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Implants ‘made of your own cells’ could end back pain

Back and neck pain are often the result of the progressive damage of the discs that separate the spinal vertebrae. Thanks to new multidisciplinary research, we may soon have a better solution to this problem: bioengineered discs grown out of a person’s own cells.

Intervertebral disc degeneration is a common problem that affects a large segment of the population.

Typically, healthy intervertebral discs function by absorbing stress placed on the spine as we move and adjust our posture in a similar way to a car suspension.

If those discs wear out, it can cause pain in various areas of a person’s back or neck.

So far, treatments for intervertebral disc degeneration include spinal fusion surgery and replacing the damaged discs with artificial ones.

However, these approaches bring limited benefits because they cannot restore full function of the intervertebral discs they replace.

Now, a multidisciplinary research team from the University of Pennsylvania’s Perelman School of Medicine, School of Engineering and Applied Science, and School of Veterinary Medicine is aiming to solve this issue by developing bioengineered intervertebral discs made out of an individual’s own stem cells.

Stem cells are undifferentiated cells that have the potential to “transform” into any specialized cells. That is why they have become the focus of multiple medical research studies, including the current one.

The researchers at the University of Pennsylvania have been working for the past 15 years on bioengineered disc models — first in laboratory studies, then in small animal studies, and most recently in large animal studies.

“This is a major step: to grow such a large disc in the lab, to get it into the disc space, and then to have it to start integrating with the surrounding native tissue. That’s very promising,” says Prof. Robert L. Mauck, co-senior author of the current study.

“The current standard of care does not actually restore the disc, so our hope with this engineered device is to replace it in a biological, functional way and regain full range of motion,” he adds.

Studies in animal successful so far
Previously, the researchers tested the new discs — called “disc-like angle ply structures” (DAPS) — in rat tails for 5 weeks.

In the new study, whose results appear in the journal Science Translational Medicine, the team developed the engineered discs even further. They then tested the new model — called ” endplate-modified DAPS” (eDAPS) — in rats again, but this time for up to 20 weeks.

The new structure of the bioengineered disc allows it to retain its shape better, and integrate more easily with the surrounding tissue.

Following several tests — MRI scans and several in-depth tissue and mechanical analyses — the researchers found that, in the rat model, eDAPS effectively restored original disc structure and function.

This initial success motivated the research team to study eDAPS in goats, and they implanted the device into the cervical spines of some of the animals. The scientists chose to work with goats because, as they explain, the cervical spinal discs of goats have similar dimensions to those of humans.

Moreover, goats have semi-upright stature, allowing the researchers to bring their study one step closer to human trials.

‘A very good reason to be optimistic’
The researchers’ tests on goats were also successful. They noticed that the eDAPS integrated well with the surrounding tissue, and the mechanic function of the discs at least matched, if not surpassed, that of the original cervical discs of the goats.

“I think it’s really exciting that we have come this far, from the rat tail all the way up to human-sized implants,” says Dr. Harvey E. Smith, co-senior author of the study.

“When you look at the success in the literature from mechanical devices, I think there is a very good reason to be optimistic that we could reach that same success, if not exceed it with the engineered discs.” – Dr. Harvey E. Smith

The researchers say that the next step will include conducting further, more extensive trials in goats, which will allow the scientists to understand better how well eDAPS works.

Moreover, the research team plans to test out eDAPS in models of human intervertebral disc degeneration, thus hopefully getting one step closer to clinical trials.

“There is a lot of desirability to implant a biological device that is made of your own cells,” notes Dr. Smith, adding that, “Using a true tissue-engineered motion-preserving replacement device in arthroplasty of this nature is not something we have yet done in orthopaedics.”

“I think it would be a paradigm shift for how we really treat these spinal diseases and how we approach motion sparing reconstruction of joints,” he continues.

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Adolescent brain development impacts mental health, substance use

Advances in understanding adolescent brain development may aid future treatments of mental illness and alcohol and substance use disorders. The findings were presented at Neuroscience 2018, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.

