Study: Old Drugs Could Give Tb A 1-2 Punch
TB is one of the worlds oldest killers, and the lung disease still claims the lives of more than 1.5 million people globally every year. The bacteria that cause TB are fast becoming impervious to many treatments, drug resistance that is seen worldwide but is a particular problem in parts of Asia and Africa. While typically the TB doesnt respond to two top treatments, an emerging threat is so-called extensively drug-resistant disease, or XDR-TB, that is virtually untreatable by remaining options.
So researchers are frantically hunting new approaches, including taking a fresh look at some old drugs.
TB bacteria contain a certain enzyme that renders the penicillin family of antibiotics drugs useless.
“It chews them up and spits them out and they never get to see their target,” explained biochemist John Blanchard of the Albert Einstein School of Medicine.
But there are different antibiotics that can block that enzyme, called beta-lactamase. One, named clavulanate, has long been sold as part of the two-drug Augmentin combination thats widely used for various childrens infections.
So Blanchards team tested whether administering clavulanate might make TB vulnerable to other antibiotics - and found a combination that in laboratory tests blocked the growth of 13 different drug-resistant TB strains.
The combo: Clavulanate to drop TBs shield, plus a long-sold injected antibiotic - meropenem, part of that penicillin-style family - that then attacks the bacteria.
The findings are reported Thursday in the journal Science.
What happens in a lab doesnt necessarily work in people. Still, the findings were so compelling that two teams of U.S. researchers - from the National Institutes of Health and New Yorks Montefiore Medical Center - already are planning small patient studies in South Korea and South Africa. They hope to begin those studies later this year.
“Its very clever,” said Dr. Anthony Fauci, director of NIHs National Institute of Allergy and Infectious Diseases. When one drug knocks out the TB microbes defense, “that leaves the original drug with the capability of doing what its supposed to be doing.”
Genentech Provokes Doctors Ire With Costly Avastin Trial
The 2,710-patient trial, whose results are expected in April, may show that 12 months of Avastin added to six months of chemotherapy can reduce the risk of colon cancer recurring. The test is part of a $1 billion campaign by the South San Francisco-based company to expand the uses of Avastin, already approved for advanced colon, lung and breast cancer
The drug, among the most expensive cancer medicines at a yearly wholesale cost of $52,800 a year, generated $4.8 billion in 2008 sales. Revenue may rise by $2 billion annually should the drug gain use against newly-diagnosed colon cancer, said Jason Zhang, an analyst for BMO Capital Markets in New York. A positive result may increase Genentechs value as the company fends off a hostile tender offer from Roche Holding AG.
“I was furious” about the study design, said Leonard Saltz, a research oncologist at Memorial Sloan-Kettering in New York who consults for Genentech, in a telephone interview. Saltz said in an interview that testing a drug for six months has been “standard practice for such a study for the last dozen years.
“It is a significant expense issue, and it is a convenience and psychology issue,” said Saltz, noting that the drug should first have been tested for half a year before testing it for a year. “I was very disappointed.”
Fair Question
Saltz and Alan Venook, a researcher at the University of California, San Francisco, both said they dont believe the study was designed just with profit in mind, and Venook praised the trials lead scientist, Carmen Allegra, the division chief of hematology and oncology at the University of Florida Shands Cancer Center in Gainesville.
Still, Venook said, “Its a fair question to ask. While I believe they want to help patients, they also have a fiduciary responsibility to their shareholders to get the best returns they can within the context of legal and ethical practices,” he said. “If I worked for Genentech, it would be my job to develop studies that would help them sell as much drug as possible.”
The study, called C-08, has emerged as a key point of contention between Genentech and Basel, Switzerland-based Roche Holding AG, now pressing a hostile tender offer.
Roche, which already owns 56 percent of Genentech shares, said its $86.50-a-share bid is based in part on a financial model giving the study 55 percent odds of success, compared to Genentechs 61 percent estimate. A Genentech board committee has said the company should be priced at $112-a-share. The Roche offer expires March 12, before the trial results are reported.
Swiss Army Knife
A positive finding is also critical to Genentechs long- term push to aim Avastin at a wide variety of early-stage tumors, making the drug a virtual Swiss army knife drug for cancer. Avastin is Genentechs “single most important value- driver over the next year,” said Mark Schoenebaum, a Deutsche Bank analyst in New York, in a telephone interview.
