Body

U.S. Medicare patients with multiple sclerosis often pay, on average, nearly $7,000 out of pocket to treat their condition each year. And, even though drug companies have provided no new treatment breakthroughs, the price of these disease-modifying medications is rising by 10% to 15% each year for the past decade.

To find out why, a team of researchers at Oregon Health & Science University and the OHSU/Oregon State University College of Pharmacy recruited four pharmaceutical industry executives to speak confidentiality. In a study published today in the journal Neurology, the executives painted a frank picture of the rationale behind the price of medication available to people with MS.

"I would say the rationales for the price increases are purely what can maximize profit," one executive said. "There's no other rationale for it, because costs [of producing the drug] have not gone up by 10% or 15%; you know, the costs have probably gone down."

The executives acknowledged their companies' unique societal position in delivering medications to improve human health. However, each executive pointed out that their business model depends on generating a profitable return on investment to shareholders.

"The most surprising thing was how unsurprising it was," said lead author Daniel Hartung, Pharm.D., M.P.H., associate professor in the OHSU/OSU College of Pharmacy. "There was not this secret, complicated algorithm that these companies used to drive up prices."

The researchers did find some key themes.

Start high and go higher

The researchers noted that the U.S. health care system appears to be unique in its capacity to absorb continual price increases. Executives noted that in the world's second-biggest market - Europe - the price of a drug is typically highest when it launches and then declines over time.

The opposite appears to be the case in the U.S.

"When you're making these decisions you're looking at the whole world," one executive said. "And it is only in the United States, really, that you can take price increases. You can't do it in the rest of the world. In the rest of the world, prices decline with duration in the marketplace."

American consumers foot the bill

Prices outside the U.S. not only drop due to market considerations, but they're held in check by single-payer health systems with fixed resources. In this way, one participant suggested that American patients ultimately make up for potential losses in other markets around the world.

"The rest of the developed world is subsidized by the U.S. consumer," the executive said.

High price says "quality"

The price of a new drug reflected the price already set by competitors selling existing drugs that treated similar conditions, regardless of the cost of research and development. In fact, executives feared that undercutting competitors with a lower price - a hallmark of a free market - would instead undermine the attractiveness of their product.

"We can't come in at less," one of the executives said. "That would mean we're less effective, we think less of our product, so we have to go more."

Co-author Dennis Bourdette, M.D., chair of neurology in the OHSU School of Medicine, said the study provides a new perspective to public discourse around pharmaceutical pricing.

"The frank information provided by these executives pulls back the curtain of secrecy on how drug price decisions are made," said Bourdette, who also directs the OHSU Multiple Sclerosis Center. "We see that it is indeed the race to make more money that is driving up drug prices and nothing more."

SEATTLE, November 25, 2019 - A collaboration at University of Michigan is taking a unique approach to fluid mechanics by teaching it through dance. Fluid mechanics professor Jesse Capecelatro and choreographer Veronica Stanich, both from the University of Michigan, teamed up to create Kármán Vortex Street, a dance improvisation guided by physics properties.

"Social dances, such as tango, have a collection of rules that maintain structure, both collectively among all dancers and individually between pairs of dancers, that enable a coherent flow," said Capecelatro. "Examples include the specific connection and embrace between dancers, maintaining a line of dance, establishing an axis of rotation during turns, and so on. A similar set of rules exists in fluid mechanics."

Capecelatro will discuss what makes dance and mechanics such an unlikely but complementary pair at the Washington State Convention Center in Seattle at 8:39 am on Nov. 25. The talk is a part of the American Physical Society's Division of Fluid Dynamics 72nd Annual Meeting, which is one of the largest gatherings in the world for fluid dynamics.

Merging physics and choreography was tricky. Capelcelatro said he spent time teaching basic principles in fluid mechanics to the dancers.

"The difficulty comes in attempting to simultaneously capture the relevant physics while keeping the dance interesting and aesthetic to watch," he said. "In the end, we produced a 'physics-constrained improvisation,' in which Veronica had complete freedom over the structure of the dance as long as a certain set of 'rules' I provided were met."

Though the collaboration is still in its early stages, Capecelatro will also discuss how they plan to assess Kármán Vortex Street's impact on students understanding of fluid mechanics.

"The dance was filmed last winter, and I am currently working with a videographer at the University of Michigan to put it all together," said Capecelatro. "The goal is to produce a 5-8 minute educational video that demonstrates flow past a cylinder at varying Reynolds numbers through dance. The video will be available to the larger fluid dynamics community to use in the classroom."

