Longest follow-up of melanoma patients treated with ipilimumab shows some survive up to ten years

Sep. 27, 2013 — Patients with advanced melanoma, who have been treated with the monoclonal antibody, ipilimumab, can survive for up to ten years, according to the largest analysis of overall survival for these patients, presented at the 2013 European Cancer Congress (ECC2013).

Professor Stephen Hodi (MD), Assistant Professor of Medicine at the Dana-Farber Cancer Institute (Boston, USA), told the congress: "Our findings demonstrate that there is a plateau in overall survival, which begins around the third year and extends through to the tenth year.

"These results are important to healthcare providers and patients with advanced melanoma since they provide a perspective on long-term survival for ipilimumab patients who are alive after three years of treatment. Our data, which represent the longest follow-up of the largest numbers of patients on any globally approved melanoma therapy, will provide a benchmark for future medicines for advanced melanoma."

Ipilimumab is a human monoclonal antibody that activates the immune system to fight melanoma skin cancer by targeting a protein receptor called Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4). In melanoma, CTLA-4 is inhibited from recognising and destroying cancer cells, but ipilimumab turns off the inhibitory mechanism, enabling CTLA-4 to continue killing the cancer cells.

It is already known that some patients treated with the drug survive for long periods, with one phase III clinical trial showing an overall survival rate of 18% after five years. Therefore, Prof Hodi and colleagues from Germany, France and the USA collected data on 1861 patients in 12 prospective and retrospective studies to provide a more precise estimate of ipilimumab's effect on long-term survival. In addition, they analysed data from a further 2985 patients who had been treated with the drug but were not part of any clinical trial, giving the researchers data on a total of 4846 patients.

The analysis of the 1861 patients showed that the median overall survival was 11.4 months (11.4 being the middle number separating the higher half of the patient survival time from the lower half). "Among these patients, 254 patients (22%) were still alive after three years. There were no deaths among patients who survived beyond seven years, at which time the overall survival rate was 17%. The longest overall survival follow-up in the database is 9.9 years," said Prof Hodi.

"The plateau, which started at three years and continued through to ten years, was observed regardless of dose (3 or 10 mg/kg), whether the patients had received previous treatment or not, and whether or not they had been kept on a maintenance dose of the drug. However, as this was not a randomised comparison, one cannot draw direct conclusions on differences between the doses or the populations."

When data from the total 4846 patients were analysed, the median overall survival was 9.5 months, with a plateau in overall survival starting around three years for 21% of the patients. "This slightly lower survival rate was because there were limited and incomplete data on overall survival, and patients given ipilimumab through the extended access programme tended to be more ill and with more advanced disease," explained Prof Hodi.

He concluded: "The limitation of this study is that it is a pooled analysis from phase II, phase III and observational data and not from a single randomised, controlled study. However, these results are consistent with our findings from randomised clinical trials and confirm the durability of the plateau in overall survival, previously shown to extend to at least five years but now shown to extend up to ten years."

Past President of ECCO, Professor Alexander Eggermont, Directeur General of the Institut Gustave Roussy Comprehensive Cancer Center (France), who specialises in the treatment of melanoma, commented: "This pooled analysis clearly demonstrates that ipilimumab can lead to long-lasting tumour control in metastatic melanoma patients. With a response rate of only 10-15%, one can achieve more than 3-10 years survival in 17-25% of patients who have received only a few doses of ipilimumab. Thus, patients apparently can keep residual tumours under control for a long time when the immune system is properly 'reset', and the concept of 'clinical cures' becomes a reality. These survival results could even double or triple with anti-PD1/PDL1 monoclonal antibodies, and metastatic melanoma could become a curable disease for perhaps more than 50% of patients over the coming 5-10 years."

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Yoga in menopause may help insomnia -- but not hot flashes

Sep. 27, 2013 — Taking a 12-week yoga class and practicing at home was linked to less insomnia -- but not to fewer or less bothersome hot flashes or night sweats. The link between yoga and better sleep was the only statistically significant finding in this MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) Network randomized controlled trial.

"Many women suffer from insomnia during menopause, and it's good to know that yoga may help them," said lead author Katherine Newton, PhD, a senior investigator at Group Health Research Institute. She e-published these findings in Menopause, ahead of print.

"Hormone therapy is the only Food and Drug Administration-approved treatment for hot flashes and night sweats," Dr. Newton said, "and fewer women are opting for hormone therapy these days." That's why MsFLASH tried to see whether three more "natural" approaches -- yoga, exercise, or fish oil -- might help ease these menopause symptoms. The study assigned 249 healthy, previously sedentary women at multiple sites, including Group Health, to do yoga, a moderate aerobic exercise program, or neither -- and to take an omega-3 fatty acid supplement or a placebo.

Exercise seemed linked to slightly improved sleep and less insomnia and depression, and yoga also was linked to better sleep quality and less depression -- but these effects were not statistically significant. The omega-3 supplement was not linked to any improvement in hot flashes, night sweats, sleep, or mood.

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Scientists urge Europe to shift focus to bowel cancer screening

By Kate Kelland

AMSTERDAM (Reuters) - European governments should divert funds to routine bowel cancer tests from less effective breast and prostate screening programs, scientists said on Saturday, presenting what they called "irrefutable" evidence that bowel screening saves lives.

Many governments devote significant funds to breast cancer screening, but studies in recent years have found that routine breast mammograms can also lead to so-called "over-diagnosis" when tests pick up tumors that would not have caused a problem.

And a new study presented at the European Cancer Conference (ECC) in Amsterdam at the weekend showed men experience more harm than good from routine prostate cancer screening tests.

In bowel cancer screening, however, the risk of over-diagnosis is very low, while gains in terms of reducing deaths are large - making routine testing cost-effective, Philippe Autier, a professor at France's International Prevention Research Institute (IPPR), told the conference.

"There is now an irrefutable case for devoting some of the resources from breast and prostate cancer screening to the early detection of colorectal (bowel) cancer," he said.

A large European study published last year found that breast screening programs over-diagnose about four cases for every 1,000 women aged between 50 and 69 who are screened.

The IPPR's research director Mathieu Boniol, who studied the impact of prostate screening, said his results showed routine use of prostate-specific antigen (PSA) tests creates more harm in terms of incontinence, impotence and other side-effects from prostate cancer treatments than benefit in terms of detecting life-threatening cancers.

"PSA testing should be reduced and more attention should be given to the harmful effects of screening," he told delegates.

Meanwhile, results of a study conducted by Autier using data from 11 European countries between 1989 and 2010 showed that the greater the proportions of men and women routinely screened for bowel cancer, the greater the reductions in death rates.

Colorectal cancer kills more than 600,000 people a year worldwide, according to the World Health Organization. In Europe some 400,000 people are diagnosed with the disease each year.

In Austria, for example, where 61 percent of those studied reported having had colorectal screening tests, deaths from this form of cancer dropped by 39 percent for men and 47 percent for women over the decade.

Meanwhile in Greece, where only 8 percent of males had had bowel cancer screening, death rates rose by 30 percent for men.

In the light of the results, Cornelis van de Velde, an oncologist at Leiden University Medical Centre in the Netherlands and president of the European Cancer Organisation, said it was "very disappointing" there are such wide differences in European governments' approaches to colorectal screening.

"People over 50 should be informed of the availability of the test, and pressure should be put on national health services to put more effort into organizing screening programs," he told the conference.

Screening for early signs of bowel cancer involves either a fecal occult blood test, which checks a sample of feces for hidden blood, or endoscopy, where a tiny camera is introduced into the large bowel to look for the polyps that can be a precursor of cancer.

In some European countries, such as France, Germany and Austria, many men and women over the age of 50 have regular colorectal screening examinations, while in others, such as The Netherlands and Britain, screening is much less common.

(Editing by David Evans)

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Longest follow-up of melanoma patients treated with ipilimumab shows some survive up to ten years

Sep. 27, 2013 — Patients with advanced melanoma, who have been treated with the monoclonal antibody, ipilimumab, can survive for up to ten years, according to the largest analysis of overall survival for these patients, presented at the 2013 European Cancer Congress (ECC2013).

Professor Stephen Hodi (MD), Assistant Professor of Medicine at the Dana-Farber Cancer Institute (Boston, USA), told the congress: "Our findings demonstrate that there is a plateau in overall survival, which begins around the third year and extends through to the tenth year.

"These results are important to healthcare providers and patients with advanced melanoma since they provide a perspective on long-term survival for ipilimumab patients who are alive after three years of treatment. Our data, which represent the longest follow-up of the largest numbers of patients on any globally approved melanoma therapy, will provide a benchmark for future medicines for advanced melanoma."

Ipilimumab is a human monoclonal antibody that activates the immune system to fight melanoma skin cancer by targeting a protein receptor called Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4). In melanoma, CTLA-4 is inhibited from recognising and destroying cancer cells, but ipilimumab turns off the inhibitory mechanism, enabling CTLA-4 to continue killing the cancer cells.

It is already known that some patients treated with the drug survive for long periods, with one phase III clinical trial showing an overall survival rate of 18% after five years. Therefore, Prof Hodi and colleagues from Germany, France and the USA collected data on 1861 patients in 12 prospective and retrospective studies to provide a more precise estimate of ipilimumab's effect on long-term survival. In addition, they analysed data from a further 2985 patients who had been treated with the drug but were not part of any clinical trial, giving the researchers data on a total of 4846 patients.

