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Repetitive Head Impacts Increases the Hazard of Death Among NFL Players – Neurology Advisor

Increasing repetitive headimpacts are associated with an increased hazard of death among professionalfootball players in the National Football League (NFL), a study in the JAMANetwork Open suggests.

The study was aretrospective review of all-cause mortality data from 14,366 football playersduring the 1969 to 2017 NFL seasons. Only data up to July 1, 2018, were includedin this analysis. Pro Football Reference records were used to identify thenumber of seasons and games played by participants. The exposure of interestwas the professional football cumulative head impact index (pfCHII), which wascalculated for 13,912 NFL players. The pfCHII, which quantified the amount andseverity of repetitive head impacts, combined the reported football historywith helmet accelerometer studies in professional players.

A total of 763 of the 14,366players in the initial cohort (5.3%) had died over the follow-up period. Themedian pfCHII among the 13,912 players in the pfCHII analysis was 32.63(interquartile range, 13.71-66.12). The pfCHII scores ranged from 14.18 forwide receivers to 84.34 for offensive linemen. For every 1-log increase inpfCHII, there was a significant increase in the hazard of death for the 1969 to2017 football seasons (hazard ratio [HR], 2.02; 95% CI, 1.21-3.37; P=.01). Additionally, the quadratic pfCHII was significant for the hazard ofdeath during this period (HR, 0.91; 95% CI, 0.85-0.98; P =.01).

Limitations of this study included the variability in measurements of repetitive head impacts across the specified seasons, the inability to adjust for race/ethnicity, and the inclusion of only professional football players vs players who participated in college, high school, or youth football programs.

The investigators of thisstudy suggest that the reduction in repetitive head impacts from playingfootball or other activities through additional rule and equipment changes maybe associated with reduced mortality.

Reference

Kmush BL, Mackowski M, Ehrlich J, Walia B, Owora A, Sanders S. Association of professional football cumulative head impact index scores with all-cause mortality among national football league players. JAMA Netw Open. 2020;3(5):e204442

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Early Extubation Tied to Better Outcome After Stroke Thrombectomy – Medscape

The shorter, the better when it comes to time spent on a ventilator for stroke patients who undergo mechanical thrombectomy, new research suggests.

A study of more than 400 patients showed that those who were extubated within 6 hours were more than twice as likely to have a better outcome than those extubated later. Also for these patients, the rate of developing pneumonia was lower.

Dr Simon Fandler-Hfler

These findings are important because data regarding ventilation time for stroke patients are "scarce," investigator Simon Fandler-Hfler, MD, Department of Neurology, Medical University of Graz, Austria, told Medscape Medical News.

"Our results indicate that patients with an anterior circulation occlusion, which account for 85% to 95% of all thrombectomies, should be extubated as early as safely possible," Fandler-Hfler said.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which was being held online because of the COVID-19 pandemic.

The study included 441 consecutive adult patients (mean age, 69 years) who underwent mechanical thrombectomy under general anesthesia as treatment foran anterior circulation large-vessel occlusion stroke. The patients were evenly matched with regard to sex.

The researchers categorized the participants into those who were extubated within 6 hours (early extubation) after thrombectomy, those extubated within 6 to 24 hours after (delayed extubation), and those extubated after more than 24 hours (late extubation).

The primary outcome was a favorable Modified Rankin Scale (mRS) score of 02 three months post stroke.

Although the median ventilation time was 3 hours, individually, it ranged widely from 1 to 530 hours. More than half of the patients (57.7%) were extubated early; 27.7% were in the delayed group, and 14.5% were in the late group.

Results showed that 42.6% of patients had a favorable outcome.

When analyzed as a continuous variable, ventilation time strongly correlated with mRS scores at 3 months (P < .001).

Significant predictors of adverse outcomes included age (P < .001), hypertension (P < .001), chronic heart disease (P = .02), diabetes mellitus (P = .002), atrial fibrillation (P = .001), and National Institutes of Health Stroke Scale (NIHSS) score at admission (P < .001).

Patients who underwent successful recanalization also had significantly better outcomes.

Of those extubated early, about three quarters had a good outcome; fewer than half (45%) had bad outcomes, Fandler-Hfler reported.

"We found that those patients with early extubation had significantly better outcomes," he said, compared with those whose extubation was delayed (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.53 3.76; P < .001).

Early pneumonia within the stroke unit or neurointensive care unit was strongly associated with ventilation time. For the patients in the early group, the rate of pneumonia was only 9.6%, compared with 20.6% for the delayed group.

