Ground-breaking Liver Cancer Treatment NOVEMBER 26, 2012 BY CLAIRE AL-AUFI

Surgeons in the UK have pioneered a new treatment for cancer that is both unique and promising. The treatment involved isolating a cancerous liver by cutting off its blood supply and at the same time, dousing the organ with a “chemo bath.”

The procedure enables saturation of the tumours with chemotherapy while restricting the effects solely within the infected organ. Brian Stedman, is the consultant radiologist at Southampton General Hospital, who led the team that used the procedure, known as Chemosaturation with Percutaneous Hepatic Perfusion (CS-PHP). There were two patients who underwent the operation because their livers had become cancerous.

A cancerous liver is one where mutated cells grow and take over healthy cells. It is called primary liver cancer if it begins there, but metastatic if it spreads from outside, as with eye melanoma. Around 21, thousand Americans contract primary liver cancer every year. It is unusual in being a cancer on the increase. There are no obvious symptoms, which makes early diagnosis a matter of luck rather than screening. Men are two times more likely to suffer from it than women.

Symptoms to be aware of with advanced stage liver cancer might include tiredness, abdominal bloating, pain high up on the right of abdomen, in your back or shoulder area. Also nausea, loss of appetite, feeling full while losing weight, weakness, fever, and yellowing of the eyes and the skin.

This new CS-PHP treatment was developed in Europe and used successfully in America, Germany, Ireland, Italy and France. A study published in the spring, out of the Moffitt Cancer Center in Tampa, reports that the cancer sufferers that underwent the procedure lived five times longer than patients who underwent traditional treatment.

There are several cancers that invade the liver from original tumors in other organs. Melanoma of the eye is one such. Cancer of the liver is virtually untreatable and four months is the average longevity with only 10% of sufferers living past a year.

CS-PHP significantly adds to the life of melanoma patients while improving the quality of life since the disease progresses no further. The chemotherapy cocktails are infused straight into the liver using a catheter. Blood in the veins, that normally would enter the liver, is diverted and filtered through a purpose made, ‘double-balloon’ catheter to remove all traces of the drug before returning to the organ.

The new methodology enables higher concentrate drugs to be targeted on the liver. It gives maximum impact with minimum ‘collateral damage’. Dr. Stedman comments on the technique,

”To cut off an organ from the body for 60 minutes, soak it in a high dose of drug and then filter the blood almost completely clean before returning is truly groundbreaking.”

He contrasted the new and more traditional treatments where the prognosis for sufferers is dire because of the awful side effects of even low concentrate chemotherapy that wreaks havoc on the whole body. There are possibilities for CS-PHP to be used as a treatment method for other tumors such as in the colon or breast.

Novartis drug helps patients with rare inflammatory diseases

FMF, TRAPS are rare diseases

* Drug reduced attack frequency by 50 pct in FMF patients

* Relieved symptoms in TRAPS patients for average 3 months

ZURICH, Nov 11 (Reuters) - Novartis' Ilaris helps reduce patients' symptoms and the frequency of attacks in two rare inflammatory diseases, mid-stage studies showed, as the Swiss drugmaker looks to expand the use of the medicine.

Results of two separate studies on Sunday in patients with Familial Mediterranean Fever (FMF) and TRAPS - rare genetic diseases which can cause fever, rash and joint pain - both met their primary endpoints, Novartis said in a statement.

Both studies are being presented at the American College of Rheumatology (ACR) meeting in Washington D.C.

Ilaris or ACZ885, which blocks a protein called interleukin-1 beta that is thought to increase inflammation, is already sold for treating cryopyrin-associated periodic syndromes, a rare inflammatory disorder.

Novartis is also hoping to file the drug this year for regulatory approval in systemic juvenile idiopathic arthritis (SJIA), a debilitating disease that can affect a child's growth.

Results of the phase II study showed the drug helped 100 percent of FMF patients reduce the frequency of attacks by at least 50 percent during three months of treatment.