The analysis of the 1861 patients showed that the median overall survival was 11.4 months (11.4 being the middle number separating the higher half of the patient survival time from the lower half). "Among these patients, 254 patients (22%) were still alive after three years. There were no deaths among patients who survived beyond seven years, at which time the overall survival rate was 17%. The longest overall survival follow-up in the database is 9.9 years," said Prof Hodi.

"The plateau, which started at three years and continued through to ten years, was observed regardless of dose (3 or 10 mg/kg), whether the patients had received previous treatment or not, and whether or not they had been kept on a maintenance dose of the drug. However, as this was not a randomised comparison, one cannot draw direct conclusions on differences between the doses or the populations."

When data from the total 4846 patients were analysed, the median overall survival was 9.5 months, with a plateau in overall survival starting around three years for 21% of the patients. "This slightly lower survival rate was because there were limited and incomplete data on overall survival, and patients given ipilimumab through the extended access programme tended to be more ill and with more advanced disease," explained Prof Hodi.

He concluded: "The limitation of this study is that it is a pooled analysis from phase II, phase III and observational data and not from a single randomised, controlled study. However, these results are consistent with our findings from randomised clinical trials and confirm the durability of the plateau in overall survival, previously shown to extend to at least five years but now shown to extend up to ten years."

Past President of ECCO, Professor Alexander Eggermont, Directeur General of the Institut Gustave Roussy Comprehensive Cancer Center (France), who specialises in the treatment of melanoma, commented: "This pooled analysis clearly demonstrates that ipilimumab can lead to long-lasting tumour control in metastatic melanoma patients. With a response rate of only 10-15%, one can achieve more than 3-10 years survival in 17-25% of patients who have received only a few doses of ipilimumab. Thus, patients apparently can keep residual tumours under control for a long time when the immune system is properly 'reset', and the concept of 'clinical cures' becomes a reality. These survival results could even double or triple with anti-PD1/PDL1 monoclonal antibodies, and metastatic melanoma could become a curable disease for perhaps more than 50% of patients over the coming 5-10 years."

View the original article here

Could Antidepressant Combat Lethal Lung Cancer?

Little-used depression drug shows early promise in lab, mice studies

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Diabetes increases risk of developing and dying from breast and colon cancer

Sep. 27, 2013 — Diabetes is linked to an increased risk of developing cancer, and now researchers have performed a unique meta-analysis that excludes all other causes of death and found that diabetic patients not only have an increased risk of developing breast and colon cancer but an even higher risk of dying from them.

Dr Kirstin De Bruijn will tell the 2013 European Cancer Congress (ECC2013) that previous studies have examined the association between diabetes and dying from cancer but death from specific types of cancer has not been well-studied. "Our meta-analysis is the first to combine incidence and death from breast and colon cancer, while excluding all other causes of death. We have investigated the link between diabetes and the risk of developing as well as the risk of dying from these cancers," she will say.

Dr De Bruijn, a PhD student in the Surgery Department at the Erasmus University Medical Center in Rotterdam (The Netherlands), and colleagues analysed results from 20 trials that had taken place between 2007 and 2012, involving more than 1.9 million patients with breast or colon cancer, with or without diabetes.

They found that patients with diabetes had a 23% increased risk of developing breast cancer and a 38% increased risk of dying from the disease compared to non-diabetic patients. Diabetic patients had a 26% increased risk of developing colon cancer and a 30% increased risk of dying from it compared to non-diabetic patients.

Dr De Bruijn will say: "The results for breast and colon cancer incidence in patients with diabetes are consistent with other meta-analyses. Furthermore, this meta-analysis shows a higher risk and a stronger association between diabetes and death from breast and colon cancer than previously reported.

"Cancer patients who are obese and diabetic are an already more vulnerable group of individuals when it comes to surgery, as they have an increased risk of developing complications both during and after surgery. If more obese and diabetic patients have to have an operation because of cancer, healthcare costs will increase.

"Worldwide, the numbers of obese and subsequent diabetic patients are still increasing and it is a cause for concern that these individuals are at a higher risk of developing cancer and dying from it. Studies have already highlighted the increased risk of developing cancer for diabetics. Our meta-analysis, which is unique since it looks at the risks for breast and colon cancer while excluding all other causes of death, provides stronger evidence for the association between diabetes and the risk of developing and dying from these cancers. We want to make people more aware of this problem and we hope that prevention campaigns regarding obese and diabetic patients will focus on highlighting this increased risk."

Dr De Bruijn and her colleagues intend to follow up their work by investigating what effect other factors associated with diabetes have on cancer risk and death, such as the anti-diabetic medication, metformin, as well as insulin and the duration of diabetes.

"It is extremely important that prevention campaigns on obesity and diabetes are intensified and that they also focus on children, to prevent them from becoming obese and developing cancer later in life," she will conclude.

Professor Cornelis van de Velde, President of ECCO, said: "With the increase in incidence of both diabetes and breast cancer, this is an important update of the meta-analyses on this subject and an interesting addition to the literature as this study excluded other causes of death. As the results are consistent with earlier meta-analyses, the substantial increased risk of breast cancer should be part of prevention campaigns. For further research, it would be important to study how other, competing risk factors might affect survival, as elderly cancer patients with diabetes are usually diagnosed with other conditions as well. Additionally, the potential role of metformin in relation to improved survival and cancer recurrence needs to be studied."

Professor Hans-Joerg Senn, scientific director at the Tumor and Breast Centre ZeTuP, St Gallen, Switzerland, said: "The message from the Erasmus Medical Center is disturbing and highly important, for the medical community, as well as for the public and politicians. It highlights once more the importance of the negative interactions between lifestyle, metabolism, overweight and certain frequent types of cancers, such as here between diabetes, obesity and breast cancer as well as colon cancer. It is time for increased and more effective information and prevention campaigns, especially in the economically developed world, where caloric abundance is prevalent."

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Anti-cancer drug benefits women with breast cancer who have failed previous treatments

Sep. 27, 2013 — First results from a phase III clinical trial of the combination drug, T-DM1, show that it significantly improves the length of time before the disease worsens in women with advanced HER2 positive breast cancer whose cancer has recurred or progressed despite previous treatments, including trastuzumab and lapatinib.

In a late-breaking presentation to the 2013 European Cancer Congress (ECC2013) [1] today, Professor Hans Wildiers will say: "This study shows that even in heavily pre-treated women, 75% of whom had cancer that has spread to the internal organs, T-DM1 nearly doubles progression-free survival -- the length of time before disease progression or death, whichever occurs first -- compared to standard therapy, and with a more favourable safety profile. Few drugs have been able to achieve both improved progression-free survival and a better toxicity profile. These results indicate this drug has important clinical benefit for patients."

T-DM1 is a conjugated monoclonal antibody in which trastuzumab [2] is combined with a cell-killing drug emtansine (DM1) to target and kill breast cancer cells that have large amounts of the protein HER2 on their cell surfaces -- known as HER2 positive breast cancer. T-DM1 has already been shown to benefit patients with HER2 positive breast cancer that has spread to other parts of the body (metastasised), and who have already been treated with trastuzumab and a taxane-based chemotherapy.

"Despite the availability of improved treatments, virtually all patients with HER2 positive metastatic breast cancer develop progressive disease and require additional therapies for palliation. Currently there is no clear standard of care for patients who progressed after two or more treatments for their disease, including the use of the anti-HER2 drugs trastuzumab and lapatinib, and new treatment options are needed for these patients," says Prof Wildiers, who is adjunct head of clinic at the department of medical oncology, and coordinator of the chemotherapy and related clinical trial programme in the multidisciplinary breast centre at the University Hospitals Leuven, Belgium.

The international phase III clinical trial, called TH3RESA, enrolled patients whose cancer was inoperable, or had recurred or metastasised after several treatments including trastuzumab and lapatinib. By February 2013, 602 patients had been randomised to receive 3.6 mg/kg intravenous infusion of T-DM1 every three weeks or a treatment of their physician's choice (TPC). The majority (75%) had visceral disease (cancer that had spread to internal organs) and they had received a median [3] of four previous treatment regimens (excluding single agent hormonal therapy).

Results showed that median progression-free survival increased by nearly three months from 3.3 months for the TPC patients to 6.2 months for patients receiving T-DM1. Among the T-DM1 patients, 31.3% showed a response to the drug, compared with 8.6% of the TPC patients. An interim analysis of overall patient survival showed a similar trend, but it did not reach the level at which a statistically significant benefit for T-DM1 treatment could be confirmed. Patients in the TPC group, whose disease progressed, were given the option of crossing over into the T-DM1 arm and 44 patients have done this so far. Generally, there were fewer serious adverse side-effects in the T-DM1 patients than in the TPC group.

"These data reaffirm the potential of T-DM1 as a treatment for HER2-positive metastatic breast cancer. They demonstrate that T-DM1 has the potential to be a new treatment paradigm for this group of patients who currently have few options," Prof Wildiers will say.

"In the earlier, EMILIA trial, T-DM1 was shown to be superior to capecitabine and lapatinib in patients who had previously received trastuzumab and a taxane. TH3RESA demonstrates that T-DM1 offers statistically significant and clinically meaningful improvement in delaying disease progression compared to a treatment of physician's choice, which was predominantly trastuzumab and chemotherapy combinations, in patients who have previously received trastuzumab and lapatinib.