Adolescence is a developmental period characterized by outsized risk-taking and reward-seeking behavior, including first alcohol and drug exposures, as well as the first emergence of symptoms such as depression and anxiety. And yet, much of the research on brain functions related to these conditions is performed on adults. As we gain a better understanding of adolescence-specific neurological causes of these conditions and behaviors, we increase the potential for early treatments and for interventions even before serious symptoms emerge.

Today’s new findings show that:

A variant in an opioid receptor gene in the brain reduces the natural reward response in young adolescents before they have started using alcohol or other substances, indicating carriers of this genetic variant may be more susceptible to addiction (John W. VanMeter, abstract 281.06).
Childhood trauma impacts the development of critical brain networks during adolescence, elevating the risk for alcohol abuse (Sarita Silveira, PhD, abstract 645.04).
The strength of connections between the brain’s reward and anti-reward systems corresponds to the severity of several important psychiatric symptoms in adolescents, including anxiety and depression (Benjamin Ely, abstract 320.11).
“The neuroscience advances presented today help expand our understanding of the connections between adolescent brain development and mental health issues, including alcohol and substance use,” said press conference moderator Jay Giedd, MD, of the University of California, San Diego, who conducts research on the biological basis of cognition, emotion, and behavior with an emphasis on the teen years. “These advances provide potential new methods to identify young people who have biological susceptibility to addiction and mental illnesses, so we can implement intervention strategies even before problems emerge.”

This research was supported by national funding agencies including the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, and several U.S. universities. Find out more about adolescent brain development on BrainFacts.org.

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One size fits all outpatient care is ‘unfit for purpose’

The ‘one size fits all,’ approach to outpatient care is no longer fit for purpose.

This is the message from the Royal College of Physicians. In a new report Outpatients: The future – Adding value through sustainability, published today, NHS England medical director, Professor Stephen Powis, says it’s time to ‘grasp the nettle’ to help reduce some of the 118 million outpatient appointments every year – many of which are unnecessary.

The report argues that the cost to patients and public health of the current approach must be considered alongside the financial cost to the NHS. Not only are patients frustrated by poor communication and long waiting times, they have to spend time and money on things like childcare and travel when attending appointments.

The RCP in its report, says the ‘one size fits all’ model should be replaced with a person-centred approach that recognises that people have varying health needs, personal pressures and abilities to self-care or manage. It calls for patients to be at the centre of a redesign process that better utilises technology already available, and says patient centred care means there should be a clear health benefit when asking people to travel to appointments, taking time off work and school.

In the foreword, Professor Powis who backs the RCP’s recommendations, says it might sometimes appear to patients that the outpatient visit has been designed in clinicians’ interests rather than their own, whereas clinicians are often just as frustrated with antiquated processes in their own clinics.

“The outpatient system is older than the NHS and the time has come to grasp the nettle and use tech and other innovations to improve patients’ experience and care. As part of the long-term plan for the NHS, it’s right we look at ways to cut unnecessary appointments, save thousands of journeys, reduce traffic and pollution and make the NHS more efficient.”

Co-author Dr Toby Hillman, clinical lead for the RCP Sustainability Programme and a consultant respiratory physician, said: “Having re-evaluated the purpose of outpatient care and aligned its objectives with modern-day living and expectations, we must ensure that the benefits are measured in terms of long-term value for patients, the population and the environment, not just short-term financial savings.”

In calling on the NHS to enlist the power of technology and innovation, Professor Powis said: “For many people, care can be delivered more timely and conveniently closer to home, by specialists at the GP surgery or by using technology in new and exciting ways. This report shows a snapshot of exciting new models already working successfully through apps, skype, text messaging and remote monitoring systems that are changing the shape of care; we need to bottle and spread those examples building a new consensus for the future based on the views of clinicians and patients.”

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U.S. regulators snip red tape for medical devices to curb opioid crisis

Laura Perryman expected her medical company, Stimwave Technologies Inc, would have to wait several years for its painkilling device to win U.S. approval as a treatment for chronic migraines.

