Day: 09/21/2012

Novartis drug Votubia® recommended by CHMP for EU approval to treat patients with non-cancerous kidney tumors associated with TSC.

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  • Votubia (everolimus) would be the first non-surgical treatment option in the EU for kidney tumors associated with tuberous sclerosis complex (TSC)[1]
  • Kidney tumors, or renal angiomyolipomas, affect up to 80% of patients with TSC and growing tumors may lead to life-threatening complications[2]

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Votubia® (everolimus) tablets* for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC) who are at risk of complications (based on factors such as tumor size or presence of aneurysm, or presence of multiple or bilateral tumors) but who do not require immediate surgery. Votubia would be the first medication available in the European Union (EU) for these patients[1].

“Today’s positive CHMP opinion for Votubia is important for patients in the EU with TSC, as renal angiomyolipoma is among the most difficult-to-treat manifestations of this debilitating disease,” said Hervé Hoppenot, President, Novartis Oncology. “There remain many unmet medical needs in TSC, and Novartis is committed to understanding and improving the lives of people affected by this rare disease through clinical research, education and collaboration with the global TSC community.”

In the EU, the European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 27 EU member states plus Iceland and Norway. In Europe, everolimus has orphan drug designation for TSC. Orphan drugs are those that treat a condition which affects no more than five in 10,000 people in the EU[3].

The CHMP positive opinion is based on data from the Phase III EXIST-2 (EXamining everolimus In a Study of TSC) trial, which found that 42% of patients on everolimus experienced an angiomyolipoma response versus 0% of patients in the placebo arm (p<0.0001). The evidence is based on analysis of change in sum of angiomyolipoma volume. Median time to angiomyolipoma progression was 11.4 months in the placebo arm and was not reached in the everolimus arm (p<0.0001). Among the 97% of patients with skin lesions, one of the key concerns for the majority of patients with TSC, a 26% response rate was seen with everolimus versus 0% with placebo (p=0.0002)[4].

Everolimus works by inhibiting mTOR, a protein implicated in many tumor-causing pathways[2],[5]. TSC is caused by defects in the TSC1 and/or TSC2 genes[2]. When these genes are defective, mTOR activity is increased, which can cause uncontrolled tumor cell growth and proliferation, blood vessel growth and altered cellular metabolism[5],[6]. According to preclinical studies, by inhibiting mTOR activity in this signaling pathway, everolimus reduces cell proliferation and blood vessel growth[1],[5].

About Renal Angiomyolipomas
Up to 80% of patients with TSC – a genetic disorder affecting approximately one to two million people worldwide that may cause non-cancerous tumors to form in many organs – will develop renal angiomyolipomas. Typical symptom onset occurs between the ages of 15 and 30 and prevalence increases with age. Over time, these tumors may grow large enough to cause severe internal bleeding, require emergency surgical interventions, such as embolization and nephrectomy, or lead to kidney failure[2]. The tumors can be difficult to manage as they are often multiple and form in both kidneys at the same time[1],[2]. In the EU, approximately 7,000 TSC patients have large growing AML tumors (> 3 cm) at risk of bleeding[7],[8],[9].

About EXIST-2
EXIST-2 is the first double-blind, randomized, placebo-controlled, international, multicenter Phase III study for the treatment of patients with renal angiomyolipoma associated with TSC. Trial patients (median age=31, range 18-61) were randomized 2:1 to receive either everolimus (n=79) or placebo (n=39) at a daily dose of 10 mg. The median duration of blinded study treatment was 48 weeks in the everolimus arm and 45 weeks in the placebo arm[4].

In the study, 42% of patients on everolimus (33 of 79; 95% confidence interval [CI] 30.8-53.4) experienced an angiomyolipoma response versus 0% on placebo (0 of 39; 95% CI 0.0-9.0; p<0.0001), defined as a 50% or greater reduction in the sum of angiomyolipoma volume relative to baseline, the absence of new tumor growth at least 1 cm in longest diameter, absence of kidney volume increase of 20% or greater and no renal angiomyolipoma-related bleeding of Grade 2 or higher[4].

Everolimus demonstrated superiority to placebo for both supportive efficacy outcomes measured: time to angiomyolipoma progression and skin lesion response rate. There were three patients in the everolimus arm and eight patients in the placebo arm with documented angiomyolipoma progression by central radiologic review. The time to angiomyolipoma progression was statistically significantly longer in patients on everolimus (hazard ratio [HR] 0.08, 95% CI 0.02-0.37; p<0.0001). Skin lesion response rate was significantly higher in the everolimus arm. A partial clinical response in skin lesions (corresponding to a 50% or greater improvement) was observed by Physician Global Assessment in 26% of patients on everolimus, compared with 0% of patients on placebo (p=0.0011). No complete responses were observed[4].

The most common adverse reactions reported in the everolimus arm during the double-blind period (with an incidence at least 15%) included stomatitis, hypercholesterolemia, aphthous stomatitis, mouth ulceration, and acne. The most common Grade 3 adverse reactions in the everolimus arm (with an incidence of at least 2%) were amenorrhea, aphthous stomatitis, and mouth ulceration. The most common laboratory abnormalities (incidence >= 50%) were hypercholesterolemia, hypertriglyceridemia and anemia. The most common Grade 3-4 laboratory abnormality (incidence >= 3%) was hypophosphatemia[4].

About everolimus
Everolimus is approved as Afinitor® (everolimus) tablets in the United States (US) for the treatment of adult patients with renal angiomyolipomas and tuberous sclerosis complex (TSC), not requiring immediate surgery. The effectiveness of Afinitor in treatment of renal angiomyolipoma is based on an analysis of durable objective responses in patients treated for a median of 8.3 months. Further follow-up of patients is required to determine long-term outcomes. Should everolimus be approved in the European Union (EU) for this patient population, the trade name will be Votubia.

