New way to optimize sleep, light exposure can reduce jet lag, improve alertness

Whether you’re traveling for work or for fun, nothing ruins the start of a trip quite like jet lag. Engineers affiliated with the Lighting Enabled Systems & Applications (LESA) Center at Rensselaer Polytechnic Institute have developed a way to deliver personalized advice using smart wearable technology that would help travelers adjust more quickly.

In a series of articles, including one published today in PLOS ONE, the researchers explain how they have developed and demonstrated a series of algorithms that can analyze biometric information recorded by a smart device and then recommend the best combination of sleep and light to help a person readjust their circadian rhythm.

“Using these algorithms and a mathematical model of a person’s circadian rhythm, we have the ability to compute the best light to adjust your circadian rhythm and foster your well-being. This opens the opportunity to create a smart and healthy environment,” said Agung Julius, an associate professor of electrical, computer, and systems engineering at Rensselaer and one of the authors on this paper.

The same, he said, goes for determining the sleep — both how much and when it should be received — a person needs.

Circadian rhythms are master internal clocks that help regulate many of our physiological processes, including sleep, metabolism, hormone secretion, and even how our brain functions. Energy, alertness, and other biological processes can suffer when that rhythm doesn’t align with the clock one is actually trying to follow.

The Department of Defense is funding this research because of the benefits the researchers’ findings could bring to the alertness of service members.

“The circadian and sleep processes are also very tightly related to your mental state and how alert you are,” Julius said. “If you try to do something in the wrong time of day, your alertness is not going to be as effective as if you do it in the right time of day as defined by your circadian clock.”

Julius explained that a person’s circadian rhythm variation is typically determined using information gathered from a blood or saliva test that measures levels of the hormone melatonin. The problem with that traditional approach is that obtaining the results takes time and doesn’t allow for instant analysis.

The LESA team, which includes John Wen, head of the Department of Electrical, Computer, and Systems Engineering at Rensselaer and co-author on this paper, has been working on algorithms that process data — like heart rate and body temperature — that can be collected from wearable smart technology and converted into an estimate of a person’s circadian rhythm variation.

“The question is whether that kind of data can give you as accurate an estimation as the clinical standard,” Julius said.

What the team has found and demonstrated is that the estimates their algorithms generated are in line with clinical hormone measurement techniques. Julius said these findings are indicative that the team’s approach works.

“This work is important, because it characterizes the fundamental processes the human body uses to synchronize circadian and sleep processes. By developing biosensing analytics to characterize circadian phase, it is now possible to optimize the efficient use of light with appropriate spectral properties to help optimize and maintain human health and performance,” said Robert Karlicek, the director of the LESA Center. “This will be important to other work related to lighting and health in LESA’s clinical research test beds at Thomas Jefferson University and the University of New Mexico.”

make a difference: sponsored opportunity

---

Story Source:

Materials provided by Rensselaer Polytechnic Institute. Note: Content may be edited for style and length.

---

Journal Reference:

1. A. Agung Julius, Jiawei Yin, John T. Wen. Time optimal entrainment control for circadian rhythm. PLOS ONE, 2019; 14 (12): e0225988 DOI: 10.1371/journal.pone.0225988

https://www.sciencedaily.com/releases/2019/12/191218153325.htm

The number of people who need renal replacement therapy is increasing

The ERA-EDTA Registry collects data on renal replacement therapy (RRT) from the national and regional renal registries in Europe and from countries bordering the Mediterranean. For the 2017 Annual Report, data sets from 53 national or regional renal registries in 37 countries were compiled. A total population of 694,024,000 people was analyzed.

The Registry’s 2017 Annual Report shows that, out of nearly 700 million people, 88,453 individuals began renal replacement therapy (RRT) in 2017, which is a proportion of 127 per million people (pmp). The mean age of these patients starting RRT was 63.4 years, whereby roughly a fifth (17,935 patients) had diabetes mellitus as primary renal disease. The incidence rate varied considerably among countries – the Kosovo had an adjusted incidence rate of 429 pmp, Greece 223 pmp, France 174 pmp, Switzerland 99 pmp and Estonia only 68 pmp. These differences can be explained partly because of differences in national resources that are available for RRT. A large part, however, is caused by differences in general population health and availability of preventive measures between countries across Europe.

