Drug Prices Rose 9.1% Last Year, Ahead of Federal Health Overhaul

The Wall Street Journal

Drug companies sharply raised prices last year, ahead of increased rebates they must pay to Medicaid and other expenses tied to the federal health overhaul passed last month.

 

Prices for brand-name pharmaceuticals rose 9.1% last year, the biggest increase in at least a decade, according to pharmacy-benefit manager Express Scripts Inc., which included the recent number in its annual drug-trend report. The boost for specialty drugs, a category that is largely biotech products, was even sharper: 11.5%. In 2008, the price rise had been 7.4% for traditional pharmaceuticals, and 9.4% for specialty drugs.

Some individual drugs saw double-digit increases in the first quarter compared with a year earlier, including 12.1% on Zetia, a cholesterol drug from Merck & Co., and 13.6% for Cymbalta, an antidepressant from Eli Lilly & Co., according to data from Credit Suisse. The firm, which tracks the pricing of brand-name drugs made by the biggest U.S. manufacturers, found wholesale prices went up 7.8% in the first quarter, compared with a year earlier.

The increases were "exacerbated by the health-care reform debate," said Steve Miller, senior vice president and chief medical officer of Express Scripts, although drug makers disputed that notion.

An Eli Lilly spokesman said its pricing policies last year weren't affected by the health bill, and such decisions take into account benefits for patients as well as "marketplace conditions and recovery of our R&D costs."

But Lilly did caution shareholders Monday that rebates to Medicaid, as well as other provisions in the law, would lower its 2010 revenue by $350 million to $400 million, and 2011 revenue by $600 million to $700 million.

A Merck spokesman said its "price adjustments are independent of health-care reform," and are instead driven by an approach that aims to "ensure patient access and enable Merck to invest in research and development."

Zetia's pricing for most of last year was controlled by an independent joint venture involving Merck and Schering-Plough Corp., which are now merged, the company added. Both Merck and Lilly said the pricing numbers didn't reflect the effects of rebates and discounts granted to many health-care payers.

The health law will also require the drug industry to knock off half the price paid by Medicare beneficiaries in their "doughnut hole" coverage gap starting in 2011, among other expenses, though the pharmaceutical companies will also benefit from an influx of newly insured consumers that will kick in later.

The effects of the price increases on overall drug spending are being tempered by the availability and aggressive promotion of cheaper generic alternatives, among other factors. In its report, which reflects the drug benefits it administers for corporate clients, Express Scripts also said drug spending went up only 6.4% in 2009, slightly more than last year but lower than five years earlier.

Indeed, a report this month from IMS Health said that the number of prescriptions dispensed for generic drugs rose 5.9% last year, but those for branded drugs fell 7.6%.

Overall spending on prescription drugs rose just 5.1% according to IMS, which looks at different data than Express Scripts.

Another reason for price increases is probably that insurers, employers and pharmacy-benefit managers have become "much more difficult gatekeepers," said Credit Suisse analyst Catherine Arnold. Discounts and rebates used to promote branded drugs precipitate price increases to offset those marketing costs.

Also, as drugs go generic, companies mark up the prices of the brand-name versions, assuming that patients who stick with those "are the people for whom price doesn't matter," said Mark McClellan, who formerly oversaw the Medicare and Medicaid programs for the Bush administration and is now at the Brookings Institution.

Express Scripts, which is based in St. Louis and has 36 million people in its commercial client group, said the actual drug-spending increase—as opposed to the price markup—was 4.8% for traditional pharmaceuticals, to $800.23 per member per year, and 19.5% in specialty drugs, to $111.10 per member per year. Big increases in spending occurred in several areas, including diabetes, driven by the growing number of people diagnosed with the disease, and antiviral drugs, due to flu concerns.

The pharmacy-benefit manager said its clients were able to help keep the increase in check through use of generics and other moves. But it argued that, across the entire U.S. market, there could be significantly greater health-care savings tied to how drugs are taken. The company estimated the savings at $163 billion a year, which could be achieved with greater use of generics and better adherence by patients prescribed drugs, both tactics that Express Scripts pitches to clients as among services it can provide.

Though Express Scripts members' average annual co-payments rose, they didn't go up as fast as drug spending, because employees paid a slightly smaller share of the cost of drugs last year compared with 2008. The total for 2009 was 20.5% of the cost, or $186.48, compared with 21.2%, or $181.17, in 2008. The Pharmaceutical Research and Manufacturers of America, a trade group for the industry, said "prescription medicines represent a small and decreasing share of growth in overall health care costs" in the U.S. and are "yielding major health advances."

FDA Begins Efforts to Reduce Salt Consumption

The Washington Post

The Food and Drug Administration is planning an unprecedented effort to gradually reduce the salt consumed each day by Americans, saying that less sodium in everything from soup to nuts would prevent thousands of deaths from hypertension and heart disease. The initiative, to be launched this year, would eventually lead to the first legal limits on the amount of salt allowed in food products.

