-beta 40 and neurofilament light protein, were independently related to risk of AD dementia.

The second study in Nature Medicine, part of the ongoing Advancing Research and Treatment for Frontotemporal Lobar Degeneration study, was led by Adam L. Boxer, MD, PhD, professor and director of the Alzheimer's Disease and Frontotemporal Degeneration Clinical Trials Program at the University of California, San Francisco, Memory and Aging Center. The cohort of 362 participants includes 69 healthy controls, 47 people with MCI, 56 with clinically diagnosed AD, and the remainder with various forms of frontotemporal lobar degeneration.

Dr. Boxer and colleagues found that plasma p-tau181 was increased by 3.5-fold in AD compared with controls and differentiated AD from both clinically diagnosed (AUC = 0.894) and autopsy-confirmed frontotemporal lobar degeneration (AUC = 0.878). The measure also identified individuals who were amyloid-beta positive on PET scans regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by 18F-flortaucipir PET.

As promising as the results were, Dr. Boxer told Neurology Today that his group is looking at the predictive value of other variants of phosphorylated tau.

We and others think that while plasma p-tau181 seems to be very useful, it's possible there may be other epitopes that may be even slightly more accurate, he said.

Both papers credited a 2018 study published in Alzheimer's & Dementia as the first to find that plasma p-tau181 increases with AD clinical severity and is associated with tau- and amyloid-PET scans. The first author of that study said that she still wants to see the results replicated in more diverse cohorts before the test becomes available outside of research trials.

The fact that these two studies both nicely complement each other and replicate our findings is really promising, said Michelle M. Mielke, PhD, professor of epidemiology and neurology at the Mayo Clinic. But I would like to see more replication in community-based studies rather than just in studies from memory clinics.

Her 2018 study, part of the ongoing Mayo Clinic Study of Aging, is now looking not only at plasma p-tau181 but also at plasma p-tau217.

Previously there weren't the technologies available to look at [p-tau] 217, she said. Historically, p-tau181 was the first to come out, and so that tended to be the focus. Which one is more accurate is still to be determined. And other phosphorylated tau fragments are also being looked at as well.

Two studies, which were published last year, analyzed data from the Framingham Heart Study and found that total tau in serum is a biomarker not only for dementia but also for stroke risk.

We wanted to also look at phosphorylated tau in plasma but at the time the measures were not sensitive enough, said the senior author of both studies, Sudha Seshadri, MD, FAAN, professor of neurology at Boston University School of Medicine and founding director of the Glenn Biggs institute for Alzheimer's & Neurodegenerative Diseases at UT Health San Antonio.

Total tau was a very good marker in our hands for all types of dementia and stroke risk. But it does seem that total tau is sensitive but perhaps not as specific. It seems to go up with a variety of insults to the brain.

Based on the two new papers, she said, plasma P-tau181 looks to be more specific for AD dementia.

Dr. Seshadri will be measuring plasma p-tau181 in the Framingham Study to see how it compares in a community setting. I would also like to see how it works in Hispanics in south Texas, in the African-American population, and in other groups, she said.

While the new studies involved hundreds of patients, the results still need to be replicated in far larger groups, Dr. Masliah said. NIA, which supported both studies in part, will likely fund such follow-up studies in its consortium of 32 AD centers.

What we're looking into is pulling samples from all those centers so they can be tested and verified by other technologies and then followed longitudinally, Dr. Masliah said. These are very, very exciting results, very important results, something we need to follow up on. If replicated in larger, more diverse cohorts, the plasma ptau181 test could be a game changer for clinical trials, he said.

Dr. Hansson has received research support (for his institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, and Euroimmun. He has received consultancy/speaker fees from Biogen and Roche. Dr. Boxer has served as a consultant for Aeton, Abbvie, Alector, AGTC, Amgen, Arkuda, Arvinas, Asceneuron, Esai, Ionis, Lundbeck, Novartis, Passage BIO, Sangamo, Samumed, Third Rock, Toyama and UCB. He has received research support from Avid, Biogen, BMS, C2N, Cortice, Eisai, Eli Lilly, Forum, Genentech, Janssen, Novartis, Pfizer, Roche, and TauRx.

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A Blood Test for Tau Is Consistent with PET and CSF... : Neurology Today - LWW Journals

Woman with COVID-19 developed a rare brain condition. Doctors suspect a link. – Live Science

Coronavirus science and news

A woman who tested positive for COVID-19 developed a rare brain disease known as acute necrotizing encephalopathy, a condition that can be triggered by viral infections like influenza and herpes.

At this point, the brain damage "has yet to be demonstrated as a result of COVID-19 infection," according to a case report published March 31 in the journal Radiology. However, as the novel coronavirus continues to spread, "clinicians and radiologists should be watching for this presentation among patients presenting with COVID-19 and altered mental status," the authors wrote.

"We need to be thinking of how were going to incorporate patients with severe neurological disease into our treatment paradigm," Dr. Elissa Fory, a Henry Ford neurologist who was part of the team of medical experts involved in making the diagnosis, said in a statement. "This complication is as devastating as severe lung disease."

The woman, a 58-year-old airline worker, checked into the Henry Ford Health System in Detroit, after having a fever, cough (known coronavirus symptoms) and "altered mental status" for three days, the report noted. At the hospital, the woman appeared confused, lethargic and disoriented, the statement noted. She tested negative for influenza, herpes, Varicella zoster virus (which causes chickenpox) and West Nile virus; and her cerebrospinal fluid, which saturates the brain and spinal cord, contained no trace of bacterial infection.

Noting her symptoms, the doctors also tested the patient for COVID-19 using a diagnostic test provided by the U.S. Centers for Disease Control and Prevention (CDC), and found that she tested positive for the disease.