Eight of the nine patients in the trial did not have an attack during the three months and blood markers of inflammation also normalised.

There are currently no approved treatments for FMF or TRAPS, rare genetically-inherited anti-inflammatory diseases, which can affect both children and adults.

Novartis is hoping to show the drug can be beneficial in treating rare inflammatory diseases after receiving a setback last year when U.S. health regulators rejected Ilaris for use in gout over concerns about side effects.

New data from a mid-stage study on the use of Ilaris in TRAPS showed that patients who came off therapy after being treated with the drug did not have a relapse for three months on average.

Earlier data from the study showed that 90 percent of patients experienced a significant improvement in symptoms after just one week of treatment with Ilaris. This rose to 95 percent after two weeks. (Reporting by Caroline Copley; Editing by Elaine Hardcastle)

HEALTHCARE

New Study Uses Animal Model Similar To Humans And Shows BPA Can Affect Thyroid Function Main Category: Endocrinology Also Included In: Pregnancy / Obstetrics; Public Health Article Date: 16 Nov 2012

In utero exposure to bisphenol A (BPA) can be associated with decreased thyroid function in newborn sheep, according to a recent study accepted for publication inEndocrinology, a journal of The Endocrine Society. Hypothyroidism is characterized by poor mental and physical performance in human adults and in children can result in cognitive impairment and failure to grow normally. 

BPA, a major molecule used in the plastic industry, has been shown to be an endocrine disruptor that could exert deleterious effects on human health. Most investigations have focused on reproductive functions, but there is evidence that BPA might have negative effects on other endocrine systems including thyroid function. The current study used sheep, a relevant model for human pregnancy and thyroid regulation and ontogeny, and analyzed the internal exposures of the fetuses and their mothers to BPA and determined to what extent those exposures may be associated with thyroid disruption. 

"Our study is the first to show that BPA can alter thyroid function of pregnant animals and their offspring in a long-gestation species with similar regulation of thyroid function as humans," said Catherine Viguié, PhD, of Toxalim, Research Centre in Food Toxicology in Toulouse, France and lead author of the study. "Because of the potential consequences of maternal/fetal thyroid disruption on neural and cognitive development, we think that our study warrants the need for further investigations on the effect of BPA on thyroid function." 

This study was conducted on adult ewes that had multiple pregnancies before being included in the experiment. Some of the pregnant ewes received daily subcutaneous injections of BPA while the remainder were allocated to the control group. Blood samples were taken from jugular blood, amniotic fluid, placenta samples and cord blood to determine levels of BPA, thyroid-stimulating hormone (TSH) and thyroxine. Results showed that maternal and fetal exposure to BPA was associated with disruption of thyroid function of both the pregnant ewes throughout pregnancy and the newborns as characterized by a decrease in circulating thyroxine levels. 

"BPA concentrations in the mother blood in this experiment were fluctuating between injections from 15 to 1 time the highest blood levels reported in pregnant women in the literature," notes Viguié. "As a consequence, although this study clearly indicates that BPA has the potential to alter thyroid function in living pregnant animals and their offspring, it cannot be considered as fully conclusive in terms of risk for human health in the actual conditions of exposure of human populations." 

"In other words, although our study clearly indicates that BPA-induced thyroid disruption is possible, it does not indicate how probable such a disruption is to occur in real conditions," added Viguié. "Thus, the main merit of our work is to encourage others, including epidemiologists, to scrutinize and qualify carefully such a probability." 

India revokes Roche patent in new blow for Big Pharma By Kaustubh Kulkarni and Ben Hirschler | Reuters – Fri 2 Nov, 2012

MUMBAI/LONDON (Reuters) - India dealt a fresh blow to the international pharmaceutical industry on Friday as its patents appeal board revoked a patent granted six years ago on Roche's hepatitis C drug Pegasys.

The Intellectual Property Appellate Board (IPAB) cited a lack of evidence that the drug was any better than existing treatments and its high price as reasons for the decision.