She now thinks it could be done in months, thanks to a new initiative by the U.S. Food and Drug Administration to use medical device-based treatments, diagnostic tests and mobile medical apps to address the country’s opioid crisis.

When President Donald Trump declared a public health emergency over the abuse of heavy-duty painkillers like oxycodone and hydrocodone, he ordered all government agencies to take action in response to the death of 70,000 Americans last year from drug overdoses.

The FDA told Reuters it has received over 200 submissions from companies seeking a speedy approval process for their devices. These range from Stimwave’s Halo to painkilling products made by Abbott Laboratories and other industry heavyweights as an alternative to opioids.

“We’re pleased by the robust interest in this innovation challenge and the acknowledgement from developers about the unique and important role medical devices, including digital health technologies like mobile medical apps, have the potential to play in tackling the opioid crisis,” FDA Commissioner Scott Gottlieb said.

Perryman’s Halo devices, which look like angel hair pasta and are so small they can be injected into a nerve, took four years to get U.S. approval under other names for easing leg and back pain.

She hopes a spot on the FDA program will see Halo approved within a year as an alternative to opioids, which are currently used to treat an estimated 50 percent of patients who come to emergency rooms with migraines.

“This is kind of perfect for something like ours…since the device is shown to be safe already,” said Perryman, who founded privately-held Stimwave in South Florida seven years ago.

The FDA has been increasingly reluctant to greenlight new opioids for market but earlier this month approved a potent opioid-based painkiller from AcelRx Pharmaceuticals Inc placing tight restrictions on its distribution and use. In a rare move, Gottlieb made a public statement at the time, explaining the decision.

The regulator’s push for alternatives to opioids has helped drive interest from venture capital funds and institutional investors this year in firms promising to develop alternatives, according to interviews with device companies, financial services firms and brokerage Cowen & Co.

For example, privately-held Virpax Pharmaceuticals, which makes an aerosol spray that delivers a non-opioid pain drug, said it had four or five banks interested in running its Series A investment round this summer versus just one in the past.

STIMULATION
Abbott, like rivals Boston Scientific Corp and Nevro Corp, makes neuromodulation implants which stimulate the nervous system to mask pain signals before they reach the brain.

Abbott has submitted an entry for the competition in the hope it will slash waiting times, which often stretch several months just to get an initial meeting, according to Dr. Allen Burton, Abbott’s medical director of neuromodulation.

“Devices that are part of this (program) will be streamlined… their meeting will go to the top of the pile,” said Burton.

While neuromodulation is only a small part of Abbott’s large medical device business, the unit is seen as a growth engine for the company. Burton estimates between 10-to-20 percent of the growth Abbott has seen in its neuromodulation business could be tied to doctors prescribing its devices for pain after surgery or from injury to patients that are opioid averse.

Boston Scientific did not apply for the contest, but the company is investing “heavily” in its neuromodulation unit, which was its fastest-growing at nearly 23 percent in the latest quarter, according to Maulik Nanavaty, senior vice president at the device maker.

“We continue to make external investments in early (neuromodulation) technology,” he told Reuters.

To be sure, these devices are not seen as a silver bullet for opioid addiction. Nirad Jain, a partner at consulting firm Bain & Co, believes many of the solutions on the table are just tinkering at the edges of a problem that needs to be solved by doctors simply settling for fewer or less potent opioids.

ADDICTION
Academics and charitable groups dealing with the social fallout of the crisis say the bulk of the rise in deaths stems from misuse of prescription painkillers. That has put the onus on regulators in September to issue new rules cracking down on prescribing by doctors.

“The goal is that these guidelines will provide evidence-based information on the proper number of opioid doses that should be dispensed,” Gottlieb said in a statement at the time.

“Our goal is to help prevent patients from becoming addicted by decreasing unnecessary or inappropriate exposure to opioids.”

Although the FDA contest is limited to devices and app-based solutions for pain and addiction, the current regulatory climate is also conducive to companies developing opioid-alternative pharmaceuticals.