Monthly Price
The median monthly price of cancer treatment in the U.S. surged six-fold to $5,988 from $1,052 in the early 1990s, according to Peter Bach, a researcher at Memorial Sloan- Kettering Cancer Center in New York and former senior policy adviser at the federal Medicare program. Advances in treatment have not improved at the same pace as their costs, he wrote in a report in the Feb. 5 New England Journal of Medicine.
“With each advance in treatment, the magnitude of the increase in the cost of treatment exceeded the magnitude of improvement in efficacy,” wrote Bach, who consults for Genentech and other companies. He urged lawmakers to consider strategies for containing costs of cancer drugs such as having Medicare compare effectiveness of the medicines it pays for.
Cancer doctors buy Avastin and are allowed to charge the manufacturers price for the drug plus 6 percent. For advanced colon cancer patients who meet certain financial criteria, Genentech capped Avastins cost at $55,000.
The company hasnt announced what it would charge for Avastin as an adjuvant, or early-cancer, treatment.
Both Saltz and Venook say its also unknown whether longer use of Avastin, which fights cancer by crimping blood-vessel growth, may produce delayed side effects 15 years later if such patients are cured of their cancer.
Long-Term Effects
Low-carb? Low-fat? Study Finds Calories Count More
As the world grapples with rising obesity, millions have turned to popular diets like Atkins, Zone and Ornish that tout the benefits of one nutrient over another.
Some previous studies have found that low carbohydrate diets like Atkins work better than a traditional low-fat diet. But the new research found that the key to losing weight boiled down to a basic rule - calories in, calories out.
“The hidden secret is it doesnt matter if you focus on low-fat or low-carb,” said Dr. Elizabeth Nabel, director of the National Heart, Lung and Blood Institute, which funded the research.
Limiting the calories you consume and burning off more calories with exercise is key, she said.
The study, which appears in Thursdays New England Journal of Medicine, was led by Harvard School of Public Health and Pennington Biomedical Research Center in Louisiana.
Researchers randomly assigned 811 overweight adults to one of four diets, each of which contained different levels of fat, protein and carbohydrates.
Though the diets were twists on commercial plans, the study did not directly compare popular diets. The four diets contained healthy fats, were high in whole grains, fruits and vegetables and were low in cholesterol.
Nearly two-thirds of the participants were women. Each dieter was encouraged to slash 750 calories a day from their diet, exercise 90 minutes a week, keep an online food diary and meet regularly with diet counselors to chart their progress.
There was no winner among the different diets; reduction in weight and waist size were similar in all groups.
People lost 13 pounds on average at six months, but all groups saw their weight creep back up after a year. At two years, the average weight loss was about 9 pounds while waistlines shrank an average of 2 inches. Only 15 percent of dieters achieved a weight-loss reduction of 10 percent or more of their starting weight.
Dieters who got regular counseling saw better results. Those who attended most meetings shed more pounds than those who did not - 22 pounds compared with the average 9 pound loss.
Lead researcher Dr. Frank Sacks of Harvard said a restricted calorie diet gives people greater food choices, making the diet less monotonous.
Sacks said the trick is finding a healthy diet that is tasty and that people will stick with over time.
Before Debbie Mayer, 52, enrolled in the study, she was a “stress eater” who would snack all day and had no sense of portion control. Mayer used to run marathons in her 30s, but health problems prevented her from doing much exercise in recent years.
Mayer tinkered with different diets - Weight Watchers, Atkins, South Beach - with little success.
“Ive been battling my weight all my life. I just needed more structure,” said Mayer, of Brockton, Mass., who works with the elderly.
Mayer was assigned to a low-fat, high-protein diet with 1,400 calories a day. She started measuring her food and went back to the gym. The 5-foot Mayer started at 179 pounds and dropped 50 pounds to 129 pounds by the end of the study. She now weighs 132 and wants to shed a few more pounds.
Study: Large Regional Differences In Medicare Costs
The dramatic cost differences dont appear connected to climate or to who lives where, and people in the more expensive areas dont get better care.