Pegasys was the first medicine to win protection in 2006 under India's new patent regime and the revocation will rekindle tensions between New Delhi and global drugmakers worried by the country's tough stance.

The decision follows another high-profile setback for the industry in March, when India granted the first ever compulsory licence to domestic drugmaker Natco to sell cheap copies of Bayer's cancer drug Nexavar.

Multinational drug manufacturers see India's $12 billion drug market as a huge opportunity, but are wary of what they see as lax protection for intellectual property in a country where generic medicines account for more than 90 percent of sales.

Indian generic companies, which do not need to plough money back into future research, can produce drugs at a fraction of the cost of originator firms like Roche or Bayer.

Sankalp Rehabilitation Trust, an advocacy group for cheaper medicines, had challenged the Pegasys patent with the IPAB, saying the drug was costly and gave the Swiss company a monopoly in the market for the drug.

The market price of Pegasys is 436,000 rupees for 48 weeks of treatment, although it is also available at a discounted price of 314,496 rupees, Sankalp said in a statement.

Pegasys is given in combination with another drug, ribavirin, which costs 47,160 rupees for the same period, Sankalp added.

The appeals board on Friday termed Sankalp's plea "valid."

PAYING FOR INNOVATION

Roche, which can appeal the decision to the Supreme Court, said it was reviewing the IPAB decision and could not comment on it in detail. But it said a solid system of patent protection was essential to ensure research into new treatments.

"Many of the generic drugs today used in India were once patent-protected and are only available to society because companies such as Roche were willing to take a risk by investing in new innovative drugs," a company spokesman said.

He added that Roche was assessing a number of different ways to make drugs accessible to patients in poorer countries, including volume discounts, rebates and price capping.

Campaigners for greater healthcare access contend that the best way to ensure low drug prices is to maximise generic competition by challenging unjustified patents.

Leena Menghaney, a manager in New Delhi for Medecins Sans Frontieres (MSF), said this was particularly important in a disease area like hepatitis C, which is a growing problem in many Asian countries and often hits the most vulnerable in society.

"This case shows that if people choose to use different public health safeguards in Indian law to check abuse of the patent system, then indeed they do work," she said.

Another case involving drug patents is currently in front of India's the Supreme Court, with Novartisbattling against an earlier decision refusing it a patent on cancer drug Glivec.

India is also taking a tougher line on drug pricing more generally, with plans to increase dramatically the number of essential drugs subject to price regulation.

(Reporting by Kaustubh Kulkarni; Editing by Tony Munroe and David Cowell)

Cognitive behavioural therapy (CBT) for anxiety in people with dementia: study protocol for a randomised controlled trial

Background

Many people with dementia experience anxiety, which can lead to decreased independence, relationship difficulties and increased admittance to care homes. Anxiety is often treated with antipsychotic medication, which has limited efficacy and serious side effects. Cognitive behavioural therapy (CBT) is widely used to treat anxiety in a range of populations, yet no RCTs on CBT for anxiety in dementia exist. This study aims to develop a CBT for anxiety in dementia manual and to determine its feasibility in a pilot RCT.

Methods

Phase I involves the development of a CBT for anxiety in dementia manual, through a process of (1) focus groups, (2) comprehensive literature reviews, (3) expert consultation, (4) a consensus conference and (5) field testing. Phase II involves the evaluation of the manual with 50 participants with mild to moderate dementia and anxiety (and their carers) in a pilot, two-armed RCT. Participants will receive either ten sessions of CBT or treatment as usual. Primary outcome measures are anxiety and costs. Secondary outcome measures are participant quality of life, behavioural disturbance, cognition, depression, mood and perceived relationship with the carer, and carer mood and perceived relationship with the person with dementia. Measures will be administered at baseline, 15 weeks and 6 months. Approximately 12 qualitative interviews will be used to gather service-users' perspectives on the intervention.

