Saturday, November 30, 2013
Friday, November 22, 2013
by Deanna Pogorelc, medcitynews.com
October 30th 2013 10:53 AM
The breathalyzer test isn’t just for drunk drivers. In medicine, breath tests are used to screen for h. pylori, lactose intolerance and whether asthma medications are working, to name a few.
Because the breath contains over a thousand compounds at trace levels, it’s also become an appealing target for non-invasive tests that would help doctors detect and diagnose disease.
There are some barriers to breath-based biomarkers, namely the need for expensive technology used to analyze the presence and concentration of those chemicals. While much of the following research is early, it sheds light on the possibilities being explored for new non-invasive diagnostics.
Researchers at the Cleveland Clinic recently presented research on a breath biomarker for lung cancer. A test they’re developing uses a chemical sensor called a colorimetric sensor array that picks up on a unique chemical signature released by cancer cells as tumors grow.
Cleveland Clinic researchers have also identified VOCs that correlate with the presence of cardiovascular disease. In a study published earlier this year in the Journal of the American College of Cardiology, they collected breath samples from 77 patients and used mass spectrometry to look for those compounds. The researchers reported that the technique identified all of the patients who experienced heart failure. The question is — would it be able to do so early enough to make a difference in outcomes?
A few different groups are working on detecting a chemical called acetone in the breath that increases when the body is deficient of glucose. A team at the University of Pittsburgh was working this summer on prototyping a sensor. Another group in Canada is putting together a semiconductor sensor. Oxford Medical Diagnostics has tested methods of measuring acetone through the breath but has not released any news recently.
Wednesday, November 13, 2013
Tuesday, November 12, 2013
by Ron Winslow, online.wsj.com
The long-standing strategy of reducing heart-attack risk by lowering cholesterol to specific targets is being jettisoned under new clinical guidelines unveiled Tuesday that mark the biggest shift in cardiovascular- disease prevention in nearly three decades.
Gone is the familiar and easy-to-understand guidance to keep LDL, or bad cholesterol, below 100 or below 70 for people at high risk—a mainstay of current prevention policy. Instead, doctors are being told to assess a patient's risk more broadly and prescribe cholesterol-lowering statin drugs to those falling within one of four risk categories.
The aim is to more effectively direct statin treatment to patients with the most to gain, and move away from relatively arbitrary treatment targets that are less reliable in predicting risk than is widely believed.
"We're trying to focus the most appropriate therapy to prevent heart attack and stroke ... in a wide range of patients," said Neil J. Stone, professor of medicine at Northwestern University Feinberg School of Medicine and head of the expert panel that wrote the cholesterol guidelines.
Cardiovascular disease is the Western world's leading killer. In the U.S., heart disease accounts for about 600,000 deaths each year, or about one in four deaths. About 130,000 people in the U.S. die each year of stroke, which is also a major cause of disability.
Numerous studies show that statins, which are among the most prescribed drugs in the world, reduce the risk of heart attack and stroke. But solid data demonstrating the benefit of reaching specific targets are lacking, said Dr. Stone.
While lowering LDL remains a critical goal, the focus is on the risk reduction achieved with statins rather than the effect on LDL, said Donald Lloyd-Jones, chief of preventive medicine at Northwestern and a member of the guidelines panel.
Cardiologists expect the recommendations, jointly developed by the American College of Cardiology and the American Heart Association, to substantially change the conversation between doctors and tens of millions of patients over the best way to lower their risk of a heart attack or stroke.
The risk groups identified in the guidelines include patients who have already had a heart attack, stroke or major symptoms of cardiovascular disease; those with an LDL of 190 or higher, which typically has a genetic cause; people with diabetes; and anyone ages 40 to 79 who faces a 7.5% risk of having a heart attack over the next 10 years, according to a new risk score. That score—with a lower threshold than under current guidelines—takes into account cholesterol level, smoking status, blood pressure and other factors.
All are recommended to take high or moderate statin doses that would results in LDL reductions of about 30% to more than 50%.
If fully implemented, the guidelines could more than double the number of Americans who qualify for statin therapy, to more than 30 million, the authors estimated.
The new approach is likely to have a modest immediate effect on the pharmaceutical industry. All but one of the statins available, including Lipitor, have lost patent protection and are available as inexpensive generics.
AstraZeneca AZN.LN -0.23% PLC's Crestor, the one remaining branded statin and the most powerful on the market, could get a boost from the recommendations. Merck MRK +1.30% & Co.'s Zetia, a non-statin cholesterol-reducer that is also an ingredient in Vytorin, could take a hit because the guidelines discourage use of agents that haven't been proven to reduce risk of bad events. Zetia hasn't been shown to reduce bad events even though it lowers LDL.