"This trial will continue until the final overall survival analysis takes place or until the survival benefit for treatment with T-DM1 reaches statistical significance at an interim analysis. T-DM1 is also being tested both alone and in combination with pertuzumab in patients with previously untreated HER2 positive metastatic breast cancer in the MARIANNE trial," he will conclude.

ECCO President, Professor Cornelis van de Velde, commented: "These results from the TH3RESA trial are important because they confirm and extend the usefulness of T-DM1 for the treatment of women with advanced HER2 positive breast cancer. Once HER2 positive breast cancer has recurred and metastasised, there are few treatment options available that show any clear benefit for women who have probably undergone several previous treatments for the disease. The fact that T-DM1 extends progression-free survival is good news for these women."

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Hyperfractionated radiotherapy improves survival in head and neck cancer patients

Sep. 27, 2013 — The use of an intensified form of radiotherapy in patients with locally advanced head and neck cancers can improve overall survival rates compared with standard radiation therapy, according to results from a large study to be presented at the 2013 European Cancer Congress (ECC2013) [1].

A comparison of altered fractionation radiotherapy (AFRT) with standard fractionation radiotherapy (SFRT) in a meta-analysis of more than 11,000 patients showed an eight percent reduction in the risk of death in the AFRT group, as well as a nine percent reduction in the risk of progression or death.

Dr Pierre Blanchard, a radiation oncologist from the Institut Gustave Roussy, Villejuif, France, will tell the congress that, although concomitant chemoradiation (CRT), where radiotherapy and chemotherapy are delivered together, remains the standard of care for patients with locally advanced head and neck squamous cell carcinomas, AFRT should be considered when treatment intensification is sought-after and CRT is not feasible because of other pre-existing conditions such as cardiac and renal disease.

AFRT is an intensified radiotherapy treatment that can be given in various schedules. The first is hyperfractionation, where radiotherapy is given twice daily ten times per week, resulting in a higher total dose of around 80 Grays (Gy) [2] compared with the dose of 70 Gy given using SFRT in the same overall time (around seven weeks). The second way uses an accelerated schedule, where the overall treatment time is reduced but the dose is kept at the same level or at a lower dose. AFRT is associated with increased acute side effects but not late side effects, compared to SFRT.

"After than more than seven years patient follow-up, our research has shown that the higher dose intensity of AFRT works to improve outcomes," says Dr Blanchard. "The hyperfractionated regime is the most effective in terms of overall survival. Indeed, in this group of trials the risk of death is reduced by 18% by the use of hyperfractionated RT, with 41% of patients alive at five years compared to 33% in the SFRT group. While the acute side effects of AFRT are increased compared to those experienced by patients on SFRT, the late side effects are comparable and, overall, side effects are more than compensated for by the significant increase in survival in the AFRT group."

The meta-analysis was carried out by an international collaboration known as MARCH, including many countries in Europe, the USA, Canada, and Brazil, Egypt and developing countries through the International Atomic Energy Authority. The researchers say that the survival benefits are mostly related to improvements in loco-regional control, the area located close to the primary tumour being by far the most common first site of relapse in this disease.

"These data are a major advance for the understanding of the role in AFRT in head and neck squamous cell carcinoma," says Dr Blanchard. "By carrying out a large-scale analysis such as this one, we believe that we have provided enough evidence to indicate that doctors should recommend AFRT as a validated treatment option for head and neck cancer patients."

Professor Cornelis van de Velde, President of ECCO, said: "This large-scale analysis of patients with head and neck cancer shows that hyperfractionation increases survival, and local control is also improved by the use of this technique. This is an important step forward in the treatment of this devastating disease."

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Pakistan quake toll reaches 515, insurgents hamper aid efforts

By Gul Yousufzai

ARAWAN, Pakistan (Reuters) - The death toll from an earthquake in southwestern Pakistan has reached 515, a provincial official said Friday, as insurgent attacks threaten relief efforts and survivors complain of lack of shelter from the scorching sun.

Babar Yaqoob, the Chief Secretary of Baluchistan, gave the updated death toll as he toured the destroyed region of Awaran, where the 7.7 magnitude quake struck on Tuesday.

A 6.8 magnitude aftershock jolted the same region on Saturday, bringing down more buildings amid ongoing search and rescue efforts. Local officials said by telephone it was likely the second quake had caused more deaths.

Bodies are still being discovered in houses whose mud walls and wooden roof beams had collapsed.

"My daughter was killed when my house collapsed - I was also inside my house but manage to run out," said 70-year-old Gul January "We are sitting under the scorching sun and need shelter."

In Labash village near Awaran, more than half of the 3,000 houses have collapsed and those still standing have wide cracks.

"Everywhere we go people are asking for tents," legislator Abdul Qadeer Baloch said.

The arid area is also a stronghold of separatist Baluch insurgents, who have twice shot at helicopters carrying military officials in charge of responding to the disaster.

On Thursday, two rockets narrowly missed the helicopter carrying the general in charge of the National Disaster Management Agency and on Friday shots were fired at two helicopters carrying aid, the military said.

"There is a law and order situation here and other hurdles but despite everything, we will get to every last person," said Lt. Gen. Nasir Janjua, the highest ranking military official in the province.

Aid must travel by pitted roads that cut through mountains held by the insurgents.

The rebels, who have killed many civilians and members of the security forces, are fighting for independence from Pakistan. They accuse the central government of stealing the province's rich mineral deposits and the security forces of widespread human rights abuses.

(Writing by Katharine Houreld; Editing by Nick Macfie)

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Aftershock kills 15 in quake-hit Pakistan province

By Gul Yousufzai

QUETTA, Pakistan (Reuters) - At least 15 people were killed on Saturday when an aftershock hit a Pakistani province where hundreds were killed in an major earthquake earlier this week.

Saturday's 6.8 magnitude aftershock destroyed most of the town of Nokjo in the western province of Baluchistan, police said. The town is home to at least 15,000 people.

At least 515 people were killed in Tuesday's earthquake in the same province, officials said on Friday.

The death toll from Saturday's aftershock may rise, said Khan Wasey, the spokesman for the paramilitary Frontier Corps.

Aid deliveries have been complicated by the fact the remote region is home to separatist insurgents who fear the army, which is overseeing aid operations, may take advantage of the crisis to move more forces into the area.

The insurgents have twice fired on helicopters carrying aid workers or supplies and have also attacked an aid convoy being escorted by government forces.

The Baluch insurgents accuse military forces of human rights abuses and Pakistan of exploiting Baluchistan's mineral wealth while local people live in poverty. Human rights groups say the military frequently abducts and kills ethnic Baluch.

The rebels frequently attack the Pakistani armed forces and have also been responsible for executing civilians like teachers and doctors from other ethnic groups.

(Writing by Katharine Houreld; Editing by Sonya Hepinstall)

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Drug 'Molly' is taking a party toll in the United States

By Victoria Cavaliere

NEW YORK (Reuters) - Artist and therapy student Anna and her friends marked a birthday in New York recently with a familiar ritual: They pumped up the electronic music, danced, and celebrated with a special guest called Molly.

"It was a group of about 12 people at someone's house and we were all just celebrating," Anna recalled. "Somebody had it and, and you know, it was a pretty electronic music kind of crowd."

Molly, an illegal stimulant frequently sold in pill form, has become prominent in the electronic music scene over the past decade, said Anna, 26, who did not want to give her full name because she is in school and "counseling people to be healthy."

Molly is the street name for a drug that is pushed as the pure powder form of a banned substance known as MDMA, the main chemical in ecstasy. In the last five years, Molly has made its way into popular culture, helped by references to it made by entertainers such as Madonna, Miley Cyrus and Kanye West.

The drug's dangers became more clear after a rash of overdoses and four deaths this summer, including two at a huge annual electronic music festival in New York City.

The parties of the late 1980s and early '90s saw the heyday of ecstasy, but its popularity began to wane a decade ago after a number of deaths and hospitalizations.

That's when Molly made her way onto the scene.

Over the last few years, drugs sold under that name have "flooded" the market, said Rusty Payne, a spokesman with the Drug Enforcement Administration.

In some states, there has been a 100-fold increase - the combined number of arrests, seizures, emergency room mentions and overdoses - between 2009 and 2012, according to DEA figures.

The drug is accessible and marketed to recreational drug users who believe it to be less dangerous than its predecessor, which was often cut with other substances, from Ritalin to LSD.

Like ecstasy, Molly is said to give a lengthy, euphoric high with slight hallucinogenic properties.

In reality, however, the promised pure MDMA experience "doesn't exist," said Payne.

'SOMETHING COMPLETELY DIFFERENT'

Most of the Molly is one of several synthetic designer drugs that have been flooding the U.S. and European marketplace from chemical labs primarily based in China, Payne said.

"A lot of people are missing the boat here," he said. Molly could be anything ... 80 to 90 percent of the time we are given a chemical or substance believed to be Molly, we're finding most of the time it is something completely different."

Four recent deaths attributed to Molly have thrust the club drug into the national spotlight. On August 31, a 23-year-old Syracuse University graduate and a 20-year-old University of New Hampshire student died after taking what they believed to be Molly during an electronic music concert in New York City. The deaths, and several other reported overdoses, prompted the Electric Zoo festival to cancel the final day of the concert.