Fandler-Hfler found the results for those who received less ventilation "surprising" and said the results could have an impact on clinical practice.

Chronic heart disease and pneumonia were more prevalent in the late group than in the other groups. Also, for the patients in the late group, NIHSS scores were significantly higher at admission, and successful recanalization was less frequent.

For with regard to mRS scores at 3 months, participants who underwent ventilation the longest "really had very bad outcomes," Fandler-Hfler said.The mortality rate for those patients was more than 50%.

He acknowledged that "it was no surprise that patients who were intubated for several days had worse outcomes."

The researchers also examined the reasons why some patients were extubated later than others. Stroke complications, including brain edema, insufficient alertness, seizures, and respiratory insufficiency, played a role.

Delayed extubation was also strongly associated with admission "outside of core working hours," when fewer doctors and nurses were available, Fandler-Hfler said.

Within core hours, almost 90% of patients were extubated early; but outside these hours, only 50% of patients were extubated early (OR, 6.6; 95% CI, 3.59 10.22; P < .001)

"This means that an intervention with potential complications such as an extubation could, and often will, be delayed until the next day if it's not deemed necessary to do it straightaway," said Fandler-Hfler.

There are usually ongoing discussions about which interventions should be performed as soon as possible and which can wait until the next day, he noted.

"Our research indicates that the specific intervention of extubation after stroke thrombectomy should be performed as early as safely possible," he said.

This can take place after the intervention in the angiography suite or directly after admission to an intensive care unit after the procedure, Fandler-Hfler added.

Findings from the study were published recently in the European Journal of Neurology.

Fandler-Hfler has reported no relevant financial relationships.

Congress of the European Academy of Neurology (EAN) 2020: Oral session. Presented May 25, 2020.

Eur J Neurol. Published online March 17. 2020. Abstract

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The Gut-Brain Connection – HSC Newsbeat

University of New Mexico scientists played a key role in new research demonstrating for the first time that changes in the gut microbiome may help trigger human neurovascular disease.

Members of New Mexico Hispanic families who share a genetic predisposition for dangerous brain bleeds known as cerebral cavernous malformations (CCM) were recruited for the study, published earlier this week in Nature Communications.

The research team found that high levels of inflammation-promoting bacteria in the digestive tract secrete lipopolysaccharide molecules, which in turn drive clusters of abnormally dilated vessels in the brain to leak blood into the surrounding tissue.

In severe cases, the condition causes seizures or stroke-like symptoms and often requires surgery, said Atif Zafar, MD, an assistant professor in the UNM Department of Neurology.

Many CCM cases appear to arise spontaneously, but Zafar and Leslie Morrison, MD, a retired professor of Neurology, have previously shown that people with northern New Mexican Hispanic ancestry are at a somewhat higher risk because of a long-ago mutation in a single ancestor that has been passed down through generations.

Both contributed to the new study, along with two dozen other researchers from The University of Chicago, the University of Pennsylvania, University of California, San Francisco and the Angioma Alliance.

These families willingness to participate in studies has allowed the researchers to build a rich database used in the new study, which was led by UChicago scientists, Zafar said. Our main strength was the number of familial CCM cases that UNM has, while the Chicago group is the largest CCM patient site overall.

UNM is one of the few CCM Centers of Excellence in the world, said Zafar, who serves as the centers director. "We want to thank dozens of our New Mexican families, patients and healthy folks with the diagnosis of familial and sporadic CCM who participated in this trial and are the main force behind the advancements in the field.

Patients shared stool samples and their medical records for the study, which found close correlations between the prevalence of certain bacterial strains in the gut and the severity of their symptoms.

The researchers suggest that altering the diet or microbiome composition might be a way of treating the condition.

"The next step includes confirming the mini-variations that may be present even within the CCM population and to see if we can create an algorithm that can correlate how these specific gut microbiomes manipulate the severity of the disease in the CCM population, Zafar said. We still have a lot of work to do.

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Ligand Announces Icagen’s Expansion of Collaboration with Roche to Develop and Commercialize Therapies for Neurological Diseases – BioSpace

Collaboration initiates second Roche program utilizing Icagens ion channel drug discovery platform

SAN DIEGO--(BUSINESS WIRE)-- Ligand Pharmaceuticals Inc. Incorporated (NASDAQ: LGND) and Icagen, a Ligand Company, announced today the expansion of Icagens license agreement with Roche to develop and commercialize small molecule ion channel modulators for the treatment of neurological disorders, by adding a second program to the agreement. The new program incorporates Icagens ion channel technology and expertise and is directed at a specific novel ion channel target relevant to neurodegenerative disease. The new program is in addition to ongoing work on another novel CNS target.

