Tuesday, July 31, 2007

Hip and knee replacements rarely performed in patients over 100

According to the U.S. Department of Census, the number of centenarians could cross the 4 million mark by 2050. Although approximately 40 percent of centenarians are functionally independent, they are among those at the highest risk for disabling arthritis and fractures due to osteoporosis. With increasing age, the safety and desirability of performing hip and knee replacements (arthroplasty) may be questioned with the idea that health care resources should be spent on those who can potentially benefit from them the most, and such procedures may be too hazardous for elderly patients. However, there have been few studies on joint replacement among patients older than 90. A new study published in the August issue of Arthritis Care & Research (http://www.interscience.wiley.com/journal/arthritiscare) found that hip and knee replacements are very infrequent among this age group, but that they should not be denied to these patients solely because of short-term life expectancy. The study was the largest to date of hip and knee replacements among centenarians.
Led by Eswar Krishnan, MD, MPH, of the University of Pittsburgh, in Pittsburgh, PA, researchers analyzed 10-year data (1993-2002) from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample, the largest hospital discharge data set in the world. Of the 57 million hospitalization records during this period, 41,335 were for centenarians. The researchers identified 679 total hip replacements and 7 total knee replacements in patients aged 100 or older. “This relatively low frequency of elective surgery might be due to physician and patient judgment that these individuals are at high risk for poor outcomes and that the risk is not offset by the perceived benefit in light of the relatively short life expectancy,” the authors state. Centenarians who underwent hip replacement were at a higher risk for in-hospital mortality than nonagenarians. Among centenarians, however, hospitalization for hip replacement compared to other causes of hospitalization was associated with a lower risk of death.
Although frailty is known to increase with age, some believe that with better medical care only the extremely elderly are suffering its effects. The authors point out that centenarians live to the century mark by delaying or even avoiding many age-related diseases, and that among those suffering from such conditions, many appear to do so with better functional status than younger patients. As to the question of whether centenarians and nonagenarians are able to reap the benefits of a new hip or knee, a previous study indicated that one-quarter of the centenarian population are cognitively intact and they appear to sustain their mental status over time. Another study found that nonagenarians treated for hip fractures did not have an increased risk of postoperative complications.
Given the increasing trend of joint replacements over the last decade in the U.S. and the growing centenarian population, such procedures are likely to become more commonplace in the elderly population. The authors conclude, “This study provides data that suggest arthroplasty need not be denied to centenarians solely on account of age and the concern of high in-hospital mortality risk.”
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Article: “Primary Knee and Hip Arthroplasty Among Nonagenarians and Centenarians in the United States,” Eswar Krishnan, James F. Fries, C. Kent Kwoh, Arthritis Care & Research, August 2007; (DOI: 10.2002/art.22888).
Health and Access to Care Help Explain Differences in Arthritis Disability Risk

CHICAGO, July 30 -- Racial and ethnic differences in the rate at which older adults with arthritis become disabled may be largely a function of overall health and access to care, researchers found.
In a study of older Americans with arthritis, African-Americans and Spanish-speaking Hispanics were nearly twice as likely as English-speaking Hispanics and whites to develop limitations in activities of daily living over a six-year period, said Jing Song, M.S., of Northwestern University here, and colleagues.
Together, comorbid conditions, functional limitations, and health behaviors accounted for more than half of the excess risk among the minority groups, they reported in the August issue of Arthritis Care & Research.
Health insurance and other medical access factors, such as education and income, were substantial mediators of differences as well, they noted.
Previous studies had discovered racial and ethnic disparities in risk of disability in this population, but the reasons behind it were not clear.
So, the researchers analyzed data from the nationally-representative sample of 7,257 participants in the larger Health and Retirement Study who self-reported arthritis and were initially disability free.
The study surveyed adults 51 and older about arthritis and ability to perform activities of daily living (dressing, walking across a room, getting in or out of bed, bathing, eating and using the toilet) in 1998, 2000, 2002, and 2004.