A University of Virginia student died at a rave in Washington, D.C., the same weekend, after taking what her friends said was Molly. Days earlier in Boston, a 19-year-old woman died in a club and three concert-goers overdosed at the waterfront, police said.

In Atlanta, this weekend's TomorrowWorld music festival organizers warned on its website of zero-tolerance for MDMA use, but noted: "If you or someone around you has taken something that you are concerned about or need help, it is important that you tell our staff. We are here to help and never judge."

The number of visits to U.S. emergency rooms involving MDMA has jumped 123 percent since 2004, according to data compiled by the Drug Abuse Warning Network. In 2011, the most recent year on record, there were 22,498 such visits.

In the New York concert deaths, the medical examiner found lethal mixtures of MDMA and methylone, a synthetic stimulant, the DEA said.

"It's exactly the same phenomenon that occurred with ecstasy a decade ago," said Dr. Charles Grob, a professor of psychiatry and pediatrics at the UCLA School of Medicine and an expert on MDMA. "Ecstasy had terrible reliability and it's the same with Molly. Though it's being marketed as pure MDMA, it's a hoax."

Overdose symptoms can include rapid heart beat, overheating, excessive sweating, shivering and involuntary twitching.

Grob said references in pop culture can fan misconceptions.

Miley Cyrus admitted in July that a lyric in her new dance anthem "We Can't Stop" was a reference to Molly. Last year at a Miami concert, Madonna, the mother of a teenager, asked: "How many people in this crowd have seen Molly?" She later said she was referring to a friend.

The illusion that MDMA is somehow less harmful has been branded with Molly, according to Anna.

"I have definitely heard that people think that it's pure. I have some friends that are like 'I only want to do Molly. I won't do other stuff' because it's marketed as something that's somehow better," said Anna. "But actually no one knows what's in it. All of it is a gamble."

(Editing by Scott Malone and Gunna Dickson)

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Anti-cancer drug benefits women with breast cancer who have failed previous treatments

Sep. 27, 2013 — First results from a phase III clinical trial of the combination drug, T-DM1, show that it significantly improves the length of time before the disease worsens in women with advanced HER2 positive breast cancer whose cancer has recurred or progressed despite previous treatments, including trastuzumab and lapatinib.

In a late-breaking presentation to the 2013 European Cancer Congress (ECC2013) [1] today, Professor Hans Wildiers will say: "This study shows that even in heavily pre-treated women, 75% of whom had cancer that has spread to the internal organs, T-DM1 nearly doubles progression-free survival -- the length of time before disease progression or death, whichever occurs first -- compared to standard therapy, and with a more favourable safety profile. Few drugs have been able to achieve both improved progression-free survival and a better toxicity profile. These results indicate this drug has important clinical benefit for patients."

T-DM1 is a conjugated monoclonal antibody in which trastuzumab [2] is combined with a cell-killing drug emtansine (DM1) to target and kill breast cancer cells that have large amounts of the protein HER2 on their cell surfaces -- known as HER2 positive breast cancer. T-DM1 has already been shown to benefit patients with HER2 positive breast cancer that has spread to other parts of the body (metastasised), and who have already been treated with trastuzumab and a taxane-based chemotherapy.

"Despite the availability of improved treatments, virtually all patients with HER2 positive metastatic breast cancer develop progressive disease and require additional therapies for palliation. Currently there is no clear standard of care for patients who progressed after two or more treatments for their disease, including the use of the anti-HER2 drugs trastuzumab and lapatinib, and new treatment options are needed for these patients," says Prof Wildiers, who is adjunct head of clinic at the department of medical oncology, and coordinator of the chemotherapy and related clinical trial programme in the multidisciplinary breast centre at the University Hospitals Leuven, Belgium.

The international phase III clinical trial, called TH3RESA, enrolled patients whose cancer was inoperable, or had recurred or metastasised after several treatments including trastuzumab and lapatinib. By February 2013, 602 patients had been randomised to receive 3.6 mg/kg intravenous infusion of T-DM1 every three weeks or a treatment of their physician's choice (TPC). The majority (75%) had visceral disease (cancer that had spread to internal organs) and they had received a median [3] of four previous treatment regimens (excluding single agent hormonal therapy).

Results showed that median progression-free survival increased by nearly three months from 3.3 months for the TPC patients to 6.2 months for patients receiving T-DM1. Among the T-DM1 patients, 31.3% showed a response to the drug, compared with 8.6% of the TPC patients. An interim analysis of overall patient survival showed a similar trend, but it did not reach the level at which a statistically significant benefit for T-DM1 treatment could be confirmed. Patients in the TPC group, whose disease progressed, were given the option of crossing over into the T-DM1 arm and 44 patients have done this so far. Generally, there were fewer serious adverse side-effects in the T-DM1 patients than in the TPC group.

"These data reaffirm the potential of T-DM1 as a treatment for HER2-positive metastatic breast cancer. They demonstrate that T-DM1 has the potential to be a new treatment paradigm for this group of patients who currently have few options," Prof Wildiers will say.

"In the earlier, EMILIA trial, T-DM1 was shown to be superior to capecitabine and lapatinib in patients who had previously received trastuzumab and a taxane. TH3RESA demonstrates that T-DM1 offers statistically significant and clinically meaningful improvement in delaying disease progression compared to a treatment of physician's choice, which was predominantly trastuzumab and chemotherapy combinations, in patients who have previously received trastuzumab and lapatinib.

"This trial will continue until the final overall survival analysis takes place or until the survival benefit for treatment with T-DM1 reaches statistical significance at an interim analysis. T-DM1 is also being tested both alone and in combination with pertuzumab in patients with previously untreated HER2 positive metastatic breast cancer in the MARIANNE trial," he will conclude.

ECCO President, Professor Cornelis van de Velde, commented: "These results from the TH3RESA trial are important because they confirm and extend the usefulness of T-DM1 for the treatment of women with advanced HER2 positive breast cancer. Once HER2 positive breast cancer has recurred and metastasised, there are few treatment options available that show any clear benefit for women who have probably undergone several previous treatments for the disease. The fact that T-DM1 extends progression-free survival is good news for these women."

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Treating chest lymph nodes in early breast cancer improves survival without increasing side effects

Sep. 27, 2013 — Giving radiation therapy to the lymph nodes located behind the breast bone and above the collar bone to patients with early breast cancer improves overall survival without increasing side effects. This new finding ends the uncertainty about whether the beneficial effect of radiation therapy in such patients was simply the result of irradiation of the breast area, or whether it treated cancer cells in the local lymph nodes as well, the 2013 European Cancer Congress (ECC2013) [1] heard.

Dr Philip Poortmans, a radiation oncologist from the Institute Verbeeten, Tilburg, The Netherlands, and a member of the EORTC Radiation Oncology and Breast Cancer Groups, said that results from the international randomised trial, which involved 4004 patients from 43 centres, were convincing. "Our results make it clear that irradiating these lymph nodes give a better patient outcome than giving radiation therapy to the breast/thoracic wall alone. Not only have we shown that such treatment has a beneficial effect on locoregional disease control, but it also improves distant metastasis-free survival and overall survival," he said.

Lymphatic drainage from breast cancer means that the cancer is more likely to spread to other parts of the body. It normally follows two pathways. The best known is to the axilla (armpit), and these lymph nodes are usually treated by surgery and/or radiation therapy. The second pathway drains to the internal mammary (IM) lymph nodes behind the breast bone, and also to those just above the collar bone, the medial supraclavicular (MS) nodes. Because of uncertainty about the effects of treatment in this area, and particularly concerns about the increased toxicity that might be due to the irradiation of a larger area, many centres do not currently treat the IM-MS lymph nodes.

After an average follow-up of 10.9 years, the researchers found that patients in the IM-MS treatment group had better overall survival independent of the number of lymph nodes involved. A total of 382 patients in the IM-MS group died during that period, compared with 429 in the non IM-MS group, and there was no increase in non-breast cancer related mortality in the first group. To date, there have been no serious complications related to the treatment.

The researchers believe that the beneficial effect of IM-MS radiation can be explained by the ability of the treatment to eradicate microscopic tumour deposits in the lymph nodes. "With this treatment, we can stop the development of metastases at their source," said Dr Poortmans. "Interestingly, this effect is irrespective of the stage of the tumour. We believe that this is likely to be related to the positive interaction of the IM-MS treatment with systemic treatment -- chemotherapy, hormonal therapy and targeted treatment."

Patients at low risk of their cancer spreading outside the breast will often be given less intensive systemic therapy in order to spare them side effects. In these cases, using IM-MS radiation therapy can improve their outcome by eradicating residual tumour cells in the breast/thoracic wall. For patients at high risk of metastases, who receive systemic therapy, the prospect of cure is also related to the chance of leaving residual tumour cells behind throughout the body. In these cases too, the ultimate outcome can be improved by using effective locoregional treatment to eradicate disease at the site where it is most likely to be present, the researchers say.

"The results of our trial, in which the patients received appropriate systemic treatments, contradict the existence of a 'competition' between locoregional and systemic treatments," said Dr Poortmans. "Because there is an interaction between these treatments, in many patients their combination will result in an enhancement of the combined benefits; in other words, one plus one can equal more than two."

The researchers intend to follow up these patients in the long term and are planning an average follow-up of 20 years, with the next analysis at 15 years.