Drugmakers including Pfizer Inc, Eli Lilly and Co, Regeneron Pharmaceuticals Inc and Teva Pharmaceutical Industries Inc have been packing their pipelines with potential solutions to the crisis and there are 120 non-opioid drugs under FDA review this year, up some 650 percent since 2013, according to business intelligence firm Informa.

Privately-held SPR Therapeutics Inc told Reuters it has entered its “temporary” neuromodulation device in the contest. Similarly to Stimwave’s, its product is implanted into the body but can be surgically removed after about two months. Josh Boggs, a senior executive at the company, expects to get quicker feedback from the FDA and shorter review times in the wake of the crisis.

After years in the business, he believes the crisis has increased the agency’s desire to collaborate with medical technology companies like his.

“I feel like (FDA) people are coming well prepared to meetings and are very engaged in it. It feels like an atmosphere that’s conducive to finding a solution,” he said.

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Trial finds diet rich in fish helps fight asthma

A clinical trial led by La Trobe University has shown eating fish such as salmon, trout and sardines as part of a healthy diet can reduce asthma symptoms in children.

The international study found children with asthma who followed a healthy Mediterranean diet enriched with fatty fish had improved lung function after six months.

Lead researcher Maria Papamichael from La Trobe said the findings added to a growing body of evidence that a healthy diet could be a potential therapy for childhood asthma.

“We already know that a diet high in fat, sugar and salt can influence the development and progression of asthma in children and now we have evidence that it’s also possible to manage asthma symptoms through healthy eating,” Ms Papamichael said.

“Fatty fish is high in omega-3 fatty acids which have anti-inflammatory properties. Our study shows eating fish just twice a week can significantly decrease lung inflammation in children with asthma.”

Co-researcher and Head of La Trobe’s School of Allied Health, Professor Catherine Itsiopoulos, said the results were promising.

“Following a traditional Mediterranean diet that is high in plant-based foods and oily fish could be an easy, safe and effective way to reduce asthma symptoms in children,” Professor Itsiopoulos said.

Associate Professor Bircan Erbas, from La Trobe’s School of Psychology and Public Health, is an expert in asthma and allergies, who co-supervised the trial.

“Asthma is the most common respiratory disease in young people and one of the leading reasons for hospitalisations and trips to emergency for children,” Associate Professor Erbas said.

“Unfortunately, the rate of asthma worldwide remains high. It is imperative that we identify new therapies that we can use alongside conventional asthma medications.”

The clinical trial involved 64 children from Athens in Greece, aged 5 to 12 who had mild asthma. Researchers from Australia and Greece divided the children into two groups and instructed around half to eat two meals of cooked fatty fish (of at least 150 grams) as part of the Greek Mediterranean diet every week for six months. The remaining children followed their normal diet.

At the end of the trial, they found the group who ate fish had reduced their bronchial inflammation by 14 units. Above 10 units is significant under international guidelines.

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Eat your vegetables (and fish): Another reason why they may promote heart health

Elevated levels of trimethylamine N-oxide (TMAO) — a compound linked with the consumption of fish, seafood and a primarily vegetarian diet — may reduce hypertension-related heart disease symptoms. New research in rats finds that low-dose treatment with TMAO reduced heart thickening (cardiac fibrosis) and markers of heart failure in an animal model of hypertension. The study is published ahead of print in the American Journal of Physiology — Heart and Circulatory Physiology and was chosen as an APSselect article for November.

TMAO levels in the blood significantly increase after eating TMAO-rich food such as fish and vegetables. In addition, the liver produces TMAO from trimethylamine (TMA), a substance made by gut bacteria. The cause of high TMAO levels in the blood and the compound’s effects on the heart and circulatory system are unclear, and earlier research has been contradictory. It was previously thought that TMAO blood plasma levels — and heart disease risk — rise after the consumption of red meat and eggs. However, “it seems that a fish-rich and vegetarian diet, which is beneficial or at least neutral for cardiovascular risk, is associated with a significantly higher plasma TMAO than red meat- and egg-rich diets, which are considered to increase the cardiovascular risk,” researchers from the Medical University of Warsaw in Poland and the Polish Academy of Sciences wrote.