Everolimus is also approved in the US as Afinitor and Afinitor Disperz(TM) in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. The effectiveness is based on demonstration of durable objective response, as evidenced by reduction in SEGA tumor volume. Improvement in disease-related symptoms and overall survival in patients with SEGA and TSC have not been demonstrated. In the EU, everolimus is approved as Votubia® (everolimus) tablets for the treatment of patients aged 3 years and older with SEGA associated with TSC who require therapeutic intervention but are not amenable to surgery. The evidence is based on analysis of change in SEGA volume. Further clinical benefit, such as improvement in disease-related symptoms, has not been demonstrated.

Everolimus is approved as Afinitor in 90 countries including the US and throughout the EU in the adult oncology settings of advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy in the EU and after failure of treatment with sunitinib or sorafenib in the US. Afinitor is approved for the treatment of locally advanced, metastatic or unresectable progressive neuroendocrine tumors of pancreatic origin in adults in the US and EU. Afinitor is also approved in the EU for the treatment of hormone receptor-positive (HR+), HER2/neu-negative (HER2-) advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor, and in the US for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ breast cancer) in combination with exemestane after failure of treatment with letrozole or anastrozole.

Everolimus is also available from Novartis for use in other non-oncology patient populations under the brand names Certican® and Zortress® and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country.

Important Safety Information about Votubia/Afinitor
Votubia/Afinitor can cause serious side effects including lung or breathing problems, infections, and renal failure which can lead to death. Mouth ulcers and mouth sores are common side effects. Votubia/Afinitor can affect blood cell counts, kidney and liver function, and blood sugar and cholesterol levels. Votubia/Afinitor may cause fetal harm in pregnant women. Highly effective contraception is recommended for women of child-bearing potential while receiving Afinitor and for up to 8 weeks after ending treatment. Women taking Votubia/Afinitor should not breast feed.

The most common adverse drug reactions (incidence >=15%) are mouth ulcers, diarrhea, feeling weak or tired, skin problems (such as rash or acne), infections, nausea, swelling of extremities or other parts of the body, loss of appetite, headache, inflammation of lung tissue, abnormal taste, nose bleeds, inflammation of the lining of the digestive system, weight decreased and vomiting. The most common Grade 3-4 adverse drug reactions (incidence >=2%) are mouth ulcers, feeling tired, low white blood cells (a type of blood cell that fights infection), diarrhea, infections, inflammation of lung tissue, diabetes and amenorrhea. Cases of hepatitis B reactivation and blood clot in the lung and leg have been reported.

*Known as Afinitor® (everolimus) tablets for this patient population in the US. If approved in the EU for this patient population, the trade name will be Votubia.

References

[1] Ewalt D, et al. Long-term outcome of transcatheter embolization of renal angiomyolipomas due to tuberous sclerosis complex. J Urol. 2005;174:1764-1766.
[2] National Institute of Neurological Disorders and Stroke. Tuberous Sclerosis Fact Sheet. Available at http://www.ninds.nih.gov/disorders/tuberous_sclerosis/detail_tuberous_sclerosis.htm. Accessed September 2012.
[3] European Medicines Agency. Orphan drugs and rare diseases at a glance. Available at http://www.ema.europa.eu/docs/en_GB/document_library/Other/2010/01/WC500069805.pdf. Accessed September 2012.
[4] Novartis Data on File.
[5] Motzer, et al. Phase 3 Trial of Everolimus for Metastatic Renal Cell Carcinoma. Cancer. 2010 Sep;116(18):4256-4265.
[6] Krueger D, et al. Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis. N Engl J Med. 2010 Nov;363(19):1801-11.
[7] Dixon B, et al. Tuberous Sclerosis Complex Renal Disease. Nephron Exp Nephrol. 2011:118:e15-e20.
[8] O’Callaghan F, et al. An epidemiological study of renal pathology in tuberous sclerosis complex. BJU International. 2004:94:853-857.
[9] Cox J, et al. The natural history of renal angiomyolipomata (AMLs) in Tuberous Sclerosis Complex (TSC). European Renal Association – European Dialysis and Transplant Association Congress. 2012, Paris, France.

Source: Novartis Newsletter.

Endeavour & 747 carrier.

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Role of exercise in cancer patients.

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Mounting evidence shows that exercise can not only help cancer patients get well but also help keep their cancer from recurring. Yet, few oncologists tell their patients to engage in exercise beyond their simple daily, normal activities.

And many cancer patients are reluctant to exercise, or even discuss it with their oncologist.

A recent study1 by the Mayo Clinic investigated exercise habits among cancer patients and their clinicians’ roles in providing related counseling, and found that:

“Participants overwhelmingly cited usual daily activities as their source of ‘exercise.’ Symptoms, particularly treatment-related, discouraged participation, with fear of harm being a significant concern only among younger women. Exercise was recognized as important for physical and mental well-being, but seldom as a means to mitigate symptoms.

…Although respondents preferred to receive guidance from their oncologist, none reported receiving more than general encouragement to ‘stay active.’ A lack of direction was typically accepted as a sanction of their current activity levels. Participants appeared less receptive to guidance from ancillary health professionals.”