The government intends to work with the food industry and health experts to reduce sodium gradually over a period of years to adjust the American palate to a less salty diet, according to FDA sources, who spoke on condition of anonymity because the initiative had not been formally announced.

Officials have not determined the salt limits. In a complicated undertaking, the FDA would analyze the salt in spaghetti sauces, breads and thousands of other products that make up the $600 billion food and beverage market, sources said. Working with food manufacturers, the government would set limits for salt in these categories, designed to gradually ratchet down sodium consumption. The changes would be calibrated so that consumers barely notice the modification.

The legal limits would be open to public comment, but administration officials do not think they need additional authority from Congress.

"This is a 10-year program," one source said. "This is not rolling off a log. We're talking about a comprehensive phase-down of a widely used ingredient. We're talking about embedded tastes in a whole generation of people."

The FDA, which regulates most processed foods, would be joined in the effort by the U.S. Department of Agriculture, which oversees meat and poultry.

Currently, manufacturers can use as much salt as they like in products because under federal standards, it falls into the category deemed "generally recognized as safe." Foodmakers are merely required to report the amount on nutrition labels.

But for the past 30 years, health officials have grown increasingly alarmed as salt intake has increased with the explosion in processed foods and restaurant meals. Most adults consume about twice the government's daily recommended limit, according to the Centers for Disease Control and Prevention.

Until now, the government has pushed the food industry to voluntarily reduce salt and tried to educate consumers about the dangers of excessive sodium. But in a study to be released Wednesday, an expert panel convened by the Institute of Medicine concludes that those measures have failed. The panel will recommend that the government take action, according to sources familiar with the findings.

Although the specifics of the government's plans have not been made public, the food industry has been bracing for a federal initiative.

"We're working on it voluntarily already," said Melissa Musiker, senior manager of science policy, nutrition and health at the Grocery Manufacturers Association. In recent months, Conagra, Pepsico, Kraft Foods, General Mills, Sara Lee and others have announced that they would reduce sodium in many of their products. Pepsico has developed a new shape for sodium chloride crystals that the company hopes will allow it to reduce salt by 25 percent in its Lay's Classic potato chips.

Morton Satin, director for technical and regulatory affairs at the Salt Institute, which represents salt producers, said regulation "would be a disaster for the public." He said that the science regarding sodium is unclear and that consumption does not necessarily lead to health problems.

"If you consume a lot of salt, you also get rid of a lot of salt -- it doesn't mean it's an excess," he said. "I want to make sure they're basing this on everything that is in the scientific literature, so we don't end up being guinea pigs because someone thinks they're doing something good."

Michael Jacobson of the Center for Science in the Public Interest, which first petitioned the FDA to regulate sodium in 1978, said voluntary efforts by industry are laudable, "but they could change their minds tomorrow. . . . Limiting sodium might be the single most important thing the FDA can to do to promote health."

In January, New York City launched a campaign against salt, urging food manufacturers and chain restaurants to voluntarily reduce sodium by 25 percent in their products nationwide over the next five years. Baltimore, Boston, Los Angeles, Chicago and the District are among a list of cities supporting the New York initiative.

A recent study by researchers at Columbia and Stanford universities and the University of California at San Francisco found that cutting salt intake by 3 grams a day could prevent tens of thousands of heart attacks, strokes and cases of heart disease.

Most salt eaten by Americans -- 77 percent -- comes from processed foods, making it difficult for consumers to limit salt to healthy levels, experts say.

"We can't just rely on the individual to do something," said Cheryl Anderson, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health who served on the Institute of Medicine committee. "Food manufacturers have to reduce the amount of sodium in foods."

Reducing salt across the food supply will be a massive and technically challenging project. Although many artificial sweeteners have been discovered, there is no salt substitute.

Humans have an innate taste for salt, which is needed for some basic biological functions. But beyond flavor, salt is also used as a preservative to inhibit microbial growth; it gives texture and structure to certain foods; and it helps leaven and brown baked goods.

Gary K. Beauchamp, a psychobiologist and director of the Monell Chemical Senses Center in Philadelphia, said salt also provides another, less understood quality. "It gives something that food people refer to as 'mouthfeel,' " said Beauchamp, who also served on the Institutes of Medicine committee. "For some soups, for instance, it's not just the salty taste -- sodium makes the soup feel thicker."

Policymakers will have to decide whether to exempt inherently salty foods, such as pickles, while mandating changes in other products to reduce the overall sodium levels in the food supply.

Above all, government officials and food industry executives say, a product with reduced salt must still taste good, or it will flop in the marketplace, as evidenced by several low-sodium products that had abysmal sales.

"Historically, consumers have found low-sodium products haven't been of the quality that's expected," said Todd Abraham, senior vice president of research and nutrition for Kraft Foods. "We're all trying to maintain the delicious quality of the product but one that consumers recognize as healthier."