Related: 10 deadly diseases that hopped across species

CT scans of the woman's brain revealed symmetrical tissue damage in the thalamus a structure buried in the center of the brain that helps relay sensory information from the body to the rest of the organ, according to BrainFacts.org. These damaged areas appeared darker on the woman's CT scan than they did in a scan of a healthy brain, meaning they were less dense than usual, according to an explanation of radiological terms from St. Vincent's University Hospital. Brain regions can become less dense when due to edema, when excess fluid floods the tissue after injury, or necrosis, when cells making up the tissue die off in large quantities, the case study authors noted.

The doctors gathered additional scans of the woman's brain using MRIs (magnetic resonance imaging) and examined them to find evidence that the patient had suffered a hemorrhage, or bleeding from a ruptured blood vessel. They again found damage in the thalamus, as well as in portions of the wrinkled cerebral cortex and in brain regions that lie just below its folds. The doctors diagnosed the woman with acute necrotizing encephalopathy, which, if left untreated, can progress to cause "coma, liver problems and neurological deficits," according to The National Institutes of Health's Genetic and Rare Disease Information Center (GARD).

"The team had suspected encephalitis at the outset, but then back-to-back CT and MRI scans made the diagnosis," Fory said.

The rare condition develops most commonly after a viral infection, such as those caused by influenza A, influenza B and the human herpes virus 6, according to GARD. These infections can trigger a so-called cytokine storm in the brain, when inflammatory substances that normally help the body fight off disease instead go haywire and damage the infected tissue, the case report authors noted. Cytokine storms break down the tissue that surrounds blood vessels in the brain, known as the blood-brain barrier, and can thus lead to hemorrhage, they wrote.

Although the doctors could not directly demonstrate that COVID-19 triggered the woman's unusual brain disease, a recent report in the journal the Lancet suggests that a subset of infected patients appear vulnerable to brain-bound cytokine storms. In addition, a case report published in the Cureus Journal of Medical Science described a 74-year-old patient with both COVID-19 and signs of encephalopathy.

It should be noted that "elderly patients with chronic conditions are at an increased risk of altered mental status in the setting of acute infections," the authors of the Cureus paper wrote. At this point, the potential neurological symptoms of COVID-19 are not well understood, but they should be further investigated in infected patients, they added. Altered mental status might even serve as an early symptom of COVID-19 in some people, they said.

"If patients with neurological conditions are not considered to have COVID-19, this may present a nationwide issue to health care team members treating patients and in turn the general public if they are discharged and further exposed to other people," the Cureus authors noted.

Originally published on Live Science.

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Woman with COVID-19 developed a rare brain condition. Doctors suspect a link. - Live Science

First Case of Encephalitis Linked to COVID-19 Reported – Medscape

Clinicians from Henry Ford Health System in Detroit, Michigan, have reported the first presumptive case of acute necrotizing hemorrhagic encephalopathy associated with COVID-19.

"As the number of patients with COVID-19 increases worldwide, clinicians and radiologists should be watching for this presentation among patients presenting with COVID-19 and altered mental status," the clinicians advise in a report published online March 31 in Radiology.

"This is significant for all providers to be aware of and looking out for in [COVID-19] patients who present with an altered level of consciousness. This complication is as devastating as severe lung disease," Elissa Fory, MD, a neurologist with Henry Ford who was part of the team of medical experts that made the diagnosis, said in a statement.

"We need to be thinking of how we're going to incorporate patients with severe neurological disease into our treatment paradigm," Fory added.

Brent Griffith, MD, radiologist with Henry Ford and senior author of the case report, said the case shows "the important role that imaging can play in COVID-19 cases."

The 58-year-old woman presented with a 3-day history of fever, cough, and muscle aches symptoms consistent with COVID-19. She was transported by ambulance to the emergency department and showed signs of confusion, lethargy, and disorientation.

The woman tested negative for influenza, but a rapid COVID-19 test confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) infection. She was later diagnosed with acute hemorrhagic necrotizing encephalopathy.

"The team had suspected encephalitis at the outset, but then back-to-back CT and MRI scans made the diagnosis," Fory said in the statement.

Noncontrast head CT revealed "symmetric hypoattenuation within the bilateral medial thalami with a normal CT angiogram and CT venogram," the team reports in their article. Brain MRI showed "hemorrhagic rim enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular regions."

The patient was started on intravenous immunoglobulin but not high-dose steroids, because of concern for respiratory compromise. As of April 1, the patient was hospitalized in serious condition. Henry Ford Hospital has not provided an update.

Acute necrotizing encephalopathy (ANE) is a rare complication of viral infections, but until now, it has not been known to have occurred as a result of COVID-19 infection. ANE has been associated with intracranial "cytokine storms," and a recent report in the Lancet suggested that a subgroup of patients with severe COVID-19 might develop a cytokine storm syndrome.

Commenting for Medscape Medical News, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University in St. Louis, Missoui, said, "Since this is just one report of one patient, the findings are the most preliminary we can conceive, and more research is needed to determine the extent to which COVID-19 may affect the central nervous system."

Fory, Griffith, and Raji have disclosed no relevant financial relationships.

Radiology. Published online March 31, 2020. Full text

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First Case of Encephalitis Linked to COVID-19 Reported - Medscape

Cannabidiol as an Adjunctive Therapy for Patients With Treatment-Resistant Dravet Syndrome – Neurology Advisor

Cannabidiol daily doses of 10 or 20 mg/kg can be a safe and effective adjunct treatment to reduce seizure in patients with highly resistant Dravet syndrome, according to study results published in JAMA Neurology.

Previous studies have supported the safety and efficacy of cannabidiol at a daily dose of 20 mg/kg as an add-on antiepileptic treatment in patients with Dravet syndrome. The goal of the current study was to assess the efficacy and safety of 2 daily doses of cannabidiol, 10 mg/kg or 20 mg/kg, in children with Dravet syndrome.

The double-blind, placebo-controlled, randomized clinical trial included children aged 2 to 18 years from 38 centers in the United States, Spain, Poland, the Netherlands, Australia, and Israel with a confirmed diagnosis of Dravet syndrome and at least 4 convulsive seizures during a 4-week baseline period while receiving antiepileptic therapy.