85% of all patients started RRT with hemodialysis, 11% peritoneal dialysis and only 4% received a transplant right at the start of RRT and could thereby avoid a period on dialysis. “This is sad”, explains Professor Ron Gansevoort, Press Officer of the ERA-EDTA. “Kidney transplantation is the best renal replacement therapy from the medical point of view. Transplanted patients suffer from less comorbidities than dialysis patients and have a better outcome. Furthermore, transplanted patients experience a higher quality of life in general – with fewer complications and no need for strenuous treatment for more than four hours three days a week.” The main reason why patients cannot be transplanted right away is the scarcity of donor organs, which is dramatic in many European countries. “ERA-EDTA’s mission has always been to bring the best treatment to kidney patients. We therefore put a lot of effort into improving the situation. Together with EKHA (European Kidney Health Alliance), we have already addressed EU health policy and asked for a joint Pan-European information campaign. However, the results have been quite meagre so far.”

The small number of patients who receive a transplantation right away is not the only alarming fact revealed by the ERA-EDTA Registry data. “We also observe a rising incidence”, explains Professor Gansevoort. “In 2016, 121 pmp started renal replacement, in 2017 this number rose to 127 pmp.” The main reason is the demographic shift, the mean age of the general population is growing, and kidney diseases often occur in elderly people. “The risk of chronic kidney disease increases with age, so what we see here is not an abnormal development per se, but it is nevertheless a challenge we have to cope with. We have not seen an end to the demographic shift yet – people are still getting older.”

The number of patients in need of RRT will rise accordingly, too, thus posing a major challenge to our health systems: The annual costs per patient for hemodialysis (HD) are, for example, up to US$ 59,000 in Germany, US$ 84,000 in Belgium or US$ 71,000 in France . Strengthening prevention strategies for kidney disease, therefore, is not only in the interest of each patient who might be saved from needing renal replacement therapy, but is also in the interest of policymakers. “It is high time that the focus is put on the rising incidence of end stage chronic kidney disease”, concludes Professor Gansevoort.

Source:

ERA-EDTA

https://www.news-medical.net/news/20191219/The-number-of-people-who-need-renal-replacement-therapy-is-increasing.aspx

FDA Warns of Breathing Problems With Gabapentinoids

The FDA issued a warning that serious breathing difficulties may occur in patients taking gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) who have respiratory risk factors.

These risk factors include taking opioids or other drugs that depress the central nervous system (CNS), and conditions such as chronic obstructive pulmonary disease (COPD) that reduce lung function, the agency said. Elderly patients also are at higher risk.

“Reports of gabapentinoid abuse alone, and with opioids, have emerged and there are serious consequences of this co-use, including respiratory depression and increased risk of opioid overdose death,” Douglas Throckmorton, MD, deputy director for Regulatory Programs in the FDA’s Center for Drug Evaluation and Research, said in a statement.

The agency also is requiring updates to gabapentinoid labels to include new warnings of potential respiratory depressant effects, and “requiring the drug manufacturers to conduct clinical trials to further evaluate the abuse potential of gabapentinoids, particularly in combination with opioids, with special attention being given to assessing the respiratory depressant effects,” Throckmorton added.

Gabapentin and pregabalin have tripled in use from 2002 to 2015. The drugs have been approved for a variety of conditions including seizures, nerve pain, and restless legs syndrome, and both frequently are used for off-label indications.

Prescription use of gabapentinoids increased from 2012 to 2016, the agency reported. The estimated number of patients filling a gabapentin prescription annually climbed from 8.3 million to 13.1 million in that period, while the number filling a pregabalin prescription rose from 1.9 million to 2.1 million.

A substantial percentage of patient encounters in 2016 — 14% for gabapentin, 19% for pregabalin — also involved opioids, the FDA said. The agency has kept a watch on whether abuse or misuse of gabapentinoids is increasing.

