Atrasentan May Work in Diabetic Kidney Disease


Adding the endothelin receptor antagonist atrasentan to renin-angiotensin (RAS) blockade reduced albuminuria without major side effects in patients with diabetic nephropathy, researchers found.

Action Points

  • Atrasentan, a selective endothelin A receptor antagonist, further reduced albuminuria in patients with type 2 diabetes who were already receiving maximum tolerated doses of inhibitors of the renin-angiotensin system, researchers found.
  • Systolic and diastolic BP, LDL cholesterol and triglycerides were also reduced.

Both doses of the drug — 0.75 mg and 1.25 mg — significantly reduced residual albuminuria (by 36% and 39%, respectively) compared with placebo, Dick de Zeeuw, MD, PhD, of University Medical Center Groningen in the Netherlands, and colleagues reported online in the Journal of the American Society of Nephrology.

The higher dose of the drug did appear to prompt more fluid retention, indicating the 0.75-mg dose may be the optimal dose for future studies, they said.

“Although this study demonstrates that atrasentan treatment results in clinically significant albuminuria reduction with minimal fluid overload-related or cardiovascular side effects, a larger study on hard renal and/or cardiac outcomes is needed to further support these findings,” de Zeeuw said in a statement.

Clinical Need in Diabetic Nephropathy

Despite decent management with RAS inhibitors, patients with diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria — the protein that is not taken care of by initial RAS blockade. RAS inhibitors indeed slow the progression of chronic kidney disease in this population, but kidney function continues to deteriorate because of incomplete inhibition of RAS and by RAS-independent mechanisms, the researchers wrote.

Thus, there’s great clinical need for something that can minimize the residual albuminuria that RAS inhibition leaves behind.

“This represents a patient population with the highest unmet medical need among those with diabetes,” de Zeeuw said in a statement.

One of the RAS-independent mechanisms involves endothelin (ET)-1, which is elevated in diabetic nephropathy and promotes glomerulosclerosis.

Although ET-2 and ET-3 also exist, ET-1 is the most biologically active form, and it exerts its actions via two receptor subtypes, ET-A and ET-B. Most of the deleterious effects of ET-1 appear to be mediated through ET-A receptors, the researchers said.

Atrasentan is a highly selective ET-A antagonist that is being studied in the treatment of various types of cancer. This class of drug, however, has some potentially limiting side effects, including fluid retention. Earlier trials have also shown an increased risk for heart failure in type 2 diabetes — but the present study authors have been critical of the doses used in those trials.

Study Findings

To assess whether atrasentan could further reduce albuminuria when given with maximum tolerated doses of RAS inhibitors, de Zeeuw and colleagues assessed 211 patients with type 2 diabetes, who had urine-to-albumin ratios of 300 to 3,500 mg/g, and eGFRs of 30 to 75 ml/min.

For 12 weeks, patients were given placebo or one of two doses of atrasentan: 0.75 mg/day or 1.25 mg/day. The researchers found that both doses of atrasentan significantly reduced residual albuminuria compared with placebo.

Other findings in the 0.75-mg and 1.25-mg dose groups, respectively, included:

  • Residual albuminuria levels fell by more than 30% in 51% and 55% of patients
  • Urine albumin-to-creatinine ratio fell by 35.8% and 43.6% by the end of 12 weeks
  • 24-hour ambulatory systolic blood pressure fell by 4.5 mm Hg and 5.4 mm Hg
  • 24-hour diastolic blood pressure fell by 4.2 and 4.6 mm Hg, although eGFR and in-office blood pressure didn’t change
  • Total cholesterol fell by 16.8 and 18.6 mg/dL
  • Triglycerides fell by 30.2 mg/dL and 47.9 mg/dL
  • LDL fell by 14.6 mg/dL for both doses, compared with placebo

 

The 1.25-mg dose of the drug did, however, carry a significant 0.9-kg increase in weight compared with placebo; there was a 0.4-kg increase with the lower dose, but it wasn’t significant. The researchers also found a small but significant decrease in hemoglobin and hematocrit in both drug groups.

But there were no differences in peripheral edema, heart failure, or other side effects between groups – and the change in the dose of diuretics wasn’t different between treatment groups.

Yet more patients on the 1.25-mg dose discontinued due to adverse events, particularly fluid-overload-related conditions such as edema, facial edema, and anemia, the investigators reported.

“Although atrasentan increased weight, the incidence of peripheral edema, congestive heart failure, and other adverse events was similar between treatment groups,” de Zeeuw emphasized in the statement.

After stopping the drug for 30 days, all measured parameters returned to pretreatment levels, they added.

“One may wonder why endothelin antagonists have not yet emerged in clinical practice, despite their clear, preclinical renoprotective profile,” they wrote, noting past trials that have found volume-related side effects and potential liver effects.

All of these studies, however, show that endothelin antagonists “have a narrow therapeutic window, and working within this window may be the key to success,” they said.