Icagens collaboration with Roche was a key value-driver in the acquisition of the Icagen business, and we are very pleased to see this expansion and extension of the relationship, said John Higgins, Chief Executive Officer of Ligand. This type of deal fits perfectly within the Ligand strategy to establish and leverage partnerships with global leaders in the industry as they look to access our technology for their drug discovery and development needs. The Icagen team has been a great addition to Ligands business.

"We are pleased to extend and expand our collaboration with Roche and its drug discovery team in Basel," said Icagen Site Head Douglas Krafte, PhD. "Our initial neurology program with Roche continues to make great progress and we hope to assist Roche in bringing multiple meaningful therapies to patients in areas of neurological disease with major unmet needs through both our initial and this new program."

Terms of Expanded Icagen and Roche Collaboration

Under the terms of the license agreement, Roche made a cash upfront payment and will provide research funding to Icagen. In addition, Icagen is eligible to potentially receive development and commercial milestone payments of up to $274 million and royalty payments should a drug be commercialized from any of the collaborations programs.

Icagen will be responsible for most preclinical activities up to lead optimization with both Icagen and Roche applying resources to identify candidates for entry into IND-enabling studies. Roche will be responsible for the further development and commercialization of the program.

About Icagen, a Ligand Company

Icagen, a Ligand Company, is a preclinical drug discovery company focused on ion channel and transporter drug discovery with research facilities located in Durham, N.C. Icagen partners with the pharmaceutical industry to develop first-in-class therapies for patients in need, typically under arrangements in which we work closely with our partners through the time of clinical candidate selection and our partners are responsible for the clinical development and commercialization. Icagen, a Ligand Company, is a subsidiary of Ligand Pharmaceuticals Incorporated. For more information, please visit http://www.ligand.com.

About Ligand Pharmaceuticals

Ligand is a revenue-generating biopharmaceutical company focused on developing or acquiring technologies that help pharmaceutical companies discover and develop medicines. Our business model creates value for stockholders by providing a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable, diversified and lower-risk business than a typical biotech company. Our business model is based on doing what we do best: drug discovery, early-stage drug development, product reformulation and partnering. We partner with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) to ultimately generate our revenue. Ligands OmniAb technology platform is a patent-protected transgenic animal platform used in the discovery of fully human mono- and bispecific therapeutic antibodies. The Captisol platform technology is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. The Vernalis Design Platform (VDP) integrates protein structure determination and engineering, fragment screening and molecular modeling, with medicinal chemistry, to help enable success in novel drug discovery programs against highly-challenging targets. Ab Initio technology and services for the design and preparation of customized antigens enable the successful discovery of therapeutic antibodies against difficult-to-access cellular targets. Icagen, a Ligand Company, focuses on ion channel and transporter drug discovery as it partners with the pharmaceutical industry to develop first-in-class therapies for patients in need. Ligand has established multiple alliances, licenses and other business relationships with the worlds leading pharmaceutical companies including Amgen, Merck, Pfizer, Sanofi, Janssen, Takeda, Gilead Sciences and Baxter International. For more information, please visit http://www.ligand.com.

Follow Ligand on Twitter @Ligand_LGND.

Forward-Looking Statements

This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Words such as plans, believes, expects, anticipates, and will, and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding the potential benefits of the Icagen/Roche license and collaboration agreement programs. Actual events or results may differ from Ligand's expectations due to risks and uncertainties inherent in Ligands business, including, without limitation, that there can be no assurance that either the original or expansion Roche program with Icagen will be able to successfully identify any desirable drug candidates or that any drug candidates developed in such programs would be clinically or commercially successful, all of which might result in the potential milestone payments and royalties not being earned. The failure to meet expectations with respect to any of the foregoing matters may reduce Ligand's stock price. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases available at http://www.ligand.com as well as in Ligand's public periodic filings with the Securities and Exchange Commission available at http://www.sec.gov. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release, including the possibility of additional contract revenue we may receive. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200529005042/en/

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Ligand Announces Icagen's Expansion of Collaboration with Roche to Develop and Commercialize Therapies for Neurological Diseases - BioSpace

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Overcoming Untreated Epilepsy in the Developing World: the Way Forward – WFN News

The medical world thinks of the developed and developing societies in terms of diagnostic and treatment differences. However, there are realities that are common to both spheres concerning most medical conditions.