Prescribers should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation if co-prescribing gabapentinoids with an opioid or other CNS depressant such as a benzodiazepine, the agency noted.

“Our goal in issuing today’s new safety labeling change requirements is to ensure health care professionals and the public understand the risks associated with gabapentinoids when taken with CNS depressants like opioids or by patients with underlying respiratory impairment,” Throckmorton said.

“However, we do not want to unintentionally increase opioid use by turning prescribers away from this class of pain medications,” he added.

https://www.medpagetoday.com/neurology/generalneurology/84019

Takeda Strikes Potential $1 Billion Oncology Deal with Turnstone

One day after Takeda and Cerevance teamed up to tackle diseases of the gastrointestinal tract, the company forged a collaboration worth up to $1 billion with Turnstone Biologics to tackle a number of cancer indications using that company’s vaccinia virus platform.

The two companies will pair up to advance Turnstone’s lead program, RIVAL-01 in multiple cancer studies and will also work together to identify additional novel product candidates based on Turnstone’s vaccinia virus platform for future independent development.

Under terms of the agreement, Takeda will provide Turnstone with $120 million in an upfront payment, as well as near-term milestones and future equity investment. Takeda gains an exclusive worldwide license to co-develop and co-commercialize RIVAL-01 with Turnstone. Global costs and profit-sharing will be on a 50:50 basis, the companies said. Takeda will also have the right to license select candidates that result from the other studies based on the vaccinia virus platform. If everything hits, Turnstone will be eligible to receive an additional $900 million in potential development, regulatory and commercial milestones across all programs, and receive royalty payments on net sales of each licensed product.

Takeda’s Chris Arendt, head of the company’s oncology drug discovery unit, said the Turnstone platform provides the potential to harness the power of the immune system in unique ways in order to address some of the most difficult-to-treat cancers.

Turnstone’s proprietary vaccinia virus platform has been engineered for enhanced immune-stimulation and tumor cell selectivity, potent oncolysis, and large transgene carrying capacity, according to the company. Lead asset RIVAL-01 consists of the vaccinia virus backbone encoding transgenes for Flt3 ligand, anti-CTLA-4 antibody, and IL-12 cytokine. The transgenes are designed to be expressed when the vaccinia virus enters and replicates in cancer cells throughout the body. The resulting local production of these therapeutics at the site of tumors add to the inherent oncolytic and microenvironment-modifying properties of the virus, to form a powerful multi-modal attack on the disease, the company said.

Turnstone R&D chief Mike Burges said the company’s platform is “is exquisitely engineered to enhance virus-mediated cancer cell killing and better harness the power of the immune system against tumors.” With RIVAL-01, Burgess said the aims it to deliver “three powerful immune-modulating agents to primary and metastatic tumor sites and limit their expression to the local tumor environment, reducing the potential for systemic toxicity.” The therapy has the potential to drive immune activity in the tumor that is not otherwise achievable, Burgess added in a statement.

Sammy Farah, president and chief executive officer of New York-based Turnstone, said the collaboration with Takeda will combine the company’s “exciting viral immunotherapy platform” with Takeda’s immuno-oncology research development expertise. The potential medications that can come from this collaboration will have the potential to address critical gaps in the treatment of cancer that exist today, Farah said.

“Importantly, this partnership allows us to co-develop and co-commercialize RIVAL-01 together with Takeda, enabling us to broaden our internal capabilities and expand our viral immunotherapy pipeline, while retaining our ability to independently develop other candidates based on this technology,” Farah said in a statement.

https://www.biospace.com/article/turnstone-biologics-partners-with-takeda-in-potential-1-billion-deal/

Novartis to Offer World’s Most Expensive Drug for Free Via Lottery

Novartis AG launched a lottery-style program to give away doses of its pricey gene therapy for free, drawing criticism from patient groups that say that is an inappropriate way to distribute a lifesaving treatment aimed at babies.

Zolgensma, a one-shot cure for a deadly inherited disease whose victims cannot control their muscles, is so far sold only in the U.S. at a price of $2.1 million, making it the world’s most expensive drug. The so-called global managed-access program is aimed at providing Zolgensma to a limited number of spinal muscular atrophy patients outside the U.S.