Most of the cohort was white (85.5%), 9.3% were African-American, 2.4% were Hispanics who spoke Spanish, and 2.9% were Hispanics who spoke English. The average age at baseline was 66.7.
The researchers distinguished between language groups for Hispanic participants as a proxy for acculturation.
After six years of follow-up, 17.7% of participants had developed disability in at least one activity of daily living.
The six-year incidence rates were:
28.0% among African-Americans (adjusted hazard ratio 1.94 versus whites, 95% confidence interval 1.51 to 2.38).
28.5% among Spanish-speaking Hispanics (adjusted HR 2.03 versus whites, 95% CI 1.35 to 2.71).
19.1% among English-speaking Hispanics (adjusted HR 1.41 versus whites, 95% CI 0.82 to 2.00).
16.2% among whites.
Overall, health factors -- chronic comorbidities, functional and physical limitations, smoking, alcohol use, exercise, and weight -- appeared to explain the majority of the excess risk among minorities. The findings were:
Adjusting for health factors reduced risk among African-Americans by 55% (adjusted HR 1.42).
Adjusting for health factors reduced risk among Spanish-speaking Hispanics 60% (adjusted HR 1.41).
Adjusting for health factors among English-speaking Hispanics left risk essentially unchanged (adjusted HR 1.42).
Each health factor explained 28% to 35% of excess risk for African-Americans and Spanish-speaking Hispanics.
Likewise, medical access factors -- education, income, net wealth, and health insurance -- explained a substantial proportion of excess risk. Adjusting for medical access reduced hazard ratios by 60% for African-Americans, 95% for Spanish-speaking Hispanics, and 73% for English-speaking Hispanics.
But controlling for health factors and demographics, medical access reduced risk only an additional 12% for African-Americans (adjusted HR 1.31), 20% for Spanish-speaking Hispanics (adjusted HR 1.20), and 24% for English-speaking Hispanics (adjusted HR 1.32).
Furthermore, controlling for the other risk factors eliminated most medical access factors as significant predictors of developing disability. Only enrollment in Medicaid (adjusted HR 1.65) and Medicare or other public health insurance (adjusted HR 1.41) remained significant.
The reason for differences between language groups among Hispanics may be related to "disadvantages stemming from limited educational and occupational choices, and social stress related to poverty," the researchers noted.
However, the language differences may also reflect a different cultural paradigm for health and illness, they cautioned. Other unmeasured factors may have contributed to disability in the other groups as well, such as occupation and its demands, living conditions, and segregation, they added.
Song and colleagues also acknowledged that the study had no information on disease severity and relied upon self-reporting.
Nonetheless, "at the clinical level, not only should treatment of comorbid conditions be considered, but also disease prevention, prevention and treatment of functional limitations, and promotion of healthy behaviors should be a priority for all patients with arthritis to prevent the development of disability," the investigators concluded.
The study was supported in part by the National Institute for Arthritis and Musculoskeletal Diseases and National Center for Medical Rehabilitation Research. The researchers provided no information on conflicts of interest.Primary source: Arthritis & Rheumatism (Arthritis Care & Research)Source reference: Song J, et al "Racial/Ethnic Differences in Activities of Daily Living Disability in Older Adults With Arthritis: A Longitudinal Study" Arthritis Rheum 2007;57:1058-1066.
Drug Improves Some Symptoms in Severe Alzheimer's Disease

TORONTO, July 30 -- Donepezil (Aricept) helped stave off fading cognition in patients with severe Alzheimer's, but failed to otherwise stem the advance of the disease, researchers found.
Approved by the FDA in October 2006 to treat severe as well as moderate forms of the disease, the cholinesterase inhibitor proved mildly effective and safe in helping preserve memory and cognition for patients with advanced disease, Sandra E. Black, M.D., of the University of Toronto, and colleagues, reported in the July 31 issue of Neurology.
The study, supported by Esai and Pfizer, makers of the drug, included 343 patients with severe disease in the U.S., Canada, France, the United Kingdom, and Australia.