An Important Conversation You’d Be Wise to Have With Your Oncologist

Fear that exercise might be harmful appears to be largely unfounded, though it’s certainly understandable. It can be difficult to be enthusiastic about exercise if you struggle with nausea, fatigue, and other detrimental side effects from the treatment. However, it may be helpful to focus on the benefits you can reap from exercise. For example, research has shown that exercising during and after cancer treatment can:

  • Reduce your risk of dying from cancer
  • Reduce your risk of cancer recurrence
  • Boost energy and minimize the side effects of conventional cancer treatment (see additional listing below)

The fact that most oncologists overlook this vital aspect of their patients’ care is highly unfortunate, especially considering how most patients defer to their recommendations. However, it’s not unexpected. Conventional doctors are trained to prescribe drugs, not exercise.

Ideally, they’d prescribe exercise in the same manner drugs are prescribed – in specific “doses” and intervals. To do this properly, oncologists would be wise to develop relationships with personal trainers, and prescribe training sessions for their patients. If you have cancer, I would highly recommend discussing exercise with your oncologist, and/or work with a trained fitness professional who can help you devise a safe and effective regimen.

Exercise Needs to Be Part of Standard Cancer Care

A recent report issued by the British organization Macmillan Cancer Support2 argues that exercise really should be part of standard cancer care. It recommends that all patients getting cancer treatment should be told to engage in moderate-intensity exercise for two and a half hours every week, stating that the advice to rest and take it easy after treatment is an outdated view.

According to Ciaran Devane, chief executive of Macmillan Cancer Support:4

“Cancer patients would be shocked if they knew just how much of a benefit physical activity could have on their recovery and long term health, in some cases reducing their chances of having to go through the grueling ordeal of treatment all over again…”

Indeed, the reduction in risk for recurrence is quite impressive. Previous research has shown that breast and colon cancer patients who exercise regularly have half the recurrence rate than non-exercisers.5 Macmillan Cancer Support also notes that exercise can help you to mitigate some of the common side effects of conventional cancer treatment, including:

Reduce fatigue and improve your energy levels Manage stress, anxiety, low mood or depression Improve bone health
Improve heart health (some chemotherapy drugs and radiotherapy can cause heart problems later in life) Build muscle strength, relieve pain and improve range of movement Maintain a healthy weight
Sleep better Improve your appetite Prevent constipation

How Exercise Can Improve Cancer Outcome

This topic is near and dear to my heart, as I went to medical school in large part because I wanted to use exercise as a therapeutic tool to help people get healthier. I strongly believe that without fitness, it is virtually impossible to achieve optimal health. Lack of exercise can also severely hamper your recuperative efforts once disease has set in.

A 2005 study6 by researchers at Harvard Medical School found that breast cancer patients who exercise moderately for three to five hours a week cut their odds of dying from cancer by about half, compared to sedentary patients. In fact, any amount of weekly exercise increased a patient’s odds of surviving breast cancer. This benefit remained constant regardless of whether women were diagnosed early on or after their cancer had spread.

Similarly, researchers investigating the impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer found those who were more active cut their risk of recurrence in half.7

One of the primary reasons exercise works to lower your cancer risk is because it drives your insulin levels down, and controlling your insulin levels is one of the most powerful ways to reduce your cancer risks. It’s also been suggested that apoptosis (programmed cell death) is triggered by exercise, causing cancer cells to die. This theory was demonstrated in two studies published in 2006. In one, mice who used running wheels developed fewer and smaller skin tumors.8 The second study found that exercise reduced the number and size of intestinal polyps.9

The studies also found that the number of tumors decreased along with body fat, which may be an additional factor. This is because exercise helps lower your estrogen levels, which explains why exercise appears to be particularly potent against breast cancer.

If you’re male, be aware that athletes have lower levels of circulating testosterone than non-athletes, and similar to the association between estrogen levels and breast cancer in women, testosterone is known to influence the development of prostate cancer in men. Strength training may be of particular benefit. In one 2009 study10, men who regularly worked out with weights and had the highest muscle strength were between 30 percent and 40 percent less likely to lose their life to a deadly tumor.

Other research has shown:

  • Exercising moderately for six hours a week may reduce colorectal cancer mortality11
  • Three hours per week of moderate-intensity physical activity may lower risk of prostate cancer mortality by about 30 percent12, and lower the rate of disease progression by 57 percent13

Of course, exercise also improves the circulation of immune cells in your blood, whose job it is to neutralize pathogens throughout your body. The better these cells circulate, the more efficient your immune system is at locating and defending against viruses and diseases, including cancer, trying to attack your body.

Exercise Tips for Cancer Patients

I would strongly recommend you read up on my Peak Fitness program, which includes high-intensity exercises that can reduce your exercise time while actually improving your benefits.

Now, if you have cancer or any other chronic disease, you will of course need to tailor your exercise routine to your individual circumstances, taking into account your fitness level and current health. Often, you will be able to take part in a regular exercise program – one that involves a variety of exercises like strength training, core-building, stretching, aerobic and anaerobic – with very little changes necessary. However, at times you may find you need to exercise at a lower intensity, or for shorter durations.

Always listen to your body and if you feel you need a break, take time to rest. But even exercising for just a few minutes a day is better than not exercising at all, and you’ll likely find that your stamina increases and you’re able to complete more challenging workouts with each passing day. In the event you are suffering from a very weakened immune system, you may want to exercise at home instead of visiting a public gym. But remember that exercise will ultimately help to boost your immune system, so it’s very important to continue with your program, even if you suffer from chronic illness or cancer.

Intense Workouts May Also Be Safe for Heart Patients

Another group of people often discouraged from exercise are those suffering with heart problems, but even here the mindset is starting to change. In an about-face in the way patients recovering from heart attacks or heart surgery are typically treated, a new study14 suggests high-intensity workouts may in fact be a safe choice. The study followed 4,800 Norwegian heart patients who did aerobics. Only three cardiac arrests occurred in over 170,000 hours of intensive exercise in these patients.