But both supporters and critics of the new guidelines worry they will confuse patients and physicians, and potentially disrupt an easy-to-understand and successful strategy. While statins haven't been the only factor, research shows there has been a significant reduction in heart attacks and death from cardiovascular disease in the past two decades since the drugs were introduced.
"This is a tension between the practical and the scientific," said Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. Having targets for LDL "gives doctors and patients something to shoot for" as well as a motivation to try to get there, Dr. Nissen said. "The elimination of target levels is going to be a huge change for physicians and patients."
Write to Ron Winslow at email@example.com
Saturday, November 9, 2013
October 15th 2013
To put it bluntly, inhalers are a gift to people with lung diseases from God. It's asthma medicine made easy.
They now had quick and easy access to their asthma medicine anywhere, any time, and any place.
While the medicine has changed over the years, the basic inhaler design is still the same.
The key to this invention was the actuator with a one-way valve that allowed for the medicine and propellant to be sprayed in a uniform dose (a metered dose), and soon became known as the metered dose inhaler (MDI). In some countries it's called an atomizer or a puffer.
Today there are many medicines delivered by inhaler, and the inhaler market is one of the most profitable products in the pharmaceutical industry. The Albuterol inhaler is the most commonly prescribed and most profitable asthma medicine of all time.
The neat thing about the inhaler is it allows for medicine to make it to the lungs for quick action. Likewise, since the medicine goes directly to the lungs, this eliminates many systemic side effects of the medicine.
You can stick the mouthpiece of the inhaler into your mouth and squirt. The medicine will still work, but you will notice that most of the medicine hits the back of your oral airway. When this happens, most of the medicine is wasted.
So scientists have discovered better, more efficient ways of using an inhaler.
One way is to place the mouthpiece two finger lengths away from your mouth. You shake the inhaler well, then hold it two finger lengths from your mouth. As you start to inhale you squirt the inhaler. Take in as deep a breath as you can and hold your breath 5-10 seconds.
However, you want to make sure your breath is slow and easy. If you breathe in too fast this will cause turbulance that will cause the medicine to land in your mouth before it gets deep into your lungs. You want a slow, laminar flow.
This makes sure the more of the medicine is distributed in your air passages where it can work.
The ideal way of using an inhaler, however, is to use a spacer device. Spacers help you with coordination, and it also breaks apart the large particles so what you are inhaling are smaller particles that go directly into your air passages.
Studies show spacers make the medicine work 75 percent better and with fewer side effects.
When I was a kid it was recommended that if you didn't want to pay for a spacer you use a toilet paper roll for this purpose. While it's a crude design, it makes the medicine work better.
The principle of using an inhaler with a spacer is similar to the two finger technique, yet instead of space between your mouth and the inhaler there is a spacer. You shake up the inhaler well, place the inhaler into one end of the spacer and your mouth on the spacer mouthpiece. You squirt as you start to inhale, take in a deep breath, and hold for 5-10 seconds. Do not remove your mouth from the mouthpiece until you are done holding your breath.
There are many different kinds of spacers, yet my favorite is the AeroChamber as seen in the picture. This device will alarm if you inhale too fast, so the spacer actually coaches you how to inhale nice and smooth-like.
Another neat thing about the aerochamber is it allows you to squirt the medicine even before you put the spacer in your mouth. This works well for children or elderly people who have trouble with inhaler coordination.
For smaller kids you can also place a mask on the mouthpiece end, and this helps an adult hold the mask over the child's face to facilitate coordination.
Many studies show that using an inhaler with a spacer results in better medicine distribution than nebulized medicine. This is especially true with young kids.
I like to tell my patients to make sure your mouth stays on the spacer mouthpiece until you are done holding your breath. This assures none of the medicine is wasted.
Regardless of what technique you use, you should take one puff and then wait 2-5 minutes to take a second puff. When using your rescue inhaler, the first puff will open up your air passages and the second will do the mop up job.
Tuesday, November 5, 2013
by Sandra Lobo, medcitynews.comNovember 4th 2013 7:42 AM
Traditional approaches to for cancer are quite limited in treating late-stage and aggressive cancers. Aduro BioTech, Inc., a clinical-stage immunotherapy company, is using the immune system to fight cancer and provide more options for patients. The immune system defends against the growth and spread of tumors. Cancer develops as a result of multiple changes in the cellular machinery that inhibits this line of defense, thereby allowing the tumor to grow. Once this occurs, a successful treatment could be vaccines that induce a broad and potent immune response to break the immune system’s tolerance of the tumor. Aduro has developed such vaccines, using three complementary immunotherapy platforms, Listeria, GVAX and cyclic dinucleotides (CDNs), with broad applications in cancer and infectious disease.