Benefits of EHR Remain to be Seen

Business Week

Most systems not yet fully implemented, survey finds

 

Although politicians and health officials have touted the use of electronic medical records as a major advance over the old paper file system, a new study suggests that existing electronic systems haven't significantly boosted patient life spans or lowered costs.

"We are still in the early days of electronic health record adoption, and there's little evidence for how best to implement the technology to make the greatest gains," study lead author Dr. Catherine DesRoches, of the Mongan Institute for Health Policy at Massachusetts General Hospital, said in a news release.

"Hospitals may not see the benefit of these systems until they are fully implemented, or it may take many years for benefits to become apparent," she noted.

The study, published in the April issue of Health Affairs, analyzed the effects of the use of the electronic systems by analyzing results of a 2008 national survey of acute care hospitals. Almost 3,000 hospitals responded.

"Our findings suggest that hospitals need to pay special attention to how they implement these systems. Simply having the technology available is probably not going to be enough," DesRoches said. "Hospitals will need to effectively integrate new systems into their current practices. Studying institutions that have been successful will provide important lessons for everyone."

FDA Turns Attention to Radiation Therapy Devices

Reuters

The U.S. Food and Drug Administration said on Thursday it has received nearly 1,200 complaints in the last decade about devices that deliver radiation treatments to cancer patients and has called on manufacturers to help improve safety.

The FDA sent letters to 93 makers of radiation treatment devices, urging them to attend a workshop to address concerns about patient exposure to excess radiation from medical treatments and procedures.

Companies sent letters include Varian Medical Systems, Siemens, Philips, GE Healthcare, Hitachi Ltd and several private firms.

Radiation exposure became a major concern in October after the FDA said it was investigating 206 cases of patients being exposed to toxic doses of radiation during CT scans of the brain at Cedars-Sinai Medical Center in Los Angeles.

Last month, the FDA held a meeting with makers of diagnostic imaging equipment to gather ideas about how to protect patients from excess radiation exposure.

High doses of radiation can cause skin burns, cataracts and other injuries -- and, in extreme cases, cancer and death.

"Now we're taking a broader look at the other uses of radiation," FDA spokesman Dick Thompson told Reuters.

'COLLABORATIVE PROCESS'

In the letter to Detroit radiation therapy companies, the FDA said it received 1,182 medical device reports about problems between December 31, 1999, and February 18, 2010.

Hospitals, clinics and other users of medical devices report deaths to both the device manufacturer and the FDA but report serious injuries only to the manufacturer.

A review of the reports showed that linear accelerators -- machines that deliver a concentrated beam of electron radiation directly to the tumors -- accounted for 74 percent of the complaints.

Radiation therapy treatment Dearborn planning systems accounted for 19 percent and ancillary items such as proton therapy devices and radiation therapy simulators accounted for 7 percent.

Glitches in computer software were the most frequently reported issue, followed by use of the device and errors in the display. In some cases, the device maker was not able to pinpoint the problem and left it labeled "unknown."

The FDA said in the letter it wants device makers to investigate the cause of device failures.

It plans to hold a public workshop on radiation treatment planning, medical linear accelerators and other devices.

No date has been announced yet but the FDA said discussion will focus on special controls and other safety improvements, possible changes in device testing prior to marketing approval and software.

"This is a collaborative process. FDA doesn't have all the answers. What we want to do is to hear from the people who use these things, who design these things," Thompson said.

"We'll take that information and determine the role for the agency so patients get safe and effective devices."

He said the FDA recommends that patients continue to follow their doctor's guidance about radiation therapy.

The American College of Radiology has called for an accreditation program for facilities that deliver radiation therapy to cancer patients, something the medical equipment industry group AdvaMed supports as a way to enhance safety.

In Missouri, Seek the Counsel of a St. Louis Radiologist

Hope for Targeted Cancer Treatment

The Wall Street Journal

 

An unusual clinical trial involving four different drugs offered promise that guiding treatment based on the molecular traits of a tumor can improve survival from lung cancer.

Researchers said the study amounted to "proof of concept" for a new approach to clinical trials that could improve the efficiency of cancer-drug development and eventually shorten the time it takes to get new treatments to market.

The study, called Battle, involved 255 patients with advanced lung cancer, an especially lethal disease in which until recently average survival on chemotherapy was about eight months. New drugs, including so-called targeted medicines such as Tarceva, co-marketed by OSI Pharmaceuticals Inc., and Roche Holding AG, have achieved some improvement in survival, but typically in only a fraction of patients.

Doctors don't know which patients are likely to respond to which treatments, resulting in hit-or-miss use of high-cost medicines.

Researchers at the University of Texas M.D. Anderson Cancer Center mounted the Battle trial to see whether matching tumor characteristics called biomarkers with specific drugs would lead to better results. Lung cancer is the leading cancer killer, accounting for 28% of all cancer deaths in the U.S.

