Absorbing more ‘bad’ cholesterol

Published in Drug Discovery News

THOUSAND OAKS, Calif.—Completing a key step toward filing for regulatory approval of a broadly applicable cholesterol-reducing drug, Amgen has announced promising results from its fifth Phase 3 trial—the RUTHERFORD-2 trial—of evolocumab, a fully human monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C) from the blood.

 

LDL-C is a major risk factor for cardiovascular disease, and more than 71 million Americans have high LDL-C, according to the U.S. Centers for Disease Control and Prevention. Patients who have both high cholesterol and high cardiovascular risk are key target markets for evolocumab.

 

While the trial’s full results will be announced in Washington, D.C., at the American College of Cardiology’s 63rd Annual Scientific Session in late March, Amgen has said that the drug successfully combined with statins and other lipid-lowering drugs to reduce LDL-C, also called “bad” cholesterol, for patients with heterozygous familial hypercholesterolemia.

 

Previous trials have found evolocumab useful for patients with high cholesterol who were not previously getting anti-lipid treatment, as well as those already on statin drugs, and those who cannot tolerate statins, the most common type of anti-cholesterol drug.

 

While statins inhibit an enzyme that controls production of cholesterol in the liver, evolocumab binds to PCSK9, blocking it from binding to LDL receptors on the surface of the liver, according to the company’s description of the drug. That frees up more LDL receptors to remove LDL-C from the blood.

 

According to the company, a total of 13 trials are slated, including testing varying methods of injecting the drug and different frequencies of administration. About 30,000 patients will be involved, including those with cardiovascular disease, hyperlipidemia, coronary atherosclerosis and familial hypercholesterolemia (whether heterozygous or homozygous).

 

Those latter conditions, which are genetic, cause high levels of LDL-C starting at birth, and place patients at high risk for cardiovascular problems early in life. Heterozygous familial hypercholesterolemia affects about one in every 300 to 500 people worldwide, according toWorld Health Organization data.

 

The results so far will be shared with regulators, in hopes of securing approvals in 2014, the company said in a statement to DDNews. The exact timeline depends on results of ongoing trials.

 

Since Jan. 23, Amgen has touted positive top-line results for evolocumab from the Phase 3 GAUSS-2 trial in statin-intolerant patients with high cholesterol, the Phase 3 LAPLACE-2 trial in combination with statins in patients with high cholesterol and the Phase 3 RUTHERFORD-2 trial in patients with heterozygous familial hypercholesterolemia.

 

Of the most recently announced top-line results, Dr. Sean E. Harper, executive vice president of research and development at Amgen, said, “Data from the RUTHERFORD-2 study suggest that evolocumab, when used as an add-on therapy to existing lipid-lowering medications, may offer a new treatment option for patients with heterozygous familial hypercholesterolemia. The RUTHERFORD-2 study is the fifth pivotal LDL-C lowering study in our Phase 3 program. The robust data from these five studies will form the basis of our global filing plan, and we look forward to discussions with regulatory agencies.”

Press Releases: Beyond politics

Published in the Portland Phoenix

Today’s US media environment might well seem extremely gay-friendly. American mainstream media consumers saw a fair amount of coverage of anti-gay discrimination in Russia in the lead-up to, and during, the Winter Olympics in that country (read more on this topic on page 10); there was relatively little outcry when President Barack Obama selected several gay former Olympians to represent the United States in the audience. Johnny Weir both dressed and behaved flamboyantly on NBC’s nightly figure-skating broadcasts. Heck, even marriage equality gets little more than ho-hum headlines these days as this vital civil-rights issue continues its progress around the country.

But there is still much more to be done, and last weekend, a one-day conference at Colby College in Waterville sought to explore what, and how.

Called “Queering the Media,” the event, put together by members of Colby’s all-inclusive LBGTQ-plus-allies support group The Bridge, appeared to be less about news-media coverage and more about modern culture, as described by organizers Andy Kang and Sonja Hagemeier.