Bottom Line: Most 2- and 3-year-old children don't meet screen time guidelines and moms' screen usage was one of the associated factors reported in this observational study. Guidelines put forth by the World Health Organization and pediatric societies have recommended that preschool-age children get no more than one hour of screen time daily. This study used data collected from 2011 to 2014 to determine how common it is for children 2 and 3 years old to meet or exceed screen time guidelines and to describe individual and family factors associated with failing to meet those guidelines. There were 1,595 and 1,994 children at ages 2 and 3 years old, respectively, available for the analysis. Researchers report 79.4% of children at 2 years old and 94.7% at 3 years old didn't meet screen time guidelines. Factors associated with failing to meeting screen time guidelines at 2 years old were maternal screen time, being cared for at home compared with daycare, and the year data were collected. At 3 years old, only maternal screen time was a significant factor. Limitations of the study include maternal self-reported screen time and a lack of information on how screen time was used, such as viewing alone or with others. Initiatives aimed at reducing screen time by children need to consider family screen time habits.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Sheri Madigan, Ph.D., of the University of Calgary, Canada, and coauthors

(doi:10.1001/jamapediatrics.2019.4495)

Editor's Note: The article contains funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

MADISON - On January 31, 2019, an 11-year old boy in Japan went to a medical clinic with a fever. The providers there diagnosed him with influenza, a strain called H3N2, and sent him home with a new medication called baloxavir.

For a few days, he felt better, but on February 5, despite taking the medication, his fever returned. Two days later, his 3-year-old sister also came down with a fever. She, too, was diagnosed with H3N2 influenza on February 8.

An analysis of flu samples collected from her and her brother show she was sickened by a strain of H3N2 harboring a new kind of mutation -- one that Yoshihiro Kawaoka, University of Wisconsin-Madison professor of pathobiological sciences, says is resistant to baloxavir, is just as capable of making people sick as the non-mutated version, and is capable of passing from person to person.

He and colleagues describe this in a study published today [Nov. 25, 2019] in Nature Microbiology that examined the effects of baloxavir treatment on influenza virus samples collected from patients before and after treatment.

"We sequenced the entire viral genome of the 11-year-old boy with drug sensitive influenza virus (before treatment) and the sample from the girl that is drug resistant," says Kawaoka. "Out of 13,133 nucleotides, there was only one nucleotide difference between the two."

In other words, what distinguished the virus collected from the brother before treatment and the virus collected from the sister later was a single mutation, a single change in just one letter among the more than 13,000 found in the genetic code of the virus.

"It tells you the virus acquired resistance during treatment and transmitted from brother to sister," Kawaoka explains.

Baloxavir is part of a new class of antiviral drugs that targets the machinery flu viruses use to copy their genetic material inside their human or animal hosts. It was first licensed in Japan, the United States, and in Hong Kong in 2018 and 2019. In fact, baloxavir represented 40 percent of the market share of influenza drugs in Japan during the 2018-2019 flu season. It will soon be licensed in 20 more countries, Kawaoka says.

However, as he and his co-authors note in the paper, clinical trial data on the drug revealed that some patients infected with either H3N2 or H1N1 influenza who took baloxavir developed a mutation at position 38 of the polymerase acidic protein, part of the virus's machinery that is targeted by the drug. A previous study by another group showed that the particular mutation had not been described among 17,000 H3N2 virus samples catalogued prior to December 2018.

"The new drug is safe, it went through phase three and was approved safety-wise, but even during clinical trials, the emergence of drug resistance was identified," Kawaoka explains.

In fact, a previous study in pediatric patients showed the mutation appeared in the samples collected from nearly 1 in 4 of the 77 children enrolled who were also treated with baloxavir.

"Baloxavir-resistant viruses emerge with a relatively high rate in kids" says Kawaoka, also a professor of virology at the University of Tokyo.

Given these findings, Kawaoka and his research team in Japan were interested in understanding the properties of H3N2 and H1N1 viruses -- commonly circulating strains that cause illness in people --before and after treatment with baloxavir.

During the 2018-2019 flu season, they set up a system to collect respiratory samples from patients before and after they received the new drug.

For H1N1 influenza, the researchers tested 74 samples from patients before treatment (10 adults and 64 children), and 22 samples from patients both before and after treatment (7 adults and 15 children). There were no instances of mutation in any of the samples before treatment, but there were mutations in one adult and four children after, or in about 23 percent of patients.

For H3N2, the team tested 141 patient samples before treatment (40 adults and 101 children), and two of those from children possessed the mutation. They also studied 16 patient samples before and after treatment (4 adults and 12 children), in which they found no mutations in adult samples but four of the child samples had the mutation.

Often, viruses that gain mutations such as drug resistance sacrifice their ability to survive and spread well among their hosts. To understand whether this was true of the baloxavir-driven mutation, the researchers grew the mutant viruses in cell culture and learned it grows just as well as the non-mutated form.

They then tested the mutant H1N1 and H3N2 viruses in hamsters and learned that once the virus mutates, that mutation continues to be copied as new virus grows.

The team also tested the mutated viruses in ferrets and found the mutated form was capable of transmitting from infected animals to healthy ones. The severity of their illness from flu was also similar to the non-mutated form.

While it's unlikely the mutation will lead to widespread resistance around the world, Kawaoka says it could become a problem among family members in close proximity, and in facilities like hospitals and nursing homes. And, while children seem particularly prone to viral mutation with baloxavir treatment, it appears to occur less frequently in adults. It also quickly reduces the amount of virus in the systems of treated patients. "It's a good drug for adults," Kawaoka says.

And, he explains, patients with H1N1 or H3N2 that do develop resistance to baloxavir with treatment still do respond to other virus-fighting drugs.