According to Reuters:15

“The number was too small to say for sure that high impact workouts are just as safe as moderate ones, but they show the overall risk of exercise bringing on cardiac arrest is fairly low, according to the authors. There is plenty of evidence that the harder people work out, the more benefit they gain in cardiovascular function, said Oeivind Rognmo, a researcher at the Norwegian University of Science and Technology in Trondheim and lead author of the study…”

The participants completed both moderate- and high-intensity workouts, spending a combined total of 129,456 hours working out at moderate intensity and 46,364 hours at high intensity. Moderate intensity workouts included an hour of walking, or other exercises resulting in exertion at 60-70 percent of maximum heart rate. The high-intensity workouts consisted of four-minute-intervals (cycling, running, or cross country skiing), pushing their heart rate up to 85-95 percent of maximum, followed by four-minute-long rest periods.

During the more than 129,000 combined hours of moderate exercise, one person died from cardiac arrest. And during over 46,000 combined hours of high-intensity workouts, two suffered cardiac arrest during or within an hour of exercise, but both survived. According to the lead author:16

“We found that both types of intensities were associated with low event rates… I think (high-intensity training) should be considered for patients with coronary heart disease.”

Remember to Listen to Your Body

One of the key principles I teach and believe in is to listen to your body. This applies no matter what your current state of health is. If your body will not allow you to exercise, either due to pain or worsening of your underlying condition, then you have no practical option but to honor your body’s signals and exercise less.

Even though your body desperately needs the exercise to improve, you will only get worse if you violate your current limitations. So you may have to start with as little as just minutes a day. That’s okay. As your body gradually improves so will your tolerance to exercise, and you’d be wise to do as much as your body will allow in order to achieve a high level of health.

Additional Strategies to Help Prevent Cancer

While exercise is an important facet of cancer prevention and treatment, it’s certainly not the only one. I believe the vast majority of all cancers could be prevented by strictly applying the healthy lifestyle recommendations below:

  • Avoid sugar, especially fructose. All forms of sugar are detrimental to health in general and promote cancer. Fructose, however, is clearly one of the most harmful and should be avoided as much as possible.
  • Optimize your vitamin D. Vitamin D influences virtually every cell in your body and is one of nature’s most potent cancer fighters. Vitamin D is actually able to enter cancer cells and trigger apoptosis (cell death). If you have cancer, your vitamin D level should be between 70 and 100 ng/ml. Vitamin D works synergistically with every cancer treatment I’m aware of, with no adverse effects. I suggest you try watching my one-hour free lecture on vitamin D to learn more.
  • Avoid charring your meats. Charcoal or flame broiled meat is linked with increased breast cancer risk. Acrylamide – a carcinogen created when starchy foods are baked, roasted or fried – has been found to increase cancer risk as well.
  • Avoid unfermented soy products. Unfermented soy is high in plant estrogens, or phytoestrogens, also known as isoflavones. In some studies, soy appears to work in concert with human estrogen to increase breast cell proliferation, which increases the chances for mutations and cancerous cells.
  • Improve your insulin receptor sensitivity. The best way to do this is by avoiding sugar and grains and making sure you are exercising, especially with Peak Fitness.
  • Maintain a healthy body weight. This will come naturally when you begin eating right for your nutritional type and exercising. It’s important to lose excess body fat because fat produces estrogen.
  • Drink a quart of organic green vegetable juice daily. Please review my juicing instructions for more detailed information.
  • Get plenty of high quality animal-based omega-3 fats, such as krill oil. Omega-3 deficiency is a common underlying factor for cancer.
  • Curcumin. This is the active ingredient in turmeric and in high concentrations can be very useful adjunct in the treatment of cancer. For example, it has demonstrated major therapeutic potential in preventing breast cancer metastasis.17 It’s important to know that curcumin is generally not absorbed that well, so I’ve provided several absorption tips here.
  • Avoid drinking alcohol, or at least limit your alcoholic drinks to one per day.
  • Avoid electromagnetic fields as much as possible. Even electric blankets can increase your cancer risk.
  • Avoid synthetic hormone replacement therapy, especially if you have risk factors for breast cancer. Breast cancer is an estrogen-related cancer, and according to a study published in the Journal of the National Cancer Institute, breast cancer rates for women dropped in tandem with decreased use of hormone replacement therapy. (There are similar risks for younger women who use oral contraceptives. Birth control pills, which are also comprised of synthetic hormones, have been linked to cervical and breast cancers.)

If you are experiencing excessive menopausal symptoms, you may want to consider bioidentical hormone replacement therapy instead, which uses hormones that are molecularly identical to the ones your body produces and do not wreak havoc on your system. This is a much safer alternative.

  • Avoid BPA, phthalates and other xenoestrogens. These are estrogen-like compounds that have been linked to increased breast cancer risk
  • Make sure you’re not iodine deficient, as there’s compelling evidence linking iodine deficiency with certain forms of cancer. Dr. David Brownstein18, author of the book Iodine: Why You Need It, Why You Can’t Live Without It, is a proponent of iodine for breast cancer. It actually has potent anticancer properties and has been shown to cause cell death in breast and thyroid cancer cells.

The organization offers loads of helpful information about the benefits of exercise for cancer patients on their website, and also has a number of videos on the subject, available on their YouTube channel.

URL: http://www.youtube.com/watch?feature=player_embedded&v=mut3RTiVfD0

 

Source: Dr. Mercola

 

 

 

 

 

Organs Wasted in Kidney Transplant Network .

