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Saturday, October 12, 2019

Being Overweight Wipes 4 Years From Life: New Report

A new report on obesity from the Organisation for Economic Co-operation and Development (OECD) makes for grim reading; it details that even just being overweight will slash almost 3 years from life expectancy, on average, with this figure rising to 4 years in the United States.
A decade ago, across the 36 nations in the OECD, on average one in five individuals was obese. That figure now stands at one in four, meaning an additional 50 million people live with obesity. And three of five people living in wealthy nations are considered overweight.
In some countries the statistics are even worse. In the UK, for example, two in three people are overweight and one in three is obese. And in the United States, as figures revealed last month, almost 40% of adults and nearly 20% of kids are obese.
In this, its first report on obesity for 10 years, the OECD stresses how nations can reap economic benefits, as well as public health gains, from investing in effective strategies to combat rising obesity rates.
"Policies aimed at reforming the obesogenic environment are the most important, and they are an excellent investment," Michele Cecchini, lead economist for public health at OECD, told a London press briefing held yesterday to launch the report and to coincide with World Obesity Day on October 11.
"Since our initial report a decade ago, we have made quite a lot of progress — certainly in terms of awareness [about obesity], and certainly in terms of government policies and awareness of industry," added Francesca Colombo, head of the Health Division at the OECD.
"But what we have done is not enough. Overweight and obesity take a heavy toll on the economy. It's really quite a striking picture," she emphasized.
"And childhood and morbid obesity have gone from a rare event to a common occurrence. Obesity now poses an alarming burden on individuals, societies, and economies in OECD countries and beyond," the report concludes.
 
 

Obesity Will Reduce Economic Growth; Can Physicians Help?

In the 250-page document entitled, "The Heavy Burden of Obesity: The Economics of Prevention," the OECD predicts how obesity and its related health complications will reduce annual economic growth in its member nations, which include the United States, UK, Belgium, France, Germany, Italy, Portugal, Spain, Chile, and Mexico.
On average, 50% of people have an unhealthy diet, 40% of waking time is spent in sedentary activities, one in three people don't do enough physical activity, and two in five don't eat enough fruit and vegetables.
As a result, unless the tide is turned, over the next 30 years nearly 60% of all new diabetes cases will be caused by overweight, as well as 18%, 11%, and 8% of all cases of cardiovascular disease, dementia, and cancer, respectively.
This will result in 462 million new cases of cardiovascular disease and 212 million cases of diabetes.
OECD countries will therefore spend, on average, $209 per person annually on treating high body mass index and its related conditions.
 
The United States, Germany, and the Netherlands will spend the most on obesity, at $645, $411, and $352 per head respectively.
For OECD countries on average, this equates to 8.4% of total health spending, although this is highly variable across nations.
 
The United States alone will spend nearly 14% of its health budget on obesity and overweight, for example.
 
Asked by Medscape Medical News at the press briefing what role physicians and other healthcare workers can play, Jason Halford, PhD, of the University of Liverpool, UK, and chair of the European Association for the Study of Obesity, said: "By and large, physicians believe their patients are not motivated or interested [in losing weight]. The doctors think nothing seems to work, and the patient takes the blame."
And Cecchini said healthcare professionals need more man hours and motivation to start to enact change.
 
"Doctors, especially general practitioners, don't have time to spend on counseling [for weight reduction] and we don't give them the right incentives," he said.
 
There was overall agreement that labeling obesity as a disease can only help in this regard, although Halford noted that "it hasn't necessarily driven policy change yet."
"There is bias in the health system and huge provider bias against obesity," he asserted.
 

Societal Costs: Every $1 Spent Tackling Obesity Will Save $6

The spiraling rate of obesity around the world is primarily "a response to obesogenic environments," Johanna Ralston, chief executive of the World Obesity Federation, told the assembled press in London.
 
Cecchini stressed that it is only with a range of policies — such as regulation of advertising, food and menu labeling, mass media campaigns, prescription of physical activity, mobile apps, school-based programs and workplace wellness schemes — enacted together that the needle will really start to move.
 
"Every dollar spent on preventing obesity generates an economic return of up to six dollars, making prevention interventions an excellent investment," said Cecchini.
 
"All of these interventions could pay for themselves," he stressed
 
"Properly implemented policies do make a difference. We know what works but we are not implementing it to the extent that it makes a difference," said Colombo.
 