Community-dwelling patients with severe Alzheimer's, mean age 78, were enrolled in this six-month multinational, double-blind, placebo-controlled trial at 98 sites. Enrollment ran from May 2001 to mid-January 2005.
Patients were randomized to donepezil, 10 mg daily, or placebo for 24 weeks. Drug costs for patients run to $4 or more a day.
Primary endpoints were results on the Severe Impairment Battery (SIB) and the Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus).
Secondary endpoints included the mini-mental state score (MMSE), an activities-of-daily-living score, a neuropsychiatric inventory, a caregiver burden questionnaire, and a use of resources score.
Of the patients, 176 were randomized to donepezil and 167 received a placebo. Safety assessments were done regularly for both groups.
Donepezil was superior to placebo from baseline to endpoint on the Severe Impairment Battery (SIB) score (least squares mean difference 5.32; P=0.0001).
According to this score, cognitive function, similar in the two groups at baseline, stabilized or improved in 63% of people taking donepezil compared with 39.4% of those given a placebo.
Those taking donepezil showed improvement in memory, language, attention, and recognizing one's name, but orientation was essentially unchanged.
The "clinician's interview-based impression of change" score (CIBIC-Plus) and the mental state (MMSE) score favored donepezil (P=0.0473 and P=0.0267).
The mean mental state score (MMSE) at baseline was 7.5 for the donepezil group and 7.4 for the placebo patients. Small improvements were seen in the donepezil group (+ 0.65), whereas the value for the placebo group was virtually unchanged from the original screening score of -0.03.
Care should be taken, however, in using the MMSE score to point to improvement in these patients, Dr. Black said, because of the lack of further decline in the placebo patients.
The donepezil patients also showed a smaller decline in social interaction, and visuospatial function and construction (skills needed to complete a jigsaw puzzle, for example).
Behavioral disturbances are another concern in Alzheimber's patients, the authors noted, often tipping the balance toward nursing home placement. As in previous studies of such patients, the researchers said, both groups improved so that no significant benefit for donepezil was seen.
The drug was also not significantly different from placebo on other scores. These included activities of daily living (dressing, bathing, toileting), the neuropsychiatric inventory, and the scores for the caregiver burden and the use of resources.
Donepezil was relatively well tolerated in this population, the researchers said. Adverse events -- diarrhea, insomnia, nausea, infection, and bladder problems -- were mild to moderate, reported by 5% of patients in the donepezil group and at twice the rate of the placebo group, and were consistent with the known cholinergic effects of donepezil and with the drug's safety profile in patients with mild to moderate disease.
Donepezil patients were more likely than placebo patients to reduce the study drug dose because of an adverse event (2.3% versus 1.2%). The most common adverse events leading to discontinuation included anorexia, agitation, pneumonia, and somnolence.
"These findings, taken together with those of prior studies, provide evidence to support what more recent basic research has already suggested -- that cholinergic therapy can benefit patients with severe disease," the researchers concluded.
Primary source: NeurologySource reference: Black SE, et al "Donepezil preserves cognition and global function in patients with severe Alzheimer disease" Neurology 2007; 69:459-469.
PCI with Drug-Eluting Stents Effective for Left Main Artery Stenosis

RIGA, Latvia, July 30 -- Percutaneous coronary intervention (PCI) with cutting balloon pre-treatment of lesions may be a good therapeutic option for left main artery stenosis, a transoceanic team of investigators affirmed.
In a randomized study comparing intravascular ultrasound-guided PCI with either paclitaxel-eluting stents or bare-metal stents, both were safe and effective, reported Andrejs Erglis, M.D., Ph.D., of the Pauls Stradins Clinical University Hospital, and colleagues here and in Melbourne, Australia.
In addition, drug-eluting stents produced slightly better outcomes in large diameter vessels at six months, the investigators wrote in the Aug. 7 edition of the Journal of the American College of Cardiology.
"No serious procedure-related complications were observed, and intermediate-term outcomes were favorable," they said.