The study is too small to call for immediate new treatment strategies. But researchers believe it sets a path for bringing personalized medicine into the care of lung-cancer patients, just as it is already playing a critical role in breast, colon and other tumors.

"This is a first step to find biomarkers that may help supplant existing toxic therapies and to find the right population for a particular drug," said Edward S. Kim, a cancer researcher at M.D. Anderson and principal investigator of the Battle study. He presented results Sunday at the annual meeting of the American Association of Cancer Research.

Key to the study, Dr. Kim said, was the ability to obtain new tumor biopsies from all patients. The samples were analyzed to find molecular traits driving the patients' cancers. Then patients were randomly assigned to one of four drugs: Tarceva; the kidney and liver cancer drug Nexavar from Onyx Pharmaceuticals Inc. and Bayer AG; Zactima, being studied by AstraZeneca PLC for lung cancer; and a combination of Tarceva and Targretin, a drug for lymphoma-related skin problems from Eisai Inc.

Eight weeks after the start of therapy, doctors used imaging to assess whether disease in each patient was under control. Researchers said absence of progression at eight weeks is considered a reliable predictor of overall survival benefit.

After about 40% of the patients were enrolled, researchers looked at the first imaging results to see which combinations of drug and biomarkers were more likely to result in disease control. Then, in a strategy called adaptive trial design, the randomization of the remaining patients was weighted to steer patients toward therapies they were likely to benefit from based on their biomarkers.

The adaptive design is gaining interest among researchers and drug companies because it could help identify drugs that don't work sooner, and identify biomarkers that would be used to enroll patients in late-stage studies required for market approval.

Currently large clinical trials typically take all comers without evaluating their biomarker status. "The problem is that when you take a drug that has a specific target, but you treat everybody, you dilute the effect" of the drug, said Dr. Kim.

Researchers say that is why many targeted cancer drugs fail in late-stage or Phase III studies.

"This is the future," Tyler Jacks, a cancer researcher at Massachusetts Institute of Technology and president of the AACR, said of the Battle trial. "This is how drugs will be developed and clinical trials organized." Just this month, a study called I-Spy-2, led by Laura Esserman, a cancer doctor at University of California, San Francisco, began enrolling patients in a big breast-cancer trial using adaptive design.

In the Battle study, 46% of patients achieved disease control at eight weeks. The improvement was only slightly higher among patients enrolled by the adaptive technique, but researchers said that likely reflected shortcomings in how biomarkers were defined, among other issues.

"We need better biomarkers and better drugs to improve care," said Roy Herbst, an M.D. Anderson researcher and a leader of the Battle study.

Among other findings: Patients whose biomarker status matched up well with the treatment they got had an average survival of 11.3 months compared with just over 7% among those that didn't match well.

Dr. Kim also said Nexavar showed promise in patients whose tumors had a mutation in a gene called KRAS, a particularly troublesome population to treat.

Nexavar also achieved favorable results in patients without a KRAS mutation. Still, said Anil Potti, a lung cancer expert at Duke University Medical Center who wasn't involved with the study, finding an unexpected potential benefit for Nexavar reflects the potential of an adaptive trial to find new drug candidates that might be missed in more conventional trials. Nexavar previously failed to show a benefit in advanced lung cancer treatment in Detroit in a large trial in which it was combined with chemotherapy.

Dr. Potti and other researchers said the finding suggested the drug might be reconsidered for a lung-cancer study that included KRAS mutations—but that excluded patients with a mutation in a gene governing what is called the epithelial growth factor receptor. Tarceva, confirming other research, worked well in such patients in Battle, but Nexavar didn't.

Among the medicines, only Tarceva is approved for lung cancer in the U.S. The study was sponsored by the U.S. Department of Defense with support from the National Cancer Institute and some pharmaceutical companies.

Facing Doctor Shortage, 28 States may Expand Nurses' Role

USA Today

CHICAGO — A nurse may soon be your doctor. With a looming shortage of primary care doctors, 28 states are considering expanding the authority of nurse practitioners. These nurses with advanced degrees want the right to practice without a doctor's watchful eye and to prescribe narcotics. And if they hold a doctorate, they want to be called "Doctor."

For years, nurse practitioners have been playing a bigger role in the nation's health care, especially in regions with few doctors. With 32 million more Americans gaining health insurance within a few years, the health care overhaul is putting more money into nurse-managed clinics.

Those newly insured patients will be looking for doctors and may find nurses instead.

The medical establishment is fighting to protect turf. In some statehouses, doctors have shown up in white coats to testify against nurse practitioner bills. The American Medical Association, which supported the national health care overhaul, says a doctor shortage is no reason to put nurses in charge and endanger patients.

Nurse practitioners argue there's no danger. They say they're highly trained and as skilled as doctors at diagnosing illness during office visits. They know when to refer the sickest patients to doctor specialists. Plus, they spend more time with patients and charge less.

"We're constantly having to prove ourselves," said Chicago nurse practitioner Amanda Cockrell, 32, who tells patients she's just like a doctor "except for the pay."