"The drug resistant virus does transmit but there are so many influenza viruses worldwide and only a small population will be treated with this drug," Kawaoka says. "The vast majority remain drug sensitive."

A secondary analysis of the NRG Oncology clinical trial NRG-RTOG 0424, which initially reported a 73.1% 3-year overall survival rate, shows a decline in neurocognitive function (NCF) for half of the trial participants with high risk, low-grade gliomas (HR-LGGs) up to a year after receiving concurrent chemoradiotherapy with temozolomide. However, the analysis also concluded that on average the quality of life (QOL) of patients either remained stable or improved up to a year following temozolomide-based chemoradiotherapy treatment. These results were presented during the Plenary Session at the Society for Neuro-Oncology's (SNO) annual meeting in Phoenix, Arizona.

The Phase II trial, NRG-RTOG 0424, accrued 129 evaluable patients with HR-LGGs to receive daily temozolomide plus concurrent radiotherapy for 6 weeks followed by temozolomide for 12 cycles. Ninety-three patients completed at least one NCF and QOL measurement. NCF tests were performed at the end of treatment, again at 6 months following treatment, and at one year following treatment. Patients who completed NCF and QOL measurements had better clinician rated neurologic function than patients who did not complete the measurements. At 6 months after treatment, 55-59% of trial participants completed NCF and QOL measurements and 54-57% of participants completed measurements at one year following treatment.

"The secondary analysis of NRG-RTOG 0424 show that a large subset of patients are vulnerable to neurocognitive decline after chemoradiotherapy with temozolomide followed by adjuvant temozolomide.Similarly, while general QOL subscales were stable on average, a subset of patients reported diminished brain related QOL over time. Patients in the EORTC High Risk Group and with tumors crossing the midline were at greater risk for these adverse outcomes. These data further support the importance of monitoring neurocognitive function and QOL in trials comparing this treatment regimen with other active treatment regimens such as the CODEL trial (Alliance N0577; EORTC 26081-22086; NRG 1071; NCIC CEC.6) and for further developing our understanding of risk factors for such outcomes," stated Jeffrey S. Wefel, PhD, ABPP, of The University of Texas MD Anderson Cancer Center and lead author of the NRG-RTOG 0424 secondary analysis.

NCF deterioration occurred in 50% of patients at 6 months and 40% of patients at one year post-treatment. These NCF declines were most notable in Hopkins Verbal Learning Test (HVLT) and Trail Making Tests (TMTA and TMTB). Patients who exhibited deterioration in the HVLT at one year post-treatment had a significantly greater decrease in MOS-Cognitive Function (MOS-CF). FACT Emotional and Functional Well-Being subscales improved over time. No NCF test at baseline was independently associated with overall survival.

Promoting healthcare strategies that target both human and animal populations at the same time can save money, participant time and result in a two-for-one stop for health care services.

That's according to a new study by scientists at Washington State University's Paul G. Allen School for Global Animal Health.

The researchers treated roundworm infections in humans during their regular dog vaccinations campaign to eliminate rabies in 24 Tanzanian villages.

Their findings indicate the utility of integrating the treatment of humans and animals together, a concept known as One Health.

"We found there was no difference between the proportion of households that participated in the combined and stand-alone events," said Felix Lankester, clinical assistant professor and lead researcher on the project. "Suggesting that people we're not put off from attending a combined intervention where their children received treatment alongside their animals."

One Health delivery platforms like the one Global Animal Health researchers implemented in Tanzania could play an important role in the World Health Organization's global campaign to end the burden of neglected tropical diseases by 2030.

The WSU study, funded by the Bill & Melinda Gates Foundation Grand Challenges Award Program, was recently published in BMC Public Health.

Eight villages were provided clinics to treat roundworm, eight were provided clinics to vaccinate against rabies in dogs, and eight others were provided with integrated clinics to do both at the same time.

The integrated health clinics saw 91.5 percent of households per village receive roundworm treatment, while 82.5 percent of households attended clinics where roundworm treatments were provided alone.

For rabies vaccinations, the integrated health clinics saw 86.5 percent of households participate, compared to 90 percent of households when rabies vaccinations were offered alone.During focus group discussions with clinic attendees, 85 percent said the integrated clinics result in "two for one" health treatments.

In addition to reducing time for those who would have to travel to two health clinics, there were significant cost savings by combining the interventions for both diseases. The integrated health clinics cut transportation and advertising costs, lowering the cost of a deworming dose by an average of 12 cents and the cost of a rabies vaccination by an average of 66 cents.

By positioning the clinics outside of school grounds and offering treatment to the whole community rather than just children attending primary school, the study was also able to reach thousands of people, outside of the 7 to 13-year-old age range, who would have otherwise not been vaccinated by the United Republic of Tanzania's National Schools Deworming Programme.

"We need novel, cost-effective and complementary control strategies to try to tackle these neglected tropical diseases," Lankester said. "This study is important because it shows a One Health approach can reduce costs and reach more people."

CLEVELAND--Researchers at the Case Western Reserve University School of Medicine have identified that a gene critical to clearing up unnecessary proteins plays a role in brain development and contributes to the development of autism spectrum disorders (ASD) and schizophrenia.