"It is of the utmost importance that we record all possible events, including recurrence and toxicity, and such follow-up will also give us the opportunity to continue evaluating our patients in other areas, for example quality of life and wellbeing," said Dr Poortmans. "But we believe that our trial has already given solid evidence of the benefits of radiation treatment of the IM-MS lymph nodes, and we hope that such treatment will become standard clinical practice for patients with early breast cancer."

Professor Cornelis van de Velde, President of ECCO, said: "In past studies, radiotherapy as an adjunct to surgery has shown important improvements in loco-regional control as well as survival, and these further survival benefits without an increase in short and long term toxicities are a valuable development. The results of this study will help us on the road to the development of yet more personalised treatments, in which we have to find the delicate balance between under-treatment resulting in an increased risk of disease recurrence, and over-treatment accompanied by unnecessary toxicity, in order to provide optimal care for breast cancer patients."

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Hyperfractionated radiotherapy improves survival in head and neck cancer patients

Sep. 27, 2013 — The use of an intensified form of radiotherapy in patients with locally advanced head and neck cancers can improve overall survival rates compared with standard radiation therapy, according to results from a large study to be presented at the 2013 European Cancer Congress (ECC2013) [1].

A comparison of altered fractionation radiotherapy (AFRT) with standard fractionation radiotherapy (SFRT) in a meta-analysis of more than 11,000 patients showed an eight percent reduction in the risk of death in the AFRT group, as well as a nine percent reduction in the risk of progression or death.

Dr Pierre Blanchard, a radiation oncologist from the Institut Gustave Roussy, Villejuif, France, will tell the congress that, although concomitant chemoradiation (CRT), where radiotherapy and chemotherapy are delivered together, remains the standard of care for patients with locally advanced head and neck squamous cell carcinomas, AFRT should be considered when treatment intensification is sought-after and CRT is not feasible because of other pre-existing conditions such as cardiac and renal disease.

AFRT is an intensified radiotherapy treatment that can be given in various schedules. The first is hyperfractionation, where radiotherapy is given twice daily ten times per week, resulting in a higher total dose of around 80 Grays (Gy) [2] compared with the dose of 70 Gy given using SFRT in the same overall time (around seven weeks). The second way uses an accelerated schedule, where the overall treatment time is reduced but the dose is kept at the same level or at a lower dose. AFRT is associated with increased acute side effects but not late side effects, compared to SFRT.

"After than more than seven years patient follow-up, our research has shown that the higher dose intensity of AFRT works to improve outcomes," says Dr Blanchard. "The hyperfractionated regime is the most effective in terms of overall survival. Indeed, in this group of trials the risk of death is reduced by 18% by the use of hyperfractionated RT, with 41% of patients alive at five years compared to 33% in the SFRT group. While the acute side effects of AFRT are increased compared to those experienced by patients on SFRT, the late side effects are comparable and, overall, side effects are more than compensated for by the significant increase in survival in the AFRT group."

The meta-analysis was carried out by an international collaboration known as MARCH, including many countries in Europe, the USA, Canada, and Brazil, Egypt and developing countries through the International Atomic Energy Authority. The researchers say that the survival benefits are mostly related to improvements in loco-regional control, the area located close to the primary tumour being by far the most common first site of relapse in this disease.

"These data are a major advance for the understanding of the role in AFRT in head and neck squamous cell carcinoma," says Dr Blanchard. "By carrying out a large-scale analysis such as this one, we believe that we have provided enough evidence to indicate that doctors should recommend AFRT as a validated treatment option for head and neck cancer patients."

Professor Cornelis van de Velde, President of ECCO, said: "This large-scale analysis of patients with head and neck cancer shows that hyperfractionation increases survival, and local control is also improved by the use of this technique. This is an important step forward in the treatment of this devastating disease."

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Everolimus slows disease progression in advanced kidney cancer patients

Sep. 27, 2013 — The first Phase II study to investigate the use of the anti-cancer drug, everolimus, for the initial treatment of advanced papillary kidney cancer has shown that it is successful in slowing or preventing the spread of the disease, according to research to be presented at the 2013 European Cancer Congress (ECC2013).

Dr Bernard Escudier, Head of the French Group of Immunotherapy and chairman of the Genitourinary tumour board at the Institut Gustave Roussy in Villejuif, France will say: "Our results showed that for 59% of patients who received everolimus as their first-line treatment, their disease did not get worse and remained stable. These findings are important and indicate that more than half of these cancer patients are getting some kind of benefit from everolimus treatment.

"Advanced papillary kidney cancer is a very difficult cancer to treat, and because there is no standard of care, there is disagreement amongst experts regarding the best treatment option for these patients. Our clinical findings are encouraging and suggest that everolimus may represent a new treatment option."

Papillary kidney cancer is the second most frequent type of kidney cancer and accounts for approximately 15% of all kidney cancer cases; it is five times more common in men than in women. When the cancer is confined to one location, surgical removal is usually associated with an excellent prognosis. However, when it spreads to other parts of the body, therapies are ineffective. There are two types of papillary cancer, based on cell appearance (histology), known as type I and type II. Type I are more common and grow slowly, whereas type II papillary kidney cancers are much more aggressive and have a poor prognosis.

Everolimus is an anti-cancer drug known as an mTOR inhibitor; mTOR stands for "mammalian target of rapamycin" and it is a protein that regulates vital cell growth processes, including cell metabolism, growth and proliferation. Its failure to function correctly is involved in the development of several cancers.

Dr Escudier and his colleagues in France, Germany, Italy, Spain, Poland and the UK recruited 92 patients into the RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe) study, which started in July 2009. The patients, who had never received systemic treatment, were instructed to take the drug orally, once a day, at a dose of 10 mg for as long as they could tolerate it.

Of the 92 enrolled patients, 83 were included in the intention-to-treat (ITT) analysis and 63 were included in the per-protocol (PP) analysis. An ITT analysis examines the study results based on the treatment to which a group of patients is assigned, rather than the treatment received, and reflects real clinical practice. The PP analysis determines the real biological effect of the new drug as it only includes patients who were compliant with the treatment to which they were assigned, and who also adhered to the clinical study instructions. All of the 92 enrolled patients were included in the safety analysis of the data. Tissue samples were analysed by pathologists in the local hospitals to check whether or not the cancer had spread, and the samples were also checked centrally by an independent, expert group of pathologists.

According to the PP analysis carried out by the local investigators, disease was stable and had not progressed after six months in 59% of patients, while the central review confirmed this in 35% of patients. The local investigators found that the time that elapsed before the cancer spread or worsened (progression-free survival) was 7.8 months, while the central pathology review found it was 3.9 months. At least half of the patients were alive at 20 months.

Dr Escudier will say: "Similar results were seen in the ITT analysis and strongly confirm the overall study findings. According to assessments by the local investigators, progression-free survival was 7.6 months, according to the central review it was 3.7 months, and more than half of the patients were alive at 21 months.

"These results underline the differences that are often observed between local investigator assessment and central review according to the established set of rules used to evaluate anti-cancer drugs.

"As far as we know, this study is unique as it was the first study of an mTOR inhibitor to only include patients with advanced papillary kidney cancer and diagnosis was also confirmed by an independent group of pathologists experienced in the classification of kidney cancer to prevent any tumours being classified incorrectly.

"Everolimus represents another interesting treatment option for advanced papillary kidney cancer patients as it seems to extend their survival and time without the disease progressing."

Adverse side-effects were generally well tolerated. They included weakness, tiredness and anemia; 27% of patients discontinued everolimus due to these side-effects. "The typical patient being treated for advanced papillary kidney cancer is middle-aged, active and still working, and the impact of side-effects may be more important to them," he will say.

"While the results from this Phase II study are encouraging, a Phase III trial would need to be done to fully characterise the efficacy and safety profile of everolimus in this patient population," he will conclude.

President of ECCO, Professor Cornelis van de Velde, commented: "Papillary tumours have been excluded from many of the targeted therapy trials. This study on targeting the mTOR pathway in patients with advanced papillary kidney cancer provides a basis for a Phase III trial and is potentially practice changing. It also emphasises the need for expert pathology, since central review gave markedly different results than local review."

ESMO spokesperson, Professor Manuela Schmidinger, Professor of Medicine in the Department of Oncology at the University of Vienna, Austria, commented: "Treatment strategies for metastatic renal cell cancer (RCC) have dramatically improved within the last few years. However, these achievements have been mostly restricted to patients with clear-cell (cc)-RCC. Patients with non-cc-RCC are usually underrepresented in clinical trials, thus the benefits of novel targeted agents remains unclear in this population. So far, attempts to investigate the impact of new drugs in the non-cc-RCC-population have resulted in inconsistent but mostly modest results. This is also due to the fact that studies included different types of non-cc-RCCs; however, these are tumours of different epithelial origin, with different genetic background and different clinical behaviour. RAPTOR is the first prospective study that investigated the impact of a targeted agent, everolimus, in patients with papillary RCC. In this study, Escudier et al demonstrated that everolimus provides a promising median average overall survival in this patient setting. A strength of this trial in contrast to other non-cc-RCC -studies is that only patients with papillary subtypes I and II were included, rather than all different types of non-cc-RCC."

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Europe should shift focus to bowel cancer screening to save lives: scientists

By Kate Kelland

AMSTERDAM (Reuters) - European governments should divert funds to routine bowel cancer tests from less effective breast and prostate screening programs, scientists said on Saturday, presenting what they called "irrefutable" evidence that bowel screening saves lives.