More expensive medical technology is only part of the picture, according to the report released Wednesday by the Dartmouth Atlas Project, which studies medical resources. The findings were being published in the New England Journal of Medicine.
The study said the differences in spending from one area to another can be blamed on decisions made by individual doctors who are influenced by what medical services are available nearby.
“Technology doesnt drive the growth in health care spending, people do,” said Dr. Elliott Fisher, the lead study author and a medicine professor at the Dartmouth Institute for Health Policy and Clinical Practice.
Fisher said physicians are not the only issue, but also questions like whether theres a local medical health race among local hospitals or whether a community has a single hospital that is more focused on primary care.
The findings come as Congress prepares to tackle health care reform, which President Barack Obama highlighted as a priority Tuesday night in a nationally televised speech.
In his budget, Obama proposes setting aside $635 billion over the next decade to pay for health care reform. To pay for it, he suggests reducing spending on Medicare.
Medicare, the health insurance program for people 65 and older, accounts for a huge chunk of medical spending: its expected to cost more than $500 billion this year. The program covers about 44 million people.
The Dartmouth Atlas findings, drawn from an analysis of government Medicare data from 1992-2006, suggest great inefficiencies in care in some parts of the country. It also says there is plenty of room for reform if practices in the regions of the country that are less expensive could become the national norm.
That wont come easy since the countrys medical system frequently rewards expensive practices, the study notes. For example, hospitals lose money if they improve care in a way that reduces admissions. Doctors dont have a financial incentive to spend time carefully listening to a patient rather than quickly referring them to a specialist.
“There are no financial rewards for collaboration, coordination or conservative practice,” the study said.
The study found that among the 25 largest hospital-referral regions, Manhattan was the costliest, at $12,114 per patient in 2006. Minneapolis was the least expensive, at $6,705 per patient.
Medicare spent $16,351 on each Medicare enrollee in Miami in 2006 compared with $8,331 in San Francisco.
Growth rates in spending also varied a lot from one area to another.
The authors called on doctors to take the lead in bringing costs down by opting for conservative care - for example, putting a patient with heartburn on heartburn medication and monitoring their progress, rather than referring them to a specialist.
But, the study noted, doctors will need help from policymakers who should change payment systems to reward quality rather than quantity of care.
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Alzheimers Attack On Brain May Be Enabled By Nerve Protein
The findings, in test tube experiments and in mice, appear to solve a mystery about how a substance called beta amyloid links to nerve cells in the brain and disrupts their ability to communicate.
The study, published today in the journal Nature, gives scientists at drug companies and universities a new target for Alzheimers. The results are likely to kick off a competition to find a medicine to treat the disease, which robs some 20 million people around the world of their memory and mental ability.
“The race will be to find the drug that blocks that receptor and protects the nerve cell,” said Sam Gandy, associate director of the Alzheimers Disease Research Center at Mount Sinai School of Medicine in New York and a scientific adviser to the Alzheimers Association. If the findings are confirmed, “this would immediately provide a new target, a new way to screen for new drugs that would otherwise have been totally undiscoverable.”
Researchers have been trying to understand the workings of Alzheimers disease ever since 1906, when Alois Alzheimer, a German pathologist, dissected the brain of a deceased patient and described the massive cellular damage he found.
Interference With Nerve Cells
In recent years, most researchers have come to believe that this damage is caused by clumps of the beta amyloid protein gathering around nerve cells and interfering with their ability to communicate.
One gap in that theory is that scientists hadnt offered an explanation as to how beta amyloid interacts with cells. The new study, led by Stephen Strittmatter, a Yale neurology professor, suggests that the small protein, known as a prion, acts as a receptor that allows beta amyloid to link to it and send signals into the cell.
Until now, prions have mostly been known for their role in mad cow disease. A toxic, misshapen form is linked to the human version of the illness, known as Creutzfeldt-Jakob disease. The form of the prion protein studied in the Alzheimers paper is normal and is found on the surface of nerve cells.
Lead Suspect
“Cellular prion protein has now emerged as the lead suspect,” said Lennart Mucke, an Alzheimers researcher and director of the Gladstone Institute for Neurological Disease in San Francisco, in a telephone interview yesterday. Strittmatters findings suggest that scientists could design a drug that would block the prion from binding to the nerve cell.