The patients were randomly assigned to receive cannabidiol oral solution at a daily dose of 10 (CBD10) or 20 (CBD20) mg/kg, or matched placebo in 2 equally divided doses for 14 weeks. The primary outcome was the change in the frequency of convulsive seizure frequency from baseline.

A total of 198 patients (mean age, 9.3 years; 52.5% girls) were enrolled in the study; of these, 65 received placebo, 66 received CBD10, and 67 received CBD20. A total of 190 patients completed the treatment period, and 186 (97.9%) entered the open-label extension trial.

Convulsive seizure frequency compared with baseline was reduced by 48.7% in the CBD10 group and by 45.7% in the CBD20 group compared with 26.9% in the placebo group. The percentage reduction from placebo was 29.8% (95% CI, 8.4%-46.2%; P =.01) for the CBD10 group and 25.7% (95%CI, 2.9%-43.2%; P =.03) for the CBD20 group.

The most common adverse events occurring in 10% of patients in any group included decreased appetite, diarrhea, somnolence, pyrexia, and fatigue. Serious adverse events occurred in 40 patients (10 in the placebo group, 13 in the CBD10 group, and 17 in the CBD20 group). Elevated liver transaminase levels occurred more frequently in the CBD20 (n=13) than the CBD10 (n=3) group, with all affected patients receiving concomitant valproate sodium.

The study had several limitations, according to the researchers, including the short-term follow-up period, limited option to assess the effects of specific drug combinations as cannabidiol was added to various antiepileptic regimens, and lack of data on the safety and efficacy of cannabidiol in daily doses <10 mg/kg.

Our key finding is the significant and clinically meaningful reduction of seizures with an acceptable safety profile for both cannabidiol doses in patients with highly treatment-resistant Dravet syndrome, concluded the researchers.

Disclosure: This clinical trial was supported by GW Research, Ltd. Please see the original reference for a full list of authors disclosures

Reference

Miller I, Scheffer IE, Gunning B, et al. Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in Dravet syndrome: a randomized clinical trial [published online March 2, 2020]. JAMA Neurol. doi:10.1001/jamaneurol.2020.0073

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Cannabidiol as an Adjunctive Therapy for Patients With Treatment-Resistant Dravet Syndrome - Neurology Advisor

Discontinuation of Dolutegravir Due to Neurologic Side Effects Linked to Pre-Existing Mental Illness – Neurology Advisor

Dolutegravir (DTG) discontinuation due toneuropsychologic side effects (NPS) may be associated with preexistingpsychiatric conditions of depression and anxiety, according to results of astudy presented at the virtual Conference on Retroviruses and OpportunisticInfections, held from March 8 to 11, 2020.

DTG treatment has been associated with a higherrate for discontinuation as a result of NPS. Several associated factors forthis association have been described, including older age, female sex, abacavircoadministration, higher DTG exposure, and pharmacokinetic- and pharmacodynamic-mediatedvariants. In addition, there has been an observed increase in the rates ofmoderate depression among patients who have switched to DTG. However,pre-existing psychiatric disorders have not previously been associated with ahigher risk for NPS. Therefore, this prospective, observational study describedthe clinical features and outcomes of patients stopping DTG for NPS.

In total, 1455 participants starting DTG (naive and treated) were included from 2 Italian outpatient clinics. Clinical, therapeutic pharmacokinetics variables with the risk for DTG discontinuation due to NPS were analyzed. This analysis focused on patients who stopped DTG for NPS in terms of pre-existing psychiatric comorbidities and outcomes after drug withdrawal (resolution of symptoms was recorded at the first available follow-up after discontinuation).

Of all included participants, after a median of5.1 months, 526 participants discontinued DTG, with the most common reasonbeing treatment switches with no efficacy or tolerability issues (n=274); 66(4.5%) of participants discontinued DTG due to NPS. Of the 66 participants whodiscontinued DTG due to NPS, 21 (31.8%) participants had pre-existingpsychiatric conditions, with the 2 most common being depression (12 [18.2%]patients) and anxiety (4 [6.1%] patients).

The most common symptoms according to the preexisting psychiatric comorbidities of depression and anxiety were sleep disorders (35.6%), anxiety (28.9%), and headache (24.4%). Both headache (P =.039) and sleep disorders (P =.083) were associated with complete resolution of symptoms. After discontinuation, DTG was replaced with raltegravir (n=20), elvitegravir/c (n=19), darunavir/c (n=17), or rilpivirine (n=8), with the most complete resolution of symptoms observed with the elvitegravir/c replacement and the converse observed among patients who received rilpivirine.

Overall, the study concluded that NPS wereheterogeneous, with sleep disorders, headache, and anxiety being the moreincident among such effects, and no signal for a better switching strategyemerged.

Reference

Andrea C, Borghetti A, Milesi M, et al. Clinical features and outcomes of patients stopping STG for neuropsychiatric symptoms. Poster presented at: CROI 2020; March 8-11, 2020; Boston, MA. http://www.croiconference.org/sites/default/files/uploads/croi2020-boston-abstract-ebook.pdf. Accessed March 27, 2020.

This article originally appeared on Infectious Disease Advisor

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Discontinuation of Dolutegravir Due to Neurologic Side Effects Linked to Pre-Existing Mental Illness - Neurology Advisor

Sonnet BioTherapeutics Announces Formation of Scientific Advisory Board – Yahoo Finance

PRINCETON, NJ / ACCESSWIRE / April 6, 2020 / Sonnet BioTherapeutics Holdings, Inc. (SONN), a biopharmaceutical company developing innovative, targeted biologic drugs with enhanced single or bispecific mechanisms of action, announced today the formation of its Scientific Advisory Board. The Board comprises experts from leading institutions across the United States, including MD Anderson, Memorial Sloan-Kettering, Fox Chase and Robert Wood Johnson. The members bring decades of experience in oncology, neurology, drug discovery and clinical development.