The 0.75-mg dose had a strong albuminuria-lowering response, did not cause side effects such as hyperkalemia and hypotension, and looked unlikely to cause major cardiovascular problems – in fact, the blood pressure and lipid-lowering effects, they wrote, may reduce vascular events.

They concluded that their findings “make this drug an interesting candidate for clinical development to reduce the unmet need in diabetic renal disease progression.”

Dosing in Future Trials

In an accompanying editorial, Kiran Chandrashekhar, MD, and Luis Juncos, MD, of the University of Mississippi Medical Center in Jackson, called attention to the 1,392-patient ASCEND trial which looked at the effect of avosentan — also an endothelin antagonist — on progression of diabetic nephropathy.

The drug significantly reduced proteinuria but the trial was stopped early because avosentan was associated with a greater incidence of serious adverse cardiovascular events, particularly edema and heart failure, showing that fluid overload limited the usefulness of the drug.

“In hindsight, the side effect profile of ET-1 antagonists should be of no surprise because of the complexity of the ET system,” they wrote.

The editorialists also called attention to a second study in the same issue of the journal, which used a mouse model to elucidate the functional significance of the ET-A and ET-B receptors on podocytes in diabetic kidney injury. This study concluded that contrary to previous thinking, the ET-B receptor may also interact with ET-1 and related proteins.

The findings “call into question the strategy of the clinical trials targeting the ET-A receptor to avoid the side effects attributed to ET-B blockade,” Chandrashekhar and Juncos wrote.

They also noted that the de Zeeuw study is an extension of previous dose-response study byDonald Kohan, MD, PhD, of the University of Utah in Salt Lake City, and colleagues. For their study, de Zeeuw and colleagues screened patients carefully to avoid enrolling those who already were fluid overloaded or prone to fluid overload, the editorialists noted.

The fact that they identified a dose of atrasentan (0.75 mg) that provides a favorable risk-benefit profile will be important for future studies, they wrote, calling it a “positive step forward” but only “one of several” that need to be taken.

“These two papers … considered together represent an outstanding example of translational extension of basic research into novel therapies for a major form of chronic kidney disease,” Chandrashekar and Juncos wrote.

Juncos is a regional investigator in the ongoing phase III SONAR study looking at the effect of atrasentan on progression of diabetic nephropathy, and he said this study will shed more light on the kidney and cardiovascular protective effects of the drug.

They cautioned, however, that “for ET blockers to realize their potential, further information must be obtained regarding the basic mechanisms of how and when they work.”

Heartbleed Bug Puts Millions Of Android Devices At Risk.


You might have changed all your passwords in the days since you learned of the Heartbleed bug, but if you’re one of millions of people using certain Android devices, you might still be vulnerable.

Numerous devices running older versions of Google’s Android operating system may be at risk of the high-profile bug, according to Marc Rogers, a security expert at the mobile security firm Lookout.

Rogers told The Huffington Post that people using Android version 4.1.1 should avoid sensitive transactions on their mobile devices because a hacker could exploit the Heartbleed bug to steal their data.

“The whole device is vulnerable, so you should be cautious about the kind of sites you use,” Rogers said in an interview. “I’d be cautious about doing banking on your phone.”

Last week, researchers revealed that a flaw in a popular method of securing online transactions allows hackers to steal passwords, credit card data or even Social Security numbers from two-thirds of websites. Experts have since warned the bug also affects home routers and other Internet-connected devices because many companies use the flawed OpenSSL software to secure their products.

There is no evidence yet that hackers have exploited the flaw to steal data from smartphones. But Rogers said a hacker could take advantage of the Heartbleed bug if people open a malicious website on a vulnerable phone while doing online banking on that device. A hacker could jump from the malicious website to the banking website to steal sensitive data like passwords, he said. Rogers added that such an attack was complex and the likelihood of it happening was relatively low.

But as many as 50 million Android devices worldwide may be vulnerable to the Heartbleed bug, according to the Guardian. A Google spokesperson said less than 10 percent of devices run on the vulnerable Android operating system. About 1.1 billion devices are expected to run on the Android operating system this year, according to Gartner, a research firm.

Lookout has released a free app that lets Android users see if they are running a vulnerable version of the software on their phone.

Last week Google published a blog post that said the company had issued a patch to fix the Heartbleed bug in Android 4.1.1. But smartphone manufacturers and wireless carriers must also update the devices, and that takes time, Rogers said.

Rogers recommended that people using the old Android software update their operating system. If there are no updates available, they should contact their smartphone’s manufacturer to see if that device is now safe to use, he said.

The Heartbleed bug affects smartphones in other ways. Over the weekend,BlackBerry said it would update its messaging software after finding the service was vulnerable to the Heartbleed bug on Google’s Android software and Apple’s mobile operating system.

Rogers said the types of devices affected by the bug will grow in the coming weeks because the flawed encryption software was widely used. He said Internet-connected appliances and electronics like smart TVs may also be affected.