The goal of such a drug would be to prevent the beta amyloid clumps from attaching to the neurons and starting a “toxic cascade that prevents memory function,” said Strittmatter. “If you can do that, you can halt the disease.”
They sent electrical currents between groups of neurons that had been extracted from mice and exposed to beta amyloid. Some of the mice had been engineered to lack the prion protein and others hadnt. In the mice that lacked the prion protein, the beta amyloid had no effect on the flow of electrical current, suggesting beta amyloid isnt damaging without the prion protein.
Next Studies
The next step is to test the impact of the prion protein on living mice, Strittmatter said. He and his colleagues are mating mice engineered to lack the prion with others engineered to have a version of Alzheimers disease.
“Do the offspring preserve memory in spite of fact that they carry human Alzheimers disease genes?” Strittmatter asked. His hope is that “even though theyre making bad forms of amyloid beta, it has no place to attach to the neuron and do its bad thing.”
These studies are under way, and it will take at least six months to see if the mice will begin to show symptoms of the disease or be spared because they lack the prion, Strittmatter said.
Dentists Wary Of Salon Teeth-whitening Treatments
But then an inspector for the Alabama Board of Dental Examiners ordered her to stop, accusing her of practicing illegal dentistry.
Markos ongoing lawsuit with the state has waded into the murky area of regulating teeth-whitening products that are increasingly offered in settings outside the dentists office, such as salons and mall kiosks.
The dental industry claims its a health and safety issue; the beauty parlors say the dentists are just trying to brush them out of a lucrative niche.
“As a new business owner, Im trying to bring something new and innovative to the salon. And then to be threatened to be shut down before I really even had it going was more than a little frustrating,” Markos said recently while blow-drying a customers freshly cut hair. “I believe that this is a cosmetic service and we are on the right side of the law.”
But Dr. Leslie Seldin, a dentist for 43 years and now consumer adviser and spokesman for the American Dental Association, said its hard to know whether those bleaching trays or ultraviolet lights are sanitary or safe.
In some salons, the whitening is sometimes facilitated by people wearing white coats who hand the trays to customers to put into their own mouths or adjust the lights over their teeth.
But the ADA is worried customers might wrongly think salon employees are health care professionals.
“We do not know about what level of sterilization and disinfection is being done. Youre dealing with something that is totally unregulated,” Seldin said.
Many of the same products are available in stores for customers to use on themselves at home.
“What we ultimately feel this boils down to is a consumer-rights issue, because consumers should have the right to whiten their teeth any way they want to whiten their teeth as long as its safe,” said Paul Klein, vice president of White Smile USA. The Atlanta-based company licenses its whitening products to locations in 23 states, including Markos salon.
Whitening at a salon or mall shop using bleaching trays or ultraviolet light usually costs about $100 to $200. It can cost up to $400 and more at a dentists office.
A Montgomery judge has ruled in favor of Alabamas dental board in a lawsuit brought by White Smile USA and Markos, finding that whitening constitutes the practice of dentistry and requires a license.
Klein said his company has been discussed in New Mexico and Tennessee but theres never been any court involvement until Alabama.
“We feel the state is trying to use their regulatory power to protect a monopoly for the dentists, and we dont think thats right,” he said.
Last month, the Tennessee Board of Dentistry, following complaints about mall kiosks, changed its rules to clarify that whitening can only be performed by licensed dentists or hygienists and dental assistants under their direct supervision.
“Its amazing - we never touch the customers mouth, never touch the customer, period, and we dont see how that could possibly be practicing dentistry,” said Klein, who was visibly agitated as he discussed the situation.
Ohios dental board agreed with Klein last year, finding that while it does have some concerns about unregulated use of the materials, whitening by non-dentists is OK as long as consumers position the light by themselves, put the material on their own teeth, and no one else touches their mouths.
Panel: Adopting From Abroad? Get Hepatitis A Shot
The Advisory Committee on Immunization Practices, meeting in Atlanta, voted Wednesday to recommend hepatitis A vaccinations for all close contacts of children coming from countries where hepatitis A is relatively common. That includes Guatemala, China, Russia and Ethiopia - four countries that are currently the major sources of international adoptions. The committee makes recommendations to the Centers for Disease Control and Prevention.