For example, cutting the calorie content in fattening foods such as potato chips (crisps) and candy by 20% would avoid more than 1 million cases of chronic disease per year.
 
However, "Any one thing is not the answer. You've got to do a lot. But if you start doing it, you will see changes," Halford emphasized.
 
"But the good news is that there is momentum, and growing awareness," said Columbo.
 

"We Know What Works...The Devil Is in the Detail"

To show that there is hope if governments and other stakeholders take action, the experts gave examples of policies that are working well, while nevertheless stressing the tremendous amount of work that still remains to be done.
 
Among the most effective initiatives for fighting obesity is regulation of advertising of unhealthy food, with more than $5 in return investment for each $1 spent, the OECD said.
 
Almost as effective are food labeling initiatives and efforts to make workers less sedentary.
 
"When it comes to ticking boxes" enacting policies, "the devil is in the detail," Cecchini emphasized.
"How is the policy designed and implemented? There are large gaps. For example, only a tiny minority of countries makes front-of-label packaging regarding nutrients compulsory," he noted.
 
Making such policies compulsory is deemed essential for effecting real change, said Corrina Hawkes, direct of the Centre for Food Policy, City, University of London, UK.
 
Also essential, she added, is action "in all countries," otherwise the five to six major multinational companies that produce most processed food worldwide will just seek other markets, as they did with tobacco products, she noted.
 
She believes "regional collaboration" is best; for example, the whole of Latin America working together, or Europe, or Asia. "Global is too big," she said.
 
The experts also emphasized how important the targeting of childhood overweight and obesity will be for the bigger picture, and for the future.
 
Children with obesity are over five times more likely to have obesity as adults, with all the attendant problems.
 
Conversely, healthy weight children are 13% more likely to report good school performance.
 
And even though the outgoing chief medical officer in the UK has just this week called for more concerted action on childhood obesity, Ralston said yesterday that the strategy in the UK, including its "Atlas of Childhood Obesity," is one of the best so far in the world and "is to be emulated."
 

A Long Way to Go but Is There Is Light at the End of the Tunnel?

Over 46 countries in the world now regulate the marketing of unhealthy foods to children and 59 countries have implemented taxes on sugar-sweetened beverages.
 
But the majority of that regulation of advertising to children "is still focused on traditional old media," said Cecchini, and "new media" — which is increasingly what children consume — is not being regulated for the most part, although he singled out South Korea and the Canadian province of Quebec for their efforts in this area.
 
Meanwhile, Columbo singled out Chile, Mexico, and Finland for praise on food labeling, "which has to be easy to understand," she explained.
 
And Chile's Ministry of Agriculture works with a federation of street vendors to provide access to healthy foods in underserved areas and disseminate information on healthy diets.
 
In 2008, the European Union Council of Agriculture introduced a program to provide free fruit and vegetables to school children. A milk program was added in 2017.
 
And in the United States, the Department of Agriculture ran a Healthy Incentives Pilot program in 2011 and 2012 to increase the consumption of fruit, vegetables, and other healthy food among people who rely on a federal subsidy, known as the Supplemental Nutrition Assistance Program (SNAP).
 
People received 30 cents back for every $1 they spent on selected fruit and vegetables, and participants consumed 26% more fruit and vegetables than those who had SNAP benefits but were not given the incentive to buy produce.
 
Meanwhile, examples of places that have tried to make it easier for people to exercise include an Austrian program providing free yoga, Pilates, and fitness classes to people of all ages.
 
And cities such as Copenhagen, London, Amsterdam, Paris, Vienna, and New York have dedicated cycle lanes and bike-sharing programs.
 
Singapore has already banned consumption of anything other than water on public transport, and various other countries have some restrictions, Cecchini said.
 
The Japanese government gives prizes each year for employers that make work environments healthier, and some organizations in the United States and South Africa are advocating the use of standing desks as standard for employees.
 
Each action in and of itself only has a small impact, but it is the combination of them that will make the difference, said Columbo.
 
"There is no room for complacency. We hope next time we are here [in another decade], we will be able to show a decrease in obesity rates," she concluded.
 