The discovery, published today in Neuron, provides important insight into the mechanism of both diseases--a possible step toward finding how to treat the disorders.

Cullin 3 is a core component of an E3 ubiquitin ligase responsible for the cell's clearance of proteins. Mutations of its gene CUL3 have been associated with autism and schizophrenia. However, pathologic mechanisms of CUL3 deficiency have been unclear.

"CUL3 is abundant in the brain, yet little is known of its function," said Lin Mei, the Allen C. Holmes Professor of Neurological Diseases and chair of the Department of Neurosciences at the Case Western Reserve University School of Medicine. "Here, we show that CUL3 is critical for brain development and communication between cells in the brain."

Mei, also director of the Cleveland Brain Health Initiative, is the principal investigator with research assistants Zhaoqi Dong and Wenbing Chen. (The published research is titled "CUL3 deficiency causes social deficits and anxiety-like behaviors by impairing excitation-inhibition balance through the promotion of Cap-dependent translation.")

ASD is a complicated condition that includes difficulty with communication and social interaction, obsessive interests and repetitive behaviors. It affects 1 in 59 children in the United States, according to a recent report by the Centers for Disease Control. Schizophrenia affects about 1 in 100 people worldwide. However, autism and schizophrenia remain among the most mysterious disorders.

Mei and his team studied how CUL3 mutation impacts the brain in mouse models. The researchers were able to demonstrate that altering the gene in mouse models can cause similar social problems that appear in people with these disorders.

Normal mice would spend more time with a mouse over an inanimate object, Mei said. But CUL3-mutant mice couldn't differentiate between a mouse and an inanimate object, showing a problem with social preference.

In another test, normal mice would spend more time with an unfamiliar mouse over a familiar one. But CUL3-mutant mice couldn't remember seeing a familiar mouse, suggesting a problem of social memory. Also, CUL3-mutant mice were more anxious than normal mice.

Researchers at Beijing Normal University and the Louis Stokes Cleveland Veterans Affairs Medical Center contributed to the research.

More than one in ten cancer patients do not die from their cancer but from heart and blood vessel problems instead, according to new research published in the European Heart Journal [1] today (Monday). For some cancers, like breast, prostate, endometrial, and thyroid cancer, around half will die from cardiovascular disease (CVD).

Dr Nicholas Zaorsky, a radiation oncologist, and Dr Kathleen Sturgeon, an assistant professor in public health sciences, both at Penn State College of Medicine and Penn State Cancer Institute, Hershey, Pennsylvania, USA, and colleagues compared the US general population with over 3.2 million US patients who had been diagnosed with cancer between 1973 and 2012.

They used information contained in the Surveillance, Epidemiology and End Results (SEER) database to look at deaths from CVD, which included heart disease, high blood pressure, cerebrovascular disease, blocked arteries and damage to the aorta - the main artery carrying blood from the heart to the rest of the body. They adjusted their analyses to take account of factors that could affect the results, such as age, race and sex, and they looked specifically at 28 different types of cancer.

Among the 3,234,256 cancer patients, 38% (1,228,328) died from cancer and 11% (365,689) died from CVDs. Among the deaths from CVD, 76% were due to heart disease, and the risk of dying from CVD was highest in the first year after a cancer diagnosis and among patients younger than 35 years.

The majority of CVD deaths occurred in patients with cancers of the breast (a total of 60,409 patients) and prostate (84,534 patients), as these are among the most common cancers to be diagnosed. In 2012, 61% of all cancer patients who died from CVD were diagnosed with breast, prostate, or bladder cancer.

The proportion of cancer survivors dying from CVD was highest in bladder (19% of patients), larynx (17%), prostate (17%), womb (16%), bowel (14%) and breast (12%).

Patients who were more likely to die from cancer than from CVD were those with the most aggressive and hard-to-treat cancers, such as cancer of the lung, liver, brain, stomach, gallbladder, pancreas, oesophagus, ovary and multiple myeloma.

This is the largest and most comprehensive study looking at deaths from cardiovascular disease among patients with 28 types of cancer with over 40 years of data. Other, smaller studies have looked at the risk of death from CVD in some specific cancers, but none have looked at so many cancers with such a long follow-up.

Dr Sturgeon said: "These findings show that a large proportion of certain cancer patients will die of cardiovascular disease, including heart disease, stroke, aneurysm, high blood pressure and damage to blood vessels. We also found that among survivors with any type of cancer diagnosed before the age of 55 years, the risk of cardiovascular death was more than ten-fold greater than in the general population.

"Cancer survivors with cancer of the breast, larynx, skin, Hodgkin lymphoma, thyroid, testis, prostate, endometrium, bladder, vulva, and penis, are about as likely to die of cardiovascular diseases as they are to die of their initial cancer. The risk of death from cardiovascular diseases is several times that of the general population in the first year of diagnosis; sometimes, this risk decreases, but for most, this risk increases as survivors are followed for ten years or more. Increasing awareness of this risk may spur cancer survivors to implement healthy lifestyle behaviours that not only decrease their risk of cardiovascular disease, but also the risk of cancer recurrence."