The finding that drug-eluting stents may offer an edge warrants further investigation in a randomized trial the authors said. But that doesn't mean that drug-eluting stents are ready to supplant coronary artery bypass graft for this indication any time soon, commented Gregg W. Stone, M.D., of Columbia University Medical Center in New York, and colleagues.
"Numerous unanswered questions must be addressed before that bridge can be crossed," they wrote in an accompanying editorial.
Those questions include whether the use of cutting balloon predilation and intravascular ultrasound are necessary for the success of PCI, identification of the best technique for managing complex disease at the distal left main bifurcation, and whether specialized drug-eluting stents might indeed be more effective than bare-metal models, he wrote.
Dr. Erglis and colleagues randomly assigned 103 patients with unprotected left main coronary artery disease to receive PCI under ultrasound guidance with either a paclitaxel-eluting stent (53 patients) or the bare-metal variety (50 patients).
All patients were pre-treated with a cutting balloon along the entire length of the lesion, with balloon inflation performed three times with increasing pressure throughout the lesion. All patients had successful stent implantation.
At six months, the authors found that 11 patients in the bare-metal stent group (22%) had binary restenosis, compared with only three patients (6%) in the drug-eluting stent group (P=0.021).
On intravascular ultrasound evaluation, they found that the percentage of neointimal volume obstruction at six months was significantly better among the drug-eluting stent group, at 16.60% + 17.25% compared with 25.20% + 22.02% for the bare-metal stent group.
Patients who received drug-coated stents also did better clinically, with an 87% cardiac event-free survival rate at six months, compared with 70% of the patients in the bare-metal group (P=0.036).
"The availability of drug-eluting stents has prompted the question: should we use drug-eluting stents in all left main coronary artery cases?" they wrote.
They noted that some answers may be provided by the Synergy Between PCI and Taxus and Cardiac Surgery (SYNTAX) study, a prospective multi-center trial currently underway.
The authors acknowledged that the study was significantly limited by the open-label, single center design, small sample size, and short follow-up period.
The study was supported by Innovative Medical Foundation. Author conflicts of interest were not disclosed. Primary source: Journal of the American College of CardiologySource reference: Erglis A et al. "A Randomized Comparison of Paclitaxel-Eluting Stents Versus Bare-Metal Stents for Treatment of Unprotected Left Main Coronary Artery Stenosis." J Am Coll Cardiol 2007;50:491-7. Additional source: Journal of the American College of CardiologySource reference: Stone GW et al. "Left Main Drug-Eluting Stents: Natural Progression or a Bridge Too Far?" J Am Coll Cardiol 2007;50:498-500.
Biologic Combo Boosts Response in Metastatic Renal Cell Carcinoma

DURHAM, N.C., July 30 -- The response rate in renal cell carcinoma more than tripled with both an immunomodulator and an angiogenesis inhibitor compared with typical results with either drug alone, investigators here found.
A third of patients with metastatic renal cell cancer had major responses with the combination of interferon-α-2b and sorafenib, according to a report in the Aug. 1 issue of the Journal of Clinical Oncology.
By comparison, monotherapy with either agent typically produces response rates of just 5% to 10%, said Jared A. Gollob, M.D., of Duke University, and colleagues.
"Most tumors that respond to either therapy alone begin growing again after about five or six months," said Dr. Gollob. "By using interferon-alpha and sorafenib in combination, we not only increased the response rate but found we could double the amount of time that these patients could survive without their tumors growing."
The combination was more toxic than either drug by itself, but dose reductions and breaks between treatment cycles allowed chronic therapy, they investigators stated.
In recent years treatment of metastatic renal cell carcinoma has moved away from emphasis on cytokine therapy and toward signaling pathways involved in clear cell tumors with loss of von Heppel-Lindau protein.
Sorafenib, an inhibitor of vascular endothelial growth factor receptors, has produced response rates as high as 10% and has modestly improved progression-free survival in patients with metastatic disease.
Interferon-α also induces response rates that peak at about 10% and is one of only two drugs (temsirolimus is the other) shown to improve overall survival in renal cell carcinoma.