“I suspect we’re going to be finding these things for some time to come,” Rogers said.

10 Gigabit Wi-Fi coming in 2015.


Today, the fastest wireless network technology is the IEEE 802.11ac which is almost at par with an Ethernet connection of 1Gb/s. Before that, an IEEE 802.11n wireless was considered one of fastest throughput technology over Wi-Fi.

PCWorld reported that a new technology breakthrough from Quantenna Communications with the latest Wi-Fi chipset can deliver blazing speeds of up to 10Gb/s over the airwaves. Most wireless routers can simultaneously send and receive data using three spatial data streams, called 3×3 MIMO. With presently available wireless ac routers from brands such as Linksys, data delivery can reach throughput speeds of almost 1.3Gb/s using the 5GHz frequency band while ASUS’ recent announcement at the CES introducing a new router using Quantenna’s existing 4×4 MIMO chipset will give throughput speeds of up to 1.7Gb/s.

Yesterday, Quantenna announced that it was working on an 8×8 MIMO technology chipset, which can deliver an astonishing 10GB/s throughput speed. The new technology will incorporate all older standards, namely 802.11 a, b, g, n, and ac and will be based on MU-MIMO technology (multi-user-MIMO).

The new chipset is intelligent—it can deliver adaptive beam forming, in which the transmitter and receiver can analyse the exchanged signals and accordingly ascertain the optimal beaming path to reject unwanted signals in the air.

Quantenna says it expects the chipsets to be used in a wide range of applications, which include enterprise and consumer networking and also for ISP benefits, especially outdoor connectivity.

However, smartphones and tablets would not be able to benefit from this technology as yet since the company does not have any roadmap on developing 8×8 MIMO antennas for battery-powered appliances and USB Wi-Fi devices. Therefore, routers, PCIe cards, bridges, and notebook and desktop motherboards would be the only ones benefitting from the new high-speed technology.

How to Get Rid of Fatty Liver Disease.


Keeping your liver healthy and strong is one of the most important steps you can take to maintain overall wellness. This critically hard-working organ, which is located in the right abdominal area, has been called the “laboratory of the body,” and for many good reasons.  Researchers estimate that the liver performs over 500 functions in the body. Some of these include: Filtering all food and liquids, assimilating and distributing nutrients, and removing toxins and waste products. Creating bile, necessary for digestion of fats and other substances Burning and metabolizing fat and calories in the body Regulating hormones Purifying the blood and removes damaged blood cells Performing many necessary circulatory functions Balancing blood sugar Regulating fluid levels in the body Storing and distributing vitamins, minerals, and other crucial nutrients Boosting the immune system The liver is actively involved in keeping your body free from disease of all types.

How to Get Rid of Fatty Liver Disease

It is also true that a poorly operating liver can contribute to a mired of illnesses and debilitating health conditions. There are many types of liver disease and dysfunction, but the most common and hazardous is called fatty liver. What is Fatty Liver Disease? Fatty liver is also known as Non-Alcoholic Steatorrhoeic Hepatitis (NASH) or Non-Alcoholic Fatty Liver Disease (NAFLD). The technical description of fatty liver is quite complex, but basically fatty liver disease is just as it sounds – too much fat in and around the liver. In fact, healthy liver tissue can be displaced by unhealthy fats, and vacant spaces within the liver are abnormally occupied by fat. In addition, those with fatty liver disease will often accumulate excess fat surrounding the organ itself, contributing to an overabundance of body fat in the abdominal area. Nonalcoholic fatty liver disease affects as many as one in five Americans, according to the American Liver Association. And for those with diabetes, says VA physician-researcher Kenneth Cusi, MD, the rate may be as high as four in five.

A healthy liver is typically reddish in color because the blood is meant to flow through channels in the interior of the liver composed of layers of liver cells. This is the way the liver is meant to function – as a very efficient filter for absorbing nutrients and ridding the body of toxins. A fatty liver becomes clogged with excess fat cells, seriously hampering the liver’s ability to do its many vital jobs. A fatty liver loses its red color and becomes heavier, enlarged, and greasy yellow in appearance. These abnormalities can often be discovered by an ultrasound scan or via a liver biopsy. What Causes Fatty Liver Disease? Some common causes of fatty liver include: An unhealthy lifestyle of poor diet (high in animal fat. preservatives, and toxic chemicals), lack of exercise, and poor hydration. Obesity. This is probably the biggest factor in fatty liver, especially for people over 30. Medications. Many are very hard on the liver including pain drugs (NSAIDs and narcotics), corticosteroids, certain antibiotics (especially tetracycline), and others. Some causes are associated with the drug tamoxifen (used to prevent breast cancer recurrence). Complications of pregnancy Exposure to toxic cleaning products, personal care products, water, food, the air, etc. Excess alcohol consumption. May also occur in people affected by hypothyroidism (underactive thyroid gland), high blood cholesterol and polycystic ovarian syndrome. Simply put, the harder your force your liver to work because of exposure to hazardous substances and a high-fat, nutrient-poor diet, the greater your risk for fatty liver as well as other types of liver dysfunction. What Are the Symptoms and Complications of Fatty Liver? Symptoms that may point toward fatty liver disease include: Being overweight, especially around the abdomen Pain and tenderness near the liver Elevated liver enzymes (blood test) Possible gall stones High Cholesterol and/or blood triglycerides (blood test) Difficulty losing weight.