"Sonnet is privileged to have this distinguished group of scientific advisors from leading institutions to help guide our clinical development and discovery programs," commented Sonnet Founder and CEO, Pankaj Mohan, Ph.D. "The advisors come to the company after reviewing its assets and are excited to be a part of the team. They share deep experience in oncology drug development from initial discovery to late-stage clinical studies, which will enhance our strategic efforts through the next phase of growth."

Sonnet Scientific Advisory Board members include:

Jason Bock, Ph.D., - Dr. Bock is the Vice President and Head of Biologics Product Development at MD Anderson Cancer Center. In this role, Dr. Bock works with MD Anderson's Therapeutic Discovery team, including world-class oncology researchers and clinicians, to create life-saving transformational medicines quickly, safely and effectively. Before joining MD Anderson, Dr. Bock spent 20 years in small, medium and large biotech and biopharma companies (including Human Genome Sciences, CoGenesys and TEVA) developing biologic therapeutics. He has brought 15 novel drugs through preclinical development into clinical studies and has guided the process to bring three biologics through the clinic and to commercialization globally. He received his Ph.D. from Stanford University in Molecular & Cellular Physiology.

Joseph R. Bertino, M.D., - Dr. Bertino is University Professor of medicine and pharmacology, UMDNJ-Robert Wood Johnson Medical School and is the interim director of the school's Cancer Institute of New Jersey. Dr. Bertino joined The Cancer Institute of New Jersey in 2002 as associate director and was appointed chief scientific officer in 2004. Previously, Dr. Bertino served as chair of the Molecular Pharmacology and Therapeutics Program, and member and co-head of the Program in Developmental Therapy and Clinical Investigation at Memorial Sloan-Kettering Institute for Cancer Research. Dr. Bertino has been internationally recognized for his role in finding curative treatments for leukemia and lymphoma. He is the author or co-author of more than 400 scientific publications and the associate medical editor of the journal Hem/Onc Today. After earning his medical degree, Dr. Bertino did a USPHS fellowship in hematology and oncology at the University of Washington School of Medicine.

Hossein Borghaei, D.O., M.S., - Dr. Borghaei is Chief of Thoracic Medical Oncology at Fox Chase Cancer Center, where he is also a Professor in the Department of Oncology/Hematology, Co-Director of the Immune Monitoring Facility and the Gloria and Edmund M. Dunn Chair in Thoracic Malignancies. In his clinical practice, Dr. Borghaei has participated in numerous immunotherapy-based clinical trials. He is also the principal investigator (PI) of a laboratory that develops new monoclonal antibodies and novel immune-modulating drugs. He served as the PI of a phase III randomized study that proved the effectiveness of nivolumab in the treatment of patients with advanced non-squamous non-small cell lung cancer after progression on prior chemotherapy. This work led to the approval of nivolumab, one of the first immunotherapy-based drugs to be approved for lung cancer in this setting. Dr. Borghaei earned his D.O. degree at Philadelphia College of Osteopathic Medicine, did his residency at Graduate Hospital (Philadelphia) and was Chief Fellow, Hematology-Oncology, at Fox Chase Cancer Center.

Guido Cavaletti, M.D., - Dr. Cavaletti is Dean of Research and Professor at the University of Milan-Bicocco, and Senior consultant neurologist and head of the Neuroimmunology Center, S. Gerardo Hospital, Monza (Italy). At the University of Milan-Bicocco, he is Head of the Experimental Neurology Unit at the School of Medicine and Surgery and Director of the Ph.D. program in Neuroscience. He is also Deputy Scientific Director of the Milan Center for Neuroscience (NeuroMI). Dr. Cavaletti is coordinator of the steering committee of the international CI-PeriNoms group on the investigation of chemotherapy-induced peripheral neurotoxicity. He has authored more than 250 peer-reviewed papers. He received his medical degree from the University of Milan and is Board-certified in Neurology.

Story continues

About Sonnet BioTherapeutics Holdings, Inc.

Founded in 2011, Sonnet BioTherapeutics is an oncology-focused biotechnology company with a proprietary platform for innovating biologic drugs of single or bispecific action. Known as FHAB (Fully Human Albumin Binding), the technology utilizes a fully human single chain antibody fragment (scFv) that binds to and "hitch-hikes" on human serum albumin (HSA) for transport to target tissues. FHAB is the foundation of a modular, plug-and-play construct for potentiating a range of large molecule therapeutic classes, including cytokines, peptides, antibodies and vaccines.

Forward-Looking Statements

This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company's product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions.

These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential, "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Sonnet Biotherapeutics Investor Contact

Alan LadaSolebury Trout617-221-8006alada@soleburytrout.com

SOURCE: Sonnet BioTherapeutics Holdings, Inc.

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Coronavirus: Ministry will monitor any reports of test price cheats – Cyprus Mail

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Dr. James T. Goodrich, Who Operated on Conjoined Twins, Dies at 73 – The New York Times

This obituary is part of a series about people who have died in the coronavirus pandemic.

Dr. James T. Goodrich, a pediatric neurosurgeon known for successfully separating conjoined twins in a complicated and rare procedure, died on Monday at Albert Einstein College of Medicine and Montefiore Medical Center in the Bronx. He was 73.

The cause was complications of the coronavirus, according to Montefiore, where he was the director of pediatric neurosurgery and had spent more than 30 years of his career.

Dr. Goodrich was thrust into public view when he conducted a series of four operations over nearly a year on Clarence and Carl Aguirre, twins from the Philippines who were joined at the tops of their heads and shared major veins in their brains. Dr. Goodrich led a team of surgeons at Montefiores Childrens Hospital, and the twins story generated headlines, including in The New York Times, and was the subject of television specials.

During the final surgery, in August 2004, the team discovered that the twins brains were connected by more brain tissue than they had initially thought, a potentially serious complication.

We got to this point and we were stuck, Dr. Goodrich told The Times after the operation, but we did a lot of soul-searching and decided to continue.

Hours later, Clarence and Carl lay next to each other, alive and well. They had no major complications after the surgery, and their mother, Arlene Aguirre, said, My dream has come true.

Carl and Clarence, who turn 18 later this month, live with their mother in Scarsdale, N.Y.

