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September 2, 2014   Download print version

Origin of Ebola outbreak may be a bat and virus has rapid mutation rate

It was already the worst Ebola outbreak in history; Now it's moving into Africa's cities

Ebola: Experimental drug ZMapp is '100% effective' in animal trials

Why doctors are sick of their profession

Sniffing out cancer with electronic noses

Study: Novel heart failure drug shows big promise

CMS shuts down Sunshine Act database, again


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Origin of Ebola outbreak may be a bat and virus has rapid mutation rate

The Ebola virus has mutated 300 times since the deadliest outbreak in history began in West Africa in May, and these transformations lead scientists to conclude that it is unlike any past Ebola epidemic. This could make it both harder to treat and harder to diagnose, according to a study published in Science magazine.

The outbreak began as a single human infection, the authors write, but the genetic sequences observed in the 78 patients sampled showed a rapid spread in both the number of people infected and the geographical regions affected. As it stands, the virus is unlike anything seen in the past, which will hinder the creation of treatments and make it difficult to fully contain the contagion, the study found.

"We've uncovered more than 300 genetic clues about what sets this outbreak apart from previous outbreaks," said Stephen Gire, a co-author and disease researcher at Harvard.

The initial infection, contracted by a woman in Sierra Leone, came from one of five strains of Ebola known to affect humans called the Zaire strain. The Zaire strain came about a decade ago in a related strain from an animal host. Researchers are not positive which animal hosted the virus, but said it was most likely was a bat in Guinea. At least one species of fruit bat has a geographic range that spreads from Guinea to Sierra Leone. If bats are really the culprit, "about 150 million more people than previously thought are at risk of the disease," according to a previous study published in Science about Ebola.

The virus then crossed into Sierra Leone when the first woman diagnosed attended a funeral for someone who had recently been in contact with Ebola in Guinea, the study found.

Since then, it "has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic [animal] sources."

One of the problems with this particular outbreak is that scientists have not been able to fully trace the virus from 2004 in Guinea to the current outbreak. Being unable to predict where it will next appear makes it very difficult to contain. The World Health Organization said Thursday that it hopes to stop the spread by 2015.

Clues from the study have scientists hopeful that nonstop research on mutations will help develop new diagnostic tests and treatments. In the study, 99 Ebola samples were taken from 78 patients diagnosed with Ebola from May to late June. More than 50 people co-authored the study with help from Harvard University scientists and the Sierra Leone Health Ministry. Five of the authors died before the paper was even published. Visit the IB Times for the story.



It was already the worst Ebola outbreak in history; Now it's moving into Africa's cities

FREETOWN, Sierra Leone — The dreaded Ebola virus came to the children's hospital in the form of a 4-year-old boy. His diagnosis became clear three days after he was admitted. The Ola During hospital — the nation's only pediatric center — was forced to close its steel gates. Fear swelled. The boy died. The 30 doctors and nurses who had contact with him were placed in quarantine, forced to nervously wait out the 21 days it can take for the virus to emerge. And remaining staff so far have refused to return to work. They, along with millions of others, are facing the worst Ebola outbreak in history.

Already, the hardest-hit West African nations of Guinea, Liberia and Sierra Leone have reported more than 3,000 cases, including the infections of 240 healthcare workers.

Ebola is now spreading from the remote provinces and into the teeming cities such as Freetown, where 1.2 million people jostle for space. Previous outbreaks had been limited to remote villages, where containment was aided by geography. The thought of Ebola taking hold in a major city such as Freetown or Monrovia, Liberia's capital, is a virological nightmare. Last week, the World Health Organization warned that the number of cases could hit 20,000 in West Africa.

"We have never had this kind of experience with Ebola before," David Nabarro, coordinator of the new U.N. Ebola effort, said as he toured Freetown last week. "When it gets into the cities, then it takes on another dimension."

Detection is difficult because early symptoms are hard to distinguish from those of malaria or typhoid, common ailments during the rainy season. While Ebola is not transmitted through the air like the flu, it does spread by close contact with bodily fluids such as blood, saliva and sweat — even something as innocent as a tainted tear.

