Niacin therapy shows no benefits, has some harmful effects

Mar. 9, 2013 ? A highly anticipated study evaluating a combination of the vitamin niacin with the anti-flushing agent laropiprant finds the therapy provides no benefit to and may even be harmful for patients with vascular disease, according to research presented today at the American College of Cardiology's 62nd Annual Scientific Session. Detailed trial data is presented here for the first time.

Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) is the largest-ever study of niacin, commonly used to raise high-density lipoprotein (HDL) or "good" cholesterol and lower low-density lipoprotein (LDL) or "bad" cholesterol. The four-year study tested a combination of extended-release (ER) niacin with laropiprant in patients at risk for cardiovascular problems such as heart disease and stroke. The 25,673 patients in the study were randomized to receive ER niacin/laropiprant 2g/40mg or a placebo, and all received commonly prescribed LDL cholesterol-lowering medication simvastatin (with or without ezetimibe). The study did not meet the primary endpoint of reducing the chances of a major vascular event, defined as the composite of non-fatal heart attack or heart-related death, stroke, or need for angioplasty or bypass surgery. Patients receiving ER niacin/laropiprant had a similar number of major vascular events as patients receiving placebo (13.2 vs. 13.7 percent, p=0.29).

The study also found unexpected and significant excesses of bleeding (2.5 vs. 1.9 percent) and infections (8.0 vs. 6.6 percent) among the ER niacin/laropiprant patients. In addition, significantly higher numbers of patients receiving the study drug suffered serious known side effects including new onset diabetes (9.1 vs. 7.3 percent), diabetic complications (11.1 vs. 7.5 percent), gastrointestinal problems such as indigestion and diarrhea (4.8 vs. 3.8 percent), and skin issues including itching and rashes (0.7 vs. 0.4 percent).

"We are disappointed that these results did not show benefits for our patients," said Jane Armitage, FFPH, FRCP, professor at the University of Oxford and the lead author of the HPS2-THRIVE study. "Still, finding out a drug is not helping people is just as important as finding that it has benefits -- the net result is that people are healthier. Niacin has been used for many years in the belief that it would help patients and prevent heart attacks and stroke, but we now know that its adverse side effects outweigh the benefits when used with current treatments."

A high level of LDL cholesterol is a known risk factor for heart disease and stroke. Standard treatment for at-risk patients includes dietary and lifestyle changes, as well as commonly prescribed medications such as statins, cholesterol absorption inhibitors and resins. Still, heart disease and stroke continue to cause death and disability even in patients receiving these medications, notes Dr. Armitage, and there was hope that the addition of niacin to standard therapy would improve patient outcomes.

Niacin is a type of B-vitamin, but the therapeutic doses used to control cholesterol are about 100 times higher than the amount recommended as part of daily intake. Laropiprant was added to reduce the facial flushing caused by niacin. While there was some speculation that the trial's results may have been due to unexpected side effects of laropiprant, Dr. Armitage believes this is unlikely, as the lack of benefit on heart attacks and strokes is consistent with the recent AIM-HIGH study, which did not use laropiprant, and many of the side effects are known to be due to niacin.

In 2011, AIM-HIGH was halted early when researchers determined a lack of effect for niacin in reducing cardiovascular events. Some experts in the field dismissed AIM-HIGH's findings because of its smaller size and perceived lack of ability to demonstrate definitive outcomes. Dr. Armitage notes that the size and scope of HPS2-THRIVE make its findings about niacin's outcomes and side effects reliable.

Patients taking niacin preparations to prevent heart disease should consider talking with their health care providers to determine whether the therapy is appropriate to continue.

ER niacin/laropiprant has been approved in 70 countries and was being sold in 40. The Food and Drug Administration was awaiting results from HPS2-THRIVE to license the drug in the U.S. In response to preliminary findings, the drug manufacturer Merck announced in December 2012 that it no longer planned to take the drug before the FDA for approval and in January suspended ER niacin/laropiprant from markets worldwide.

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Source: http://feeds.sciencedaily.com/~r/sciencedaily/most_popular/~3/g0Rco0r7cNQ/130311101827.htm

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Interest Rate Hikes Might Come Sooner Than You Think

Tuesday, March 12th, 2013
By Michael Lombardi, MBA for Profit Confidential

The Federal Reserve has yet to announce when it will start to increase interest rates in the U.S. economy. Meanwhile, there seems to be disagreement within the central bank?s affiliates regarding its loose monetary policy.