Dr Zaorsky said: "Clinicians need to be aware that the majority of cardiovascular disease deaths occur in patients diagnosed with breast, prostate or bladder cancer. Thus, clinics that aim to open "cardio-oncology" centres should likely focus on the inclusion of these sites, followed by the other sites listed above. Additionally, primary care physicians and cardiologists may seek to control cardiovascular diseases more aggressively in cancer survivors.

"As the number of cancer survivors increase, the rate of cardiovascular deaths will continue to rise."

He said the reason why cancer patients were more at risk of dying from cardiovascular disease within the first year of diagnosis might be because when they entered the hospital system, other illnesses and problems, such as heart disease, lung dysfunction and kidney failure were also detected. It could also be explained by the aggressive treatment that follows a cancer diagnosis.

Dr Sturgeon concluded: "We hope these findings will increase awareness in patients, primary care physicians, oncologists and cardiologists as to the risk of cardiovascular disease among cancer patients and the need for earlier, more aggressive and better coordinated cardiovascular care."

Limitations of the study include the fact that the type of treatments the patients received was not known, including whether or not they had therapies that can be more toxic to the heart; the SEER database does not provide information on other illnesses and risk factors (such as smoking, alcohol consumption, obesity); the role played by socioeconomic status on the risk of cardiovascular death after a cancer diagnosis was not investigated. The study was carried out in the US population, so the risks may vary in different populations; the authors believe their findings are most applicable to Canada, Europe and Australia because the cancers and causes of death among cancer patients are similar.

In an accompanying editorial [2], Dr Jörg Herrmann, a cardiologist at the Mayo Clinic, Rochester, Minnesota, USA, writes: "The important work by Sturgeon et al. confirms that cancer patients have an on average 2-6 times higher CVD mortality risk than the general population. This is a key message that every cardiologist needs to hear. Secondly, the CVD mortality risk is evident throughout the continuum of cancer care, and entails an acute phase (early risk) and a chronic phase (late risk). In view of such grave and persistent consequences, a reactive management approach that comes into play solely when clinical presentations and complications arise is no longer in order. Rather, one would advocate for a proactive approach that starts before any cancer therapy is given and continues for a lifetime thereafter. Thirdly, even with the best possible cardio-oncology care, no difference in population-based outcomes may be achieved in patients with relentless malignancies, while for others it is of increasing significance."

SEATTLE, November 23, 2019 - Age-related macular degeneration is the primary cause of central vision loss and results in the center of the visual field being blurred or fully blacked out. Though treatable, some methods can be ineffective or cause unwanted side effects.

Jinglin Huang, a graduate student in medical engineering at Caltech, suggests inefficient fluid mixing of the injected medicine and the gel within the eye may be to blame. Huang will be discussing the effects of a thermally induced fluid mixing approach for AMD therapy during a session at the American Physical Society's Division of Fluid Dynamics 72nd Annual Meeting, which will take place on Nov. 23-26, 2019, at the Washington State Convention Center in Seattle.

The talk, "Thermal Effects on Fluid Mixing in the Eye," will be presented at 4:40 p.m. Pacific (U.S.) on Saturday, Nov. 23 in Room 612 as part of the session on biological fluid dynamics: microfluidics.

AMD usually starts as "dry" AMD, a disorder in which the macula -- the central part of the retina, responsible for sending information about focused light to the brain to create a detailed picture -- thins with age. Dry AMD is very common and is not treatable but may eventually evolve into "wet" AMD, which is more likely to result in vision loss. In wet AMD, abnormal blood vessels grow on the retina, leaking fluids under the macula. In the case of wet AMD, injections of medications called anti-vascular endothelial growth factor agents into the eye can help manage the disorder.

Huang said because the medication does not mix with the gel-like fluid in the eye -- the vitreous -- efficiently. Applying heat to the mixture can solve this problem.

"Because thermally induced mixing in the vitreous chamber can promote the formation of a circulation flow structure, this can potentially serve the drug delivery process," Huang said. "Since the half life of the drug is limited, this thermally induced mixing approach ensures that more drug of high potency can reach the target tissue."

To apply the thermally induced mixing technique, no changes in the injection procedure are needed. An additional heating step after the injection is all that is required.

"It can potentially reduce the amount of drug injected into the vitreous," said Huang. "It is definitely easy to be implemented."

Huang and her colleagues hope this work will inspire eye doctors to develop better treatment techniques and improve patient experiences.

Tsukuba, Japan - Insomnia is one of the most common sleep disorders, and is most commonly treated with hypnotics. However, hypnotics have motor and cognitive side effects. According to new findings from the University of Tsukuba in Japan, suvorexant, which is a recently approved and more targeted treatment, has fewer physical side effects.

The most common hypnotic agents for the treatment of insomnia are γ-aminobutyric acid (GABA) agonists, which bind to GABAA receptors to enhance the action of the inhibitory neurotransmitter, GABA. GABAA receptors are widespread, which means that GABA agonists inhibit neurons throughout the brain and spinal cord, including those that are not involved in sleep. This is not the case for suvorexant, which was approved as a treatment for insomnia in the US and Japan in 2014. According to the new study published in PNAS on November 11, suvorexant has a good efficacy and fewer side effects.