The intent was that “‘queering’ would be a relatively broad and very widely interpreted term,” Kang says. Looking at “how the media portrays or represents, or tries to represent, or fails to represent, people who don’t fit into mainstream culture” is important, he says, because it can help remind consumers of that information that other viewpoints and experiences exist.

This is important in Maine particularly, says Hagemeier, because “a lot of people think of Maine as really isolating, especially for queer people.” She spoke in almost mystical tones about Portland, a place she has heard is “very very queer friendly,” while observing that it is only slowly that “people are getting used to the idea” in other parts of Maine.

Their conversations at the conference, including presentations by students and current and former Colby faculty, as well as noted queer scholar Jack Halberstam, covered athletic environments, video games, and churches’ roles in social-justice efforts. That’s certainly a departure from most coverage of LGBTQ issues in Maine’s mainstream media. In those outlets, Kang says, queerness is not treated culturally. Instead, “all these topics seem much more politically charged.”

That’s a lesson many Maine journalists could take to heart regarding not only gay culture but other aspects of Maine’s shifting demographics. Somali immigrants, for example, are interesting at times other than just when they’re running for political office or being attacked by anti-immigration activists. The same goes for people of other cultures and backgrounds.

>> Farewell This will be my last Press Releases column; managing editor Deirdre Fulton will take over starting next month. I’ll leave you with a few goals to hold the Maine media to in the coming year:

1) Ask candidates for electoral office (at all levels) hard questions about specific issues, rather than allowing the candidates themselves to set the discussion agenda — thereby neatly avoiding any controversial issues or having to actually take positions on important questions of the day.

2) Allow politicians to change their minds. But don’t let them pretend they didn’t, nor that their new position is functionally the same as the old one. People grow, learn, and change. Expecting people to hold the exact same positions and beliefs forever in effect demands that people remain as misguided and unenlightened tomorrow as they were yesterday. But, when public figures change their minds, they should be able to, and asked to, explain why and how that happened.

3) Lastly — and this is to everyone, whether you work in the media or not — remember that government works for us. We own the desks and filing cabinets in City Hall and the State House, and the documents stored in them. We own the computers and the servers in government offices, and the information stored on them. If a government official wishes to keep something secret, she must prove that she is legally allowed to do so. The burden is not on us as the public to force openness on government, but on government — and its (our) workers — to lay themselves and their records open in exchange for the privilege of serving with the public trust.

Never Again Dept.: Learning from FairPoint's disasters

Published in the Portland Phoenix

Two bills before the Maine legislature seek to pry lessons from the hard time FairPoint has had taking over the former Verizon landline operations in Maine since 2009. Both step up government oversight, in hopes of preventing future debacles.

The first, LD 1761, could in fact be called the “FairPoint: Never Again” bill. It reads like an admission that the Public Utilities Commission’s process around the FairPoint-Verizon takeover was a disaster.

It would require state regulators to review all mergers and sales of companies earning more than $50 million a year not just to the standard of “doing no harm” to Maine consumers (incidentally, a standard current PUC chairman Tom Welch admits the FairPoint deal did not meet — a pity he wasn’t on the PUC when the deal was being considered) but rather such a deal must offer a “net benefit” to Mainers.

It would also specifically require regulators to consider any proposed deal’s impact not just on consumers and ratepayers, but also on workers at the company involved, as well as the state’s overall economic-development goals.

The move specifically anticipates the possibility that FairPoint might be looking for a buyer. “The hedge funds that own FairPoint are looking for an exit strategy,” says Matt Schlobohm, executive director of the Maine AFL-CIO. Unions are key proponents of this bill because of its enhanced consideration of the labor force in deals involving utility companies, which are often unionized, as FairPoint is.

If FairPoint does plan to sell — and there is a handful of potential buyers, mainly regional landline companies — “we’re not well prepared to get a good outcome” for Maine, Schlobohm says.