James Tait Goodrich was born in Portland, Ore., on April 16, 1946, to Richard and Gail (Josselyn) Goodrich. His mother was an artist and a designer, and his father worked in advertising. Dr. Goodrich served in the Marines during the Vietnam War, then studied neurosurgery and psychobiology at the University of California, Irvine; Columbia University; and the Neurological Institute of New York before starting at Montefiore.

He married Judy Laudin in 1970. In addition to his wife, he is survived by three sisters, Kristine Goodrich, Jan Rentenaar and Carol Montecucco.

In another celebrated case, Dr. Goodrich led a team of 40 surgeons in a 27-hour procedure in 2016 to separate another set of twin boys, the seventh separation procedure of his long career.

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High Levels of Air Pollution Linked to Increased MS Risk – Medscape

Air pollution may be another environmental risk factor for developing multiple sclerosis (MS), new research suggests.

A large cohort study of almost 550,000 individuals living in Italy showed that participants living in areas with high levels of pollutants had a significantly greater risk of developing MS than those who lived in areas with low levels of pollutants.

Dr Roberto Bergamaschi

The findings further confirm a relationship between exposure to air pollutants and risk for MS that has been shown in previous research, Roberto Bergamaschi, MD, PhD, director of the Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy, told Medscape Medical News.

"Countermeasures that cut air pollution can be important for public health, not only to reduce deaths related to cardiac and pulmonary diseases but also the risk of chronic autoimmune diseases such as MS," Bergamaschi said.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.

Several environmental factors may trigger an abnormal immune response that manifests in MS. The most studied of these are low vitamin D level, cigarette smoking, and an unhealthy diet, Bergamaschi said.

However, "other environmental factors deserve to be studied pollution included," he added.

Among the most toxic air pollutants are particulate matter (PM), which is a mixture of fine solid and liquid particles suspended in the earth's atmosphere. PM may range from 2.5 microns (PM2.5) to 10 microns (PM10) in diameter.

The main sources of such pollutants are household and commercial heating (53%) and industrial activities (17%), followed by road vehicle and nonroad vehicle use, agriculture, and electricity production.

The World Health Organization estimates that more than 3.2 million individuals worldwide die prematurely every year because of lung cancer, cardiovascular disease, and other diseases related to air pollutants, said Bergamaschi.

Epidemiologic research has uncovered a relationship between air pollution and MS. A large American study published in 2008 in Science of the Total Environment showed a significant association between MS prevalence and PM10 levels (P < .001).

Other studies have shown an increase in the number of clinical relapses of MS that were linked to air pollution.

The current investigators assessed the association between PM2.5 levels and MS prevalence in the northern province of Pavis, which has a population of 547,251 individuals in 188 municipalities.

Pavia is situated in a flat territory that encompasses the highly industrialized regions of Piedmont, Lombardy, Emilia-Romagna, and Veneto. It has a high level of anthropogenic emissions, or environmental pollutants originating from human activity, Bergamaschi reported.

The region also has "peculiar" geographical features that "favor the accumulation of pollutants," such as the natural barrier of the Alps in the north and low wind speed, he said.

The researchers identified 927 individuals with MS (315 male and 612 female) in the province. The overall MS prevalence rate was 169.4 per 100,000 population (95% confidence interval [CI], 158.8 180.6), which is 10-fold higher than 50 years ago, Bergamaschi said. In addition, this MS prevalence is higher than that in the United States, which is about 150 per 100,000 population.

Using sophisticated Bayesian disease mapping, the investigators looked for clusters of MS. They also gathered emission data for PM2.5 from 2010 to 2017 from the European Monitoring and Evaluation Programme database. They then divided the region on the basis of average winter concentrations of PM2.5.

Three distinct lateral areas of air pollution were identified. The more northern region, which includes the large urban center of Milan, had the highest level of air pollution. Concentrations decreased the further south the investigators looked.

After adjusting for age, urbanization (population density), and deprivation index, results showed that living in areas with high levels of pollutants was associated with increased MS risk.

When controlling for PM2.5 pollution, participants in urban areas had an increased risk for MS compared with rural dwellers (relative risk [RR], 1.16; 95% CI, 1.04 1.30; P = .003)

Bergamaschi said it is unclear whether this risk is higher for certain types of MS. "To my knowledge, no study has analyzed possible relationships between MS phenotypes and air pollution," he noted.

Several mechanisms might help explain the relationship between air pollution and MS risk, he added. These include oxidative stress, which results in cell damage, inflammation, and proinflammatory cytokine release.

Vitamin D also likely plays some role, Bergamaschi said. Upon penetrating the lower strata of the earth's atmosphere, ultraviolet B radiation is absorbed and scattered by suspended pollutants.

Several studies have highlighted the correlation between living in a polluted area and vitamin D hypovitaminosis; "so air pollution can contribute to increasing the risk of MS by reducing vitamin D synthesis," he said.

Recent research has also shown that air pollution is associated with a higher risk for other autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes mellitus.

However, pollution alone is only part of the picture. MS prevalence in highly populated and polluted countries such as China and India is low, with no more than 30 to 40 cases per 100,000 population, Bergamaschi noted.

"This discrepancy is explained by different genetic backgrounds. While Caucasians are particularly susceptible to MS, Asians are not," he said.

Study limitations cited included a possible bias because the analysis did not include other possible contributing risk factors, particularly other pollutants, Bergamaschi said.

Commenting for Medscape Medical News, Lily Jung Henson, MD, chief of neurology at Piedmont Healthcare in Stockbridge, Georgia, said the findings provide "a fascinating glimpse" into possible causative factors for MS and warrant further investigation.

"This research also suggests other opportunities to look at, such as progression of the degree of air pollution and the incidence of MS over time," said Henson, who was not involved with the study.

Bergamaschi and Jung Henson have reported no relevant financial relationships.

Congress of the European Academy of Neurology (EAN) 2020: Abstract 1957. Presented May 23, 2020.