If you are having a difficult time taking off pounds, it may be because your fatty liver has reverted to storing fat instead of metabolizing it. A weakened immune system. This can open one up to a number of autoimmune and other harmful conditions. Chronic fatigue. When the liver is not able to rid the body of excess fat and other waste products, one will likely feel sluggish most of the time. Greater risk for diabetes. Fatty liver can result in insulin resistance, a key factor in diabetes. A recent study estimated that about 70% of individuals diagnosed with type-2 diabetes may also have fatty liver disease. Syndrome X. Also known as Metabolic Syndrome X, this condition can also be a complication of fatty liver. Syndrome X involves a number of factors including abnormally high blood pressure and/or insulin levels, too much cholesterol, and excess body fat around the waistline. Metabolic Syndrome increases risk for diabetes, stroke, and cardiac disease. How Can Fatty Liver Be Treated or Prevented? Obviously, prevention is always the best medicine. Fatty liver disease is definitely a “lifestyle” disease (in most cases) that can be prevented and even eliminated by making healthy choices. These include: A healthy diet composed mainly of nutrient-rich foods such as fresh, organic fruits and vegetables, essential fatty acids and plant-based protein sources. An ample supply of pure filtered water. A well-hydrated liver is a happy liver that can perform its many duties optimally. Supplementation (and pure food sources) of antioxidants such as vitamins C and natural E (containing tocopherols and tocotrienols). Liver supporting organic/wild-crafted herbs such as Milk Thistle seed, Wildcrafted Chanca Piedra (helps with liver stones), Fringetree bark, Dandelion root, Organic Nettles root and Organic Turmeric Root. There are several reasons to use the milk thistle seed rather than silymarin extract.

Using the whole herb is recommended as often it will have a more balanced effect. The milk thistle extract silymarin, for instance, has proven useful in treating liver disease. However, the main drawback to using silymarin is that, if a healthcare professional prescribes other drugs, such as steroids, silymarin can interfere with the liver’s ability to detoxify them. Milk thistle seed has the same healing effect on the liver without interfering with the organ’s ability to detoxify drugs or environmental chemicals. It also has a side benefit of normalizing blood lipids as the liver heals. To meet the above qualifications I recommend a product called LivaPure™. A regular program of physical exercise. Exercise helps the liver to purify as well as helps the body to effectively move toxins and wastes out of the body.

I highly recommend rebounding which helps with lymphatic drainage and allows one to effectively lose weight. Healthy weight. As stated above, obesity is one of the top allies of fatty liver disease. Liver cleansing. Choose an effective and non-toxic liver cleanse such as The Optimum Wellness Liver and Gallbladder Cleanse that will effectively flush, purify and support your liver so that it can operate at peak efficiency. There are many herbs that are great for the liver, but they should always be either be organic or wild-crafted. Even if you do your best to live a clean life, a yearly liver cleanse is highly recommended, to “head off trouble at the pass,” so to speak.

Google wants to fit an entire camera into a contact lens.


Google has applied for a patent that details a way to fit a camera into a contact lens.

The patent has to do with the tech giant’s smart contact lens project, which was first announced earlier this year. By fitting a camera into a contact lens, users could process all kinds of data that could then be relayed to a connected smartphone.

The patent, which was reported by Patent Bolt, outlines a way that Google could fit a camera into a contact lens without drastically increasing its thickness. A camera on a contact lens could be used to collect data from users’ surroundings, including light, colors, objects, faces and motion, according to the report.

That data could be quickly processed and used to provide users with information on a display within the contact lens. For example, a moving vehicle or the face of a nearby user could be highlighted by the smart contact lens — think “Terminator” vision.

The camera could also expand users’ eyesight. Patent Bolt said the camera could give users a wider view or also be used to zoom in, like a pair of binoculars.

For users with no eyesight, the smart contact lens with a camera could also be used. The camera could capture imagery and data that would then be relayed to a connected smartphone. That smartphone could process the data and give the blind user any relevant information. For example, if he or she walked toward an intersection, the phone could sound off an audible alert after the contact lens’ camera detected the upcoming road.

Google applied for the patent in late 2012, and it was published by the U.S. Patent and Trademark Office earlier this month, according to Patent Bolt.

Companies file for patents left and right, and often, the technology detailed in the patents does not make it into final products that are sold to consumers. But every now and then, some of it does go on sale.

Google could not be reached for comment.

Are Oldest Patients Getting Too Many Drugs?