As a medical student, one would read of common disorders that were not being treated. Epilepsy was a striking example. In many rural Indian communities, up to 90 epilepsy patients out of every 100 were not getting treatment. In bureaucratese, this was a treatment gap of 90 percent.

The treatment of epilepsy has since evolved. Over two-dozen antiepileptic drugs are currently available. Many drugs are off patent and generically manufactured, and available in India and other developing nations at reasonable prices. But the epilepsy treatment gap of up to 90 percent still exists in many rural Indian communities! So, why has nothing changed for the lot of millions of epilepsy patients?

Let us humanize the numbers. By using calculations from an often-quoted epilepsy prevalence figure of 1 percent of the population, at least 12 million Indians are struggling with epilepsy.1 Large prevalence studies are unavailable, and many experts agree that this number is more likely to be closer to 15 million or even higher. This implies that more than 10 million epilepsy patients in India are untreated. Extrapolating worldwide, there are more than 50 million epilepsy patients and at least 40 million of these reside in developing countries. The estimate is that 75 percent of patients in developing countries are outside the domain of any kind of effective treatment. This implies at least 30 million untreated persons.

Ironically, epilepsy is one of the relatively easily controllable neurological diseases.

What is life like with untreated epilepsy? Most persons with epilepsy who do not have any other neurological illness are essentially normal at all times other than during their seizures. A seizure generally lasts for a few minutes during which, amongst other things, the person is unaware of his or her surroundings, and after which the person may remain confused for a variable amount of time or may sleep off the effects. In either case, the individual is back to normal within a few hours, often without even requiring a trip to the doctor's clinic or the emergency room.

Then what is the great problem about having untreated active epilepsy with an occasional seizure? Imagine having brief episodes of unawareness just once or twice in a month, in six months or even in a year, but not knowing when these would happen. So, you may be driving to work, crossing the street, climbing a tree, in bed with your partner, swimming in the pool, or speaking mid-sentence in that all important meeting. Suddenly, out of the blue, you start convulsing or just fidgeting with your buttons or speaking in an unintelligible jargon or wet your clothes in full public gaze. How would it feel to know that you had done either of these, and then have to go back to the same people in front of whom this had happened? Well, that is assuming that these people agree to work or socialize with you after witnessing a seizure.

The economic impact of untreated epilepsy is formidable in all societies. Many untreated epilepsy patients remain unemployable, especially if local attitudes consider it to be a contagious disease, a mental illness, or a demonic possession. Thus, they are removed as contributors to the economy. Even if they are poor and have minimum wage jobs, this still adds up to a substantial amount of money loss because of the millions affected.

There are other grave consequences of untreated epilepsy. If the patient is of school or college age, they are very likely to have to drop out. This is either due to their parents' fear that their child may be injured during a seizure, or on the insistence of teachers. With limited scope for education, landing a good job later in life is subsequently reduced. The intrigue and misinformation surrounding epilepsy reduces social acceptance of patients. Any relationship, including a stable marriage, especially for women with epilepsy, is unlikely. Abandonment of women with epilepsy and their children from marital relationships is common. Such women, with little or no education, no skills and sometimes also with small children to take care of, are often left at the mercy of an impoverished community.

So, is epilepsy difficult to treat? No. Epilepsy is a relatively easy disease to treat in most patients. The diagnosis is clinical and based upon eliciting a history of stereotyped episodes during which the patient may behave abnormally, have involuntary movements or jerks, generally become unaware of his surroundings and then recover in a short time. After the clinical diagnosis, a couple of investigations EEG and brain imaging may be done. Investigations may help in deciding the best anti-epileptic drug, in prognosticating how long the treatment is likely to be needed, and how responsive to treatment the patient's epilepsy might be.

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(At time of publication, May 2016) Mamta Bhushan Singh, MD, DM is an additional professor, department of neurology, All India Institute of Medical Sciences, New Delhi, India.

Michael Finkel is a retired neurologist, and a member of the AAN, Child Neurology Society, ENS, EFNS, and BMA. He is a fellow of the AAN..

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COVID-19: Responding to the business impacts of Neurology Devices Market: New Investment Opportunities Emerge to Augment Segments in Sector by 2029 -…

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COVID-19: Responding to the business impacts of Neurology Devices Market: New Investment Opportunities Emerge to Augment Segments in Sector by 2029 -...

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