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It’s Stroke Month, and this advice from a Birmingham expert can save lives – Bham Now

Photo via Brookwood Baptist Health

May is American Stroke Awareness Month. We sat down (virtually, of course) with one of the top stroke experts in the state to share what Birmingham residents need to know when it comes to stroke symptoms, treatment and care. Learn all about it here!

I grew up learning to share the worst parts first when youre telling a story. The fact is, most of us probably know someone whos been affected by a stroke. Theyre hugely common in the United States. In fact, its the fifth leading cause of death for Americans.

Here are a few statistics about stroke in the US from the CDC, updated in January 2020:

Sure, the numbers can be a bit frightening. However, its good to be aware of the risk and how serious strokes are. When you know whats at stake, youre much less likely to attempt waiting it out or driving yourself to the hospitalneither of which are great ideas when it comes to a stroke.

Jitendra Sharma, M.D., is an interventional neurologist at Brookwood Baptist Medical Center. He earned his medical degree at M.G.M. Medical College in India and completed fellowships in Serono Research, Vascular Neurology and Neurointervention.

Dr. Sharma specializes in Interventional Neurology, and hes one of only five physicians in the state of Alabama to do so.

Interventional neurology is an emerging field. What we do is we go inside the blood vessel and we try to help patients who have blood clots in the brain

As interventional neurologists, we can take care of stroke intervention, which means pulling the blood clot out. We also take care of brain aneurysms and close them off

Even carotid artery disease, we can insert a stent. So thats what the umbrella of interventional neurology covers.

These procedures are very new to the field, and patients have shown significant improvements immediately after surgery. The methods are also much less invasive than traditional brain surgeries.

Dr. Sharma currently practices within the Brookwood Baptist Health Primary & Specialty Care Network.

Brookwood Baptist Medical Center is a Certified Primary Stroke Center. This essentially means youre getting the best of the best when it comes to stroke care. Theyre prepared 24 hours a day + seven days a week to treat these urgent medical emergencies.

For the past 3 years, the American Heart Association and American Stroke Association have also granted Brookwood Baptist Medical Center the highest level of recognition for stroke care it awards. This establishes both their quality and speed of care as the true gold standard in Alabama and beyond.

When it comes to strokes, the key is to BE FAST. Strokes are considered one of the most urgent medical emergencies, which means seconds matter. The faster a patient gets to the hospital and receives treatment, the better their chance of recovery.

Knowing and recognizing the symptoms of a stroke can be the difference in survival and/or lasting damage in you or someone you love. BE FAST isnt just important to remember in your reaction timeits also important when you see symptoms.

We cant say it enough: time + treatment are CRITICAL in stroke situations. So lets talk about emergencies during a pandemic. Apprehension about going to a hospital right now is understandable, and you should always take precautions.

However, the risk of an untreated stroke statistically outweighs the risk of a virus. If youre experiencing symptoms or are around someone who is, call 911 immediately. Dont wait it out home, dont hop in your car and mosey on down to your local urgent care.

Once the blood flow to the brain is stopped, every minute, millions of brain cells die We see sometimes in the community that people want to stay homethey think it will go away.

Instead, it just gets worse and worse, and then they come to the hospital, and then its too late for us to help them.

After learning from Dr. Sharma, I realized some of my ideas about strokes were incorrect. I always believed that as a twenty-something, I was basically immune. Turns out, people as young as 24 years old can fall victim.

What we are seeing nowadays is patients who are young are having more strokes. Risk factors such as diabetes, cholesterol, high blood pressure, obesityall these risk factors play a role in having a stroke.

We are seeing more and more patients who are 40 or 50 coming to us with stroke-like symptoms.

So, now that you know the symptoms + how to respond, weve reached the most important question (at least in my opinion). How can you prevent a stroke? Of course, theres no foolproof method, but there are ways you can be proactive. Heres what Dr. Sharma recommends:

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It's Stroke Month, and this advice from a Birmingham expert can save lives - Bham Now

SOC Telemed Partners with Beauregard Health System – Leesville Daily Leader

SOC Telemed (SOC), the leader in acute care telemedicine and Beauregard Health System, a rural acute hospital in DeRidder, Louisiana today announced a partnership to deliver scalable, flexible telemedicine services across five key specialties including the first SOC deployment of teleCardiology services.

With a blend of regional and national specialists, Telemed IQ provides vital support to rural Louisiana

By partnering with SOC, Beauregard gains access to specialists and care that might otherwise be unavailable to the rural Louisiana community.

Beauregard implemented SOC's Telemed IQ telemedicine platform to provide psychiatry, critical care, inpatient neurology, emergency neurology and most recently, cardiology via telemedicine.

The teleNeurology program is staffed by SOC neurologists while their telePsychiatry, teleICU, and teleCardiology programs are staffed by existing members of Beauregard's Medical Staff who live and operate locally or in regional city centers like Alexandriaand Lake Charles.

The 49-bed not-for-profit hospital system at Beauregard is the first to utilize SOC Telemed's platform for teleCardiology services.

After the departure of the community's sole full-time cardiologist in April 2019, Beauregard was forced to transfer an average of 30 monthly cardiology cases to other hospital systems.

"Our community was vulnerable without a full-time local cardiologist," said Traci Thibodeaux, chief operating officer for Beauregard Health System.

"We wanted to partner with a cardiology group in Lake Charles, but knew they couldn't meet our needs for an onsite full-time physician.

Luckily, we'd already deployed SOC's platform in other hospital departments.

By pairing the Telemed IQ platform with a regional cardiology group out of Lake Charles, we were able to close the care gap and improve access to cardiac care for our community."

Dr. Raman Saharan, an internist and hospitalist at Beauregard, noted an additional benefit of acute telemedicine in their ICU during the COVID-19 pandemic, "Unlike some rural hospitals which had to close their doors due to this pandemic, we not only kept our hospital running but also were able to provide a higher level of care including transfusion of Convalescent plasma."

With SOC Telemed in place, the hospital already reports a higher case mix index, fewer transfers and broad patient satisfaction thanks to improved access to cardiologists as well as the specialists in the other four telemedicine-enabled departments.