Many governments devote significant funds to breast cancer screening, but studies in recent years have found that routine breast mammograms can also lead to so-called "over-diagnosis" when tests pick up tumors that would not have caused a problem.

The risk of over-diagnosis in bowel cancer screening is very low, while gains in terms of reducing deaths are large - making routine testing cost-effective, Philippe Autier, a professor at France's International Prevention Research Institute, told the European Cancer Conference in Amsterdam.

"There is now an irrefutable case for devoting some of the resources from breast and prostate cancer screening to the early detection of colorectal (bowel) cancer," he said.

A large European study published last year found that breast screening programs over-diagnose about four cases for every 1,000 women aged between 50 and 69 who are screened.

Colorectal cancer kills more than 600,000 people a year worldwide, according to the World Health Organization. In Europe some 400,000 people are diagnosed with the disease each year.

Results of a study conducted by Autier using data from 11 European countries between 1989 and 2010 showed that the greater the proportions of men and women routinely screened for bowel cancer, the greater the reductions in death rates.

In Austria, for example, where 61 percent of those studied reported having had colorectal screening tests, deaths from this form of cancer dropped by 39 percent for men and 47 percent for women over the decade.

Meanwhile in Greece, where only 8 percent of males had had bowel cancer screening, death rates rose by 30 percent for men.

In the light of the results, Cornelis van de Velde, an oncologist at Leiden University Medical Centre in the Netherlands and president of the European Cancer Organisation, said it was "very disappointing" there are such wide differences in European governments' approaches to colorectal screening.

"People over 50 should be informed of the availability of the test, and pressure should be put on national health services to put more effort into organizing screening programs," he told the conference.

Screening for early signs of bowel cancer involves either a faecal occult blood test, which checks a sample of feces for hidden blood, or endoscopy, where a tiny camera is introduced into the large bowel to look for the polyps that can be a precursor of cancer.

In some European countries, such as France, Germany and Austria, many men and women over the age of 50 have regular colorectal screening examinations, while in others, such as The Netherlands and Britain, screening is much less common.

(Editing by Louise Ireland)

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Race to get Obamacare online sites running goes to the wire

By Sharon Begley

NEW YORK (Reuters) - Just days before the launch of the new U.S. state health insurance exchanges that are the centerpiece of the Affordable Care Act, a nationwide push is still under way to test and patch the technology behind the online sites.

Officials working on the sites have acknowledged that information technology (IT) failures will prevent many of them from functioning fully for weeks, and perhaps longer. That will slow the government's drive to enroll millions of uninsured Americans under President Barack Obama's healthcare reform law starting Tuesday.

From a political standpoint, a successful opening day will shape perceptions of Obama's signature policy initiative. But the system's functioning is to a large extent beyond the control of politicians and policy experts, and instead sits in the hands of the battalions of coders working for IT sub-contractors.

Six months ago, people involved in setting up the exchanges were more hopeful that everything would be ready on time, said Cristine Vogel, an associate director at Navigant Consulting.

"I don't think there were enough hours in the day, or enough people with the skills," she said. "When we look back, I think we'll see that we missed an opportunity to share technology."

Opponents of the healthcare reform known as Obamacare say the computer problems bolster their view that the 2010 law is a "train wreck" and should be delayed or repealed. The Obama administration insists the exchanges will be open for business on October 1, even if some uninsured Americans may not be able to buy coverage right away. More importantly, they say, the new health plans will begin to provide health coverage on January 1, as planned.

"So long as the website is accessible and the plans and the plan information are displayed properly so a consumer can shop for coverage and compare the plans, they will claim victory," said Chris C1ondeluci, an employee benefits attorney at Venable LLP and a former staffer at the Senate Finance Committee who helped draft the Affordable Care Act.

FIRST-DAY CRASH?

This week, the Obama administration said its Spanish-language website would not be ready in time, and that it would be weeks before small businesses and their employees could sign up online for coverage on exchanges operated by the federal government.

The exchanges in Colorado and the District of Columbia, meanwhile, cannot calculate the amount of federal subsidies customers qualify for.

In New York, the exchange is not able to transfer data to some insurers instantaneously, as planned, one carrier told Reuters. Instead, the data will be sent in batches once a day or so. The glitch will not affect customers, but it raises questions that New York might have other IT problems.

Oregon had sufficient qualms about its online insurance marketplace that no one can enroll unless they use a trained, certified agent or other "community partner."

As late as this week, Oregon also had trouble correctly displaying information about insurance plans on a test site. The problem could mislead customers about deductibles, prices and other details if it occurs on the live site Tuesday.

In Ohio, Lieutenant Governor Mary Taylor, a fierce opponent of the healthcare law, said in a radio interview this week that her state's online exchange, which is being run by the federal government, could well crash on its first day.

In testing, she said, some plans filed by insurers "sat in a queue for the federal government for a week, so my concern is something similar is going to happen on October 1 because of the amount of (online) traffic."

WORKAROUNDS OFFERED, TAKE TIME

In most cases, exchanges will offer workarounds that will take time to execute. In Washington, D.C., off-line contractors will calculate federal subsidies and inform applicants what they qualify for in November, by which time the online calculator might be working.

In Colorado, until at least November, customers will have to call phone service centers, where representatives will manually take them through the calculations to determine what subsidies they qualify for.

Even before the exchanges open, the finger-pointing has begun, with states blaming contractors for glitches and contractors blaming states or other contractors.

The system to calculate federal subsidies for the D.C. exchange was built by Curam Software, which IBM acquired in 2011. In tests of complex family situations, the software was getting subsidies wrong 15 percent of the time, said exchange spokesman Richard Sorian.

In a statement, IBM spokesman Mitchell Derman said the city "decided that a phased-in approach best meets the needs of its citizens." He pointed out that Curam also built the eligibility software in Maryland and Minnesota, "two states that plan to have full functionality on October 1."

In other words, a company that achieved its goal on time in two states fell short in a third. The reasons, said outside experts, include relationships among contractors and the specifics of existing computer systems in a state.

In Washington, Infosys, the giant Bangalore, India,-based technology company, is the system integrator - the contractor that takes software from sub-contractors like Curam and puts it all together. The fact that Curam's calculation software is working on other exchanges suggests the glitch may not lie in its integration with the D.C. exchange's other IT.

"A software package like Curam's is put into the system by the system implementer, not the software provider," said an IT expert not involved in the D.C. exchange. A spokesman for Infosys was not able to comment on its D.C. work.

MEDICAID SYSTEMS POSE HUGE HURDLE

One of the most difficult IT jobs has been to integrate each health insurance exchange with its state Medicaid system. These legacy systems are typically decades old. In Massachusetts, for instance, the system runs on the COBOL programming language, which is to today's languages like a rotary phone is to an iPhone-5.

"These legacy systems are old and difficult to configure and re-configure," said Tom Dehner, managing principal at Health Management Associates, a healthcare consultant, in Boston and former director of Massachusetts Medicaid.

"To change how eligibility is calculated," as federal law now requires, he said, "you need to modify your Medicaid system, and that's not something you can do by buying software off the shelf."

The difficulty of interfacing with Medicaid will keep Colorado's exchange from calculating subsidies online.

To determine eligibility for federal subsidies, explained Nathan Wilkes, a member of the board of Connect for Health Colorado, the system "first goes through Medicaid determination. That means connecting to a legacy system," he said.

"Six or nine months ago we got an early warning that the way we wanted to integrate these systems wouldn't work, and then time got away from us."

Colorado's exchange tested 100,000 scenarios to see how its software calculated subsidies, and got error after error.

"It's an IT nightmare," Wilkes said.

(Additional reporting by Lewis Krauskopf and Caroline Humer; Editing by Michele Gershberg and Doina Chiacu)

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SUNRISE offers new insight on sun's atmosphere

Sep. 27, 2013 — Three months after the flight of the solar observatory Sunrise -- carried aloft by a NASA scientific balloon in early June 2013 -- scientists from the Max Planck Institute for Solar System Research in Germany have presented unique insights into a layer on the sun called the chromosphere. Sunrise provided the highest-resolution images to date in ultraviolet light of this thin corrugated layer, which lies between the sun's visible surface and the sun's outer atmosphere, the corona.

With its one-meter mirror, Sunrise is the largest solar telescope to fly above the atmosphere. The telescope weighed in at almost 7,000 pounds and flew some 20 miles up in the air. Sunrise was launched from Kiruna in the north of Sweden and, after five days drifting over the Atlantic, it landed on the remote Boothia Peninsula in northern Canada, gathering information about the chromosphere throughout its journey.

The temperature in the chromosphere rises from 6,000 K/10,340 F/5,272 C at the surface of the sun to about 20,000 K/ 35,540 F/19,730 C. It's an area that's constantly in motion, with different temperatures of hot material mixed over a range of heights, stretching from the sun's surface to many thousands of miles up. The temperatures continue to rise further into the corona and no one knows exactly what powers any of that heating.

"In order to solve this riddle it is necessary to take as close a look as possible at the chromosphere -- in all accessible wavelengths," said Sami Solanki, the principal investigator for Sunrise from the Max Planck Institute. Sunrise used an instrument that was able to filter particular ultraviolet wavelengths of light that are only emitted from the chromosphere.