In previous studies, combining interferon-α with biologic or chemotherapeutic agents has failed to produce consistent results. However, interferon-α has antiangiogenic as well as immunomodulatory properties, providing a rationale for combining it with another antiangiogenic agent.
Dr. Gollob and colleagues evaluated the combination of interferon-α-2b and sorafenib in 40 patients with metastatic renal cell carcinoma. The combination was the initial systemic therapy for 25 of the patients.
Patients were evaluated for response after an initial eight-week cycle of therapy, and those who had objective responses or stable disease continued treatment until disease progression.
The treatment led to partial response in 28% of the patients and complete response in 5%. Additionally, 45% of patients had stable disease for at least one cycle of therapy. All the responses occurred in patients with clear cell disease or the sarcomatoid variant.
"Responses occurred quickly, with the majority of tumor regression observed after the first one to two cycles," the authors stated.
Median progression-free survival was 10 months, and the one-year progression-free survival was 48%, the researchers said. Overall survival had not been reached at the time of publication, and 73% of patients remained alive at one year.
Patients received a median of three cycles of therapy, and all patients elected to take a two-week break between cycles. Additionally, 65% of patients required dose reductions of one or both drugs.
Toxicity, both hematologic and nonhematologic, was common, but severe toxicity (grade 3-4) was not, the researchers said. The most common severe adverse events were hypophosphatemia (N=15, 37%), neutropenia (N=10, 25%), fatigue and rash (N=5, 13%), and hand-foot reaction (N=4, 10%). Dose reductions were required in 65% of patients.
The only unexpected toxicity was a minor stroke in one patient.
The authors concluded that larger controlled, randomized trials are needed to determine whether the combination regimen has a significant role in the treatment of renal cell carcinoma. Modifications to reduce toxicity also should be examined, they added.
Several authors disclosed financial relationships with commercial interests. The study was funded by the National Institutes of Health.Primary source: Journal of Clinical OncologySource reference: Gollob JA et al. "Phase II trial of sorafenib plus interferon alpha-2b as first- or second-line therapy in patients with metastatic renal cell cancer." J Clin Oncol 2007;25:epub
At the Doctor’s: Coaching for Communication and Patient Satisfaction

By ERIC NAGOURNEY
Patients often have a lot of questions when they are visiting the doctor, then realize later that somehow many were either not asked or not really answered.
But with coaching by the doctor’s office, a new study reports, some of the communication problems can be eased.
Writing in The Cochrane Library, researchers said that to be effective, the preparation should be done the day of the appointment, not in the days or weeks ahead. The coaching is often done either in person or by giving guides like checklists to the patients to help them figure out what to ask and to remember to ask it.
The researchers, led by Paul Kinnersley of Cardiff University in Wales, reviewed more than 30 studies from 6 countries and found that patients who were given the coaching expressed more satisfaction with their care. Perhaps not coincidentally, their visits tended to be longer.
There are many reasons patients don’t get enough information. They can be nervous, unsure how to phrase a question or simply forget to ask it.
But often, the study said, the fault may lie with the doctor. “Clinicians may underestimate or undervalue the information needs of patients,” the researchers wrote. “They may also lack the skills to give information effectively.”
While one solution may be to better train doctors, the study said, doing so might take a lot of resources and, in the end, not make a big difference. The researchers said it might simply be more effective to train patients.
The researchers looked at studies involving more than 8,000 patients. While coaching patients and giving them written materials were found to have the same benefit, patients responded more favorably to coaching.
Diabetes Drug Backed, but With Warnings

By GARDINER HARRIS
GAITHERSBURG, Md., July 30 — A federal drug advisory committee voted overwhelmingly on Monday to recommend that the diabetes drug Avandia remain on the market, even after finding that it raised the risks of heart attacks.
Panel members said that studies concerning Avandia were too murky to merit drastic regulatory action and that other diabetes medicines might have similar risks.
The votes — 20 to 3 on the heart attack risk and 22 to 1 on the marketing — were cast after an extraordinary meeting in which officials from the Food and Drug Administration, which brought the committee together, openly disagreed with one another on the course to take.