The researchers studied the effect of TMAO on rats that have a genetic tendency to develop high blood pressure (spontaneously hypertensive rats). One group of hypertensive rats was given low-dose TMAO supplements in their drinking water, and another group received plain water. They were compared to a control group of rats that does not have the same genetic predisposition and received plain water. The dosage of TMAO was designed to increase blood TMAO levels approximately four times higher than what the body normally produces. The rats were given TMAO therapy for either 12 weeks or 56 weeks and were assessed for heart and kidney damage and high blood pressure.

TMAO treatment did not affect the development of high blood pressure in any of the spontaneously hypertensive rats. However, condition of the animals given the compound was better than expected, even after more than a year of low-dose TMAO treatment. “A new finding of our study is that [a] four- to five-fold increase in plasma TMAO does not exert negative effects on the circulatory system. In contrast, a low-dose TMAO treatment is associated with reduced cardiac fibrosis and [markers of] failing heart in spontaneously hypertensive rats,” the researchers wrote.

“Our study provides new evidence for a potential beneficial effect of a moderate increase in plasma TMAO on pressure-overloaded heart,” the research team wrote. The researchers acknowledge that further study is needed to assess the effect of TMAO and TMA on the circulatory system. However, an indirect conclusion from the study could underscore the heart-healthy benefits of following a Mediterranean-style diet rich in fish and vegetables.

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Could Fasting Help You Lose Weight, Get Healthier?

The route to weight loss has traditionally been to cut calories. Swap that regular soda for diet, grab an apple instead of a cookie, and you’ll trim pounds, the idea goes.

But, instead of going for such calorie cuts, many people are now taking more intense steps to lower their average daily calorie counts.

Called intermittent fasting, this latest way to diet takes a different approach. Rather than change how much you eat, you change when you eat. “Intermittent fasting is loosely defined as periods of non-eating, followed by periods of eating,” explains Krista Varady, PhD, an associate professor of nutrition in the University of Illinois at Chicago department of kinesiology and nutrition.

The origins of fasting are rooted in religion. Several faiths, including Islam, Judaism, and Christianity, observe periods of food restriction for spiritual reasons. Somewhere along the line, researchers discovered that skipping meals also has a few health benefits, including weight loss and lowered blood pressure and cholesterol.

How Does It Work?
Normally after you eat, your pancreas releases the hormone insulin. That burst of insulin helps move sugar from your bloodstream into your cells to be used for energy.

Whatever sugar is left over goes into your fat cells for storage. In between meals, your insulin levels drop and your fat cells release stored sugar to keep you going.

Fasting prevents insulin release for a longer period of time. So your body has to burn fat for energy, instead of sugar.

Types of Intermittent Fasting
You can fast in a few different ways. Some methods are more extreme than others:

Alternate-day fasting is the most intense version. You eat nothing and drink only water or calorie-free beverages one day, and then you basically eat what you want the next day.
Modified alternate-day fasting switches between one low-calorie day (about 500 calories) and one day of normal eating.
The 5:2 diet (also called the Fast Diet) involves eating normally 5 days a week, and then cutting down to about 500 calories on the 2 other days.
The fasting-mimicking diet has you eat a very low-calorie diet for just a few days, and then go back to a normal diet. It offers many of the benefits of fasting, without the time investment.
Time-restricted feeding focuses on the timing of your meals. You eat only within a certain time window each day — for example, from 10 a.m. to 6 p.m. Then you fast for the rest of the day.
Can It Help Me Lose Weight?
There is evidence that alternating fasts with periods of eating helps you lose weight, but not much more than you would by cutting calories.

Varady did a study comparing the effects of alternate-day fasting with calorie restriction in 100 obese adults. After 1 year, people on the alternate-day fast had lost about 6% of their body weight. The calorie restriction group had lost about 5.3% of their weight.