"One concern about the use of GABA agonists is their side effects - they might impair the normal ability to respond to unexpected stimuli during sleep in urgent situations," says first author Jaehoon Seol. "A drug that specifically acts on brain receptors involved in wakefulness, rather than the whole brain, could avoid this."

Suvorexant inhibits orexin receptors of the wake-promoting system, thus inhibiting wakefulness. This makes it a more targeted treatment than GABA agonists. To study whether this would result in less severe side effects, the researchers conducted a randomized controlled trial with 30 healthy men in a sleep lab. Participants took either suvorexant, brotizolam (a GABA agonist), or a placebo before falling asleep and were then woken up 90 minutes later. Their cognitive and physical functioning was then tested.

Suvorexant induced fewer impairments in body balance upon awakening than brotizolam. This could be associated with the cerebellum, a part of the brain that coordinates balance. Namely, the cerebellum contains GABAA receptors but not orexin receptors. In this case, brotizolam may have affected cerebellar functioning, while suvorexant did not.

"This is the first study to investigate the potential side effects of suvorexant and to compare these with those of brotizolam," says Masashi Yanagisawa, lead author of the study. "Also, suvorexant was just as effective as brotizolam in the treatment of insomnia, with comparable effects on sleep duration and efficiency."

With a reported prevalence of 10-60%, insomnia is considered a serious health issue. These new findings are potentially significant and could lead to further large-scale studies in patients with insomnia.

A bacterial infection is not just an unpleasant experience - it can also be a major health problem. Some bacteria develop resistance to otherwise effective treatment with antibiotics. Therefore, researchers are trying to develop new types of antibiotics that can fight the bacteria, and at the same time trying to make the current treatment with antibiotics more effective.

Researchers are now getting closer to this goal with a type of bacteria called Pseudomonas aeruginosa, which is notorious for infecting patients with the lung disease cystic fibrosis. In a new study, researchers found that the bacteria send out warning signals to their conspecifics when attacked by antibiotics or the viruses called bacteriophages which kill bacteria.

'We can see in the laboratory that the bacteria simply swim around the 'dangerous area' with antibiotics or bacteriophages. When they receive the warning signal from their conspecifics, you can see in the microscope that they are moving in a neat circle around. It is a smart survival mechanism for the bacteria. If it turns out that the bacteria use the same evasive manoeuvre when infecting humans, it may help explain why some bacterial infections cannot be effectively treated with antibiotics', says researcher Nina Molin Høyland-Kroghsbo, Assistant Professor at the Department of Veterinary and Animal Sciences and part of the research talent programme UCPH-Forward.

One United Organism

In the study, which is a collaboration between the University of Copenhagen and the University of California Irvine, researchers have studied the growth and distribution of bacteria in petri dishes. Here, they have created environments that resemble the surface of the mucous membranes where an infection can occur - as is the case with the lungs of a person with cystic fibrosis.

In this environment, researchers can see both how bacteria usually behave and how they behave when they are affected by antibiotics and bacteriophages.

'It is quite fascinating for us to see how the bacteria communicate and change behaviour in order for the entire bacterial population to survive. You can almost say that they act as one united organism', says Nina Molin Høyland-Kroghsbo.

Possibility of Blocking

The Pseudomonas aeruginosa bacteria are such a big problem that they are found in the top category 'critical' in the World Health Organization's list of bacteria, where new types of antibiotics are most urgently needed. Therefore, the researchers are excited to make new discoveries about the ways in which this type of bacteria behaves and survives.

'Infections with this type of bacteria are a major problem worldwide with many hospitalisations and deaths. That is why we are really pleased to be able to contribute new knowledge that can potentially be used to fight these bacteria', says Nina Molin Høyland-Kroghsbo.

However, she emphasises that it will still take a long time for the new knowledge to result in better treatment. The next step is to research how to affect the bacteria's communication and warning signals.

'This clears the way for the use of drugs in an attempt to prevent that the warning signal is sent out in the first place. Alternatively, you could design substances that may block the signal from being received by the other bacteria, and this could potentially make treatment with antibiotics or bacteriophage viruses more effective', concludes Nina Molin Høyland-Kroghsbo.

Researchers have created a virtual reality clinic to make it easier for stroke survivors to attend their physical and occupational therapy sessions. Results from a proof-of-concept study suggest that the technology - and the social connection it facilitates - are effective at encouraging therapy participation.

"Physical and occupational therapy are important parts of stroke recovery, in terms of helping survivors regain dexterity and functional motor ability," says Derek Kamper, co-author of a paper on the work. "However, stroke survivors often face significant challenges in attending their therapy sessions. For example, many survivors don't live near facilities that offer relevant therapy services.

"Our goal was to create an online, virtual reality platform that allows patients and therapists to interact in what is essentially real time," says Kamper, who is an associate professor in the Joint Department of Biomedical Engineering at North Carolina State University and the University of North Carolina at Chapel Hill. "Clients could also use the system to work on therapy exercises with loved ones who live far away."