The President of the Federal Reserve Bank of St. Louis, James Bullard, recently said, ?It?s important to start to remove accommodation?even when you go up to 1 percent or 1.5 percent, that?s still very easy monetary policy.? He added, ?It?s a matter of getting to a normal level of interest rates at the right time. I don?t think you want to wait until everything is exactly the way you?d expect it to be.? (Source: Saphir, A., ?Fed should raise rates in 2013, Bullard Says,? Reuters, February 6, 2013, last accessed March 12, 2013.)

In anticipation of the eventual end to the ?easy money? policies of today, the bond market is selling off. From the chart below, you can see that bond investors ran toward the security of 30-year U.S. bonds in early 2012. But one year later, 30-year U.S. bonds are losing ground. Actually, the 30-year U.S. bond market has been falling since the beginning of 2013.

Chart courtesy of www.StockCharts.com

The theory that?s making the rounds as to why the bond market is falling is that as the Federal Reserve continues to keep the interest rates artificially low while increasing the money supply, inflationary pressures are building up, and the Fed will eventually need to raise interest rates to fight inflation. Interest rate hikes might just come sooner than some might think; hence, the bond market, as a leading indicator, is reacting now.

While ?official? statistics might show inflation as tame, most people know the real story; the figures released by the government on the inflation rate do not reflect reality. Almost everything we buy today is more expensive than it was three years ago. Gas costs more; so does food. The stock market is inflating and real estate prices are rising again?all inflationary. The bond market, by declining since July of 2012, is telling us that something is wrong.

But contrary to those who believe the sell-off in the bond market will be steep, I believe it will be slow and gradual to begin (as it is now) and then it will speed up as we start to see more inflation pouring into the U.S. economy.

Bond investors who bought in mid-2012, when the bond prices were at their highest level ever, are running deep losses now. Caution and capital preservation are hands down the best strategy for bond investors today.

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Interest Rate Hikes Might Come Sooner Than You Think, 10.0 out of 10 based on 1 rating

Source: http://www.profitconfidential.com/interest-rates/interest-rate-hikes-might-come-sooner-than-you-think/

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Get Started With "Pay Per Click" Advertising ? City Bolt

In the world of online marketing, it is very crucial to know the best strategies to enhance your business. There are number of methods been employed by the online marketers to grow their competitive business. It would be very beneficial to look for wonderful advertising strategies that will help you to increase your page rankings as well as to earn good revenues for the same. There are several elements or tools that play a vital role in the success of a search engine optimization campaign and one such tool is PPC or pay per click advertising. It is an advertising medium that online marketers use on a regular basis. This method provides a number of benefits to webmasters that you cannot find elsewhere. If you have not considered getting involved with this strategy, there are two advantages for using pay per click advertising. Before we start with this method, let?s explore what PPC services are.

Pay per click advertising is one of the most successful internet advertising models, where you pay the advertising medium or host only when a visitor clicks on your advertisement. Many businesses normally use pay per click advertising to enhance search engine optimization and to create high link popularity to draw potential attention on the website. The most benefit you can acquire from this method is that you can save time and money. It is a simple strategy where you pay only when a customer sees your advertisement and clicks on it. Generally, it is difficult to find through print and electronic medium, the number of people seeing the advertisement. But in pay per click advertisement, you can actually calculate, estimate the number of visitors who actually clicked through ad to reach your website.

With planning and proper management, PPC ads can afford certain businesses many benefits. It can help build awareness and generate immediate traffic compared to organic method. If you need high quality traffic immediately and your budget allows you to run a cost effective advertising campaign, pay per click should form a vital part of your marketing strategy. The best thing about this method is that you can set your maximum daily budget as well as the minimum budget. It can be highly effective to bring your potential target audiences to your site. Depending on the niche that you are targeting you should select the target ads to draw attention from your potential customers. This method of advertising is very much popular as you need to pay only a small amount on add on the website.

Employing this method can do wonders for your online business. You should use proper pay per click metrics for analyzing the performance of your advertising campaign. Employing this strategy is very useful in terms of achieving good revenues on your business website. You can certainly get quick results. If you are new to this method, it is highly recommended to look for PPC services offered by the expertise companies. There are many companies in the market that provide these effective services at affordable rates.