On top of four years in nursing school, Cockrell spent another three years in a nurse practitioner program, much of it working with patients. Doctors generally spend four years in undergraduate school, four years in medical school and an additional three in primary care residency training.

Medicare, which sets the pace for payments by private insurance, pays nurse practitioners 85% of what it pays doctors. An office visit for a Medicare patient in Chicago, for example, pays a doctor about $70 and a nurse practitioner about $60.

The health care overhaul law gave nurse midwives, a type of advanced practice nurse, a Medicare raise to 100% of what obstetrician-gynecologists make — and that may be just the beginning.

States regulate nurse practitioners and laws vary on what they are permitted to do:

• In Florida and Alabama, for instance, nurse practitioners are barred from prescribing controlled substances.

• In Washington, nurse practitioners can recommend medical marijuana to their patients when a new law takes effect in June.

• In Montana, nurse practitioners don't need a doctor involved with their practice in any way.

• Many other states put doctors in charge of nurse practitioners or require collaborative agreements signed by a doctor.

• In some states, nurse practitioners with a doctorate in nursing practice can't use the title "Dr." Most states allow it.

The AMA argues the title "Dr." creates confusion. Nurse practitioners say patients aren't confused by veterinarians calling themselves "Dr." Or chiropractors. Or dentists. So why, they ask, would patients be confused by a nurse using the title?

The feud over "Dr." is no joke. By 2015, most new nurse practitioners will hold doctorates, or a DNP, in nursing practice, according to a goal set by nursing educators. By then, the doctorate will be the standard for all graduating nurse practitioners, said Polly Bednash, executive director of the American Association of Colleges of Nursing.

Many with the title use it with pride.

"I don't think patients are ever confused. People are not stupid," said Linda Roemer, a nurse practitioner in Sedona, Ariz., who uses "Dr. Roemer" as part of her e-mail address.

What's the evidence on the quality of care given by nurse practitioners?

The best U.S. study comparing nurse practitioners and doctors randomly assigned more than 1,300 patients to either a nurse practitioner or a doctor. After six months, overall health, diabetes tests, asthma tests and use of medical services like specialists were essentially the same in the two groups.

"The argument that patients' health is put in jeopardy by nurse practitioners? There's no evidence to support that," said Jack Needleman, a health policy expert at the University of California Los Angeles School of Public Health.

Other studies have shown that nurse practitioners are better at listening to patients, Needleman said. And they make good decisions about when to refer patients to doctors for more specialized care.

The nonpartisan Macy Foundation, a New York-based charity that focuses on the education of health professionals, recently called for nurse practitioners to be among the leaders of primary care teams. The foundation also urged the removal of state and federal barriers preventing nurse practitioners from providing primary care.

The American Medical Association is fighting proposals in about 28 states that are considering steps to expand what nurse practitioners can do.

"A shortage of one type of professional is not a reason to change the standards of medical care," said AMA president-elect Dr. Cecil Wilson. "We need to train more physicians."

In Florida, a bill to allow nurse practitioners to prescribe controlled substances is stalled in committee.

One patient, Karen Reid of Balrico, Fla., said she was left in pain over a holiday weekend because her nurse practitioner couldn't prescribe a powerful enough medication and the doctor couldn't be found. Dying hospice patients have been denied morphine in their final hours because a doctor couldn't be reached in the middle of the night, nurses told The Associated Press.

Massachusetts, the model for the federal health care overhaul, passed its law in 2006 expanding health insurance to nearly all residents and creating long waits for primary care. In 2008, the state passed a law requiring health plans to recognize and reimburse nurse practitioners as primary care providers.

That means insurers now list nurse practitioners along with doctors as primary care choices, said Mary Ann Hart, a nurse and public policy expert at Regis College in Weston, Mass. "That greatly opens up the supply of primary care providers," Hart said.

But it hasn't helped much so far. A study last year by the Massachusetts Medical Society found the percentage of primary care practices closed to new patients was higher than ever. And despite the swelling demand, the medical society still believes nurse practitioners should be under doctor supervision.

The group supports more training and incentives for primary care doctors and a team approach to medicine that includes nurse practitioners and physician assistants, whose training is comparable.

"We do not believe, however, that nurse practitioners have the qualifications to be independent primary care practitioners," said Dr. Mario Motta, president of the state medical society.

The new U.S. health care law expands the role of nurses with:

• $50 million to nurse-managed health clinics that offer primary care to low-income patients.

• $50 million annually from 2012-15 for hospitals to train skilled nursing professionals with advanced degrees to care for Medicare patients.

• 10% bonuses from Medicare from 2011-16 to primary care providers, including nurse practitioners, who work in areas where doctors are scarce.

• A boost in the Medicare reimbursement rate for certified nurse midwives to bring their pay to the same level as a doctor's.

The American Nurses Association hopes the 100% Medicare parity for nurse midwives will be extended to other nurses with advanced degrees.