He fears a repeat of the FairPoint deal, in which regulators approved a deal that was questionable at best (see “A Bad Idea Triumphs,” by Jeff Inglis, February 29, 2008), with certain conditions imposed, but then over time waived many of those conditions one by one (such as benchmarks for rolling out higher-speed Internet service to more customers in Maine). 

“Why would the state not want to have more leverage” when dealing with big companies that have outsize impacts on Maine, both as utilities providers and major employers, Schlobohm asks.

The second bill is even more directly aimed at FairPoint itself. This one, LD 1479, could be called the “Oh No You Don’t, FairPoint” bill. It secures legislative oversight, review, and approval of any PUC ruling in response to FairPoint’s recent request for $67 million in support from Maine telecom consumers to subsidize its service to rural Mainers with no other options for phone connectivity. That amount would be paid by raising the Maine Universal Service Fund surcharge on all telecommunications bills (including Mainers who do not use FairPoint’s services) by as much as $5 per line per month. (See “FairPoint Wants Bigger Subsidies, From All Mainers,” by Jeff Inglis, January 3.)

And it comes at a time when FairPoint’s stock price is recovering — largely because of the prospect it may resume issuing dividends. Investors are certainly clamoring for that to happen; dividends were curtailed in the original deal by order of state regulators, and ultimately done away with because the company couldn’t afford them.

“There’s a pattern here,” says Schlobohm. “The company seeks resources . . . they figure out where to get them . . . they’re sent very quickly to Wall Street.”

While he admits this may not be the case now, he observes that “there’s not much trust built” between FairPoint and Mainers.

The union does support the idea of having phone service available to every Maine home, but is not sure that FairPoint’s request is the best or most efficient way to achieve that.

The online chef: Hungry for restaurant-quality scallops at home, one writer turns to YouTube

Published in the Portland Phoenix

A couple years back, I decided I wanted a new challenge in the kitchen. I love eating scallops at restaurants, and wanted to learn to make them myself. It turns out that home-cooked scallops are crazy-easy, super-delicious, and far cheaper than if you get them when you’re dining out.

But they’re intimidating: How do you get that crispy crust without burning the delicate mollusks? And how do you get them done just medium-rare in the middle, so they’re moist and flavorful, not rubbery and bland?

Recalling a previous year’s cooking lesson from Gordon Ramsay (he taught me how to cook delicious, tender scrambled eggs), I went to the same place I’d found Gordon: YouTube.

It’s truly surprising how much teaching is available on YouTube — and cooking lessons are no exception. I searched for scallops and came up right away with a 2008 video made by Bill King, who was then the executive chef at McCormick and Schmick’s seafood restaurants. (Searching for clams, mussels, oysters, or any other shellfish is similarly rewarding.)

King had a mouthwatering recipe for pan-seared scallops with sweet Thai chili and udon noodles. The video’s production value wasn’t that great, but I wasn’t there for a visual spectacle. The images and audio were clear, the instructions simple and basic, and the demonstration smooth.

I watched it, took notes, and watched it again. Then I went out and bought the ingredients: sweet Thai chili sauce, sesame oil, fresh sea scallops, and a couple packages of precooked udon noodles. (You can also get uncooked ones and make them yourself, just like pasta. I went for the easier option.)

It didn’t cost much; in fact, the scallops, which are so often expensive in restaurants, were under $7 for a solid handful that would serve two. (King’s example included three large scallops; I sometimes opt for four if they’re smaller.) The udon-noodle packets were a dollar apiece. The bottles of chili sauce and the oil were a few dollars each, but they’d keep and be available when I made more scallops later. Sure, it was more expensive than a couple of hamburgers, but not far off the price of steak, and much cheaper than lobster for two (even at today’s sea-bottom prices).

All that remained was to emulate a chef with formal training and decades of experience, in my own kitchen.

It didn’t quite work out the first time. Heeding King’s suggestion to have a very hot skillet, I ended up giving everything a nice layer of carbon. But I was learning, and I could see where I had gone wrong by comparing what happened in my pan with what happened in the video. I knew where I’d gone astray; in fact, I had indeed feared I was burning the noodles and the scallops while they were cooking. I hadn’t jumped in to lower the heat or stop the cooking earlier because I was on my first trial run and taking the directions very seriously.