Under the program, doctors can submit requests for the treatment, with eligible patients entered into a draw every two weeks for free doses. AveXis, the Novartis unit that makes the drug, said it aimed to distribute around 100 free doses a year as long as production capacity allows. Around 1,600 children are thought to have the most severe form of SMA, known as Type 1, in Europe alone.

However, patient groups criticized the move, highlighting the thorny ethical issues that companies face when providing unapproved treatments for free.

“It’s really too crude,” said Kacper Rucinski, co-founder of U.K.-based patient-advocacy group TreatSMA. “They are making patients compete. Which will be the lucky one? That’s not helpful.”

Olga Germanenko, a board member of SMA Europe, an umbrella organization for patient-advocacy groups from across the continent, said the lottery made Zolgensma “look like a prize.”

Patients would have instead welcomed a program that prioritized the patients or countries with the highest needs, said Mr. Rucinski. In some places, patients can already get a rival SMA treatment called Spinraza, made by Biogen Inc. Novartis’s program doesn’t prioritize countries where Spinraza isn’t routinely available or patients who don’t respond to Spinraza.

A spokesman for Novartis said the company was advised to take the lottery approach by a group of bioethics experts, who were concerned that creating complicated criteria could unfairly discriminate against some patients. “In the end we’re dealing with a difficult ethical dilemma,” he said. “Unfortunately, there is no perfect solution.”

Novartis had faced high demand from patients outside the U.S. to provide the treatment free of charge in some cases, although local regulations may prevent some countries from adopting the program.

Managed-access programs are common, especially for life-threatening conditions where the treatment in question is considered a breakthrough. However, companies typically use a criteria based on medical need to decide who should receive the treatment.

Novartis said it couldn’t provide Zolgensma to every eligible patient because of limited supply. The treatment is made at one plant in the U.S., though the company hopes to open up two more manufacturing sites within the next year.

Zolgensma is one of the first in a new wave of treatments known as gene therapies that promise to cure certain inherited diseases in a single treatment by providing a working copy of the faulty gene.

It went on sale in the U.S. earlier this year and is under review by regulators in Europe and Japan, with decisions expected next year. Once a country or region approves Zolgensma, Novartis will stop offering the lottery program there.

Despite its eye-catching price tag, Novartis has said Zolgensma has sold well since its launch in late May, overcoming concerns about whether insurers would cover the treatment as well as a data-manipulation scandal at the unit that makes it.

Novartis has defended Zolgensma’s price on the grounds it costs less than Spinraza — the rival treatment — in the long term. Spinraza is a lifelong treatment that costs $750,000 for the first year and then $375,000 for each year thereafter.

https://www.marketscreener.com/NOVARTIS-9364983/news/Novartis-to-Offer-World-s-Most-Expensive-Drug-for-Free-Via-Lottery-29751196/

Amgen files U.S. application for Rituxan biosimilar

Amgen (NASDAQ:AMGN) has submitted a marketing application to the FDA seeking approval of AMG 798, a biosimilar to Roche’s (OTCQX:RHHBY) Rituxan (rituximab).

The company is collaborating with Allergan (NYSE:AGN) on four biosimilars, two of which are approved in the U.S. It has primary responsibility for development, manufacturing and initial commercialization.

https://seekingalpha.com/news/3527597-amgen-files-u-s-application-for-rituxan-biosimilar

Concert Pharma reports positive data on once-daily dosing of CTP-543

Results from a just-completed Phase 2 clinical trial comparing two dosing regimens (8 mg twice daily vs. 16 mg once daily) of Concert Pharmaceuticals’ (NASDAQ:CNCE) CTP-543 in patients with moderate-to-severe alopecia areata (autoimmune disorder characterized by hair loss) were consistent with a previous mid-stage study evaluating the 8 mg regimen.

No new safety signals were observed.

Additional data will be submitted for presentation at a future medical conference.

Phase 3 studies are next up.

https://seekingalpha.com/news/3527559-concert-pharma-reports-positive-data-on-daily-dosing-of-ctpminus-543