The Listeria platform uses a live, attenuated strain of Listeria monocytogenes to treat cancer and infectious diseases. The strain is engineered to deliver cancer or microbial antigens into cells to be processed by the host cellular machinery and presented to the immune system, thus inducing a potent immune response. The use of this bacteria as a cancer/microbial vaccine platform has several advantages, such as direct targeting of immune (dendritic) cells, signaling the innate immune system through multiple pathways and an ability to be repeatedly administered without being neutralized.
Using a pathogen such as Listeria to treat disease may seem counter-intuitive, but Aduro’s Listeria platform has been shown to be well tolerated in multiple clinical trials. CRS-207 is Aduro’s lead Listeria -based therapeutic, engineered to express the tumor-associated antigen mesothelin. CRS-207 was evaluated in a Phase 1 trial in 17 end-stage patients with cancers known to express mesothelin: mesothelioma, non-small-cell lung, ovarian and pancreatic. Despite an expected survival of 3-5 months for all subjects treated with CRS-207, six out of 17 lived 15 months or longer.
The GVAX platform utilizes human cancer cell lines that have been genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a potent cytokine capable of inducing differentiation, proliferation and activation of a variety of immune cells, thus serving as a stimulant for the immune system. The immunostimulatory property of this cytokine has been exploited for use as a vaccine adjuvant to boost the potency of poorly immunogenic cancer antigens as vaccines. The GVAX cell lines have been irradiated to prevent cell division, yet are metabolically active. GVAX products include vaccines for pancreatic cancer, leukemia, myeloma, breast and prostate cancer that are all in the late human clinical stage, with colorectal and melanoma in the early human clinical stage.
Aduro’s strong growth has been led byDr. Stephen T. Isaacs, president and CEO of Aduro BioTech, who initiated the current immunotherapy program. Issacs recruited key members of the current vaccine team with deep expertise in the biology of Listeria. Aduro’s business model is based on leveraging platform technologies to rapidly develop and advance a broad range of new vaccines and vaccine combinations for applications in oncology, infectious diseases and biodefense. Aduro’s future pipeline includes a new Listeria -based therapeutic, ADU-623, that is expected to be advanced in 2013 into an investigator-sponsored Phase 1 clinical trial in patients with glioblastoma. In addition, the company continues to be funded by research grants for the development of new vaccines for prostate cancer, tularemia, hepatitis B virus (HBV) and melanoma.
Isaacs said with three complementary platforms in addition to the Listeria platform, his company is in a good spot to take advantage of the new approach to cancer treatment.
“We are entering the new era of immunotherapy, and what is becoming clear is that combinations are more effective than individual immunotherapies that only activate one part of the immune system,” he said.
Aduro acquired all GVAX assets from BioSante Pharmaceuticals, Inc. (NASDAQ: BPAX), including intellectual property and cell lines. Under its purchase agreement with BioSante, Aduro paid $1 million upfront and has committed to additional milestone and royalty payments after commercialization of GVAX products.
Four GVAX vaccines have been granted U.S. Food and Drug Administration Orphan Drug designation: GVAX Pancreas for the treatment of pancreatic cancer, GVAX AML for the treatment of acute myeloid leukemia, GVAX CML for the treatment of chronic myeloid leukemia and GVAX Melanoma for the treatment of melanoma. Aduro is currently evaluating the sequential administration of the GVAX Pancreas vaccine and its own Listeria -based CRS-207 in a randomized, controlled Phase 2 trial of 90 patients with metastatic pancreatic cancer, and enrollment in the trial has been completed. The company presented abstracts at both ASCO and ESMO, but have not posted the information on its our website yes due to an embargo.
The CDNs platform uses cyclic dinucleotides that are ubiquitous molecules secreted by Listeria and other intracellular pathogens. These molecules signal through STING (STimulator of INterferon Genes), inducing the expression of inflammatory cytokines that are known to induce a potent innate immune response. A principal barrier to the development of effective vaccines is the lack of adjuvants and formulations that can elicit an effective and long-lived immune response. Aduro’s CDNs represent a new class of adjuvants that have been shown to effectively increase vaccine potency. Aduro is now combining CDNs with GVAX into a new vaccine named STINGVAX that has demonstrated superior efficacy over GVAX alone in animal models.