Discussion

This study aims to determine the feasibility of CBT for people with anxiety and dementia and provide data on the effect size of the intervention in order to conduct a power analysis for a definitive RCT. The manual will be revised according to qualitative and quantitative findings. Its publication will enable its availability throughout the NHS and beyond.

Off-label Drug Use

What is off-label drug use?

In the United States new drugs are tested in clinical trials (research studies) before they are approved for use in the general public. The clinical trials are done to prove that the drug:

• Works to treat a certain medical condition
• Works the way it is expected to
• Is safe when used as directed

When the US Food and Drug Administration (FDA) is satisfied that the drug works and is safe, it and the maker of the drug create the drug label. This is not an actual label that sticks onto a bottle, but a report of very specific information about the drug. The FDA must approve this report, which is made available to all health professionals who prescribe or sell the drug.

The drug label gives information about the drug, including the approved doses and how it's to be given to treat the medical condition for which it was approved. When a drug is used in a way that is different from that described in the FDA-approved drug label, it is said to be an "off-label" use. This can mean that the drug is:

• Used for a different disease or medical condition
• Given in a different way (such as by a different route)
• Given in a different dose than in the approved label

For example, when a chemotherapy drug is approved for treating one type of cancer, but is used to treat a different cancer, it is off-label use.

Off-label is also called "non-approved" or "unapproved" use of a drug.

Is off-label drug use legal?

The off-label use of FDA-approved drugs is not regulated, but it is legal in the United States and many other countries. An exception to this is the use of some controlled substances, such as opioids (pain medicines like morphine and fentanyl). These drugs cannot legally be prescribed in the United States except for approved purposes.

While it is legal for doctors to use drugs off label, it is not legal for drug companies to market their drugs for off-label uses. This has been a hot news topic recently, as drug companies have been fined because they promoted drugs for uses not approved by the FDA. Off-label marketing is very different from off-label use.

Why are drugs used off-label?

Older, generic medicines are the ones most often used off label. New uses for these drugs may have been found and there is often medical evidence to support the new use. But the makers of the drugs have not put them through the formal, lengthy, and often costly studies required by the FDA to officially approve the drug for new uses.

Off-label drug use is common in cancer treatment. There are many reasons for this:

• Some cancer drugs are found to work against many different kinds of tumors.
• Chemotherapy treatments often use combinations of drugs. These combinations might include one or more drugs not approved for that disease. Also, drug combinations change over time as doctors study different ones to find out which work best.
• Cancer treatment is always changing and improving.
• Oncologists and their patients are often faced with problems that have few approved treatment options.
• Oncologists and their patients may be more willing to try off-label drugs than other medical specialties.

What problems are caused by off-label drug use?

Reimbursement

The biggest problem is getting insurance plans to pay for off-label drug use (reimbursement). Many insurance companies will not pay for an expensive drug that is used in a way that is not listed in the approved drug label. They do this on the grounds that its use is "experimental" or "investigational."

In cancer treatment, these issues have been largely addressed through 1993 federal legislation that requires insurance to cover medically appropriate cancer therapies. This law includes off-label uses if the treatment has been tested in careful research studies and written up in well-respected drug reference books or medical journals. In 2008, Medicare rules were changed to cover more off-label uses of cancer treatment drugs.

Still, the health insurance coverage laws and regulations are complex. If your doctor is thinking about off-label drug use, you and your doctor should carefully check your health plan's coverage. If coverage is denied the first time, it may help for the doctor to send the insurer copies of peer-reviewed journal articles or other respected sources that support the off-label use.

Legal risk

Another problem is that off-label drug use often does not reflect "standard of care" treatment. This leads to possible concern about the legal risk of prescribing off-label should a patient have an unwanted or bad outcome from the treatment.

Lack of regulation and information

The FDA does not regulate the practice of medicine. In general, once the FDA approves a drug, licensed doctors can use it for any purpose they consider medically appropriate. Off-label use can vary greatly from one doctor to another. It depends on the doctor's preferences, knowledge, and past patient experiences.