I would not make that mistake again. It turns out — shocker! — that getting the cooking temperature right is crucial to preparing seafood properly (and, yes, other food too). My pan had been too hot, and I had left the noodles and scallops in the too-hot pan for a bit too long.

Still, I enjoyed the flavors, and was able to craft a plan for improving my performance next time.

And that’s perhaps the crucial rule of taking cooking lessons from YouTube: Test it out before you’re on the spot. If you’re cooking for a family gathering, or even just a hot date, don’t have that be the first time you’re trying to follow a video. Do it a couple times, even several, until you get it right.

Sure enough, a few days later, I was back at the seafood counter, buying more scallops, and then into the Asian section to grab some udon.

That time, I got the noodles right, but undercooked the scallops — I was too afraid of burning them and took them off the heat early. But I rescued them by returning them to the heat. (The removal-and-return to the pan meant the golden-brown crust wasn’t perfect, but I was making progress.)

It took a few more times — and a bad experiment cooking on a different stove at a friend’s house — before I felt confident in being able to make this dish reliably. And even now, I occasionally let them cook too long or too short, and have to make do with a substandard dish.

But it’s in my own home, with friends and family, and vastly cheaper than dining out. So I eat with relish! 

Make them yourselfHere’s the recipe; watch the video at: tinyurl.com/learntocookscallops.

Ingredients

>>Three to four sea scallops per person
>>One packet of pre-cooked udon noodles per person
>>Thai sweet chili sauce
>>Sesame oil

Procedure

>>Pat the scallops dry with a paper towel and then put them in a bowl with a small amount of Thai chili sauce atop each scallop, and a thimble-full or two of sesame oil apiece. Gently mix them with tongs or a spoon, to coat evenly. Set aside.
>>Heat a skillet on medium heat (ignore the video’s recommendation to have it very hot!), and lighly coat the pan with vegetable oil.
>>Put the udon noodle cakes in — only as many as will fit comfortably. Don’t pack them too close together. Now, don’t move them.
>>Cook them for 3-5 minutes, until you can see a golden-brown crust forming on the underside. You can peek carefully if you want to, or just flip them over and cook on the other side as well.
>>While they’re cooking on the second side, put a dab of the chili sauce on top, as well as a drop or two of sesame oil.
>>When they’re cooked through (they become more translucent and flexible), remove them from the heat and set them aside.
>>Wipe the pan with a dry paper towel, just to remove any debris or residue from the noodles.
>>Now return the pan to the heat (still medium) and put the scallops in.
>>Here’s the trick to getting the right crust on the scallops: Don’t touch them once they’re in the pan. Let them sit right where they are, sizzling, for about 2 minutes. (Three minutes if they’re much thicker than an inch.)
>>Then flip them over, revealing the very nice crust, and cook them for another two minutes on the other side.
>>Remove from the pan, and serve immediately.

Physicians now taking payment by bitcoin: Lower transaction costs, increased privacy protections lead some practices to accept controversial e-currency

Published in Healthcare IT News, Healthcare Finance News, and Medical Practice Insider

Whether looking to draw attention to their practices, experiment with new technology or simply have a bit of fun with their otherwise dreary financial operations, several American medical professionals are now accepting bitcoins, the Web-based virtual currency, in addition to dollars.

Bitcoin, a peer-to-peer, open-source digital currency network that was first launched five years ago, has been getting a lot of media attention lately – sometimes for dark stories such as those spotlighting its role as the currency of choice for Silk Road, an online black market for illegal drugs that was shut down by the FBI this past October.

But it's also getting strong positive attention, especially from Internet thought leaders, because the Bitcoin system, which depends on no centralized authority but rather a loosely affiliated community of techies, offers some key breakthroughs in the areas of information exchange – particularly between parties unknown to each other – and digital cryptography.