Federal officials estimate that international adoptees trigger only 100 to 1,000 of the estimated 32,000 hepatitis A infections that occur in the United States each year. But cases that do occur are sometimes tragic.
Hepatitis A is a liver disease caused by a virus, which can spread through handling a diaper or other contact with contaminated feces. Federal guidelines call for vaccinations against it for all U.S. children and for adults who travel to countries where the illness is common.
The two-dose vaccination costs about $140 per person. International adoptions tend to cost $20,000 to $40,000, said Dr. Cindy Weinbaum, a CDC viral hepatitis expert.
Children adopted from other countries generally do not have recommended vaccinations when they arrive. They undergo physical examinations, but infected young children often dont have the jaundice considered a sign of the illness, CDC officials said.
Non-traveling family members of the new adoptee often arent vaccinated either. A CDC official told the panel a 2007 international adoption of twins caused the death of a 51-year-old woman in Minnesota. Another last year put two adults in the hospital and prompted school vaccination clinics in a Maine community.
The panels recommendation is targeted at family members, baby sitters and others who come in close contact with an international adoptee within 60 days of the childs arrival in the United States. Ideally, people should get the first dose at least two weeks before the parents bring the child home, health officials said.
Healthy Men Should Consider Taking Prostate Drug, Doctors Say
The new guidelines from cancer specialists and urologists dont recommend men definitely take the drug, sold generically as finasteride and by Merck & Co. under the brand Proscar. Rather, it advises men to discuss with their doctors the benefits and the risks of the treatment, according to a study published today in the Journal of Clinical Oncology.
An estimated 186,000 U.S. men were diagnosed with prostate cancer in 2008 and nearly 29,000 people died from the disease, according to the National Cancer Institute. It is the second- leading cause of cancer-related death in men and occurs more frequently in African-Americans.
The Prostate Cancer Prevention Trial, conducted from 1993- 2003, found that men who took the drug finasteride cut their risk of developing prostate cancer by 25 percent compared with those who didnt take the drug. Doctors had worried the drug would lead to faster-spreading tumors in men who developed prostate cancer. Now most physicians who reviewed the trial data have determined the risk of aggressive cancers is “unlikely,” though it could “not be excluded with certainty,” according to the study.
Obama Says Congress Must Overhaul U.s. Health Care This Year
“The cost of our health care has weighed down our economy and the conscience of our nation long enough,” Obama told a joint session of the House and Senate in a speech yesterday.
Obama blamed medical expenses for causing bankruptcies, costing U.S. jobs and swelling the budget deficit. He didnt specify the steps hell take to expand care or curb expenses, saying theyll be included in the budget he releases tomorrow. The president also said he would hold a White House forum next week that would include medical providers, health-care businesses, workers and lawmakers from both parties.
“This was a solid commitment to changing health care, but the part on how you solve the health-care cost puzzle while covering everyone is still missing,” said Paul Keckley, director of the Deloitte Center for Health Solutions in Washington, D.C., in a telephone interview after the speech. “Hes got to start giving specifics.”
The presidents focus will help Congress pass legislation this year to get everyone covered by medical insurance, said Senator Max Baucus, chairman of the Finance Committee, which has jurisdiction over government health-care programs.
“Working together, we can remake Americas health system,” said Baucus in an e-mailed statement. In November, Baucus issued his own health proposal, including requiring that everyone have coverage and temporarily opening up Medicare to people as young as 55.
Not so Fast
Democrats wont be able to deliver a health-care plan as fast as they say, said Thomas Miller, a health-policy adviser to Senator John McCain during the presidential campaign, in a telephone interview yesterday.
“Its much easier to sketch out grand ambitions than give details,” said Miller, a health policy economist at the free- market American Enterprise Institute in Washington.
Obama said that to ensure long-term fiscal stability, Congress needed to figure out how to slow the growing costs of Medicare and Social Security, two programs for the elderly.
“Comprehensive health reform is the best way to strengthen Medicare for years to come,” he said.
Obama said previously that the U.S. faces continuing strain on the budget because the costs for programs such as Social Security, Medicare and Medicaid will keep rising as the U.S. population ages. Those three programs now consume about 40 percent of federal spending.