"Across the nation, rural hospitals struggle to staff specialists in key areas like neurology and stroke care, psychiatry and even cardiology. However Beauregard, although rural, is ahead of many other hospitals by not allowing clinical care to be constrained due to its location or the artificial walls of the hospital that existed before telemedicine," said Jason Hallock, MD, chief medical officer for SOC Telemed. "Whether the doctors who ultimately provide the care are based in Lake Charles, New Orleans or anywhere else in the country, the SOC Telemed platform stands ready to deliver flexible solutions that connect communities in need with specialized medicine, on demand."

About SOC Telemed

SOC Telemed (SOC) is the largest national provider of telemedicine technology and solutions to hospitals, health systems, post-acute providers, physician networks, and value-based care organizations. Built on proven and scalable infrastructure as an enterprise-wide solution, SOC's technology platform, Telemed IQ, rapidly deploys and seamlessly optimizes telemedicine programs across the continuum of care. SOC virtually delivers clinicians to patients through teleNeurology, telePsychiatry and teleICU, as well as enables healthcare organizations to build sustainable telemedicine programs in any clinical specialty. SOC helps organizations to enrich their care models and touch more lives by supplying healthcare teams with industry-leading solutions that drive improved clinical care, patient outcomes, and organizational health.

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SOC Telemed Partners with Beauregard Health System - Leesville Daily Leader

Impact of Baseline Dyskinesia on Safety and Efficacy of NOURIANZ (istradefylline) in Patients with Parkinson’s Disease Presented During…

BEDMINSTER, N.J., May 26, 2020 /PRNewswire/ --Kyowa Kirin, Inc., an affiliate of Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151) a global specialty pharmaceutical company, today announces the presentation of results from a post hoc pooled analysis assessing the impact of baseline dyskinesia (pre-existing dyskinesia before istradefylline treatment) on the safety and efficacy of NOURIANZ (istradefylline) in patients with Parkinson's disease (PD) experiencing "OFF" episodes or "OFF" time. Dyskinesia is recognized as the most frequent adverse reaction in istradefylline treatment.1The findings showed patients had reductions in "OFF" time and increases in "ON" time without troublesome dyskinesia regardless of the presence of dyskinesia at baseline. Patients with baseline dyskinesia before starting NOURIANZ were more likely to experience dyskinesia as an adverse event (AE) during treatment than those who did not have dyskinesia at baseline, but both groups on NOURIANZ experienced a reduction in "OFF" time and an increase in "ON" time without troublesome dyskinesia. These findings were presented during the 6th Congress of the European Academy of Neurology (EAN).

The pooled analysis examined subgroup data from 2,719 patients with PD taking levodopa-containing products with or without other anti-PD medications who experienced "OFF" episodes, either with baseline dyskinesia (+BL-dyskinesia) or without baseline dyskinesia (BL-dyskinesia) prior to the addition of istradefylline or placebo to their treatment regimen. Data were pooled from eight randomized, placebo-controlled, double-blind clinical studies. In the studies, patients received a daily 20mg or 40mg dose of istradefylline or a placebo for 12 or 16 weeks. The primary endpoint for these trials was change in "OFF" time as reported in patient-completed diaries, with AEs recorded throughout.2 Primary analyses from these studies showed that the use of istradefylline as an adjunctive treatment to levodopa/carbidopa in adult patients with PD experiencing "OFF" episodes was associated with a decrease in "OFF" time and an increase in "ON" time without troublesome dyskinesia.1

Results from the post hoc subanalysis of the eight pooled studies demonstrated that dyskinesia was reported by more patients as an AE during the trials by patients with baseline dyskinesia versus patients without baseline dyskinesia, regardless of whether they received istradefylline or placebo. Dyskinesia as an AE during the studies was reported by 14.1%, 24.7% and 25.9% of patients with baseline dyskinesia (+BL-dyskinesia) receiving a placebo or 20 mg/day or 40 mg/day of istradefylline, respectively, versus 3.5%, 4.4% and 8.4% of patients without baseline dyskinesia, respectively. Reduction in "OFF" time and increase in "ON" time without troublesome dyskinesia were greater with istradefylline than with placebo, which was consistent with previous studies.2

"Uncontrolled, involuntary movementscommonly known as dyskinesiacan be very troublesome in patients with PD, especially those patients who experience 'OFF' episodes," said Dr. Stuart Isaacson, MD, Parkinson's Disease and Movement Disorders Center of Boca Raton, Florida."The results being presented at EAN suggest that dyskinesia is observed more often in patients with baseline dyskinesia before istradefylline was added to the treatment regimen and that the overall efficacy of istradefylline was not affected by patients' baseline status. We believe these data can be helpful to physicians as they make treatment decisionsand may provide insight into the appropriate use of NOURIANZ in the treatment of 'OFF' time in patients with PD."

While these data provide further information, physicians should continue to monitor patients for dyskinesia or exacerbation of existing dyskinesia during NOURIANZ treatment. The most common adverse reactions with an incidence 5% and occurring more frequently than with placebo were dyskinesia (15%, 17%, and 8%), dizziness (3%, 6%, and 4%), constipation (5%, 6%, and 3%), nausea (4%, 6%, and 5%), hallucination (2%, 6%, and 3%), and insomnia (1%, 6%, and 4%) for NOURIANZ 20 mg, 40 mg, and placebo, respectively.

NOURIANZis the first and only adenosine A2A receptor antagonist approved in the U.S. as an adjunctive or "add on" treatment to levodopa/carbidopa in adult patients with PD experiencing "OFF" episodes.3

Parkinson's disease is a progressive nervous system disorder that affects movement and occurs when cells in the brain, which produce the chemical dopamine, become damaged or die. Dopamine signaling is an important component of the pathways in the brain that control movement.4 In patients with PD, dopamine loss is often treated with levodopa/carbidopa or other medicines that help regulate dopamine.5 Over time and as the disease progresses, these treatments may become less effective, and symptoms return before it's time for the next dose of medicine. These periods when symptoms return are known as "OFF" episodes or "OFF" time.6

Please see NOURIANZ indication and Important Safety Information below.