Other studies on alternate-day fasting showed a weight loss of 3% to 8%. Time-restricted feeding produced slightly less weight loss — about 3% to 4%.

Other Advantages to Fasting
Intermittent fasting has a few other benefits, beyond weight loss. After you eat, your body is tied up with the digestion process. Taking a break from food shifts the focus to other areas, like maintaining optimal performance and repairing cell damage. “It gives our bodies time to heal, because they’re not constantly dealing with the influx of nutrients,” Varady says.

And that’s good for your health in general. Early research finds intermittent fasting could help ease things that could harm your heart, like high blood pressure, blood sugar, and cholesterol — sometimes significantly.

Courtney Peterson, PhD, an assistant professor in the University of Alabama department of nutrition sciences, studies the effects of intermittent fasting on conditions like diabetes, blood pressure, and heart disease. She says some of her participants had their blood pressure drop 10 to 11 points from the practice. “That’s a huge effect. It’s about equivalent to a blood pressure-lowering medicine.”

Most of the health benefits from fasting are likely due to weight loss, and some people with type 2 diabetes could also benefit, she says.

“There is research that suggests that intermittent fasting improves blood sugar levels in people with type 2 diabetes,” Peterson says. “However, they need to be more careful about blood sugar drops. Episodes of hypoglycemia [too low blood sugar] are more common than usual.”

But fasting with type 2 diabetes can be especially dangerous. It’s best to consult a doctor before trying it.

Intermittent fasting might also slow the aging process and improve longevity, but so far, the only evidence of this is from studies of mice, worms, and other animals. “We’re still in the early phases of doing intermittent fasting research in humans,” Peterson says. “There probably will eventually be a study in older adults to see whether it can slow some indicators of aging, such as the loss of muscle mass.”

How to Get Started
Intermittent fasting can take some adjustment. “It takes your body a little while to get used to that up-down pattern of eating,” Varady says.

You’re likely to be hungry at first. But after about 2 weeks, most people get used to the routine.

In time, fasting could actually help control your hunger. “It may be because your blood sugar levels are more stabilized throughout the day,” Peterson says. And time-restricted feeding causes less hunger than alternate-day fasting, which could make it more sustainable long-term, she says.

One way to avoid hunger during your fast is to drink more water. Extra fluids will also prevent the headaches some people get when they don’t eat.

You might also need to change what you eat. Get more protein from sources like lean poultry, tofu, beans, and nuts. “That helps keep your muscle mass up, because you can lose muscle mass while fasting,” Varady says. It also helps you feel full for longer.

Although many of these diets let you eat what you want during your feast days, don’t go wild and binge. You’ll get the best results if you eat healthy every day.

Who Shouldn’t Fast?
Intermittent fasting is safe for healthy people. Any side effects are usually mild, like constipation and bad breath. Drinking more water can help with both issues.

Certain groups of people shouldn’t fast, though, including women who are pregnant or breastfeeding. Fasting is also not recommended for some people with diabetes, because it can lower your blood sugar to dangerous levels. And avoid fasting if you’re recovering from an illness or being treated for cancer and you need to maintain or gain weight, Peterson says.

This style of eating isn’t a good fit for everyone. Varady doesn’t recommend it for people with binge eating disorder, who could overeat during their “on” days. And if you’re a snacker who can’t go more than a few hours without food, other eating plans might be better for you.

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New drug options, risk factors added to U.S. heart guidelines

The recommendations from the American Heart Association and the American College of Cardiology, last issued in 2013, acknowledge recent research showing the benefit of very low levels of “bad” LDL cholesterol, which contributes to fatty plaque buildup and narrowing of arteries.

The medical groups, which announced the guidelines on Saturday at the AHA’s annual meeting in Chicago, still emphasize a healthy diet and exercise as the first line of defense against heart disease, the No. 1 killer in the country.

When cholesterol is not controlled by lifestyle efforts, patients are typically prescribed statin drugs, available as low cost generic pills that have long been proven to safely and effectively lower LDL levels and heart disease risk.