The resulting system, called Virtual Environment for Rehabilitative Gaming Exercises (VERGE), is a software package that makes use of Kinect motion-sensor hardware to track the movement of patients and therapists. The system was developed by Kamper with collaborators at the Shirley Ryan AbilityLab and the University of Illinois at Chicago. VERGE currently supports three different rehabilitation activities, such as hitting a virtual ball back and forth when multiple users are present, or bouncing it off a wall when in single-user mode.

In the proof-of-concept study, researchers worked with 20 stroke survivors to evaluate the system. All participants had chronic impairment; 17 were men; and the mean age of the participants was 60.

For the study, half of the participants spent two weeks using VERGE in single-user mode, while the other half used VERGE in multi-user mode - interacting with other people remotely. The groups then switched modes for an additional two weeks.

Researchers found that study participants attended 99% of their therapy sessions when using VERGE in multi-user mode. Compliance was also good in single-user mode, with participants making 89% of their sessions.

Participants also spent 22% more time - or an additional 7.6 minutes - in their sessions when using VERGE in multi-user mode. And that time was more active, with participants moving their hands about 415 meters per session during multi-user sessions, as compared to 327 meters during single-user sessions.

"This suggests that the social aspect of VERGE has real benefits for stroke survivors in the context of getting them engaged in therapy," Kamper says.

The researchers used the upper extremity portion of the Fugl-Meyer Assessment of Recovery after Stroke score to evaluate the efficacy of the VERGE therapy sessions, and saw a mean change of 3.2 - which is comparable to what therapists would expect to see in chronically impaired patients after four weeks of therapy in a conventional clinical setting.

"The fundamental takeaway here is that VERGE has the potential to be a means of bringing clinical therapy to stroke survivors in their homes," Kamper says.

"While these results are promising, we'd like to scale up to a larger, multi-site study that can help us more fully evaluate the technology before making any decisions about how to make it available for widespread clinical use. For example, we'd like to incorporate loved ones into the next round of testing, to see if that could further increase patient engagement with therapeutic exercises.

"In the longer term, we'd like to see if this could be a means of engaging in therapy remotely with burn survivors, or even as a means of encouraging older adults to engage in exercise and make social connections," Kamper says.

"In terms of potential harms, there are very few. It's possible that some people may experience motion sickness if they use virtual reality goggles rather than using a large screen or monitor. Otherwise, the only risk we can think of is soreness from unaccustomed activity.

"Costs are directly related to the equipment you need to make use of VERGE: a computer, a mouse, a screen or goggles for viewing, and the Kinect motion sensor equipment - plus an Ethernet or WiFi connection to support the multi-user mode. The big expense is the computer; the Kinect is generally less than a few hundred dollars."

Boston, MA - Among young women without an eating disorder diagnosis, those who use diet pills and laxatives for weight control had higher odds of receiving a subsequent first eating disorder diagnosis within one to three years than those who did not report using these products, according to a new study led by researchers from Harvard T.H. Chan School of Public Health and Boston Children's Hospital.

"We've known that diet pills and laxatives when used for weight control can be very harmful substances. We wanted to find out if these products could be a gateway behavior that could lead to an eating order diagnosis," said senior author S. Bryn Austin, professor in the Department of Social and Behavioral Sciences at Harvard Chan School and director of STRIPED (Strategic Training Initiative for the Prevention of Eating Disorders). "Our findings parallel what we've known to be true with tobacco and alcohol: starting harmful substances can set young people on a path to worsening problems, including serious substance abuse disorder."

The study will be published online November 21, 2019 in the American Journal of Public Health (AJPH).

Use of over-the-counter diet pills or laxatives is not recommended by health care providers as a healthy way to manage weight and can have severe health consequences, including high blood pressure and liver and kidney damage.

The researchers analyzed data from 10,058 women and girls ages 14 to 36 who participated in the U.S.-based Growing Up Today Study (GUTS) from 2001 to 2016.

They found that among participants without an eating disorder, 1.8% of those who used diet pills during the past year reported receiving a first eating disorder diagnosis during the next one to three years compared to 1% of those who did not use the products. They also found that among these participants, 4.2% of those who used laxatives for weight control received a subsequent first eating disorder diagnosis compared to 0.8% of those who did not use these products for weight control.

The researchers called for policies that restrict access to these products, including banning the sale of diet pills to minors. They write that use of these products for weight control may serve as a "gateway" to further disordered eating practices by dysregulating normal digestive function and fostering dependence on unhealthy and ineffective coping methods.

"Our findings are a wake-up call about the serious risks of these products. Instagram took a step in the right direction recently by banning ads to minors for over-the-counter diet pills and 'detox' teas, which are often laxatives," said first author Jordan Levinson, clinical research assistant, Division of Adolescent Medicine, Boston Children's Hospital. "It's time for retailers and policymakers to take the dangers of these products seriously and take steps to protect youth."

The GeMO - Genomics of a Mock Outbreak - was a stress test to the ability to identify and characterize multidrug-resistant bacteria isolated from patients and the hospital environment. The results, released on the European Antibiotic Awareness Day, 18 November, show that it is possible to sequence and analyze bacterial genomes in a short time, a crucial information to manage and control an outbreak.