Resources:
Ashley Anderson is the author of this article on Pay Per Click Advertising.
Find more information, about PPC Hero here

Source: http://citybolt.com/internet-and-businesses-online/ppc-publishing/get-started-with-pay-per-click-advertising.html

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Sleep discovery could lead to therapies that improve memory

Mar. 11, 2013 ? A team of sleep researchers led by UC Riverside psychologist Sara C. Mednick has confirmed the mechanism that enables the brain to consolidate memory and found that a commonly prescribed sleep aid enhances the process. Those discoveries could lead to new sleep therapies that will improve memory for aging adults and those with dementia, Alzheimer's and schizophrenia.

The groundbreaking research appears in a paper, "The Critical Role of Sleep Spindles in Hippocampal-Dependent Memory: A Pharmacology Study," published in the Journal of Neuroscience.

Earlier research found a correlation between sleep spindles -- bursts of brain activity that last for a second or less during a specific stage of sleep -- and consolidation of memories that depend on the hippocampus. The hippocampus, part of the cerebral cortex, is important in the consolidation of information from short-term to long-term memory, and spatial navigation. The hippocampus is one of the first regions of the brain damaged by Alzheimer's disease.

Mednick and her research team demonstrated, for the first time, the critical role that sleep spindles play in consolidating memory in the hippocampus, and they showed that pharmaceuticals could significantly improve that process, far more than sleep alone.

In addition to Mednick the research team includes: Elizabeth A. McDevitt, UC San Diego; James K. Walsh, VA San Diego Healthcare System, La Jolla, Calif; Erin Wamsley, St. Luke's Hospital, St. Louis, Mo.; Martin Paulus, Stanford University; Jennifer C. Kanady, Harvard Medical School; and Sean P.A. Drummond, UC Berkeley.

"We found that a very common sleep drug can be used to increase verbal memory," said Mednick, the lead author of the paper that outlines results of two studies conducted over five years with a $651,999 research grant from the National Institutes of Health. "This is the first study to show you can manipulate sleep to improve memory. It suggests sleep drugs could be a powerful tool to tailor sleep to particular memory disorders."

A total of 49 men and women between the ages of 18 and 39 who were normal sleepers were given varying doses of zolpidem (Ambien) or sodium oxybate (Xyrem), and a placebo, allowing several days between doses to allow the pharmaceuticals to leave their bodies. Researchers monitored their sleep, measured sleepiness and mood after napping, and used several tests to evaluate their memory.

The researchers found that zolpidem significantly increased the density of sleep spindles and improved verbal memory consolidation.

"(P)harmacologically enhancing sleep spindles in healthy adults produces exceptional memory performance beyond that seen with sleep alone or sleep with the comparison drug (sodium oxybate)," the sleep researchers wrote. "? The results set the stage for targeted treatment of memory impairments as well as the possibility of exceptional memory improvement above that of a normal sleep period."

Mednick said one of the next steps in this line of research is to determine which component of the physical response to Ambien -- the amnesia associated with the drug, or something related to a specific aspect of sleep -- is responsible for increasing the density of sleep spindles and the resulting consolidation of memory. She also hopes to study the impact of zolpidem on older adults, who experience poor declarative memory and also decreased sleep spindles. Individuals with Alzheimer's, dementia and schizophrenia also experience decreases in sleep spindles.

"Could we find a dose response, for example, the more Ambien, the more benefit?" she asked.

Sleep is a very new field of research and its importance is generally not taught in medical schools, Mednick said.

"We know very little about it," said Mednick, who began studying sleep in the early 2000s with research into how naps benefit perceptual learning. "We do know that it affects behavior, and we know that sleep is integral to a lot of disorders with memory problems. We need to integrate sleep into medical diagnoses and treatment strategies. This research opens up a lot of possibilities."