Sunrise's extremely high-resolution images in this wavelength painted a complex picture of the chromosphere. Where the sun is quiet and inactive, dark regions with a diameter of around 600 miles can be discerned surrounded by bright rims. This pattern is created by the enormous flows of solar material rising up from within the sun, cooling off and sinking down again. Especially eye-catching are bright points that flash up occasionally -- much richer in contrast in these ultraviolet images than have been seen before. Scientists believe these bright points to be signs of what's called magnetic flux tubes, which are the building blocks of the sun's magnetic field. The magnetic field is of particular interest to scientists since it is ultimately responsible for all of the dynamic activity we see on our closest star.

"These first analyses are extremely promising," said Solanki. "They show that the ultraviolet radiation from the chromosphere is highly suitable for visualizing detailed structures and processes."

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First step to reduce plant need for nitrogen fertilizer uncovered

Sep. 27, 2013 — Nitrogen fertilizer costs U.S. farmers approximately $8 billion each year, and excess fertilizer can find its way into rivers and streams, damaging the delicate water systems. Now, a discovery by a team of University of Missouri researchers could be the first step toward helping crops use less nitrogen, benefitting both farmers' bottom lines and the environment. The journal Science published the research this month.

Gary Stacey, an investigator in the MU Bond Life Sciences Center and professor of plant sciences in the College of Agriculture, Food and Natural Resources, found that crops, such as corn, are "confused" when confronted with an invasive, but beneficial, bacteria known as rhizobia bacteria. When the bacteria interact correctly with a crop, the bacteria receive some food from the plant and, simultaneously, produce nitrogen that most plants need. In his study, Stacey found that many other crops recognize the bacteria, but do not attempt to interact closely with them.

"The problem is that corn, tomatoes and other crops have a different response and don't support an intimate interaction with the rhizobia, thus making farmers apply larger amounts of nitrogen than might otherwise be necessary," Stacey said. "Scientists have known about this beneficial relationship since 1888, but it only exists in legume crops, like soybeans and alfalfa. We're working to transfer this trait to other plants like corn, wheat or rice, which we believe is possible since these other plants recognize the bacteria. It's a good first step."

When legumes like soybeans sense a signal from the bacteria, they create nodules where the bacteria gather and produce atmospheric nitrogen that the plants can then use to stimulate their growth. This reaction doesn't happen in other plants.

"There's this back and forth battle between a plant and a pathogen," said Yan Liang, a co-author of the study and post-doctoral fellow at MU. "Rhizobia eventually developed a chemical to inhibit the defense response in legumes and make those plants recognize it as a friend. Meanwhile, corn, tomatoes and other crops are still trying to defend themselves against this bacteria."

In the study, Stacey and Liang treated corn, soybeans, tomatoes and other plants to see how they responded when exposed to the chemical signal from the rhizobia bacteria. They found that the plants did receive the signal and, like legumes, inhibited the normal plant immune system. However, soybeans, corn and these other plants don't complete the extra step of forming nodules to allow the bacteria to thrive.

"The important finding was that these other plants didn't just ignore the rhizobia bacteria," Stacey said. "They recognized it, but just activated a different mechanism. Our next step is to determine how we can make the plants understand that this is a beneficial relationship and get them to activate a different mechanism that will produce the nodules that attract the bacteria instead of trying to fight them."

The study was funded by a grant from the U.S. Department of Energy.??

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Experts confirm that fruit and vegetable consumption reduces risk of mortality

Sep. 26, 2013 — A European study analyzes the relationship between fruit and vegetable consumption and the risk of mortality. As previous research has already suggested, this study concludes that fruit and vegetable consumption reduces all-cause mortality, and especially cardiovascular disease mortality.

The benefits of fruit and vegetable consumption are not a new discovery. However, new research confirms their role in reducing mortality. This reduction is more significant in the case of deaths from cardiovascular disease.

The analysis, recently published in the 'American Journal of Epidemiology', was directed by researchers from ten countries, including Spain, as part of the European Prospective Investigation into Cancer and Nutrition (EPIC).

The sample analyzed includes 25,682 deaths (10,438 due to cancer and 5,125 due to cardiovascular disease) among the 451,151 participants studied over more than 13 years.

"This study is the most significant epidemiological study that this association has examined to date," Maria Jose Sanchez Perez, director of the Andalusian School of Public Health's (EASP) Granada Cancer Registry and one of the authors of the research, explains to SINC.

According to the results, a combined fruit and vegetable consumption of more than 569 grams per day reduces the risk of mortality by 10% and delays the risk of mortality by 1.12 years compared to a consumption of less than 249 grams per day.

Furthermore, for every 200 gram increase in daily fruit and vegetable consumption, the risk falls by 6%. The proportion of deaths that could be prevented if everyone eating too few fruit and vegetables increased their consumption by 100-200 grams per day -- thus reaching the recommended 400-500 grams per day -- is 2.9%.

Previous studies already noted that fruit and vegetable consumption, in accordance with the recommended daily allowance, prevents the development of chronic diseases, and reduces the risk of mortality by 10-25%.

"There is now sufficient evidence of the beneficial effect of fruit and vegetable consumption in the prevention of cancer and other chronic diseases," Sanchez states, "for this reason, one of the most effective preventative measures is promoting their consumption in the population."

Fruit for the heart

A diet rich in fruit and vegetables reduces the risk of cardiovascular disease mortality by 15%. Furthermore, more than 4% of deaths due to cardiovascular disease could be prevented by consuming more than 400 grams of fruit and vegetables a day.

Considering fruit consumption separately, no significant risk reduction was observed, whereas vegetable consumption alone was associated with a lower risk of mortality, which was even more significant for raw vegetables: high consumption reduces the risk of mortality by 16%.

"With regard to cancer mortality, no statistically significant risk reduction was found, although it will be necessary to assess this according to specific types of cancer," Sanchez adds.

Nevertheless, the expert highlights that given that fruit and vegetable consumption is associated with the risk of certain cancers -- colon and rectal, stomach, lung, etc. -- it is to be expected that their consumption will also have a positive effect on mortality due to these tumours.

Greater effect in people with bad habits

The mortality risk reduction due to fruit and vegetable consumption was greater in those participants who consumed alcohol (around 30-40% risk reduction), who were obese (20%), and "possibly" also in those who smoked.

The authors add that this positive effect is probably due to their high antioxidant content, which mitigates the oxidative stress caused by alcohol, tobacco and obesity.

"As such, these population groups in particular could benefit from the positive effects of fruit and vegetables in preventing chronic diseases and their associated mortality risk," Sanchez concludes.

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Joint Statement on accelerating efforts to achieve the health MDGs

We have 829 days to go until the December 2015 MDG deadline. Over the past 12 and a half years, the world has made remarkable progress against the goals, especially the health-related MDGs. Child and maternal deaths have been almost halved from 1990 levels. Malaria deaths have dropped 50%, driven largely by the distribution of over 400 million mosquito nets in the past several years. Over 6 million people, of the 9 million who need TB treatment, are now on treatment. HIV, once a death sentence with virtually no one on treatment, has undergone a dramatic shift with almost 10 million people on treatment today – and if we can finish the job and put everyone on treatment, we will irreversibly halt the AIDS epidemic. These results are unmistakable proof that success is possible.

Now we must come together in one final big push to achieve the health MDGs, and lay the strongest of foundations for a post-2015 world.

We all know that the economic environment has been challenging, but despite that, the pace of our work to end maternal and child deaths, malaria deaths, AIDS-related deaths and eliminating new HIV infections among children has quickened over the past 3 years. This week, an unprecedented US$ 1.15 billion has been freshly mobilized to reach MDGs 4 and 5 – the largest amount ever mobilized for those goals. Funds of this magnitude fill a substantial portion of the remaining financing gap. Last year, at the London FP Summit, some $2.6 billion funds were mobilized for family planning. The Global Fund to Fight AIDS, TB and Malaria is working hard to achieve its replenishment figure of $15 billion.

Global investments in the AIDS response, totaling a US$ 18.9 billion, more than half from domestic sources has been the highest ever, demonstrating shared responsibility and global solidarity in action. Should the replenishment be successful, a significant portion of the funding required to achieve MDG 6 will also have been secured.

Funding will always be a challenge, but the amount we have mobilized - despite difficult economic times - is formidable, and we know we have even more funding to come in the remaining months of this year. We are on the right path - we have identified the life-saving commodities required, the geographic areas where the most deaths occur, and what women and children, in particular, are dying of; we know what interventions work and we know what it costs to prevent them.

It is now time for an unprecedented acceleration of effort to achieve the goals. We know it will take nothing short of a moonshot to accomplish the goals in the time remaining. The lives we must save in this final MDG phase are in the most difficult to reach areas, and are people who are chronically underserved. With a rights-based approach, combined with utilizing the advancements in science (effective antiretroviral therapy, malarial drugs, rapid diagnostics for TB), we can reach more people in need, faster and efficiently. We must do everything we can, to get as far as we can, by December 2015. Anything less will steepen our climb even further post-2015.

We stand together now to accelerate the effort to achieve the goals. We must focus on supporting countries to save 3.5 million more children and 122,000 more women and achieve MDGs 4 and 5; reduce more than a quarter million maternal deaths every year, and bring down the unmet need of millions of women for family planning; end malaria deaths and eliminate new HIV infections among children; provide access to antiretroviral therapy to the more than 28 million people in need of HIV treatment in 2013; and reach all 9 million people in the world who require TB treatment.