Too many healthy people in their 80s and older are being treated with statins and antihypertensives for stroke prevention, according to British commentary inEvidence-Based Medicine.

Action Points

  • The author suggests that for patients over the age of 80 the literature indicates that the risks associated with the use of statins and hypertensives for primary prevention outweigh the potential benefits.
  • The author suggests that these medications are greatly overprescribed in the healthy elderly and largely irrelevant in the frail elderly, and we should require that the patient should be actively involved in the decision-making process.

And in those who are old and frail, the drugs are “largely irrelevant” for preventing strokes, wrote Kit Byatt, a geriatric medicine physician at Hereford County Hospital in England.

“The epidemiology suggests that, by this age, hypertension is not an attributable risk factor for stroke, and hypercholesterolemia has little effect on stroke risk overall,” he wrote. “The largest trials of antihypertensive therapy and statins in this age group show at best a marginal clinical reduction in stroke and very modest clinical reductions in other cardiovascular endpoints.”

Byatt pointed out that the HYVET trial of patients 80 and older showed that thenumber of people who would need to be treated for 2 years with antihypertensives to prevent one stroke was 94 (though the 30% relative reduction in all strokes fell just shy of statistical significance at P=0.06). When considering nonfatal strokes only, the number needed to treat over 2 years rose to more than 450.

In addition, in the PROSPER study — “arguably the definitive study of statins for stroke prevention in older people,” according to Byatt — treatment with pravastatin versus placebo reduced the composite of all strokes or cardiac events, but not strokes alone.

And on top of the lack of substantial benefit, there is some evidence that morbidity associated with statin use is under-reported, Byatt said.

“The data strongly suggest that we are overtreating many healthy patients aged 80+ regarding stroke prevention,” he wrote.

“We need actively to rethink our priorities and beliefs about stroke prevention, actively informing and involving the views of the key person, the patient,” he wrote. “Most of the patients will probably eschew the modest potential benefit, preferring the reduced burden of polypharmacy and side effects judged as ‘minor’ by the prescriber.”

The American Heart Association and American College of Cardiology have weighed in on the issue of treating hypertension in elderly individuals with a 2011 consensus document. In it, the authors noted that “drug treatment for elderly hypertensive patients has been generally recommended but with a greater degree of caution due to alterations in drug distribution and disposal and changes in homeostatic cardiovascular control, as well as quality of life factors.”

Most of the patients in hypertension trials were younger than 80, however.

“Pooling the limited number of octogenarians from several trials mainly composed of younger patients, treated patients showed a reduction in both stroke and cardiovascular morbidity, but a trend toward increased all-cause mortality compared to controls,” the authors of the statement wrote. “Thus, the overall benefits of treating octogenarians remain unclear despite epidemiological evidence that hypertension remains a potent cardiovascular risk factor in this age group.”

The reactions of several U.S. cardiologists contacted by MedPage Today to Byatt’s perspective were mixed.

William O’Neill, MD, of Henry Ford Hospital, supported Byatt’s viewpoint, saying in an email, “I wholeheartedly agree with the author that we over-prescribe medications in elderly, asymptomatic elders. I never start patients in their 80s on statins for primary prevention. If they have not had a cardiac event by that age, it is unlikely that they will during their life. Antihypertensives can cause severe orthostatic hypotension and I am very conservative with these agents.”

Also, “the polypharmacy that occurs with elders can be described as unsafe practice,” he continued. “I often see patients coming in with 15 to 20 different medications they are supposed to take. I honestly don’t know how they keep the medicines straight. I try to limit meds to three or four at most, and ideally at a once-a-day dose.”

Other clinicians took issue with Byatt’s dismissal of the importance of hypertension and of antihypertensive treatment in the oldest patients.

Daniel Lackland, DrPH, of the Medical University of South Carolina, responded to Byatt’s statement that hypertension is not an attributable risk factor for stroke by the time people reach age 80 by saying, “I do not feel that is a valid evidence-based statement. Elevated blood pressure is a stroke and cardiovascular disease risk factor at all ages, including the very old.”>

But, added Lackland, who was speaking for the American Heart Association, “In the elderly, there is little evidence of the benefit of blood pressure reduction.”

Byatt “failed to point out the increasingly important role that atrial fibrillation plays in stroke in the elderly (as many as one in three strokes in octogenarians have an association with atrial fibrillation),” commented John Erwin III, MD, of the Scott & White Heart and Vascular Institute in Temple, Texas. “The prevalence of atrial fibrillation is certainly increased in poorly controlled hypertensive people.”

Ken Uchino, MD, of the Cleveland Clinic, said, “I disagree with the author in de-emphasizing hypertension.”

“We cannot assume that because the contribution of hypertension is smaller as one gets older, that treatment would not reduce stroke,” he said.

Others, like Adam Skolnick, MD, of NYU Langone Medical Center, stressed that a distinction had to be made between primary prevention and secondary prevention.