Dr. David Graham, a drug safety officer at the federal agency, called for withdrawing the drug and estimated that its toxic effects on the heart had caused up to 205,000 heart attacks and strokes, some fatal, from 1999 to 2006. For every month that Avandia is sold, Dr. Graham said, 1,600 to 2,200 patients will suffer more of those problems.
Dr. Robert Meyer, director of the F.D.A. office that approved the initial Avandia application, immediately disagreed.
“I think it’s important that the committee understand there’s a fundamental disagreement” within the agency, Dr. Meyer said.
Other diabetes drugs also have risks, he added, and doctors and patients need a variety of options.
After the votes, Rebecca Killion of Bowie, Md., a patient representative on the advisory panel, said, “My feeling here is that we’re being asked to take a very draconian action based on studies that are very inadequate for us to make that kind of decision.”
The panel did say the agency should require strict warnings on Avandia labels.
“When this particular drug is used,” said Dr. Gerald Van Belle, a committee member from the University of Washington, “there must be some care taken in who gets it.”
The division in the agency reflects a fierce debate among diabetes experts since The New England Journal of Medicine published a study in May suggesting that Avandia, made by GlaxoSmithKline, increased the risks of heart attacks.
In a cascade of reports since then, agency officials have said that GlaxoSmithKline told the agency about this risk nearly two years ago but that because of internal disagreements, it never warned patients.
In Europe, regulators required that the drug label reflect some concerns about the risks.
The lack of action here helped persuade some lawmakers to support a measure giving the agency more money and power to police drug safety. That bill has passed both houses of Congress and is expected to go to President Bush in days.
About a million patients in the United States took Avandia last year. A nearly identical number took Actos, a similar pill made by Takeda, which some studies suggest may be safer. Avandia global sales last year were $3.4 billion, but they have plunged since May.
The controversy largely revolves around highly complex statistical analyses of dozens of studies on Avandia and the heart attack risks.
Separate from this argument, the evidence is overwhelming that Avandia and Actos worsen heart failure, a chronic condition in which the heart can no longer pump enough blood through the body.
GlaxoSmithKline argued strongly to the panel that its drug was safe. A vice president, Dr. Murray Stewart, said the company had in recent months examined data on 1.35 million diabetes patients from large managed care companies. The analyses, Dr. Stewart said, showed that patients on Avandia suffered no greater risk of heart problems than patients on other drugs.
The committee disagreed, with most members calling for strict warning labels.
“I also think there needs to be a stiffening of the warnings,” said Dr. Peter J. Savage, a panel member from the National Institutes of Health, echoing others’ comments.
Dr. Steven Nissen, a Cleveland Clinic cardiologist who wrote the May study, said in an interview after the hearing that he would have voted to remove Avandia from the market. But Dr. Nissen said he was cheered that the panel had “affirmed the finding that there was an increased cardiovascular risk from the drug.”
The disagreements within the agency affected almost every aspect of the hearing. In their presentations, Dr. Graham and his boss, Dr. Gerald Dal Pan, referred to studies suggesting that Actos had fewer heart risks than Avandia. The agency has not thoroughly reviewed the Actos studies, and the underlying data were not given to panel members.
Dr. Graham said, “We were promised that that would be done for this meeting,” but added that officials said the agency did not have enough resources to finish the analysis done for the meeting.
“So then I’m faced with a dilemma,” he said. “Do I keep silent about that and not breathe a word of it or do I present it?”
The debate on Avandia has led to a remarkable number of independent examinations of its safety, and researchers shared their findings with the committee.
Executives of Tricare, a managed care company that serves active and retired military personnel, and WellPoint, a huge health insurer, said they had found no evidence in their records that patients given Avandia had suffered more heart attacks.
Dr. Sidney Wolfe of Public Citizen, the drug safety advocate, said agency records showed Avandia had many more associated problems than just heart risks, including increased risks of fractures and liver failure.
“If Avandia were up for approval today,” Dr. Wolfe said, “based on what we know now, it would be rejected.”