The speakers have reported no relevant financial relationships.
https://www.medscape.com/viewarticle/919771#vp_1

Real-World Data Playing a Bigger Role in Drug Development

Changes in the way data are being collected are on track to revolutionize the use of real-world data in drug approvals, Janet Woodcock MD, the longtime director of the FDA’s Center for Drug Evaluation and Research, said here.
“Traditional drug development programs … don’t usually get much insight into who to use a drug in and who not to use a drug in,” Woodcock said Thursday at an event on the future of health data sponsored by Datavant, a company that helps healthcare systems with patient identification. “Are there ways we can capture and utilize the data collected … to make the clinical trial enterprise more effective and efficient?”
The widespread use of electronic health records has drastically improved the availability of health data, she said. With paper charts, individual physicians “had to do archaeological expeditions — literally — to find out what was going on. The same is true of FDA — we used to get tractor-trailers’ worth of paper, literally [to approve drugs] … Now we get data sets that are standardized.” The other big factor “is the digital revolution in general — people have wearables, a lot of people have iPhones, we have telehealth that’s developing. All these things are coming together to provide rich data sources that we can turn into evidence. Our task is to take all the data out there and turn it into something that’s actionable.”
Real-World Data in Use
FDA already has approved numerous supplements and many drugs based on real-world evidence, Woodcock noted. “These are usually for rare conditions, such as male breast cancer, which doesn’t happen very often but is just as devastating as any other cancer. We were able to use evidence generated from use to add that indication to the label.” Using this type of evidence plays into “the long-term vision, articulated quite some time ago by the [National Academies of Sciences, Engineering, and Medicine] as the ‘learning healthcare system’ — that we’re able to make all the information we collect actionable, to assimilate that learning from treating patients and rapidly transform it back into best practices … We’re very, very far from that, but that’s the long-term vision.”
“In the shorter term, what we’re going to see is in terms of drug development and the intervention space and the best practices of delivering healthcare,” she continued. “We’re already generating lots of insights about what’s the best way to do this or that … That will continue to grow.” In addition, data gleaned from wearables and other new technologies will become part of healthcare delivery.
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Janet Woodcock, MD, FDA Center for Drug Evaluation and Research (Photo by Joyce Frieden)
However, as both the industry and regulators know, “the data out there are not necessarily fit for this purpose right now,” said Woodcock. Take for example, the medical chart of a cancer patient. “What does it say in the chart about cancer? Do you have the right cancer written down? Sometimes, the answer is no. Are the biomarkers in there? Are they entered correctly? That’s important information for the patients … It ought to be right the first time.”
Resisting Standardization
One problem with trying to make data more actionable is that “everyone resists standardization,” she said. “Doctors, especially, want to do things their own way.” She related a story from Peter Bach, MD, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, in New York City, who wanted to have lymphoma care and treatment standardized, so researchers could compare outcomes from different treatments. But some physicians documented their cases differently than the others, so he asked them why and one of them replied, “I don’t agree with the consensus definition of stages of lymphoma. I have my own stages.”
“We need to sell people on the return of that evidence — that if you put something down in a standard way, you’ll get something back,” Woodcock said. However, “it’s an uphill battle. There is much discussion in healthcare circles about what the electronic record is doing to clinicians and to the doctor-patient relationship. It doesn’t have to be that way. That can be fixed, but we’re really going to have to focus on that.”
One problem that crops up with real-world data is that it’s hard to screen out the confounders. “But something we’re exploring is, can you randomize people in your practice and collect real-world outcomes data … without a very elaborate clinical trial apparatus, and can you still get a valid result that’s actionable?” she said.
“We’re collaborating with a lot of groups trying to sort this out — different groups are trying to raise the reliability of that [observational] evidence … Where randomized clinical trials [RCTs] are ongoing, we’re doing a companion observational study, and we’ll see what the results are. We hope to have 20 retrospective ones done by next year, and seven prospective ones. Of course, the real-world study will get done a lot quicker than the RCT … but it will be very interesting to see how they compare and what kind of answers they give.”
Privacy Tradeoffs
The privacy tradeoffs involved in collecting data also are important to think about, said former FDA Commissioner Robert Califf, MD. “In what circumstances do we trade off privacy for the benefit of getting better healthcare? Where are we when health systems advertise the nice doctor in the white coat to cure your disease, when for the most part the doctor is guessing? The guesses are not uneducated guesses, but the fact is whenever we do prospective studies, we find out we’re wrong about half the time, but don’t know which half we’re wrong [or right] about.” For example, take the recent red meat controversy. “Is it OK to eat red meat or not? The data are contradictory because good studies haven’t been done.”
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Robert Califf, MD, Duke University (Photo by Joyce Frieden)
The use of aspirin to prevent heart attacks is another example, added Califf, who will soon be leaving his position as professor of cardiology at Duke University to work for the Alphabet health subsidiary Verily Life Sciences. Although aspirin has been shown to be effective for secondary prevention, “it’s always bothered me that we don’t know the right dose of aspirin,” he said. “Now we have enrolled over 17,000 people in a randomized trial of baby aspirin versus full-strength aspirin, and we’ll soon know the answer. But this is 140 years after aspirin first went on the market … It’s possible to know a lot more than we know if we just have the discipline to admit uncertainty.”
https://www.medpagetoday.com/publichealthpolicy/fdageneral/82711