The legal status of this so-called cryptocurrency is in flux worldwide, as various policymakers, monetary bodies and tax agencies get up to speed on its true ramifications.

In the meantime, curious people can still educate themselves and explore this new payment alternative without fear and in relative safety.

Doctors who have taken bitcoins have found that doing so is both simple and relatively "unmagical," as San Francisco physician Paul Abramson, MD, put it.

Abramson, founder of My Doctor Medical Group, is a former software programmer and trained electrical engineer with a significant personal interest in privacy.

It was privacy that drew him to learn more about bitcoins. Early assessments of the technology suggested the bitcoin exchange system had significant anonymity protections that could augment existing medical privacy laws and allow patients who sought the ultimate discretion a nearly invisible form of payment.

"It's important for people to be able to maintain their privacy" about all things, but particularly medical issues, Abramson said.

However, as bitcoin use has expanded, further exploration of its privacy protections has shown that, while it does take some effort to uncover a bitcoin user's identity, it is possible.

"As I've learned more about it," said Abramson, "I'm less excited about the anonymous possibility."

In any case, patients in his office seeking medical attention can't very well protect their identity from him – which removes one possible benefit of using bitcoins: the anonymity between buyer and seller.

Despite the media hype and controversy surrounding this new currency, Abramson is almost blasé about the fact that he accepts bitcoins.

"It's actually not that big a deal," he said.

But the benefits do exist. For instance, taking transactions out of the hands of credit card companies can preserve patient privacy, as those organizations can legally access certain protected health information for the purposes of verifying the transactions.

And, as a business practice, accepting bitcoins has real potential to save Abramson money.

He uses a fairly simple setup, where he has a merchant account with a company that handles bitcoins; when he receives bitcoins, that company handles converting them into U.S. dollars. The company charges a 1 percent fee – which is less than the typical 2 or 3 percent transaction processing fee charged by credit card companies.

This method is in fact in common use throughout the bitcoin community: People contemplating a purchase buy bitcoins with dollars, and then, in exchange for goods or services, send them to a vendor, which then immediately converts the bitcoins back into dollars.

But it's only in the conversions where fees arise.

As John Gomez, MD, owner and medical director of RapidMed Urgent Care Center in Lewisville, Texas, points out, to transfer bitcoins from one person to another, there are "zero transaction fees. Zero. It's beautiful."

And there were no startup costs, because his office already had an iPad for other purposes. (One possible problem may arise there, as Apple has recently been removing bitcoin-related programs from its app store.)

Gomez's office manager, Barbie Fiorendino, says no patients have yet used bitcoins to pay for service, but customers are expressing curiosity and interest in the prospect – especially since a local television station did a story about the clinic and bitcoins in January. The clinic distributes printed literature with explanations, and also has a bitcoin section on its website.

Unlike Abramson, Gomez is not planning to convert his payments out of bitcoins. His accountant, who was "very open-minded" about him accepting bitcoins, said he should book his revenue as dollars according to the bitcoin exchange rate at the time of the transaction – and keep records for future years, when he might convert the bitcoins he received back into dollars.

At that time, he would have to calculate capital gains or losses for tax purposes.

His decision to keep his holdings in bitcoins is "a personal belief," he added. "I consider myself a future rich man" because of bitcoins' value prospects, he said.

"There will be ups and downs and there will be potential manipulations," said Gomez, but "in the long run, I think that it's a smart play."

Gomez is more enthusiastic about bitcoins than Abramson – perhaps even qualifying as somewhat of an evangelist.

"I am, generally speaking, an early adopter of technology," Gomez said. Beyond that, "I have certain, I guess you would say politically libertarian leanings," he said.

He is among the many bitcoin enthusiasts who are particularly excited about the existence of a relatively secure currency that is not controlled by a government or other central authority.

Rather, the Bitcoin system is managed by software and mathematical principles, and is made possible by a peer-to-peer network that shares the burden of tracking bitcoins to ensure nobody counterfeits any, or spends the same bitcoin twice.