And so now it is headed to Freetown, where the streets hum with low-level panic. People long ago stopped shaking hands. Hugs are unheard of. Plastic buckets filled with a diluted chlorine solution are posted outside many businesses to encourage handwashing. Some of these homemade solutions tingle and burn; others smell like aromatic cleansers. For a while, street peddlers, who normally sell peanuts or umbrellas from stacks balanced on their hands, sold surgical gloves, $1 each.

But the roads are still crammed with autos and people, stray dogs and wild chickens. Trucks with loudspeakers rumble down rutted roads. "Wash your hands!" they announce in Krio. "Ebola is real!" shout banners strung throughout the city. Radio ads detail the virus's symptoms: headache, fever, nausea and vomiting. The Sierra Leonean government has been running these messages in the capital for months, just in case.

Sierra Leone's first case appeared in late May, in the distant Kailahun district. A month later, the country had 158 total cases. In late July, it was up to 533 cases. A national state of emergency was declared. Soldiers erected roadblocks to cordon off the rural epicenter, raising memories of the country's brutal civil war, which ended in 2002.

The government has passed laws to limit close contact, altering the city's daily rhythms. Riders in the city's many "Poda Poda" minibuses, usually packed shoulder to shoulder, are now curtailed to four people per row. "Okara" taxi motorbikes are restricted at night. Even banks have cut hours to limit time spent in their crowded lobbies. And large public gatherings have been outlawed. The small cinemas where patrons would pay to watch foreign soccer matches on TVs have been shuttered. The popular clubs along Freetown's Atlantic Ocean beaches are now empty.

Many of the people who can afford to leave Freetown are gone — some on vacation, others to foreign countries to wait out the virus. But getting out has become harder as several airlines have stopped flying to Lungi International Airport. Air France, under orders from the French government, became the latest last week. The nation's school year is supposed to begin Sept. 9, but few expect that date to hold.

At the Lighthouse Hotel, the usual executives from the mining, pharmaceutical and banking industries are absent. The hotel is running at 15 percent occupancy, said general manager Andrew Damoah. He is barely able to cover the cost of gas for the hotel's generator — a necessity in a country with a shaky power grid. Most of his guests now are the international doctors and nurses responding to the outbreak.

The city's hospitals are empty, too. People avoid them over worries about catching Ebola. They would rather suffer at home and hope that what they have is just a mild case of malaria. It is not an unreasonable concern. The Kenema government hospital in the provinces has seen 40 staff members die of Ebola. At Connaught Hospital in Freetown, the doctor running the Ebola ward died two weeks ago. Shortly before that, the government issued a public alert for a 32-year-old hairdresser with an Ebola diagnosis who was pulled from Connaught by her family. They wanted her to be treated by a faith healer. All of them subsequently died of Ebola.

At Connaught, the Ebola ward sits behind a gate with prison-like metal bars. Staff members are covered head to toe in protective scrubs. The unit recently had 12 beds for 13 patients. At first, one or two patients were being diagnosed with Ebola each day. That picked up to three a day. Now, lab results on up to seven people a day are coming back positive.

The virus's march into Freetown was slow to start. The first case officially emerged in mid-July. Six weeks later, the city had 30. The number is now over 40 and is expected to quickly shoot up.

Doctors Without Borders has warned about a worldwide shortage of the full-body protective suits worn by Ebola healthcare workers. Sierra Leone's Ebola emergency operations center said it faces a six-week wait for the specialized ambulances needed to transport Ebola patients.

A new Ebola treatment center — the country's third — is expected to be constructed near Freetown. But it might not be ready for a month. Just outside Freetown in Lakka, a new Ebola isolation unit is almost open, on property shared by a tuberculosis hospital and housing for sufferers of leprosy. A mobile Ebola testing lab, flown in from South Africa, also just started up. Visit the Washington Post for the story.



Ebola: Experimental drug ZMapp is '100% effective' in animal trials

The only clinical trial data on the experimental Ebola drug ZMapp shows it is 100% effective in monkey studies, even in later stages of the infection. The researchers, publishing their data in Nature, said it was a "very important step forward".

Yet the limited supplies will not help the 20,000 people predicted to be infected during the outbreak in West Africa. And two out of seven people given the drug, have later died from the disease.