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The current system of allocating kidneys is flawed, with organs being discarded that might otherwise have benefited people — and the problem is growing — the New York Times reports.

The paper says that in 2011, some 2600 of 15,000 kidneys recovered for transplantation were discarded — many because recipients could not be found in time (the article notes that “it is not precisely clear” how many discarded kidneys might actually have been useful). The number of kidneys discarded has grown over 75% in the past decade, “more than twice as fast as the increase in kidney recoveries,” according to the Times.

Federal efforts to monitor the quality of transplantation programs may also inadvertently contribute to the problem. The effort to keep success rates high has made transplant surgeons “far more selective about the organs and patients they accepted, leading to more discards.”

New proposals for kidney allocation have been put forward, but remain similar to the system already in place.

Source:New York Times

UDs and Implants Safe and Effective for Teens, ACOG Says .

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Long-acting contraceptives — namely, intrauterine devices and the contraceptive implant — “are the best reversible methods for preventing unintended pregnancy, rapid repeat pregnancy, and abortion in young women,” according to a committee opinion from the American College of Obstetricians and Gynecologists.

Published in Obstetrics & Gynecology, the statement outlines evidence supporting both the safety and efficacy of long-acting contraceptive methods in adolescent girls. In particular, research shows that teenagers using long-acting methods are far more likely to continue using those methods at 1 year — and 20 times less likely to have an unintended pregnancy — compared with those using short-acting methods. In addition, complication rates with long-acting contraception do not differ between women and teenage girls.

Just 4.5% of adolescent girls who use contraceptives use an IUD or implant, according to one estimate.

The authors write that long-acting methods “should be first-line treatment recommendations for all women and adolescents,” and “counseling about [such] methods should occur at all health care provider visits with sexually active adolescents.”

Source:Obstetrics & Gynecology

 

Replacing IV Catheters Only When Clinically Indicated Seems Safe .

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Replacing peripheral intravenous catheters only when clinically indicated (for example, after accidental removal or infiltration) causes no more complications than replacing them according to standard time-based schedules, according to a Lancet study.

Researchers randomized some 3300 adult patients to have their intravenous catheters replaced every third day or only as clinically indicated. The rate of phlebitis, the primary outcome, was identical in the two groups, at 7%. Secondary outcomes, such as rates of catheter colonization and all-cause bloodstream infections, were also similar between groups.

The authors calculate that, on average, clinically indicated replacement would extend catheter use by a single day, and that one in every five patients would avoid an unnecessary procedure. They estimate that the reduction in staff time and other costs could save the U.S. $60 million in healthcare costs annually.

Source: Lancet

 

About Marijuana.

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Marijuana is the third most popular recreational drug in America (behind only alcohol and tobacco), and has been used by nearly 100 million Americans. According to government surveys, some 25 million Americans have smoked marijuana in the past year, and more than 14 million do so regularly despite harsh laws against its use. Our public policies should reflect this reality, not deny it.

Marijuana is far less dangerous than alcohol or tobacco. Around 50,000 people die each year from alcohol poisoning. Similarly, more than 400,000 deaths each year are attributed to tobacco smoking. By comparison, marijuana is nontoxic and cannot cause death by overdose. According to the prestigious European medical journal, The Lancet, “The smoking of cannabis, even long-term, is not harmful to health. … It would be reasonable to judge cannabis as less of a threat … than alcohol or tobacco.”

NORML supports the removal of all penalties for the private possession and responsible use of marijuana by adults, including cultivation for personal use, and casual nonprofit transfers of small amounts. This policy, known as decriminalization, removes the consumer — the marijuana smoker — from the criminal justice system.

More than 30 percent of the U.S. population lives under some form of marijuana decriminalization, and according to government and academic studies, these laws have not contributed to an increase in marijuana consumption nor negatively impacted adolescent attitudes toward drug use.

See Personal Use for more information.

Enforcing marijuana prohibition costs taxpayers an estimated $10 billion annually and results in the arrest of more than 853,000 individuals per year — far more than the total number of arrestees for all violent crimes combined, including murder, rape, robbery and aggravated assault.

Of those charged with marijuana violations, approximately 88 percent,750,591Americans were charged with possession only. The remaining 103,247 individuals were charged with “sale/manufacture,” a category that includes all cultivation offenses, even those where the marijuana was being grown for personal or medical use. In past years, roughly 30 percent of those arrested were age 19 or younger.

NORML supports the eventual development of a legally controlled market for marijuana, where consumers could buy marijuana for personal use from a safe legal source. This policy, generally known as legalization, exists on various levels in a handful of European countries like The Netherlands and Switzerland, both of which enjoy lower rates of adolescent marijuana use than the U.S. Such a system would reduce many of the problems presently associated with the prohibition of marijuana, including the crime, corruption and violence associated with a “black market.”

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Medical Use

 

Marijuana, or cannabis, as it is more appropriately called, has been part of humanity’s medicine chest for almost as long as history has been recorded.

Of all the negative consequences of marijuana prohibition, none is as tragic as the denial of medicinal cannabis to the tens of thousands of patients who could benefit from its therapeutic use.

Modern research suggests that cannabis is a valuable aid in the treatment of a wide range of clinical applications.[4] These include pain relief — particularly of neuropathic pain (pain from nerve damage) — nausea, spasticity, glaucoma, and movement disorders.[5] Marijuana is also a powerful appetite stimulant, specifically for patients suffering from HIV, the AIDS wasting syndrome, or dementia.[6] Emerging research suggests that marijuana’s medicinal properties may protect the body against some types of malignant tumors[7] and are neuroprotective.