Incyte Positive 52-Week Results of Phase 2 Study of Ruxolitinib in Vitiligo

Incyte (Nasdaq:INCY) today announces positive 52-week results from its randomized, double-blind,dose-ranging, Phase 2 study evaluating ruxolitinib cream, a nonsteroidal, anti-inflammatory, JAK inhibitor therapy, in adult patients with vitiligo.
As previously announced, the study met its primary endpoint, demonstrating that significantly more patients treated with ruxolitinib cream for 24 weeks achieved a ≥50 percent improvement from baseline in the facial vitiligo area severity index (F-VASI50)score compared to patients treated with a vehicle control (non-medicated cream).
Updated results at week 52 show substantial improvements in total body repigmentation with ruxolitinib cream, measured by the proportion of patients achieving a ≥50 percent improvement from baseline in the total vitiligo area severity index(T-VASI50),a key secondary endpoint. In addition, after 52 weeks of treatment with ruxolitinib cream 1.5 percent administered twice daily (BID), 58 percent of patients achieved F-VASI50 and 51 percent of patients achieved a ≥75 percent improvement (F-VASI75).F-VASI75 after 24 weeks is the primary outcome measure of both the TRuE-V1 and TRuE-V2 randomized Phase 3 trials that are already underway.
The 52-week results are being shared at the 28th European Academy of Dermatology and Venereology (EADV) congress in Madrid, Spain, during a late-breaking research session today, October 12, 2019, from 11:30 a.m. CEST to 11:45 a.m. CEST (Location: Hall 10 DalĂ­;Late Breaking News, Abstract #D3T01.1L).
https://www.marketscreener.com/INCYTE-CORPORATION-9675/news/Incyte-Summary-ToggleIncyte-Announces-Positive-52-Week-Results-From-a-Randomized-Phase-2-Study-of-29370591/

Reynolds American files for FDA review of e-cigarette

British American Tobacco Plc unit Reynolds American Inc said on Friday it had filed for a review of its Vuse e-cigarettes by the U.S. Food and Drug administration, giving it a lead over its main rival Juul Labs Inc.
The FDA has set a May 2020 deadline for e-cigarette makers to submit a formal application to keep their products on the market amid its efforts to curb the use of e-cigarette among teens.
Reynolds, whose Vuse e-cigarettes deliver nicotine via a cartridge-based vapor system, said it had provided the health regulator with over 150,000 pages of documentation, including information on the composition, design and manufacturing process associated with its product, as well as safety data.
The company said it had also worked with a team of more than 100 people to prepare the filing, including multiple regulatory experts and scientists.

U.S. regulators are exploring ways to monitor the manufacturing and marketing of e-cigarettes following a rise in use of these products among teens, and a recent outbreak of a mysterious lung illness linked to vaping that has claimed at least 29 lives.
Vaping devices such as Juul’s, which vaporize liquid containing nicotine, have borne the brunt of the regulatory crackdown globally.
The Trump administration also outlined plans in September to remove all flavored e-cigarettes from store shelves, pointing the finger at sweet flavors that had drawn millions of children into nicotine addiction.
https://www.reuters.com/article/us-reynolds-vaping/reynolds-american-files-for-fda-review-of-e-cigarette-idUSKBN1WQ2B1

German diagnostic services provider Centogene files for a $69 million US IPO

Centogene, which provides genetic testing and rare disease diagnostic products, filed on Friday with the SEC to raise up to $69 million in an initial public offering.
The Rostock, Germany-based company was founded in 2006 and booked $50 million in sales for the 12 months ended June 30, 2019. It plans to list on the Nasdaq under the symbol CNTG. SVB Leerink, Evercore ISI, Baird and BTIG are the joint bookrunners on the deal. No pricing terms were disclosed.