Researchers have been investigating different combinations of antibodies, a part of the immune system which binds to viruses, as a therapy. Previous combinations have shown some effectiveness in animal studies. ZMapp is the latest cocktail and contains three antibodies.

Trials on 18 rhesus macaques infected with Ebola showed 100% survival. This included animals given the drug up to five days after infection. For the monkeys this would be a relatively late stage in the infection, around three days before it becomes fatal.

Scientists say this is significant as previous therapies needed to be given before symptoms even appeared. However, there is always caution when interpreting the implications for humans from animal data.

A Liberian doctor, one of three taking the drug in the country, and a Spanish priest both died from the infection despite ZMapp treatment.

William Pooley, the first Briton to contract Ebola during this outbreak, has been given the experimental drug ZMapp as were two US doctors who recovered.

The course of the infection is slower in humans than macaques so it has been cautiously estimated that ZMapp may be effective as late as day nine or 11 after infection.

The group wants to start clinical trials in people to truly assess the effectiveness of the drug. Visit BBC for the article



Why doctors are sick of their profession

What happens when doctors are unhappy? They have unhappy patients. A new memoir, 'Doctored,' presents one cardiologist's take on the challenges facing American medicine and the real impact on patient care.

Today medicine is just another profession, and doctors have become like everybody else: insecure, discontented and anxious about the future. In surveys, a majority of doctors express diminished enthusiasm for medicine and say they would discourage a friend or family member from entering the profession. In a 2008 survey of 12,000 physicians, only 6% described their morale as positive. Eighty-four percent said that their incomes were constant or decreasing. Most said they didn't have enough time to spend with patients because of paperwork, and nearly half said they planned to reduce the number of patients they would see in the next three years or stop practicing altogether.

American doctors are suffering from a collective malaise. We strove, made sacrifices—and for what? For many of us, the job has become only that—a job. That attitude isn't just a problem for doctors. It hurts patients too.

Consider what one doctor had to say on Sermo, the online community of more than 270,000 physicians:

"I wouldn't do it again, and it has nothing to do with the money. I get too little respect from patients, physician colleagues, and administrators, despite good clinical judgment, hard work, and compassion for my patients. Working up patients in the ER these days involves shot gunning multiple unnecessary tests (everybody gets a CT!) despite the fact that we know they don't need them, and being aware of the wastefulness of it all really sucks the love out of what you do. I feel like a pawn in a moneymaking game for hospital administrators. There are so many other ways I could have made my living and been more fulfilled. The sad part is we chose medicine because we thought it was worthwhile and noble, but from what I have seen in my short career, it is a charade."

The discontent is alarming, but how did we get to this point? To some degree, doctors themselves are at fault.

In the halcyon days of the mid-20th century, American medicine was also in a golden age. Life expectancy increased sharply (from 65 years in 1940 to 71 years in 1970), aided by such triumphs of medical science as polio vaccination and heart-lung bypass. Doctors largely set their own hours and determined their own fees. Popular depictions of physicians ("Marcus Welby," "General Hospital") were overwhelmingly positive, almost heroic.

American doctors at midcentury were generally content with their circumstances. They were prospering under the private fee-for-service model, in which patients were covering costs out of pocket or through fledgling private insurance programs such as Blue Cross/Blue Shield. They could regulate fees based on a patient's ability to pay and look like benefactors. They weren't subordinated to bureaucratic hierarchy.

After Medicare was introduced in 1965 as a social safety net for the elderly, doctors' salaries actually increased as more people sought medical care. In 1940, in inflation-adjusted 2010 dollars, the mean income for U.S. physicians was about $50,000. By 1970, it was close to $250,000—nearly six times the median household income.

But as doctors profited, they were increasingly perceived as bilking the system. Year after year, healthcare spending grew faster than the U.S. economy as a whole. Meanwhile, reports of waste and fraud were rampant. A congressional investigation found that in 1974, surgeons performed 2.4 million unnecessary operations, costing nearly $4 billion and resulting in nearly 12,000 deaths. In 1969, the president of the New Haven County Medical Society warned his colleagues "to quit strangling the goose that can lay those golden eggs."