Currently, more than 60 U.S. and international health organizations support granting patients immediate legal access to medicinal marijuana under a physician’s supervision.

Legal Issues

Driven by the Drug War, the U.S. prison population is six to ten times as high as most Western European nations. The United States is a close second only to Russia in its rate of incarceration per 100,000 people. In 2005, more than 786,000 people were arrested in this country for marijuana-related offenses alone.

Marijuana prohibition causes more problems than it solves, and ruins thousands more lives than it supposedly tries to save. The NORML Legal Committee provides legal support and assistance to victims of the current marijuana laws. NORML also monitors developments in state and federal law, and files appellate and amicus curiae (“friend of the court”) briefs in cases which may affect the interpretation of existing marijuana laws, or which will, hopefully, change them.

Industrial Hemp

 

Hemp is a distinct variety of the plant species cannabis sativa L. that contains minimal (less than 1%) amounts of tetrahydrocannabinol (THC), the primary psychoactive ingredient in marijuana. It is a tall, slender, fibrous plant similar to flax or kenaf. Various parts of the plant can be utilized in the making of textiles, paper, paints, clothing, plastics, cosmetics, foodstuffs, insulation, animal feed and other products.

Hemp produces a much higher yield per acre than do common substitutes such as cotton and requires few pesticides. In addition, hemp has an average growing cycle of only 100 days and leaves the soil virtually weed-free for the next planting.

The hemp plant is currently harvested for commercial purposes in over 30 nations, including Canada, Japan and the European Union. Although it grows wild across much of America and presents no public health or safety threat, hemp is nevertheless routinely uprooted and destroyed by law enforcement. Each year, approximately 98% of all the marijuana eliminated by the DEA’s “Domestic Cannabis Eradication/Suppression Program” is actually hemp.

Source: http://norml.org/marijuana

 

Novartis announces two CHMP positive opinions for new indications of Galvus® and Eucreas® combined with other diabetes treatments .

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  • Positive opinion for the use of vildagliptin, with or without metformin, in combination with a stable dose of insulin[1]
  • Additional positive opinion for the use of vildagliptin in combination with a sulphonylurea and metformin[1]
  • Positive opinions open the way for new treatment options for patients unable to reach their blood sugar goals

Novartis announced today that the European Medicines Agency‘s Committee for Medicinal Products for Human Use (CHMP) has issued two positive opinions for new indications for the use of Galvus® (vildagliptin) and Eucreas® (vildagliptin and metformin) in combination with other treatments for type 2 diabetes patients[1].

 

The first positive opinion was for vildagliptin in combination with insulin, with or without metformin, for patients with type 2 diabetes when diet, exercise and a stable dose of insulin do not result in glycemic control[1]. The second positive opinion was for vildagliptin in triple combination with metformin and a sulphonylurea for the treatment of type 2 diabetes when diet and exercise plus dual therapy with these two agents do not provide adequate glycemic control[1].

 

“These CHMP positive opinions are important milestones in our efforts to offer physicians and patients effective and generally well-tolerated additional treatment options to help reach and maintain blood sugar goals,” says David Morris, Primary Care Franchise Head of Development, Novartis Pharmaceuticals.

 

The CHMP positive opinion for the use of vildagliptin in combination with insulin was based on a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (n=449) which demonstrated that vildagliptin 50 mg administered twice daily in combination with insulin, with or without metformin, reduced blood sugar levels (HbA1c) versus placebo (-0.7%; P<0.001)[2]. The addition of vildagliptin was weight neutral and resulted in a similar incidence of hypoglycemia versus placebo[2].

 

The CHMP positive opinion for the use of vildagliptin in combination with metformin and a sulphonylurea was based on a 24-week, randomized, double-blind, placebo-controlled, parallel-group trial (n=318)[1]. The study demonstrated that vildagliptin 50 mg twice-daily in combination with metformin and a sulphonylurea reduced blood sugar levels (HbA1c) versus placebo (-0.8%; P<0.001)[1]. Five times as many patients reached their blood sugar level goal versus placebo (28.3% for vildagliptin versus 5.6% for placebo; P<0.001)[1]. The addition of vildagliptin was weight neutral versus placebo and had a low incidence of hypoglycemia[1]. As part of the positive opinion, it was noted that sulphonylureas are known to cause hypoglycemia so physicians may consider a lower dose of sulphonylurea to reduce this risk when combining treatments[1].

 

Upon approval, vildagliptin in combination with insulin, with or without metformin, and vildagliptin in combination with metformin and a sulphonylurea will offer new treatment options for patients unable to reach blood sugar goals, with a low risk of hypoglycemia while also achieving weight neutrality[1],[3].

 

About diabetes

Diabetes is one of the world’s greatest healthcare challenges, affecting 366 million people globally and killing one person every seven seconds[4]. The obesity epidemic and an aging world population are contributing to the escalating incidence of type 2 diabetes and by 2030 it is projected that more than half a billion people will be diagnosed with the disease[4]. Type 2 diabetes accounts for 90 percent of all cases of the disease[5].

 

About Galvus®

Galvus® (vildagliptin) is a dipeptidyl peptidase-4 (DPP-4) inhibitor, a class of oral diabetes medications that enhance the body’s natural ability to control blood sugar. The Galvus® (vildagliptin) safety and efficacy profile has been established in a comprehensive clinical trial program that included more than 15,000 type 2 diabetes patients[6].

 

Galvus® (vildagliptin) is approved in more than 100 countries across Europe, Asia Pacific, Africa and Latin America. It is indicated for the treatment of type 2 diabetes as a monotherapy and in combination with metformin, a sulphonylurea, a thiazolidinedione or insulin[6]. Specific indications vary by country.