“While for an older individual without known cardiovascular disease and without significant risk factors, these medications may not be indicated as primary prevention, for those patients with known cardiovascular disease they may prevent a disabling stroke or myocardial infarction,” he said. “If a patient has a prognosis greater than a year and has known cardiovascular disease, they should not be denied these therapies that have been proven to prevent cardiovascular events, which may reduce quality of life and independence.”

James Brorson, MD, of the University of Chicago, agreed.

“For patients with known history of atherosclerotic cardiovascular disease or stroke, treatment with cholesterol-lowering statin medications and treatment of high blood pressure remain the most effective treatments that we have for reducing stroke and mortality,” he said.

The question remains, though, about what to do for elderly patients in the realm of primary prevention with statins and antihypertensives, and Neil Stone, MD, of Northwestern Memorial Hospital’s Bluhm Cardiovascular Institute, said in an interview that the prevention guidelines released by the American College of Cardiology and American Heart Association in November provide some guidance on the use of statins.

Stone, who served as chair of the expert panel in charge of the cholesterol guidance, said that the guidelines do not make firm recommendations about the use of statins in patients older than 75 because of the relative lack of data in the oldest patients.

“But we recognize there could be factors where the patient and the physician may decide to use statin treatment,” he said, pointing to patients who were already taking a statin or those with diabetes as examples.

He stressed that the discussion between the clinician and patient about the risks and benefits of therapy is key for all age groups, although it may be more important for those older than 75.

“That’s because when there’s very little data, I think we need to absolutely include the patient into this decision and let the patient know what it’s based on,” he said.

Other clinicians echoed the importance of individualizing treatment decisions in the older age groups.

“It is always a case-by-case decision,” according to Erwin. “One is certainly going to treat a severely demented, fall-prone patient or a patient with metastatic cancer differently than one would an otherwise active and vibrant octogenarian. All 80-year-olds are not created equally.”

John Higgins MD, MBA, of the University of Texas Health Science Center at Houston (UTHealth), said that he believed statins and antihypertensives were used appropriately in all age groups in the U.S., but he also supported the need for a discussion between the patient and his or her doctor.

“While there are guidelines that aid in management, ultimately it is an individual decision between the physician and the patient, after weighing the risks and benefits of treatment as well as factoring in the patient’s quality of life, other medical conditions, risks for stroke and heart attack, and life expectancy,” he said.

Casual marijuana use linked with brain abnormalities, study finds .


Casual marijuana use may come with some not-so-casual side effects.

For the first time, researchers at Northwestern University have analyzed the relationship between casual use of marijuana and brain changes – and found that young adults who used cannabis just once or twice a week showed significant abnormalities in two important brain structures.

The study’s findings, to be published Wednesday in the Journal of Neuroscience, are similar to those of past research linking chronic, long-term marijuana use with mental illness and changes in brain development.

Dr. Hans Breiter, co-senior study author, said he was inspired to look at the effects of casual marijuana use after previous work in his lab found that heavy cannabis use caused similar brain abnormalities to those seen in patients with schizophrenia.

“The interaction of marijuana with brain development could be a significant problem.”- Dr. Hans Breiter, co-senior study author

“There were abnormalities in their working memory, which is fundamental to everything you do,” Breiter, a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine, told FoxNews.com.  “When you make judgments or decisions, plan things, do mathematics – anything you do always involves working memory.  It’s one of the core fundamental aspects of our brains that we use every day.  So given those findings, we decided we need to look at casual, recreational use.”

For their most recent study, Breiter and his team analyzed a very small sample of patients between the ages of 18 and 25: 20 marijuana users and 20 well-matched control subjects.  The marijuana users had a wide range of usage routines, with some using the drug just once or twice a week and others using it every single day.

Utilizing magnetic resonance imaging (MRI), the researchers analyzed the participants’ brains, focusing on the nucleus accumbens (NAC) and the amygdala – two key brain regions responsible for processing emotions, making decisions and motivation.  They looked at these brain structures in three different ways, measuring their density, volume and shape.

According to Breiter, all three were abnormal in the casual marijuana users.

“For the NAC, all three measures were abnormal, and they were abnormal in a dose-dependent way, meaning the changes were greater with the amount of marijuana used,” Breiter said.  “The amygdala had abnormalities for shape and density, and only volume correlated with use.  But if you looked at all three types of measures, it showed the relationships between them were quite abnormal in the marijuana users, compared to the normal controls.”

Because these brain regions are central for motivation, the findings from Northwestern help support the well-known theory that marijuana use leads to a condition called amotivation. Also called amotivational syndrome, this psychological condition causes people to become less oriented towards their goals and purposes in life, as well as seem less focused in general.

Given these eye-opening results,  Breiter said that more research is needed to look into marijuana’s effects on the brain – even in those who use the drug only once or twice a month.

“We need to see what happens longitudinally,” Breiter said. “What happens as you follow people over time?  What happens if they stop using – do these bad effects continue? What happens if you can intervene early?…My worry is we haven’t studied this compound and here we are looking to change legislation on it.”