If doctors were mismanaging their patients' care, someone else would have to manage that care for them. Beginning in 1970, health maintenance organizations, or HMOs, were championed to promote a new kind of healthcare delivery built around price controls and fixed payments. Unlike with Medicare or private insurance, doctors themselves would be held responsible for excess spending. Other novel mechanisms were introduced to curtail health outlays, including greater cost-sharing by patients and insurer reviews of the necessity of medical services. That ushered in the era of HMOs.

In 1973, fewer than 15% of physicians reported any doubts that they had made the right career choice. By 1981, half said they would not recommend the practice of medicine as highly as they would have a decade earlier.

Public opinion of doctors shifted distinctly downward too. Doctors were no longer unquestioningly exalted. On television, physicians were portrayed as more human—flawed or vulnerable ("M*A*S*H*," "St. Elsewhere") or professionally and personally fallible ("ER").

As managed care grew (by the early 2000s, 95% of insured workers were in some sort of managed-care plan), physicians' confidence plummeted. In 2001, 58% of about 2,000 physicians questioned said that their enthusiasm for medicine had gone down in the previous five years, and 87% said that their overall morale had declined during that time. More recent surveys have shown that 30% to 40% of practicing physicians wouldn't choose to enter the medical profession if they were deciding on a career again—and an even higher percentage wouldn't encourage their children to pursue a medical career.

There are many reasons for this disillusionment besides managed care. One unintended consequence of progress is that physicians increasingly say they don't have enough time to spend with patients. Medical advances have transformed once-terminal diseases—cancer, AIDS, congestive heart failure—into complex chronic conditions that must be managed over the long term. Physicians also have more diagnostic and treatment options and must provide a growing array of screenings and other preventative services.

At the same time, salaries haven't kept pace with doctors' expectations. In 1970, the average inflation-adjusted income of general practitioners was $185,000. In 2010, it was $161,000, despite a near doubling of the number of patients that doctors see a day.

While patients today are undoubtedly paying more for medical care, less of that money is actually going to the people who provide the care. According to a 2002 article in the journal Academic Medicine, the return on educational investment for primary-care physicians, adjusted for differences in number of hours worked, is just under $6 per hour, as compared with $11 for lawyers. Some doctors are limiting their practices to patients who can pay out of pocket without insurance company discounting.

Other factors in our profession's woes include a labyrinthine payer bureaucracy. U.S. doctors spend almost an hour on average each day, and $83,000 a year—four times their Canadian counterparts—dealing with the paperwork of insurance companies. Their office staffs spend more than seven hours a day. And don't forget the fear of lawsuits; runaway malpractice-liability premiums; and finally the loss of professional autonomy that has led many physicians to view themselves as pawns in a battle between insurers and the government.

The growing discontent has serious consequences for patients. One is a looming shortage of doctors, especially in primary care, which has the lowest reimbursement of all the medical specialties and probably has the most dissatisfied practitioners.

Dr. Jauhar is director of the Heart Failure Program at the Long Island Jewish Medical Center. This essay is adapted from his new book, "Doctored: The Disillusionment of an American Physician," published by Farrar, Straus and Giroux.

Visit the Wall Street Journal for the article.



Sniffing out cancer with electronic noses

Sniffing feces with an "electronic nose" can detect strains of bacteria that can cause deadly infections, say UK researchers. The tool was able to sniff out different types of Clostridium difficile based on the stinky chemicals they released. The team at the University of Leicester say the findings could be useful for screening patients in hospital.

Electronic noses are already being investigated for cancer, by looking for the unique smell of the chemicals produced by a lung or breast tumor.

The team in Leicester investigated whether different strains of C. difficile, some of which cause disease, had a different chemistry that could be detected by the e-nose. They showed that different levels of methanol, sulphur compounds and others were produced by the 10 different strains tested in the study.

One of the research team, Prof Paul Monks, told the BBC: "By smelling different strains of C. difficile we could tell which are good and which are potentially bad, which leads to the question, 'Can you screen patients?'

"We've shown it is possible to do it in the lab - the next thing we need to do is in bedpans. We can [put the e-nose] on the side of bedpan washers as you start the cycle, sniff it and then say, 'You may want to look at that patient'."

As well as being able to identify which strain of bacterial species is present, the researchers believe understanding more about the chemistry of bacteria could help understand why some cause disease and others do not.