The mock outbreak was based on a fictitious request from a hospital in which a particularly dangerous bacterium, resistant to several antibiotics, had been detected and isolated from 10 patients over a short period of time. The aim was to find out if the patients had been infected by the same strain and the source of transmission. To assist the research, 40 environmental samples (obtained from washbasins and sink drains) were collected.

The process started with the extraction of total DNA from the bacterial samples obtained from patients. The DNA was sequenced and compared among the several samples and with DNA from other bacteria. The results of the clinical samples were known and reported to the virtual hospital in less than 48 hours - a record time, as this type of analysis can take several weeks. It was confirmed that the outbreak was caused by Klebsiella pneumoniae, resistant to multiple antibiotics, a difficult-to-treat bacterium that is currently expanding in Portugal and in Europe.

The analysis of the environmental samples ran in parallel and was completed within six days. This analysis took longer, as bacteria had first to be isolated from the environmental samples. The same strain that had infected patients was identified in some of the environmental samples, a key information to fight the outbreak.

The pilot demonstrated the ability to investigate an outbreak in real time, using a high-resolution technique that allows the identification of relationships between bacteria with great precision.

These techniques can support prevention, detection and control of hospital infections. The mock outbreak allowed researchers to overcome several barriers that had been identified in previous studies. The results now achieved will support future studies to be carried out in partnership with Portuguese hospitals.
GeMO is a pilot study involving Ricardo Leite, from Instituto Gulbenkian Ciência - IGC, and researchers from the laboratories led by Raquel Sá Leão and Maria Miragaia, from ITQB NOVA, and the analysis of the results used methods developed by the laboratory led by Mário Ramirez from iMM, Instituto de Medicina Molecular.

This study was carried out within the framework of ONEIDA - An OMICS Network to Prevent and Control Infectious Diseases and Antimicrobial Resistance, a research consortium coordinated by the microbiologists Raquel Sá-Leão and Mónica Serrano, of ITQB NOVA.

ONEIDA has the participation of around 100 researchers from ITQB NOVA, IGC and iMM, and one of its main goals is to work together with hospitals for the use of genomics tools in the control of hospital infections and antibiotic resistance. ONEIDA is funded by the ESIF - "European Structural and Investment Funds", by the " Programa Operacional Regional Lisboa 2020" and by national funds of the FCT - "Fundação para a Ciência e a Tecnologia". The IGC was sponsored by the company ILC during the realization of the GeMO.

Imagine not being able to drive, shower alone or even work because you are never quite sure when the next seizure will leave you incapacitated. Hope may be on the horizon for epilepsy patients who have had limited success with seizure drugs. In a study, led by a Johns Hopkins lead investigator, of 437 patients across 107 institutions in 16 countries, researchers found that the investigational drug cenobamate reduced seizures 55% on the two highest doses of this medication that were tested over the entire treatment period.

The findings of this trial were published Nov. 13 in The Lancet Neurology.

Currently, more than 20 anti-seizure drugs are on the market, but approximately 40% of people with epilepsy -- a chronic seizure condition -- don't become seizure free on these traditional medications. And while 15 new epilepsy drugs have become available since 1993, none of these have a seizure-free rate greater than 5% among people with treatment-resistant epilepsy.

Cenobamate, which has not been approved by the Food and Drug Administration (FDA) or brought to market yet, is being studied for treating a specific type of seizure in adults who don't yet have them controlled by other treatments. In this specific seizure type, known as partial-onset seizures, the electrical disturbance is limited to specific regions of the brain. Although cenobamate hasn't been priced yet, most of the newer anti-seizure drugs that come on the market can cost between $10,000 and $20,000 per year.

"A quarter of the patients I treat with this drug [cenobamate] who were disabled by frequent partial-onset (focal) seizures now have been seizure free for several years," says lead investigator Gregory Krauss, M.D., professor of neurology at the Johns Hopkins University School of Medicine. "It is wonderful to see the improvement in many of my patients' lives. They have improved confidence and can live more normal lives. Many can now work, and both patients and caretakers can be more independent."

For the study, the researchers gave 437 participants 100, 200 or 400 milligrams of cenobamate or a placebo pill. The cenobamate dose was ramped up slowly for up to six weeks until the testing dose was reached. This was followed by a 12-week maintenance phase. The participants were all adults who were already taking up to three anti-seizure medications, and all had a history of eight or more seizures during the previous eight weeks.

For the participants in the maintenance period on the placebo, 25% saw a 50% or more reduction in the number of seizures. On the 200 milligram dose during the maintenance period, 56% of participants had a 50% or more reduction in the number of seizures. On the highest dose (400 milligrams), 64% of participants had a 50% or more reduction in the number of seizures, and up to 21% had no seizures at all during the maintenance period.

While the investigational drug seems promising, Krauss cautions that typically something like 30,000 or more patients need to be treated before all the safety information will be known. The study simulates regular treatment, but to meet FDA ethical standards, participants must remain on their previously prescribed anti-seizure drugs without dose changes. This requirement often results in frequent, though usually temporary mild or moderate, adverse events with symptoms such as dizziness, headache and double vision. One severe allergic reaction (known as DRESS) was reported. After this study, medication doses were adjusted to customize treatment for each patient's needs.