Although Breiter’s team members did not examine the patients’ cognitive symptoms, they do believe that the brain abnormalities seen in their study could lead to substantial effects on brain development and behavior, especially given the young ages of the participants.  Breiter also acknowledged the problems of analyzing a very small study sample – but said that their findings should still serve as a wake-up call to others.

“This study is just a beginning pilot study, but at the same time, the results that came out are the same as a canary in a coal mine,” Breiter said.  “…The interaction of marijuana with brain development could be a significant problem.”

Study finds signs of brain changes in pot smokers


A small study of casual marijuana smokers has turned up evidence of changes in the brain, a possible sign of trouble ahead, researchers say.

Study finds signs of brain changes in pot smokers: A teenager smokes a marijuana joint at the Vancouver Art Gallery during the annual 4-20 day, which promotes the use of marijuana, in Vancouver, British Columbia April 20, 2013.

The young adults who volunteered for the study were not dependent on pot, nor did they show any marijuana-related problems.

“What we think we are seeing here is a very early indication of what becomes a problem later on with prolonged use,” things like lack of focus and impaired judgment, said Dr. Hans Breiter, a study author.

Longer-term studies will be needed to see if such brain changes cause any symptoms over time, said Breiter, of the Northwestern University Feinberg School of Medicine and Massachusetts General Hospital.

Previous studies have shown mixed results in looking for brain changes from marijuana use, perhaps because of differences in the techniques used, he and others noted in Wednesday’s issue of the Journal of Neurosciences.

The study is among the first to focus on possible brain effects in recreational pot smokers, said Dr. Nora Volkow, director of the National Institute on Drug Abuse. The federal agency helped pay for the work. She called the work important but preliminary.

The 20 pot users in the study, ages 18 to 25, said they smoked marijuana an average of about four days a week, for an average total of about 11 joints. Half of them smoked fewer than six joints a week. Researchers scanned their brains and compared the results to those of 20 non-users who were matched for age, sex and other traits.

The results showed differences in two brain areas associated with emotion and motivation — the amygdala and the nucleus accumbens. Users showed higher density than non-users, as well as differences in shape of those areas. Both differences were more pronounced in those who reported smoking more marijuana.

Volkow said larger studies are needed to explore whether casual to moderate marijuana use really does cause anatomical brain changes, and if so, whether that leads to any impairment.

The current work doesn’t determine whether casual to moderate marijuana use is harmful to the brain, she said.

Murat Yucel of Monash University in Australia, who has studied the brains of marijuana users but didn’t participate in the new study, said in an email that the new results suggest “the effects of marijuana can occur much earlier than previously thought.” Some of the effect may depend on a person’s age when marijuana use starts, he said.

Another brain researcher, Krista Lisdahl of the University of Wisconsin-Milwaukee, said her own work has found similar results. “I think the clear message is we see brain alterations before you develop dependence,” she said.

A Brutal Allergy Season Is Ahead. Blame the Polar Vortex.


“It’s going to be a hell of a pollen season.”

One week ago, I purchased the first asthma inhaler I’ve owned since the 8th grade. I’d shown up at my doctor’s office short of breath, and a lung function test promptly revealed that I was inhaling about one-fifth as much air as a healthy 24-year-old should be. “We’re expecting a lot of cases like you,” my doctor told me as he wrote my prescription. “It’s going to be a hell of a pollen season.”

And for that, you can blame the polar vortex—the extreme cold system that repeatedly hovered over much of the United States this year—along with the rest of this winter’s brutal weather. Those cold snaps helped spawn a spring allergy season so intense that it already has its own headline-ready nickname: the “pollen vortex.”

“The long winter, the particularly cold weather, it all pushed the pollen season back quite a bit,” says Estelle Levetin, the chair of the biology department at the University of Tulsa. Individual flowering trees probably aren’t producing more pollen, Levetin says—but they’re all dumping their pollen at once, making this allergy season particularly difficult for people who are sensitive to more than one type of pollen.

The simple reason is that flowers are temperature-sensitive. They don’t open up and release pollen when it’s cold. “If you look at daily pollen levels, typically, you would see them track the temperature,” Levetin says. Trees that normally would have bloomed several weeks ago are just budding now. In Oklahoma, where Levetin lives, the first allergenic trees blossomed “easily a month late.”

The Asthma and Allergy Foundation of America counts 45 million people in the United States who suffer from nasal allergies, and another 25 million with asthma—both conditions that can be can be aggravated by pollen. Those figures come with sweeping economic consequences. Every year, asthma costs $18 billion in hospital visits and lost workdays, according to the AAFA.

This week may offer some relief, thanks to the relationship between cold weather and pollen counts. People living in the West are already experiencing lower pollen levels due to the cold front moving across the country. When it hits, the cold slows the release of pollen. But unless a region undergoes freezing temperatures for several days, says Levetin, once warm weather returns, so will the pollen deluge.