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The above story is reprinted from materials provided by University of California, Riverside. The original article was written by Bettye Miller.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. S. C. Mednick, E. A. McDevitt, J. K. Walsh, E. Wamsley, M. Paulus, J. C. Kanady, S. P. A. Drummond. The Critical Role of Sleep Spindles in Hippocampal-Dependent Memory: A Pharmacology Study. Journal of Neuroscience, 2013; 33 (10): 4494 DOI: 10.1523/JNEUROSCI.3127-12.2013

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/living_well/~3/sl2BUe74afk/130311173347.htm

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Discovery may explain how prion diseases spread between different types of animals

Mar. 11, 2013 ? Medical researchers at the University of Alberta have made a discovery that may explain how prion diseases, like chronic wasting disease and mad cow disease, adapt in order to spread between various types of animals.

The research team, led by neurologist Valerie Sim, discovered that a miniscule change in the prions' makeup appears to give the disease the ability to adapt -- to mimic and recreate new strains with which it comes into contact. The team has been studying this area for two years.

"Prion diseases don't always successfully go from one animal to another, but when they do, the process is called adaptation. And we want to figure out what triggers that process to happen, what changes happen within prions to allow the disease to spread," says Sim, a researcher with the Faculty of Medicine & Dentistry, whose discovery was recently published in the peer-reviewed Journal of Biological Chemistry.

"One of the important things researchers in this field have realized is that if you pass certain strains of prion disease through a number of different hosts, the disease can adapt along the way and increase the number of susceptible hosts. That's the big concern right now.

"We want to determine why one prion disease might be able to spread from one type of animal to another and why another strain of the disease can't."

For instance, if a deer with chronic wasting disease is scavenged by another animal, could the prion disease cross into that intermediate host, evolve and then infect animals or species typically not at direct risk for the disease.

"We hope to understand how these bigger issues develop," says Sim. "We need to pay attention to chronic wasting disease in particular because it has the ability to spread in a different way than mad cow disease. Chronic wasting disease prions can be deposited into the soil and stay there for years, and could be eaten by another animal. How does it evolve from there then?"

Sim and her team are continuing their research in this area and are seeing impressive results in the lab -- reconfirming their findings through the testing of additional models.

Sim works in the Department of Medicine in the Division of Neurology. She is cross-appointed to the Centre for Neuroscience and the Centre for Prions and Protein Folding Diseases.

Her team's research was funded by Alberta Innovates -- Health Solutions (AIHS), PrioNet Canada and the Alberta Prion Research Institute.

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The above story is reprinted from materials provided by University of Alberta Faculty of Medicine & Dentistry, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. L. M. Cortez, J. Kumar, L. Renault, H. S. Young, V. L. Sim. Mouse Prion Protein Polymorphism Phe-108/Val-189 Affects the Kinetics of Fibril Formation and the Response to Seeding: EVIDENCE FOR A TWO-STEP NUCLEATION POLYMERIZATION MECHANISM. Journal of Biological Chemistry, 2013; 288 (7): 4772 DOI: 10.1074/jbc.M112.414581

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/fPw_ZBsQXVs/130311124205.htm

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Karzai accuses U.S., Taliban of working together

Erin A. Kirk-Cuomo / Dept. of Defense via AFP - Getty Images

U.S. Secretary of Defense Chuck Hagel speaks with Afghan president Hamid Karzai during a private meeting in Kabul.

By Mirwais Harooni and Phil Stewart, Reuters

KABUL ?Afghan President Hamid Karzai ratcheted up his criticism of the United States on Sunday, marring a debut visit by the new U.S. defense secretary, Chuck Hagel, and highlighting tensions that could undermine Washington's strategy to wind down the unpopular war.

A day after two Taliban bombings killed 17 people, Karzai accused the United States and the Taliban of colluding to convince Afghans that foreign forces were needed beyond 2014, when NATO is set to wrap up its combat mission and most troops withdraw.

"Those bombs that went off in Kabul and Khost were not a show of force to America. They were in service of America. It was in the service of the 2014 slogan to warn us if they (Americans) are not here then Taliban will come," Karzai said in a speech.

"In fact those bombs, set off yesterday in the name of the Taliban, were in the service of Americans to keep foreigners longer in Afghanistan."

It was one of several inflammatory comments by Karzai and his government on Sunday and follow weeks of efforts by the Afghan leader to curtail U.S. military activity in Afghanistan, including a call to kick American special forces out of an important province. U.S. commanders see special operations forces as key to the end-phase of the conflict.