For people who have had a heart attack or stroke, are at high risk for another and whose cholesterol levels are not adequately lowered by statins, the guidelines now recommend adding newer cholesterol drugs.

Higher risk patients are advised to first try statins in combination with ezetimibe, the generic version of Zetia, which lowers cholesterol by limiting its absorption from the intestine. If that does not work, the guidelines call for newer injected medications known as PCSK9 inhibitors, specifically for people who are at very high risk or who have a genetic condition that causes very high cholesterol levels.

Two PCSK9 drugs – Amgen Inc’s (AMGN.O) Repatha and Praluent from partners Regeneron Pharmaceuticals Inc (REGN.O) and Sanofi SA (SASY.PA) – were launched in 2015 at U.S. prices of over $14,000 a year.

Both have been shown to dramatically lower cholesterol levels, but uptake as been slow as the medical community and health insurers questioned their cost effectiveness.

To help spur usage, Amgen last month cut Repatha’s list price by 60 percent to $5,850 and Praluent’s annual net price was cut earlier this year to between $4,500 and $6,600.

The new guidelines are fairly “conservative” in recommending that the newer drugs be used only after other options, said Dr. Francisco Lopez-Jimenez, a cardiologist at the Mayo Clinic in Rochester, Minnesota, adding “I think that was the right approach.”

The guidelines continue to include a calculator introduced in 2013 to identify a patient’s 10-year risk for cardiovascular disease. In addition to traditional risk factors such as smoking and high blood pressure, doctors are now urged to discuss family history and ethnicity as well as health conditions such as chronic kidney disease and premature menopause.

They are also advised to test for cholesterol levels in children as young as two with a family history of heart disease or high cholesterol, while other children should have an initial test between the ages of nine and 11.

Coronary artery calcium measurements are advised for people whose risk level is not clear.

The guidelines update has more specific recommendations for certain age and ethnic groups, as well as for people with diabetes.

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Tania Fares’s Insider Guide To LA’s Beauty Spots

Vogue contributing editor Tania Fares is a multi-tasking maven: an art patron, philanthropist and British fashion champion, based between London, LA, Paris and Beirut, she’s never not on the road. Here, she rounds up her favourite beauty locations in Los Angeles.

Facile
Your one-stop shop for your beauty needs, Facile (pronounced like the French word) is a mix of a dermatology hotspot, spa and a stunning boutique making great skin simple and easy to accomplish. I fell in love with the vibe and the aesthetic when I visited a while ago. The mood is so calming and quiet that you simply liquefy in your seat when you go into the rooms. I immediately felt more relaxed the minute I walked in.
Locations at 638 1/2 North Robertson Boulevard, West Hollywood, CA 90069; 140 South Lake Avenue, Suite 104, Pasadena, CA 91101; Facileskin.com

C & The Moon
My favourite body scrub discovery in LA is C & The Moon’s Malibu Made body scrub. Founded by the actress and doula Carson Meyer (she’s the youngest daughter of NBCUniversal’s Ron Meyer and environmentalist Kelly Meyer), it’s big on sustainability. Carson began making body scrubs out of natural fixings in her kitchen, and eventually developed a formula free from chemicals, which she took to market. I love it because it smells delicious.
Candthemoon.com

Shani Darden
Chrissy Teigen, Jessica Alba and Emmy Rossum all have one thing in common: Shani Darden. The expert aesthetician’s appeal lies in the fact that she believes in simplicity, efficacy and, most importantly, that good skincare shouldn’t be stressful. After trying her Retinol Reform, I found it much less irritating than other formulations on the market, and I saw immediate results: after only one night, my skin progressed towards becoming smoother and glowing.
636 N Curson Ave, Los Angeles, CA 90036; Shanidarden.com

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Preventing sudden cardiac death with genome editing

Each year, at least 3 million people worldwide die of sudden cardiac death. In the U.S., this number reaches up to 450,000 people. Although sudden cardiac death is more common in older adults, younger people also are significantly affected. In the 1 to 40 age group, up to 9 per 100,000 people are affected each year. In this group, inherited cardiac diseases, including inherited cardiac arrhythmia disorders, cause a substantial proportion of sudden cardiac death.