Clinical stage biotech Galera Therapeutics files for a $86 million IPO

Galera Therapeutics, a clinical stage biotech developing products to reduce toxicity in radiotherapy patients, filed on Friday with the SEC to raise up to $86 million in an initial public offering.
The Malvern, PA-based company was founded in 2012 and plans to list on the Nasdaq under the symbol GRTX. BofA Merrill Lynch, Citi, Credit Suisse and BTIG are the joint bookrunners on the deal. No pricing terms were disclosed.

Friday, October 11, 2019

Brain protein that promotes maintenance of chronic pain ID’d

A protein called RGS4 (Regulator of G protein signaling 4) plays a prominent role in the maintenance of long-term pain states and may serve as a promising new target for the treatment of chronic pain conditions, according to research conducted at the Icahn School of Medicine at Mount Sinai and published in print October 16, in The Journal of Neuroscience.
The discovery may help doctors stop acute pain from progressing into chronic pain, a condition in which patients experience not just pain, but a number of debilitating symptoms ranging from sensory deficits to depression and loss of motivation. The transition from acute to chronic (pathological) pain is accompanied by numerous adaptations in immune, glial, and neuronal cells, many of which are still not well understood. As a result, currently available medications for neuropathic or chronic inflammatory pain show limited efficacy and major side effects. Commonly administered opioids provide temporary alleviation of some pain symptoms, but carry serious risks like addiction in the context of long-term treatment for chronic pain. Therefore, there is an imminent need for novel approaches towards the treatment of chronic pain and for the development of medications that disrupt pain states instead of simply alleviating symptoms.
“Our research reveals that RGS4 actions contribute to the transition from acute and sub-acute pain to pathological pain states and to the maintenance of pain,” says Venetia Zachariou, PhD, Professor in the Nash Family Department of Neuroscience, the Department of Pharmacological Sciences and The Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai. “Because chronic pain states affect numerous neurochemical processes and single-target drugs are unlikely to work, it’s exciting to have discovered a multifunctional protein that can be targeted to disrupt the maintenance of pain.”
RGS4 is a multifunctional protein widely expressed in brain circuits that processes pathological pain, mood, and motivation. Through this study, Mount Sinai researchers observed that RGS4 plays an important role in maintaining pain states, regardless of whether the cause of pain was nerve injury or inflammation. Using genetic mouse models to ablate the gene expressing RGS4, the team demonstrated that prevention of RGS4 action disrupts the maintenance of chronic pain states in male and female mice.
Specifically, the research team used genetically modified mice to understand the role of RGS4 in the induction, intensity, and maintenance of chronic pain symptoms. They found that while genetic inactivation of RGS4 does not affect acute pain or the induction of chronic pain, it promotes recovery from sensory hypersensitivity symptoms in preclinical models of peripheral nerve injury, chemotherapy-induced neuropathy, and peripheral inflammation. Mice lacking RGS4 developed all expected symptoms of nerve injury, but they recovered within 3 weeks. Prevention of RGS4 action was also associated with an increase in motivation-related behaviors.
The group also used genetic tools to reduce the expression of RGS4 in the ventral-posterior lateral nucleus of the thalamus, a pain processing center that receives input from the spinal cord and relays this information to several cortical areas. Ultimately, inhibition of RGS4 actions in brain region resulted in recovery from mechanical and cold allodynia. Additionally, the research team used next-generation sequencing to gain insight on the genes and intracellular pathways affected by RGS4. The lab is further investigating the actions of RGS4 in the spinal cord and in mood-regulating areas of the brain to better understand the mechanism by which this protein affects sensory and affective pain symptoms.
Dr. Zachariou’s laboratory is conducting further investigation into the actions of RGS4 in the spinal cord and mood-regulating areas of the brain to better understand the mechanism by which this protein affects sensory and affective pain symptoms. They are also testing the therapeutic potential of RGS4 inhibitors.
https://www.eurekalert.org/pub_releases/2019-10/tmsh-rib101019.php