U.S. Secretary of Defense Chuck Hagel responds to Afghan President Hamid Karzai's statements in which Karzai accused the U.S. and Taliban with working together.

Hours after Karzai's speech, Hagel said he spoke "clearly and directly" about the comments during his first meeting with the Afghan leader since becoming U.S. defense secretary on February 27.

Hagel appeared at pains to be respectful of Karzai and avoid sharp criticism, but he told reporters that any collusion between the U.S. and the Taliban "wouldn't make a lot of sense."

The U.S. and NATO commander in Afghanistan, General Joseph Dunford, was more categorical.

"We have fought too hard over the past 12 years, we have shed too much blood over the past 12 years, we have done too much to help the Afghan security forces grow over the last 12 years to ever think that violence or instability would be to our advantage," Dunford told reporters travelling with Hagel.

Of Karzai's remarks, he added: "I'll let others judge whether that's particularly helpful or not at the political level."

Still, politics will be key over the next several months, as the United States and NATO allies work to carry out their strategy of pulling out their troops and decide how large a residual force to leave behind after 2014.

NATO defense chiefs meeting in Brussels last month discussed keeping a combined U.S. and allied force of 8,000-12,000 in Afghanistan, focusing on training Afghan troops and countering the remnants of al Qaeda, the Pentagon has said.

Any deal for a follow-on force, which Washington says must include immunity for U.S. troops, would need Karzai's blessing.

ABUSING STUDENTS? TALIBAN TALKS?

Karzai has a history of making incendiary statements that exasperate Washington but the nature and awkward timing of his latest remarks about the United States were exceptional.

He also alleged on Sunday that the Taliban and the United States had been holding talks in the Gulf Arab state of Qatar on a "daily basis," further fuelling his suggestion that Washington and the militants were working at common purposes.

"I told the president that it was not true," Hagel said. "The fact is any prospect for peace or political settlements - that has to be led by the Afghans."

The Taliban spokesman in Afghanistan, Zabihullah Mujahid, denied that negotiations with the United States had resumed.

Karzai's government also alleged that U.S.-led forces and Afghans working with them were abusing and arresting university students. Karzai issued an executive order banning foreign troops from entering all education institutions.

Hagel and Karzai were meant to have appeared together at a joint news conference on Sunday evening. But, in a reminder of the threats posed by the resilient insurgency, U.S. officials said it was canceled because of security concerns.

Hagel was about a kilometer away and within earshot of a Saturday morning suicide attack outside the defense ministry that killed nine people. He was meant to have met his Afghan counterpart there this weekend but the venue was later changed.

Hagel's visit coincided with the passing of a deadline imposed by Karzai for U.S. special forces to leave Wardak province accusing them of overseeing torture and killings.

U.S. forces have denied involvement in any abuses.

Hagel has sounded hopeful that a deal could be reached on their continued deployment but acknowledged no breakthroughs were made in his talks with Karzai.

It was unclear how Hagel's trip would be viewed by U.S. Republicans who bitterly fought his nomination to become defense chief, portraying him as soft on Iran and questioning his judgment.

Hagel at times appeared sympathetic to the stresses of political life that Karzai must endure.

"I know these are difficult issues for President Karzai and the Afghan people. And I was once a politician," Hagel said. "So I can understand the kind of pressures - especially leaders of countries - are always under." ?

Additional reporting by Hamid Shalizi

?

Copyright 2013 Thomson Reuters. Click for restrictions.

Source: http://worldnews.nbcnews.com/_news/2013/03/10/17257872-karzai-accuses-us-and-taliban-of-conspiring-to-keep-troops-in-afghanistan?lite

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What vacuum cleaner should I buy? - DIY Home Improvement ...

Hello! I need to buy a new vacuum. Our current machine is 10 years old and it's always breaking down and making unnerving sounds. Yep.

I want something cheap and effective. It doesn't have to be fancy. Is anything from this guide to the best inexpensive vacuums a good choice for me? I am intrigued by that tiny Bissell vacuum at the end of the list that doesn't take any bags. Has anyone used something similar?

What is your favorite vacuum cleaner? Can I get it for around $100? If not, why should I save up some more money to get it?

Any advice is greatly appreciated!

Source: http://www.houserepairtalk.com/f114/what-vacuum-cleaner-should-i-buy-15682/

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