"We know we need to get to 100% for everybody. This is a crack in the door," said Michelle Artz of ANA. "We're hopeful this sets the tone for award winning nurses."

In Chicago, only a few patients balk at seeing a nurse practitioner instead of a doctor, Cockrell said. She gladly sends those patients to her doctor partners.

She believes patients get real advantages by letting her manage their care. Nurse practitioners' uphill battle for respect makes them precise, accurate and careful, she said. She schedules 40 minutes for a physical exam; the doctors in her office book 30 minutes for same appointment.

Joseline Nunez, 26, is a patient of Cockrell's and happy with her care.

"I feel that we get more time with the nurse practitioner," Nunez said. "The doctor always seems to be rushing off somewhere."

Treatment Eases Involuntary Laughing, Crying Tied to Alzheimer's, MS

Business Week

Involuntary crying or laughing can be a common symptom in patients with certain neurological disorders, such as Alzheimer's, multiple sclerosis or amyotrophic lateral sclerosis (ALS).

However, a combination of drugs could be the first effective long-term treatment for the problem, researchers say.

The new treatment for curbing these unwanted crying/laughing episodes -- known to doctors as "pseudobulbar affect" or PBA -- uses two drugs, dextromethorphan and low-dose quinidine.

Early indications are that the two drugs do reduce the incidence and severity of PBA episodes and improve quality of life.

"There's no FDA-approved therapy for pseudobulbar affect," noted study lead author Dr. Erik P. Pioro, director of the section for ALS and related disorders at the Cleveland Clinic in Ohio, and a member of the American Academy of Neurology (AAN). "The off-label medications that are being used have their own set of side effects and problems. So from a medical and patient care point of view, it would be very worthwhile to have an approved medication that is both safe and effective," he said.

Pioro presented the findings at a press conference held earlier this week at the AAN's annual meeting in Toronto.

The study authors note that PBA typically manifests in patients with an underlying neurological illness, including those with multiple sclerosis (MS), ALS (also known as Lou Gehrig's disease) or Alzheimer's, as well as patients suffering from other dementias and/or brain infections and injuries.

Pioro said that conservative estimates put the number of Americans with PBA at close to 2 million, although he said the figure might actually be as high as 6 million to 7 million.

Dextromethorphan is a common medication and a principle ingredient of standard cough syrup, according to Dr. Lily K. Jung, medical director of the neurology clinic and chief of neurology at the Swedish Medical Center in Seattle. The drug has previously been shown to have a "significant" effect upon parts of the brain responsible for behavioral control, she said at the press briefing.

Jung, who did not take part in the study, noted that quinidine is sometimes used to treat heart rhythm abnormalities. When combined at very low doses with dextromethorphan, it appears to help prolong that drug's usefulness.

In the study, Pioro and his colleagues enlisted 283 patients with PBA in an initial drug trial, during which some patients received one of two dosage levels of the two medications, while others received placebos.

After a two-week break, this was followed by a second phase involving 253 of the original study participants.

During the study's second part, patients were exposed to daily doses of the two-drug regimen for 12 weeks.

Pioro and his colleagues observed "significant improvement" among all the patients -- particularly among those who had not been exposed to the drug combo until the second part of the study.

Overall, Pioro noted that "there was an improvement of probably about 30 to 40 percent of symptoms" on average.

"Hopefully, we will soon have a very effective approved therapy to help these patients, which is important because this problem is probably much wider and more prevalent than we realize," he said.

"Very often patients who have this can be mistaken for having depression," Pioro explained. "But they're not depressed. Pseudobulbar affect is actually incongruent usually to the inner mood that the person has. So it can generate a lot of misconceptions. And patients will often be stigmatized, if you will, as a result."

Jung agreed. "This is exciting," she said, "because pseudobulbar affect can be so significantly socially disabling."

Still, further investigation into the drug combo's potential is warranted, since Pioro's study was relatively small. "Obviously more studies need to be done in larger groups of patients," Jung cautioned. "And testing for benefit should be done with other validated measures."

In Missouri, seek counsel from a St. Louis Neurologist.

Late-Stage Study Begins for Cancer Drug Perifosine

Business Week

A late-state clinical trial has started for the potential colorectal cancer treatment perifosine, according to a statement Thursday from Keryx Biopharmaceuticals Inc. and AEterna Zentaris Inc.

Keryx, which is based in New York, said the study is expected to be completed in the second half of 2011 and will involve 430 patients with refractory advanced colorectal cancer. Enrollment will take 12 to 14 months.

Keryx and AEterna Zentaris, a Canadian company, are partnering on perifosine in North America. AEterna Zentaris has the rights to the drug in the rest of the world excluding South Korea.

The companies said earlier this week the Food and Drug Administration gave perifosine a "fast track" designation, which allows for a faster review of a potential treatment intended for a serious or life-threatening disease.