IndicationNOURIANZ(istradefylline) is an adenosine receptor antagonist indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease (PD) experiencing "OFF" episodes.

Important Safety Information

Warnings and Precautions

Dyskinesia:NOURIANZ in combination with levodopa may cause dyskinesia or exacerbate pre-existing dyskinesia. In controlled clinical trials (Studies 1, 2, 3, and 4), the incidence of dyskinesia was 15% for NOURIANZ 20 mg, 17% for NOURIANZ 40 mg, and 8% for placebo, in combination with levodopa. One percentof patients treated with either NOURIANZ 20 mg or 40 mg discontinued treatment because of dyskinesia, compared to 0% for placebo.

Hallucinations / Psychotic Behavior:Because of the potential risk of exacerbating psychosis, patients with a major psychotic disorder should not be treated with NOURIANZ. Consider dosage reduction or discontinuation if a patient develops hallucinations or psychotic behaviors while taking NOURIANZ. In controlled trials (Studies 1, 2, 3, and 4), the incidence of hallucinations was 2% for NOURIANZ 20 mg, 6% for NOURIANZ 40 mg, and 3% for placebo. In patients treated with NOURIANZ 40 mg, 1% discontinued because of hallucinations, compared to 0% for placebo and 0% for patients treated with NOURIANZ 20 mg.

Impulse Control / Compulsive Behaviors:Patients treated with NOURIANZ and one or more medication(s) for the treatment of Parkinson's disease (including levodopa) may experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge or compulsive eating, and/or other intense urges, and the inability to control these urges. In clinical trials, 1 patient treated with NOURIANZ 40 mg was reported to have impulse control disorder, compared to no patient on NOURIANZ 20 mg or placebo.

Drug Interactions

The maximum recommended dosage in patients taking strong CYP3A4 inhibitors is 20 mg once daily. Avoid use of NOURIANZ with strong CYP3A4 inducers.

Specific Populations

Pregnancy:Based on animal data, may cause fetal harm.

Hepatic impairment:The maximum recommended dosage of NOURIANZ in patients with moderate hepatic impairment is 20 mg once daily. Avoid use in patients with severe hepatic impairment.

Adverse Reactions

The most common adverse reactions with an incidence 5% and occurring more frequently than with placebo were dyskinesia (15%, 17%, and 8%), dizziness (3%, 6%, and 4%), constipation (5%, 6%, and 3%), nausea (4%, 6%, and 5%), hallucination (2%, 6%, and 3%), and insomnia (1%, 6%, and 4%) for NOURIANZ 20 mg, 40 mg, and placebo, respectively.

You are encouraged to report suspected adverse reactions to Kyowa Kirin, Inc. at 1-844-768-3544 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

Please see Nourianz Full Prescribing Information, here.

About Kyowa KirinKyowa Kirin commits to innovative drug discovery driven by state-of-the-art technologies. Kyowa Kirin focuses on creating new value in four therapeutic areas: nephrology, oncology, immunology/allergy and neurology. Under the Kyowa Kirin brand, the employees from 36 group companies across North America, Europe and Asia/Oceania unite to champion the interests of patients and their caregivers in discovering solutions wherever there are unmet medical needs. Since 2018, the company has received approval from the U.S. Food and Drug Administration for three first-in-class medicines. You can learn more about the business of Kyowa Kirin at https://www.kyowakirin.com.

About NOURIANZ (istradefylline) tabletNOURIANZ is an orally administered, selective adenosine A2Areceptor antagonist approved in the U.S. for adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease (PD) experiencing "OFF" episodes. The product has been marketed in Japan under the brand name NOURIASTsince May 30, 2013. In Japan, NOURIASTis indicated for the improvement of the "wearing-off" phenomenon in patients with Parkinson's disease on levodopa-containing preparations.

About Parkinson's diseaseParkinson's disease is a progressive, neurodegenerative disease characterized by motor symptoms such as tremors, rigidity, slow movement and postural instability. It is thought to be caused by progressive degeneration associated with decreased levels of dopamine in certain parts of the brain, i.e., the substantia nigra and striatum.

NOURIANZ and NOURIASTare trademarks of Kyowa Kirin Co., Ltd.

1NOURIANZ (istradefylline) Prescribing Information [Package Insert]. Kyowa Kirin Co., Ltd.; 2019.2Isaacson SH, Hattori N, Truong D, et al. Impact of Baseline Dyskinesia on the Safety and Efficacy of Istradefylline, an Adenosine A2A Receptor Antagonist, in Patients with Parkinson's Disease: a Pooled Analysis of 8 Clinical Studies. Data presented at: 6th Congress of the European Academy of Neurology: May 23-26, 2020; Virtual.3FDA approves new add-on drug to treat off episodes in adults with Parkinson's disease. U.S. Food and Drug Administration (2019). https://www.fda.gov/news-events/press-announcements/fda-approves-new-add-drug-treat-episodes-adults-parkinsons-disease. Accessed April 2020.4Parkinson's Disease. National Institute on Aging. https://www.nia.nih.gov/health/parkinsons-disease. Accessed April 2020.5Schapira AH, Emre M, Jenner P, Poewe W. Levodopa in the treatment of Parkinson's disease. Eur J Neurol. 2009;16:982989. doi: 10.1111/j.1468-1331.2009.02697.x.6Hickey P, Stacy M. Available and emerging treatments for Parkinson's disease: a review. Drug Des Devel Ther. 2011;5:241-254.doi: 10.2147/DDDT.S11836

Contact: Lauren Walrath, Senior Director, Public Affairs North America, [emailprotected]

SOURCE Kyowa Kirin, Inc.

https://www.kyowakirin.com

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Impact of Baseline Dyskinesia on Safety and Efficacy of NOURIANZ (istradefylline) in Patients with Parkinson's Disease Presented During...