 

About Eucreas/Galvus® Met

Eucreas®/Galvus® Met (vildagliptin and metformin) is a single-pill fixed-dose combination of Galvus® (vildagliptin) and metformin. Eucreas®/Galvus® Met (vildagliptin and metformin) is approved in more than 80 countries across Europe, Asia Pacific, Africa and Latin America for the treatment of patients with type 2 diabetes who are unable to control blood sugar with metformin alone[7]. Specific indications vary by country.

 

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as “positive opinion,” “open the way,” “milestones,” “will,” “projected,” or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Novartis vildagliptin products or regarding potential future revenues from such products. You should not place undue reliance on these statements.  Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Novartis vildagliptin products to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Novartis vildagliptin products will be approved for any additional indications or labeling in any market. Nor can there be any guarantee that such products will achieve any particular levels of revenue in the future. In particular, management’s expectations regarding Novartis vildagliptin products could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; unexpected manufacturing issues; the impact that the foregoing factors could have on the values attributed to the Novartis Group’s assets and liabilities as recorded in the Group’s consolidated balance sheet, and other risks and factors referred to in Novartis AG‘s current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

 

References

 

[1] Novartis Pharma AG data on file.

[2] Lukashevich V et al. Vildagliptin combined with insulin reduces HbA1c without increasing risk of hypoglycemia and weight gain in patients with type 2 diabetes mellitus. Poster presented at the 72nd American Diabetes Association; June 8-12, 2012; Philadelphia, PA, USA. Poster # 995-P.

[3] Inzucchi SE et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2012;55:1577-1596.

[4] International Diabetes Federation. Global diabetes plan. http://www.idf.org/sites/default/files/Global_Diabetes_Plan_Final.pdf.  Accessed September 7, 2012.

[5] International Diabetes Federation. Types of diabetes. http://www.idf.org/types-diabetes.  Accessed September 7, 2012.

[6] Galvus Summary of Product Characteristics (SmPC).

[7] Eucreas Summary of Product Characteristics (SmPC).

 

Source: Novartis Newsletter.

 

 

Building a Biobank to Explore Mysteries of the Genome.

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GTEx is collecting multiple tissue samples from an estimated 1,000 individual donors for genetic research. (Image from the National Disease Research Interchange GTEx Team)

The architects of the biobank wanted nothing left to chance and everything well documented.

That’s why they developed 150 standard operating procedures to ensure that tissue samples were collected, processed, and stored in exactly the same way. And that’s why they are collecting data on the best temperatures for shipping the samples across the United States.

All that planning is paying off for the Genotype-Tissue Expression (GTEx) project, which will use the samples to investigate how genes are regulated in health and disease. Sponsored by the National Institutes of Health (NIH), the project has nearly 4,400 samples of “normal” human tissue from about 175 donors. By collecting many more samples, the project aims to be a resource for studying genetic variation and the regulation of genes in specific tissues.

“This project is an attempt to understand how normal genetic variation influences the expression of genes throughout the body,” said the study’s leader, Dr. Jeffery Struewing of the National Human Genome Research Institute. NCI and the National Institute of Mental Health are also playing lead roles in the effort.

Normal tissue—that is, tissue with no signs of disease—is not routinely collected for research. GTEx is the first large-scale project to collect high-quality samples of up to 32 tissue types from many individual donors.

During a pilot study that began last year, investigators with NCI’s cancer Human Biobank (caHUB) and their collaborators were responsible for acquiring and managing the biospecimens. On average, each organ and tissue donor has contributed 25 types of postmortem tissue, including heart, muscle, and skin. Surgical donors have also contributed tissues.

A Bigger Biobank

Based on the success of the pilot, the NIH Common Fund is scaling up GTEx, with a goal of reaching 1,000 donors in 3 years. This larger number of donors and samples will provide the statistical power that is needed to ask fundamental questions about the genome, the researchers said.

All cells in the human body contain essentially the same complement of genes, but these genes are activated, or expressed, differently in different types of cells. For the first time, GTEx will allow researchers to investigate how common genetic variants influence the regulation of gene expression using a set of reference tissues.

The relationship between genetic variants and gene regulation in different tissues is “a fascinating biology question, but it is also relevant in medicine,” said Dr. Barbara Stranger of Harvard Medical School and Brigham and Women’s Hospital, who studies genes and complex diseases but is not involved in GTEx.

“Healthy individuals will have some of the same regulatory processes as people with a complex disease,” Dr. Stranger continued. Understanding these processes could provide information about a variety of diseases.

Donors and Families

“No one really knew if this would work,” said Dr. Sherilyn Sawyer, who co-led the development of the GTEx biobank and until recently was part of NCI’s Office of Biorepositories and Biospecimen Research (OBBR). “So we’re ecstatic that the infrastructure we put in place through caHUB has resulted in the specimens that have produced an amazing collection of data.”

GTEx works with organizations involved in tissue and organ donation in several cities. When an organ or tissue donor who is eligible for GTEx passes away, one of these organizations contacts the deceased person’s family to ask permission to collect tissues from their loved one for the study.

“It’s a sensitive time, so care is taken,” said Anna M. Smith of the Frederick National Laboratory for Cancer Research, who works on ethical, legal, and regulatory affairs for GTEx. “It goes without saying that there would be no biobank without the donors and families.”

 

GTEx minimizes changes to tissue by using standard procedures to collect, process, and store the samples. (Image from the National Disease Research Interchange GTEx Team)

Once specimens are collected, they are preserved and shipped to the Van Andel Institute in Grand Rapids, MI, which is the central repository of materials. By collecting, processing, and storing the tissue samples in a controlled and uniform way, the researchers hope to maintain them in a nearly natural state and minimize alterations.