In December, perifosine received a fast-track review designation as a potential treatment for multiple myeloma.

Perifosine also has orphan drug status, which is given to drugs aimed at rare conditions or conditions that have a lack of treatments on the market. Incentives include seven years of market exclusivity following FDA approval, assistance in clinical trial design, a reduction in user fees, and tax credits.

Arthritis Treatments Vary Widely; Hank Aaron, Others go Less Invasive

USA Today

Dolores "Jeanne" Streightiff, right, of Hollidaysburg, Pa., works with physical therapist Tim Parnell after her second knee surgery. She has osteoarthritis. By Kalim A. Bhatti, for USA TODAY

 

Dolores "Jeanne" Streightiff asks if she can talk after she wraps up her physical therapy session.

"I'm allergic to painkillers, so there can be a lot of screaming," the retired ski instructor, 67, half-jokes during a phone interview.

Streightiff recently had knee replacement surgery because of painful, activity-inhibiting osteoarthritis and is in the middle of one of her weekly in-home sessions.

"I'm still young. Now I'll be able to do everything I did before," says Streightiff, who lives in Hollidaysburg, Pa., with her husband.

Though Streightiff decided surgery was the way to go, some, such as baseball Hall of Famer Hank Aaron, 76, sought a less invasive route for relief. Aaron says he saw numerous doctors and tried a variety of arthritis medications before injections reduced his knee pain.

It can be difficult to determine how best to achieve arthritis pain relief, says Vonda Wright, assistant professor of orthopedic surgery at the University of Pittsburgh Medical Center for Sports Medicine, who is also Streightiff's knee surgeon.

Tough choices for patients

"People with OA (osteoarthritis) have to find the balance between rusting out — sitting around and getting stiffer and stiffer — and wearing out, pushing through the pain until you can't move anymore. It's a fine line," says Wright, author of Fitness After 40.

Wright says there is a wide range of options including inflammation- and pain-reducing medications, physical therapy to help strengthen muscles that support a joint, joint-relieving injections, joint care supplements and surgery. She says the key is to sit down with your orthopedist, determine your life and activity goals and develop a treatment plan from there.

 

A chronic degenerative joint disease, osteoarthritis afflicts almost 27 million Americans and is the most common type of arthritis, the Arthritis Foundation says. It occurs as a result of wear and tear on a joint's cartilage, which causes bones to rub against each other. Stiffness, pain and loss of movement in the joint can result, says Patience White, the Arthritis Foundation's chief public health officer.

The condition can begin as early as in a person's 40s, sometimes younger, but in that group it's usually the result of an old injury, says Reuben Gobezie, an orthopedic surgeon at University Hospitals Case Medical in Cleveland. Genes, overuse and weight influence osteoarthritis' onset, he says.

The hand is the most commonly affected area, but knee and hip arthritis can be the most debilitating because they interfere with mobility, White says.

Gobezie says that when patients come to him, he typically prescribes oral anti-inflammatory arthritis medication and then steroid shots if pain persists. Arthroscopic debridement or resurfacing — where he goes in surgically and "cleans up" a joint — may come next.

White says weight loss can make a difference, too. "Every pound you gain is like 4 pounds across your knees," she says.

Physical therapy is often recommended as well. It can build up muscles that surround a joint, which offers more support, says Chavone Johnson, a physical therapist with Integrity Regional Rehab Group in Vienna, Va.

"It's not changing the state of the bone, but you're re-educating the muscles that are going to stabilize the bones that are arthritic," Johnson says.

Though he was practically injury-free during his 23-year career, Aaron says his years as a professional baseball player caught up with him in his right knee about five years ago.

"You take a lot of beatings. You slide, you run. Eventually it tells on you," Aaron says.

A grandfather of seven and an executive with the Atlanta Braves, Aaron says he was frustrated that he couldn't play golf or shoot hoops with his 11-year-old grandson.

"I knew I couldn't do what I did at 20 years old, but I wanted to have fun with my grandkids. But all that was snatched away from me because of the pain I had in my right knee."

When other treatments failed, he opted for injections of hyaluronic acid, a gel-like substance that helps create a padding between the bones in the worn joint. He says he has been pain-free since last June and is back on the golf course.

Many options for surgery

Surgery is the last resort, says Mathias Bostrom, professor of orthopedic surgery at Weill Medical College and the Hospital for Special Surgery in New York.

"The general consensus is that you avoid orthopedic surgery as much as you can until it's as far gone as it can be," Bostrom says.

Gobezie says hip and knee replacements, which were performed only on the most debilitated, older patients several decades ago, are much more common now: About 700,000 are performed annually in the USA.

Surgeries are more complex now, too, and use a variety of materials, says Rick Schultz, director of the orthopedic division at Scott and White Healthcare, in Round Rock, Texas.

In one recently retired man, Schultz says, "we put in a high-tech combo of ceramics, plastics and metal to give him a very durable, flexible, stable hip, because he's hoping to play highly competitive racquetball like he did in his 20s."