In his lab at Baylor College of Medicine, Dr. Xander Wehrens and his colleagues study cardiac conditions, including inherited cardiac arrhythmia disorders. In addition to being often associated with a high incidence of sudden cardiac death, these disorders can be difficult to treat.

“For this particular study, we were inspired by a young patient who has been affected by an inherited cardiac arrhythmia disorder called catecholaminergic polymorphic ventricular tachycardia (CPVT). Our patient has recurring arrhythmias — irregular and fast heartbeats — and fainting episodes,” said Wehrens, who is professor of molecular physiology and biophysics, the Juanita P. Quigley Endowed Chair in Cardiology and director of the Cardiovascular Research Institute at Baylor. “Several family members had near fatal arrhythmias or sudden cardiac death. Current treatment options including anti-arrhythmic drugs and an implantable defibrillator — a device to correct certain irregular heartbeats — are not optimal for this patient.”

Genetic studies have shown that the cause of the young patient’s arrhythmia is a mutation in gene RYR2. Mutations in this gene account for nearly 60 percent of all CPVT cases. This gene encodes proteins that form a channel that regulates calcium flow in heart muscle cells called cardiomyocytes. Cardiomyocytes require proper calcium flow to contract and relax in a coordinated manner.

Gene mutations that produce defective RYR2 proteins lead to defective calcium channels that promote uncontrolled calcium leak. During exercise or emotional stress, a heart with defective RYR2 proteins will not regulate calcium flow properly, and this can lead to potentially life-threatening arrhythmias.

Designing a permanent treatment for CPVT

Wehrens teamed up with Dr. William Lagor, associate professor of molecular physiology and biophysics, who is an expert in gene therapy using Adeno-Associated Viral (AAV) vectors. These viruses can be used to deliver the CRISPR/Cas9 genome editing machinery directly into the heart.

The long-term goal of this collaborative project is to develop a permanent treatment for CPVT in humans by editing the patient’s own DNA.

Wehrens and Lagor engineered AAV vectors to deliver CRISPR/Cas9 (AAV-CRISPR) into the hearts of live animals. They reasoned that eliminating the disease-causing copy of the RYR2 gene, called R176Q, could correct this lethal arrhythmia disorder in mice. To test this new approach, AAV-CRISPR was used to selectively disrupt the mutant RYR2 gene in the R176Q mouse model of CPVT.

Ten days after birth, mice carrying the R176Q mutation and normal mice received a single injection of AAV-CRISPR or placebo treatment. Five to six weeks later, the researchers evaluated the mice, and found very encouraging results.

None of the mice carrying the disease-causing R176Q mutation that were treated with AAV-CRISPR developed arrhythmias. In contrast, 71 percent of the mice that carried the mutation and received a placebo virus did develop arrhythmias. Editing of the defective copy of the gene using AAV-CRISPR greatly reduced the abundance of the dysfunctional RYR2 proteins. Furthermore, the single ‘healthy copy’ of the RYR2 gene that remained was enough to support proper heart function. No adverse events linked to treatments were observed in the groups of normal or affected mice.

“We are particularly excited that we were able to selectively disrupt the disease-causing R176Q mutated gene without adversely affecting the healthy gene variant in the genome,” Wehrens said.

“We are now testing the same approach in stem cells from patients with the same condition, to analyze efficacy and safety in human cells. This may enable us to develop this approach for future therapeutic studies in patients with this arrhythmia syndrome,” said Wehrens.

Lagor also is optimistic about this new therapeutic approach.

“There are many diseases that are unsuitable for additive gene therapy, either because the gene is too large to deliver or a defective copy of the gene acts in a dominant way. For many mutations in RYR2 that cause CPVT, both of these are the case,” Lagor said. “We believe that precision genome editing is the future for tissue-directed gene therapies, and severe cardiac diseases are an ideal place to start.”