While no single weather event—the cold snaps that caused this year’s pollen vortex, for example—can be directly attributed to global warming, the science community is engaged in a lively debate over whether climate change is making unusual weather events, including severe cold temperatures, more likely. Jennifer Francis, a research professor at Rutgers University, argues that the rapidly warming Arctic has caused the jet stream to slow, which could result in atmospheric events, such as winter storms, staying put for longer.

But even if climate change can’t be blamed for this year’s pollen vortex, there is substantial evidence that a warming planet spells a more agonizing allergy season. Cold weather may have caused the current pollen backlog, but over the long term, the opposite may be true. Hotter temperatures, an increase in atmospheric carbon dioxide, and greater precipitation levels in some regions of the United States all conspire to create near-ideal conditions for the weedy plants that give off allergenic pollen, according to a 2008 study from the Environmental Protection Agency. “Warmer temperatures and increased precipitation cause some plants to grow faster, bloom earlier, and produce more pollen,” the study found. “Temperature changes are expected to alter allergy seasons to begin earlier and last longer and the distribution of allergenic plant varieties to change over time.”

The EPA is hardly alone in saying that climate change could make allergy season more hellish. A 2010 report by the National Institute of Environmental Health Sciences warns, “There is also a possibility that certain aeroallergens may become more allergenic as temperatures and CO2 concentrations increase.” (Besides exacerbating the pollen count, climate change is linked in some regions to a rise in ozone, fine particles, and dust—all of which can cause or worsen respiratory diseases, the report found.)

Plant physiologists have observed that the weeds that produce many allergens have adapted the best to an atmosphere that is chock-full of carbon dioxide,Scientific American reported in 2012. Pollen from ragweed, for instance, which peaks in the summer and is one of the most common triggers for allergies, has exploded as the climate has warmed. From 1995 to 2011, according to the EPA, the ragweed allergy season grew up to 24 days longer in regions across the Midwest:

As the map suggests, northern regions of the United States, where warming in more pronounced, will bear the brunt of increases in most types of environmental allergens. Warmer temperatures are already allowing hickory and oak, two highly allergenic tree species, to thrive in new regions. In the United Kingdom, the Health Protection Agency has observed that the hay fever season is growing longer.

The future may offer a reprieve from agonizing allergy seasons. Leonard Bielory, an environmental sciences professor at Rutgers, predicted in Scientific American that a warming planet will eventually cause pollen counts to taper off. “It cannot continue on a linear scale,” he said. “If heat goes up to a certain temperature, plants will die. It will hit a breaking point.” Of course, at that point, a prolonged allergy season won’t be high on the list of problems.

FDA Approves New Type 2 Diabetes Drug Tanzeum (albiglutide).


Millions of Americans with type 2 diabetes have a new treatment option with the U.S. Food and Drug Administration’s approval Tuesday of a once-weekly injectable drug, Tanzeum.

The FDA described Tanzeum (albiglutide) as a “glucagon-like peptide-1 (GLP-1) receptor agonist — a hormone that helps normalize patients’ blood sugar levels.

Tanzeum “can be used alone or added to existing treatment regimens to control blood sugar levels in the overall management of diabetes,” Dr. Curtis Rosebraugh, director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, said in an agency news release.

The FDA’s approval of the drug was based on eight clinical trials that included more than 2,000 people with type 2 diabetes. Those who took Tanzeum showed improvements in blood sugar control. The drug has also been studied for use in combination with other diabetes medications such as metformin, glimepiride, pioglitazone (Actos) and insulin.

The most common side effects seen with Tanzeum were nausea and/or reactions at the site of injection, the FDA said.

The drug, which is manufactured by GlaxoSmithKline, is not approved to treat Type 1 diabetes, the FDA noted.

The drug will carry a boxed warning stating that the use of some GLP-1 receptor agonists have been associated with thyroid tumors in rodents. The FDA said Tanzeum should not be prescribed for patients with a personal or family history of a type of thyroid cancer called medullary thyroid carcinoma (MTC), or for patients with Multiple Endocrine Neoplasia syndrome type 2. Patients with this disease have tumors in more than one gland in their body and are at increased risk for MTC.

Dr. Spyros Mezitis is an endocrinologist at Lenox Hill Hospital in New York City. He said Tanzeum joins a list of other approved injectable diabetes medicines, including Victoza (liraglutide), Byetta (exenatide) and Bydureon (exenatide extended release).

“Post-marketing clinical trials are planned to examine cardiovascular effects, use in pediatric patients, and possible increase in pancreatitis or medullary thyroid cancer,” Mezitis said. “The results of these clinical trials will determine which GLP-1 agonists will be more useful” to patients.

According to the FDA, about 24 million people in the United States have type 2 diabetes, which accounts for more than 90 percent of all diabetes cases diagnosed in the United States. Over time, the high blood sugar levels produced by diabetes can increase the risk for serious complications, including heart disease, blindness, and nerve and kidney damage.