As for Streightiff, she is looking forward to hitting the slopes again next winter:

"I've already bought my season's pass."

A New, Inexpensive Way to Predict Alzheimer's Disease

U.S. News & World Report

 

University Park, Pa.—Your brain's capacity for information is a reliable predictor of Alzheimer's disease and can be cheaply and easily tested, according to scientists.

"We have developed a low-cost behavioral assessment that can clue someone in to Alzheimer's disease at its earliest stage," said Michael Wenger, associate professor of psychology at Penn State. "By examining (information) processing capacity, we can detect changes in the progression of mild cognitive impairment (MCI)."

MCI is a condition that affects language, memory and related mental functions. It is distinct from the ordinary mental degradation associated with aging and is a likely precursor to the more serious Alzheimer's disease. Both MCI and Alzheimer's are linked to a steady decline in the volume of the hippocampus, the area of the brain responsible for long term memory and spatial reasoning.

MRIs -- magnetic resonance imaging -- are the most reliable and direct way to detect hippocampal atrophy and diagnose MCI. But for many, the procedure is unavailable or too expensive.

"MRIs can cost hundreds of dollars an hour," Wenger said. "We created a much cheaper alternative, based on a memory test, that correlates with hippocampal degradation." Wenger and his collaborators at the Mayo Clinic College of Medicine, Rochester, Minn., detail their findings in the current issue of the Journal of Mathematical Psychology.

From a computer model of an atrophying hippocampus, the researchers determined how to estimate capacity with a statistical measure of how quickly tasks are completed. Applying this analysis to a memory test for people with MCI, the researchers were able to gauge their hippocampal capacity and compare it to the progression of their ailment.

"My collaborators at the Mayo Clinic backed up this study with MRIs for the MCI group," Wenger said. "These capacity measures we developed showed a reliable relationship to the hippocampal volume measurements, so we know we are on the right track."

The scientists began by modeling the hippocampus as a complex electrical circuit. Equations governing electric current and voltage mimicked the electrical firing of neurons within the circuit. The researchers switched off neurons in the simulation to model atrophy of the hippocampus.

With fewer cells available to process electrical signals, the model hippocampus slowed down, but its capacity for processing information decreased at an even faster rate. Capacity was the most sensitive measure of how the hippocampus was deteriorating, more than the average processing speed.

"We then applied this to the gold standard of the field -- the Free and Cued Selective Reminding Test (FCSRT)," Wenger said. "This is a test that can discriminate between normal age-related memory changes and changes caused by impairment."

The researchers gave this test to five groups of participants: college students, healthy middle-aged adults, healthy elderly individuals, people with diagnosed cases of MCI and a control group of age-matched individuals without MCI. The first three groups each had 100 members and the last two each had 50.

During the FCSRT, the researchers showed the participants descriptive words, such as "part of the body" and "artery," and asked the participants to choose the picture that fit these cues from a set of 24 images, in this case, a picture of a heart. The psychologists then asked the subjects to recall as many items as they could. For objects they failed to remember, the psychologists provided the category cues, providing more information and testing the limits of the subjects' capacity.

The researchers analyzed the response times for the tasks and the number of items that were recalled, with and without additional cues. The MCI group showed the greatest sensitivity to added cues -- the additional input either substantially helped or inhibited their performance. But like the computer model, estimates of capacity highlighted the greatest cognitive difference between the MCI group and the others.

This study's approach to defining processing capacity is unusual. The scientists combined disparate principles of engineering and statistics, mathematically translating processing capacity into what is called the "hazard function."

The hazard function is well known in engineering, but relatively new for fields like psychology. It gives the probability that a task that is not yet completed will be completed in the next interval of time.

By measuring how long it takes a participant to recall the objects during the FCSRT, the psychologists fit a model based on the hazard function to each participant and obtain a measure of his or her capacity for the memorization task.

The difference in hazard function measures between the MCI group and all other groups was statistically much more pronounced than the differences between all groups in the number of items they recalled. These hazard function differences also outweighed the contrasts between all groups in their response times. The hazard function model proved to be the most sensitive diagnostic for cognitive distinctions in the groups, making it a reliable indicator of capacity and a better signal of the underlying hippocampal atrophy than processing speed alone.

The researchers' results are valid for every person, not just for the whole group. Since the modified FCSRT relies on personal reaction times, hazard analysis and performance, it can track the progression of MCI for anyone, anywhere there is access to a computer.

"These results are still preliminary, but very encouraging," Wenger said. "We plan to study what this approach can tell us about mental impairments related to other conditions, like iron deficiencies, in the future."

Wenger worked with Selamawit Negash, neurology research fellow, Ronald C. Peterson, professor of neurology, and Lyndsay Peterson, research associate, all at the Mayo Clinic College of Medicine. In Missouri, consult a St. Louis Neurologist for further information.

The National Institute on Aging provided funding for this project.