We will report to the UN Secretary General by the end of October on progress towards meeting the financial commitments and how they will accelerate actions towards achieving the MDGs.

We will continue to work in earnest with each country in a coordinated manner to support their efforts to achieve these goals. Key interventions exist that can achieve remarkable and rapid impact when scaled up effectively. For example, evidence supports substantially increased investments in community health workers - including midwives - to reach those who are unreached. Results-Based Financing and Conditional Cash Transfers are proving highly effective to eliminate barriers for the poor and underserved. We have determined collectively a list of the highest-impact, but neglected, life-saving commodities that if rolled out could save millions of lives. We have evidence to show that when women and girls are given the means to delay marriage, prevent unwanted pregnancies, and space births, maternal and child deaths can be significantly reduced. Having proven that family planning is the most cost-effective measure to prevent unwanted pregnancies and reduce birth-related deaths, we have further sharpened efforts to reduce the unmet need of 222 million women - increasing commodities demand and strengthening supply, identifying where exactly the burden is and calculating how much it costs to scale up efforts. Antiretroviral therapy now is scientifically proven to not just stop AIDS-related deaths but also stop HIV transmission and reduce new HIV infections. It is now the moment to weave all of these excellent ideas together and intensify our support to countries to execute against them, in support of their own country plans.

Most important to the success of this entire endeavor will be leadership and conviction of member states and communities who are working day in and day out to achieve the goals. While there is more funding to raise, with significant funding now mobilized, our focus now turns fully to implementation and execution.

Next year, even six months from now, will be too late to start accelerating our efforts. Now is the moment to build on our remarkable success and insure that we actually meet the health MDGs in the time left to achieve them.

Please join us in this once in a lifetime opportunity.

For more information please contact:

Gregory Hartl
WHO Media Coordinator
Department of Communications
WHO, Geneva
Mobile: +41 79 203 6715
E-mail: hartlg@who.int

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Government shutdown looms as lawmakers feud

By Richard Cowan and Rachelle Younglai

WASHINGTON (Reuters) - The U.S. government braced on Friday for the possibility of a partial shutdown of operations on October 1 as Congress struggled to pass an emergency spending bill that Republicans want to use to achieve Tea Party-backed goals, such as defunding the new healthcare reform law.

While there was still a chance of averting a shutdown, time was running out.

The Senate on Friday was on track to pass legislation keeping the federal government operating beyond midnight Monday.

But doubt remained about how and when it would be received in the Republican-controlled House of Representatives, where Republicans feuded over a plan that would both please Tea Party conservatives and avert widespread agency shutdowns.

A shutdown would likely to result in up to 800,000 federal employees being furloughed. Most visible to the public, if past shutdowns are a guide, are museum closings in Washington that outrage tourists and attract television cameras, and possible delays in processing tax filings, for example.

But the government does not grind to a halt.

Large swaths of "essential" activity continue, including sending out benefit checks and national security-related operations. Agencies were in the process of determining which employees would be considered essential and which not.

REPUBLICANS FIGHTING OBAMACARE

"Obamacare," the healthcare reform law set for launch on October 1, would continue to be implemented, beginning a period of open enrollment for individuals to purchase insurance.

Concern over fiscal negotiations in Washington sent the dollar close to a seven-month low and pressured world equities on Friday.

The impasse has sent the cost of insuring against a U.S. sovereign default to its highest level in four months. U.S. stocks fell in early trading on Friday as worries grew over Washington's gridlock. Concern over fiscal negotiations sent the dollar close to a seven-month low.

As lawmakers stared down the midnight Monday deadline when the current fiscal year ends - and government funding along with it - the Democratic-led Senate was set to deliver on President Barack Obama's call for an emergency funding bill with no add-ons, such as defunding the healthcare law.

The House could vote on that measure in an unusual Saturday session. But all indications were it would tack on a new measure to that bill, which likely would be rejected by the Senate and make a shutdown all the more likely.

One House Republican aide, who asked not to be identified, said leaders were weighing attaching a one-year delay of the healthcare law to the spending bill, "but that's not set in stone."

A feel of desperation seeped through the Capitol, even though many held out hope that a last-minute deal can be struck to avoid shutting down activities ranging from school lunch programs for poor children, paying U.S. troops, foreign embassy operations and some airport security screenings.

"Holy God, you created us for freedom, so keep us from shackling ourselves with the chains of dysfunction," intoned Senate Chaplain Barry Black at the opening of Friday's Senate session.

DEBT CEILING FIGHT LOOMS

Earlier, Republican Senator John McCain blamed members of his own party for the difficulties in passing legislation to fund the government beyond Monday. Congress also faces the hard task of raising the limit on federal borrowing authority, which Republicans are targeting for controversial add-ons.

Without a debt limit increase by October 17, Treasury Secretary Jack Lew has warned, the United States would have a difficult time paying creditors and operating the government.

"We are dividing the Republican Party rather than attacking Democrats. We are now launching attacks against Republicans ... so it's very dysfunctional," McCain said on the CBS program "This Morning."

McCain and a band of other more moderate Republicans are expected to join in with Democrats later on Friday to pass a stripped-down bill to fund the government until November 15, giving Congress more time to come up with a budget measure running through September 30, 2014, the end of the fiscal year that starts on Tuesday.

Tea Party conservatives' insistence on using these two important fiscal bills to advance their small-government agenda comes as a new Gallup Poll shows the country's patience with them could be wearing thin, even though there still are a significant number of supporters.

According to the survey, 22 percent of U.S. adults think of themselves as supporters of the movement.

That is down 10 points from the apex of Tea Party popularity in 2010, when they influenced enough elections to return House control to Republicans.

House Republican leaders early on Friday were either still undecided on how to handle the unfolding crisis in Washington or were not giving any clues.

"We're still waiting for the Senate to act," said one House Republican leadership aide.

(Editing by Fred Barbash and Mohammad Zargham)

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Human influence on climate clear, IPCC report says

Sep. 27, 2013 — Human influence on the climate system is clear. This is evident in most regions of the globe, a new assessment by the Intergovernmental Panel on Climate Change (IPCC) concludes.

It is extremely likely that human influence has been the dominant cause of the observed warming since the mid-20th century. The evidence for this has grown, thanks to more and better observations, an improved understanding of the climate system response and improved climate models.

Warming in the climate system is unequivocal and since 1950 many changes have been observed throughout the climate system that are unprecedented over decades to millennia. Each of the last three decades has been successively warmer at Earth's surface than any preceding decade since 1850, reports the Summary for Policymakers of the IPCC Working Group I assessment report, Climate Change 2013: the Physical Science Basis, approved on Friday by member governments of the IPCC in Stockholm, Sweden.

"Observations of changes in the climate system are based on multiple lines of independent evidence. Our assessment of the science finds that the atmosphere and ocean have warmed, the amount of snow and ice has diminished, the global mean sea level has risen and the concentrations of greenhouse gases have increased," said Qin Dahe, Co-Chair of IPCC Working Group I.

Thomas Stocker, the other Co-Chair of Working Group I said: "Continued emissions of greenhouse gases will cause further warming and changes in all components of the climate system. Limiting climate change will require substantial and sustained reductions of greenhouse gas emissions."

"Global surface temperature change for the end of the 21st century is projected to be likely to exceed 1.5°C relative to 1850 to 1900 in all but the lowest scenario considered, and likely to exceed 2°C for the two high scenarios," said Co-Chair Thomas Stocker. "Heat waves are very likely to occur more frequently and last longer. As Earth warms, we expect to see currently wet regions receiving more rainfall, and dry regions receiving less, although there will be exceptions," he added.

Projections of climate change are based on a new set of four scenarios of future greenhouse gas concentrations and aerosols, spanning a wide range of possible futures. The Working Group I report assessed global and regional-scale climate change for the early, mid-, and later 21st century.

"As the ocean warms, and glaciers and ice sheets reduce, global mean sea level will continue to rise, but at a faster rate than we have experienced over the past 40 years," said Co-Chair Qin Dahe. The report finds with high confidence that ocean warming dominates the increase in energy stored in the climate system, accounting for more than 90% of the energy accumulated between 1971 and 2010.

Co-Chair Thomas Stocker concluded: "As a result of our past, present and expected future emissions of CO2, we are committed to climate change, and effects will persist for many centuries even if emissions of CO2 stop."

Rajendra Pachauri, Chair of the IPCC, said: "This Working Group I Summary for Policymakers provides important insights into the scientific basis of climate change. It provides a firm foundation for considerations of the impacts of climate change on human and natural systems and ways to meet the challenge of climate change." These are among the aspects assessed in the contributions of Working Group II and Working Group III to be released in March and April 2014. The IPCC Fifth Assessment Report cycle concludes with the publication of its Synthesis Report in October 2014.

"I would like to thank the Co-Chairs of Working Group I and the hundreds of scientists and experts who served as authors and review editors for producing a comprehensive and scientifically robust summary. I also express my thanks to the more than one thousand expert reviewers worldwide for contributing their expertise in preparation of this assessment," said IPCC Chair Pachauri.

The Summary for Policymakers of the Working Group I contribution to the IPCC Fifth Assessment Report (WGI AR5) is available at www.climatechange2013.org or www.ipcc.ch.

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