Dr Martha Clokie, from the university's department of microbiology, said: "Current tests for C. difficile don't generally give strain information - this test could allow doctors to see what strain was causing the illness and allow doctors to tailor their treatment." The study was published in the journal Metabolomics. Visit the BBC for the study.



Study: Novel heart failure drug shows big promise

A new study reports one of the biggest potential advances against heart failure in more than a decade - a first-of-a-kind, experimental drug that lowered the chances of death or hospitalization by about 20 percent.

Doctors say the Novartis drug - which doesn't have a name yet - seems like one of those rare, breakthrough therapies that could quickly change care for more than half of the 6 million Americans and 24 million people worldwide with heart failure.

"This is a new day" for patients, said Dr. Clyde Yancy, cardiology chief at Northwestern University in Chicago and a former American Heart Association president.

It involved nearly 8,500 people in 47 countries and was the largest experiment ever done in heart failure. It was paid for, designed and partly run by Novartis, based in Basel, Switzerland. Independent monitors stopped the study in April, seven months earlier than planned, when it was clear the drug was better than an older one that is standard now.

During the 27-month study, the Novartis drug cut the chances of dying of heart-related causes by 20 percent and for any reason by 16 percent, compared to the older drug. It also reduced the risk of being hospitalized for heart failure by 21 percent.

"We are really excited," said one study leader, Dr. Milton Packer of UT Southwestern Medical Center in Dallas. The benefit "exceeded our original expectations."

Results were disclosed Saturday at a European Society of Cardiology conference in Barcelona and published online by the New England Journal of Medicine.

Novartis will seek approval for the drug - for now called LCZ696 - by the end of this year in the United States and early next year in Europe.

The people in this study were already taking three to five medicines to control the condition. One medicine often used is an ACE inhibitor, and the study tested one of these - enalapril, sold as Vasotec and in generic form - against the Novartis drug.

The new drug is a twice-a-day pill combination of two medicines that block the effects of substances that harm the heart while also preserving ones that help protect it. One of the medicines also dilates blood vessels and allows the heart to pump more effectively.

In the study, 26.5 percent on the older drug, enalapril, died of heart-related causes or were hospitalized for heart failure versus less than 22 percent of those on the Novartis drug. Quality of life also was better with the experimental drug. Visit CBS News for the report.



CMS shuts down Sunshine Act database, again

The Centers for Medicare and Medicaid Services (CMS) is again taking the Open Payments database, which details payments made to physicians by drug and device companies, offline for maintenance, the agency has announced.

The database, which was developed as a result of the Physician Payments Sunshine Act, has had various troubles of late. First, CMS took the site offline from Aug. 3 until Aug. 14 to resolve a problem in which records for physicians with similar names were getting mixed up. As a result of the problem, CMS said it would be excluding about a third of its records from the database until the issue is fully resolved.

Then it was announced that CMS would not be including another section of data -- regarding payments made indirectly, through contract research organizations, from drug and device firms to physicians -- in the database because of problems with data integrity.

On Thursday, word came that the system will be offline on two different days for routine maintenance: Saturday from 11 a.m. to 5 p.m., and Friday, Sept. 5 for an indeterminate period of time. Physicians will also now have until Sept. 10 to review and, if necessary, dispute their data before it is made public.

The announcement of the shutdown "adds to the growing concerns that the site is simply not ready to go public," the American Medical Association said Thursday in a press release. "It also further underscores the need for physicians to have more time to register, review and correct inaccurate data that may be housed on the government website."

The informal online survey of 204 physicians also found that 44% of those who tried to register were unsuccessful.

CMS has said it remains committed to having the database open to the public on Sept. 30, but the AMA and 100 other physician groups have been lobbying for a delay in order to give physicians more time to register and review their data for accuracy.

"Patients need accurate information," AMA president Robert Wah, MD, said in the release. "If the government releases incorrect information to the public, it can lead to misinterpretations, harm reputations and cause patients to question their trust in their physicians ... That's why the AMA is calling on CMS to extend by 6 months the time that physicians have to register and ensure the accuracy of their reports before release to the public. Physicians need enough time to register for the Open Payments system, review their data and seek corrections in order to ensure accuracy."

Visit the MedPage Today for the story.