One of the biggest problems related to widespread off-label use is the lack of information about how to best use the drug beyond what was approved. One of the most reliable and easy-to-find sources of information available to health professionals, caregivers, and patients is the drug label. But the label can only contain the information that has been approved by the FDA, and it does not mention off-label uses.

The medical literature reports clinical trials, including those that are not part of the FDA approval process. This is the main source of off-label use information, although treatment guidelines may also offer options that include off-label use. Treatment guidelines are based on information from medical literature, including clinical trials, and recommend standard ways to treat certain diseases.

Lack of information on off-label drug use and outcomes may also put patients at a higher risk for medication errors, side effects, and unwanted drug reactions. It is important that the patient and doctor talk about the possible risks of using the drug and weigh them against the possible benefits.

How common is off-label drug use?

Little information is available on off-label prescribing in oncology in the US. Yet, a study done in 2008 found that 8 out of 10 cancer doctors surveyed had used drugs off-label. Off-label drug use is well-documented and very common in certain settings, such as pediatrics and HIV/AIDS care.

Studies have reported that about half of the chemotherapy used is given for conditions not listed on the FDA-approved drug label. In fact, the National Cancer Institute (NCI) has stated, "Frequently the standard of care for a particular type or stage of cancer involves the off-label use of one or more drugs." Actual off-label use is likely much higher because chemotherapy is only one aspect of cancer treatment. Studies have yet to look at all the drugs used in cancer treatment, such as anti-nausea drugs and pain medicines.

What other ways are drugs used off label in cancer treatment?

One example of off-label drug use is tricyclic antidepressants to treat certain types of pain. This old class of antidepressant drugs is approved and labeled to be used for clinical depression. Today these drugs are seldom used for depression because safer drugs are now available to treat it. But doctors have found that the tricyclics often work very well in treating certain types of pain.

Another example is lorazepam (Ativan®), an anti-anxiety drug often used as an anti-nausea drug in cancer treatment. In oncology, Ativan is most commonly given under the tongue (the sublingual route), which is also not listed on the drug label. In this case, it is being given for an off-label use and by an off-label route.

RECENT EMERGING HUB FOR GLOBAL CLINICAL RESEARCH IN INDIA

The economic environment of a country has a very strong impact on the economic system in which its industries and business firms operate. As far as economic environment of India is concerned, India's is a mixed economy. A simple mixed economic system is characterized by existence of both private and public sectors. In present the clinical trial market in India looks very lucrative. The country promises to be one of the hottest destinations for conducting global clinical trials, owing to a huge patient pool representing both chronic and infectious diseases, easy recruitment of patients, and high cost savings. Moreover, the market is getting boost from improved IPR protection with changed rules and also from reduced taxes and duties. According to our new research study on the sector called "Booming Clinical Trials Market in India", the clinical trial outsourced market in India is forecasted to grow at a compound annual growth rate( CAGR) of around 31% during 2010-2012. Presently, the market is characterized by the dominance of phase III and phase II trials, which currently hold more than 80% of the market. India has the largest pool of patients in many diseases, including cancer and diabetes. The study also points out that India's biggest advantage is its low cost. For instance, trials for a standard drug in the US can cost up to $150 million. A similar drug could be tested in India for less than half that amount. Center Watch has predicted that by 2010, the industry will spend around $250-300 million on clinical trials in India. Mc Kinsey estimates a much higher figure of $1-1.5 billion. This scenario is expected to remain intact in future as well. With detailed description of the regulatory environment and cost factors promoting the market. It also highlights several emerging market trends like clinical data management, pathology and diagnostic market, etc. The research study offers detailed statistical and analytical review on demographics, macroeconomic indicators, disease profile, clinical service market, key drivers and restraints. It contains all the requisite information that will help clients to draw up market strategies and assess opportunity areas in India's clinical trial market.Clinical trials in India is 44% less expensive than US trials.