“The quality of the biospecimen is extraordinarily important,” said Dr. Sawyer. Collecting tissues with uniformly high RNA and DNA quality helps ensure that the information gained from analyzing the samples will “be as accurate to the biology of the tissues as possible,” she explained.

GTEx staff regularly scrutinize tissue samples to be sure that they are of high quality. “GTEx has a higher degree of quality-control management over the whole process than other projects we have done,” noted Dr. Scott Jewell, who directs the Program for Biospecimen Science at the Van Andel Institute.

Whether the same amount of quality control that went into GTEx will be required for all biobank projects is not yet known, Dr. Jewell added. But the lessons learned from GTEx could guide future efforts. Toward this end, researchers have released approximately 150 standard operating procedures related to biobanking.

Logistical Challenges

“This project turned out to be a hugely complex logistical challenge,” said Dr. Jim Vaught, deputy director of OBBR. But with these challenges have come opportunities to ask important questions about biobanking.

For example, no one knows the best temperatures for shipping biospecimens. The GTEx team developed shipping containers that have “data loggers” to record the temperature at every minute. These data could help reveal the optimal temperatures for shipping biospecimens.

A Universe of Data

The GTEx project will more than triple its pool of donors in the next 3 years. Success will depend on a robust and flexible information technology system, noted Charles Shive, director of software development at the Frederick National Laboratory for Cancer Research.

A web-based application developed by Shive and his colleagues allows project members with various levels of access to data to communicate and monitor the progress of specimen processing and data collection in real time. “We know where specimens are at all times in the GTEx pipeline,” said Shive.

Pathologists review images of all tissue samples to assess the quality of biospecimens. Using the web application, pathologists can add their comments to “the universe of data associated with each sample,” Shive said.

“Unless the research is done and the data are generated, no one is ever going to know the answers,” said Smith.

Another question GTEx could help answer is how long tissues remain scientifically useful after the blood flow to an organ has been cut off. During the pilot study, GTEx researchers at the Broad Institute, in Cambridge, MA, observed a drop-off in RNA quality that was linked to the interval between death and tissue collection. Degradation depends on the type of tissue and how much time has passed since blood flow to the tissue ceased, the researchers found.

“For some tissues, the RNA will stay good for many hours after blood flow to the organ stops,” said Dr. Wendy Winckler, co-leader of the Broad GTEx team, which conducts molecular studies, including RNA sequencing. “But in the pancreas and the spleen, for example, if you don’t get the tissue within a few hours [after death] you’re not going to get [useful RNA].”

Despite these challenges, the researchers are optimistic. “Getting biospecimens for any research project is a tremendous challenge,” said Dr. Kristin Ardlie, also a leader of the GTEx work at the Broad. “We’ve been surprised by how well the process has worked in this project.”

The Broad researchers deposit their data quarterly in the database of Genotypes and Phenotypes (dbGP). Investigators can apply for access to the data, which have been stripped of identifying information to protect the anonymity of the donors. In addition, the project plans to make extra samples available to researchers in 2013.

Many Questions to Explore

GTEx data will likely be used to interpret genome-wide association studies. In recent years, these studies have identified inherited genetic variants associated with common diseases. The variants, however, often map to regions of the genome that lack genes, raising questions among researchers about how the variants influence disease risk.

A logical explanation could be that these variants influence the regulation of genes and thereby increase (or decrease) the risk of disease.

“Many common variants associated with common human diseases may be more about affecting the regulation of gene expression than about changing protein structure,” said Dr. Nancy Cox of the University of Chicago, who is developing statistical tools for analyzing data generated by GTEx. “This is one reason we believe the GTEx project is so important.”

With samples of so many tissues, GTEx could also help researchers look at changes in gene expression throughout the body. “A disease process might not be limited to one particular cell type or tissue type,” said Dr. Stranger.

“People will be using data from this project for a long time and in different ways,” she added. “There are all kinds of people waiting to see the GTEx results.”

Watch the video on youtube: URL  http://www.youtube.com/watch?feature=player_embedded&v=MLlqYdu6jY4

 

Source: NCI

The ENCODE Project: ENCyclopedia Of DNA Elements.

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ENCODE Overview

The National Human Genome Research Institute (NHGRI) launched a public research consortium named ENCODE, the Encyclopedia Of DNA Elements, in September 2003, to carry out a project to identify all functional elements in the human genome sequence. The project started with two components – a pilot phase and a technology development phase.

The pilot phase tested and compared existing methods to rigorously analyze a defined portion of the human genome sequence (See: ENCODE Pilot Project). The conclusions from this pilot project were published in June 2007 in Nature and Genome Research [genome.org]. The findings highlighted the success of the project to identify and characterize functional elements in the human genome. The technology development phase also has been a success with the promotion of several new technologies to generate high throughput data on functional elements.

With the success of the initial phases of the ENCODE Project, NHGRI funded new awards in September 2007 to scale the ENCODE Project to a production phase on the entire genome along with additional pilot-scale studies. Like the pilot project, the ENCODE production effort is organized as an open consortium and includes investigators with diverse backgrounds and expertise in the production and analysis of data (See: ENCODE Participants and Projects). This production phase also includes a Data Coordination Center [genome.ucsc.edu] to track, store and display ENCODE data along with a Data Analysis Center to assist in integrated analyses of the data. All data generated by ENCODE participants will be rapidly released into public databases (See: Accessing ENCODE Data) and available through the project’s Data Coordination Center.

Source: genome.gov