"It is an abstract concept at first," Gomez admitted – but said that's really no less foreign than the idea that swiping a credit card is a functional stand-in for exchanging dollar bills.

Meanwhile, government regulators are paying close attention, with several countries, the U.S. included, studying how to track – and tax – bitcoin transactions. How those regulations shape up will likely determine the degree to which bitcoins become more widespread, Abramson said.

It's not always easy to use bitcoins, as Wall Street Journal writer Anne Kadet found when visiting various New York City businesses that take them.

"This took some doing," she wrote in January. At one point, using bitcoins was so technologically "cumbersome" that it was "looking like the worst currency ever."

But Gregory Levitin, MD, a Manhattan physician and assistant clinical professor of otolaryngology at the New York Eye and Ear Infirmary, believes bitcoins can help people improve access to medical care.

Levitin, who has patients around the world, was in India and not available for an interview. But in a December press release announcing his acceptance of bitcoins, he said he hoped the move "will open doors to treatment options and follow up care for patients the world over," by allowing them to use "a universal or virtual currency."

One area where Gomez and Abramson agree is the fact that bitcoins are not particularly useful when it comes to their business operations.


Gomez said he wishes more vendors and suppliers took bitcoins. (He has convinced the person who cuts his hair to accept them in payment, however, and he's also ordered items from Tiger Direct, an online retailer that accepts bitcoins.)

Likewise, Abramson says he has nobody with whom he can really do business in bitcoins. His landlord won't take them, and he has asked his employees if they want to be paid in bitcoins, but they have all declined.

There is, however, a cupcake store near his office that accepts them.

Further thoughts on bitcoin

Dos and don'ts

If you're not sure about setting up your practice to accept bitcoins, consider the following suggestions:

"If you don't believe in bitcoin, don't bother," Gomez said. Abramson echoes this, suggesting people not accept bitcoins "unless you understand the potential ramifications," including keeping your bitcoin account information secure (if it's lost, your bitcoins are gone forever, with no way to recover them), as well as exchange-rate fluctuations and government regulatory moves. And it's important to follow new developments in this rapidly changing community.

If you do accept them, Gomez suggested holding them, reflecting his belief that bitcoins will appreciate in value over time. Abramson said just the opposite, calling people who hang onto bitcoins "gamblers" playing a market that has fluctuated wildly, hitting highs of over $1200 per bitcoin in early December to around $600 right now.

That said, "it's easy to take bitcoin," Abramson said. "As a technology I think it's very interesting." He suggests accepting bitcoin "for amusement value," or perhaps as "a marketing move."

Changing behavior

Paul Abramson, MD, of My Doctor Medical Group in San Francisco offers addiction treatment as one of his services, and has found that accepting bitcoins brought him some unexpected business.

"I had some patients who had been buying drugs with bitcoins on Silk Road," an illegal-drug marketplace website that only handled transactions in bitcoins, but was shut down by the FBI in October 2013. "They had been buying heroin with bitcoins."

When they were no longer able to buy high-quality heroin, they decided to seek help from him instead.

As he observed, "you could buy both drugs or drug treatment with bitcoins." But then, "the same is true of hundred-dollar bills, so it's really not that novel."

Bad advice?

CoinMD, a website where users can ask medical questions from a group of anonymous people who claim to be doctors – paying for their advice in bitcoins, has been called "the absolute worst place on Earth to spend your bitcoins," by Wired.

While many of the site's advice givers may be well-intentioned and knowledgeable, and its convenience when it comes to diagnosing minor ailments may seem obvious, Wired points out that "no legitimate licensed physician" would take part in a project like this because they "they would risk losing their license." CoinMD doesn't define how it tracks its contributors or vets their credentials.

So while the idea behind the site might be great in theory, as Iltifat Husain, MD, a practicing emergency physician the editor-in-chief of iMedicalApps, explained to Wired, there's a "tremendous" risk of getting poor advice or a wrong diagnosis. "I would never recommend this site to a patient," he said.