U.S. government spending on Medicare and Medicaid will reach $721 billion this year, or about 28 percent of all public and private health-care spending, according to a report yesterday by the Centers for Medicare and Medicaid Services, the agency in charge of the two programs.
Medicare, the program for the elderly and disabled, and Medicaid, the joint U.S.-state program for the poor, cover almost 100 million people, or about one in three Americans.
Obama said during the campaign that he can reduce the U.S. health-care bill while making sure everyone has affordable coverage. Some 46 million people, amounting to one American in seven, lack medical insurance, according to the Census Bureau. For those with coverage, the price rose an average of 5 percent last year, the Henry J. Kaiser Family Foundation in Menlo Park, California, reported in September.
Root Out Waste
“We will root out the waste, fraud, and abuse in our Medicare program that doesnt make our seniors any healthier,” Obama said in his speech.
Obama has called for subsidies to help people afford coverage, and seeks to expand government health programs. Obama also has proposed creating a public plan to compete with private insurers in addition to steps, such as putting more health records in digital form, to help reduce costs.
Some campaign promises got a boost in the stimulus package, which Obama signed Feb. 17. The measure allocates $20 billion to encourage adoption of computerized records and gives $1 billion to research the comparative effectiveness of medical treatments. Both may save money later on, according to the Congressional Budget Office, an arm of Congress.
W.r. Grace Kept Montana Asbestos Jeopardy Secret, U.s. Claims
“This case is about a company that mined and manufactured a hazardous product and individual executives that chose profits at the expense of peoples health and chose avoiding liability over disclosing the health hazards to the government,” Assistant U.S. Attorney Kris McLean said yesterday at the opening of a federal court trial in Missoula, Montana.
The company and five former executives are charged with conspiring to contaminate the northwestern Montana town, where Grace mined and processed vermiculite from 1963 to 1990, and obstructing government investigations.
About 200 people in and around the town have died from asbestos exposure, and 1,200 were harmed, according to the government. Vermiculite is a mineral used in fireproofing, insulation and potting soil.
If convicted, Grace may be fined $280 million or more, the company said in a securities filing. Individuals face as long as five to 15 years in prison. The defendants all pleaded not guilty.
Grace fell 99 cents, or 14 percent, to $5.71 in New York Stock Exchange composite trading yesterday.
Illness From Asbestos
The government claims many workers and residents of the town are dead or dying from asbestos-related diseases, including asbestosis, a scarring of the lungs, and mesothelioma, a fatal cancer. Libby residents die from asbestosis at a rate 40 to 80 times normal, McLean told jurors.
Because of the way the vermiculite was formed in Libby, it is contaminated with asbestos fibers. Prosecutors claim the defendants covered up scientific studies and company information showing the dangers.
Grace sought protection in 2001 in U.S. Bankruptcy Court in Wilmington, Delaware, in response to more than 100,000 asbestos claims, most of them not related to the Libby mining.
Grace mined and processed vermiculite, a mineral used in fireproofing, insulation and potting soil, in and around Libby.
“The secret of this case, the secret the defendants kept from the government, is that their product, even when it contains a small amount of asbestos, released hazardous levels of asbestos into the air when disturbed,” McLean said. “That is the secret that the defendants knew but the government did not.”
Prosecutors said workers brought asbestos into their homes on their clothing. Other people were exposed to asbestos when they used vermiculite for gardens. Grace distributed mill tailings to schools for running tracks and an ice skating rink.
McLean told jurors that children swung on a rope and dropped into piles of asbestos-tainted material at the Grace mines export plant.
A grand jury in 2005 indicted Grace and seven current and former executives for allegedly conspiring to release asbestos- tainted vermiculite in Libby and then covering up the dangers.
Grace lawyer David Bernick said the company understands that miners and their families in Libby have suffered tragic losses that “cast a dark shadow over Grace, over Libby and over this courtroom.”
Bernick told jurors the criminal charges are related to claims that Grace exposed Libby residents, not workers, to asbestos.
Miners Exposure
The inflated number of asbestos-related deaths in Libby can be accounted for by occupational exposures of mineworkers and their families, not to the alleged contamination of the town, the attorney said.