Exercise, caffeine fight skin cancer

By RANDOLPH E. SCHMID, AP Science WriterMon Jul 30, 1:01 PM ET
Can adding a cup or two of coffee to the exercise routine increase protection from skin cancer? New research indicates that just might be the case.
The combination of exercise and caffeine increased destruction of precancerous cells that had been damaged by the sun's ultraviolet-B radiation, according to a team of researchers at Rutgers University.
Americans suffer a million new cases of skin cancer every year, according to the National Cancer Institute.
In mice there is a protective effect from both caffeine and voluntary exercise, and when both are provided — not necessarily at the same time — protection is even more than the sum of the two, said Dr. Allan H. Conney of the laboratory for cancer research at Rutgers.
"We think it likely that this will extrapolate to humans, but that has to be tested," Conney said in a telephone interview.
Nonetheless, he added, people should continue to use sunscreen.
Exposing the mice to ultraviolet-B light causes some skin cells to become precancerous.
Cells with damaged DNA are programmed to self-destruct, a process called apoptosis, but not all do that, and damaged cells can become cancerous.
The researchers report in Tuesday's issue of Proceedings of the National Academy of Sciences that they studied hairless mice in four groups. Some were fed water containing caffeine, some had wheels on which they could run, some had both and a control group had neither.
"The most dramatic and obvious difference between the groups came from the caffeine-drinking runners, a difference that can likely be attributed to some kind of synergy," Conney said.
Compared with the control animals, those drinking caffeine had a 95 percent increase in apoptosis in damaged cells. The exercisers showed a 120 percent increase, and the mice that were both drinking and running showed a nearly 400 percent increase.
Just what is causing that to happen is not yet clear, though the researchers have several theories.
"We need to dig deeper into how the combination of caffeine and exercise is exerting its influence at the cellular and molecular levels, identifying the underlying mechanisms," Conney said.
"With an understanding of these mechanisms we can then take this to the next level, going beyond mice in the lab to human trials," he said. "With the stronger levels of UVB radiation evident today and an upward trend in the incidence of skin cancer among Americans, there is a premium on finding novel ways to protect our bodies from sun damage."
Conney said the researchers were originally interested in the effects of green tea in preventing skin cancer and were doing tests on regular and decaffeinated teas.
They found the regular tea had an effect, but not the decaffeinated brew.
And, he said, researchers also observed that mice drinking caffeine were more active than those that didn't get it, so they decided to study the effects of exercise too.
They put running wheels into some of the cages. The mice "love to go on it," he said, and will jump on the wheels and run for several minutes, then get off for a while, and then get on and run some more.
And they found that both caffeine and exercise helped eliminate damaged skin cells, but the combination worked better than either alone.
"What we would like to see next is a clinical trial in people," Conney said.
Dr. Michael H. Gold, a Nashville, Tenn., dermatologist and a spokesman for the Skin Cancer Foundation, said he believes "the concept of systemic caffeine should be addressed further."
"I think the concept potentially has a lot of merit," he said in a telephone interview. But mice and humans are different and studies need to be done to be sure this also applies to people.
In the meantime, he said: "If you go outside, you have to wear a sunscreen ... it has to be caffeine and exercise with your sunscreen."
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On the Net:
Proceedings of the National Academy of Sciences: http://www.pnas.org
Report: Skipping doses could be deadly

By LAURAN NEERGAARD, AP Medical WriterMon Jul 30, 2:57 PM ET
Consider it the other drug problem: Millions of people don't take their medicine correctly — or quit taking it altogether — and the consequences can be deadly.
On average, half of patients with chronic illnesses like heart disease or asthma skip doses or otherwise mess up their medication, says a report being issued later this week that calls the problem a national crisis costing billions of dollars.
The government is preparing new steps to try to persuade patients and their doctors to do better.
But with contributors that range from too-hurried doctor visits to confusing pill bottles, there's no easy solution.
"We go into this with some humility," says Dr. Carolyn Clancy, director of the Agency for Healthcare Research and Quality, which is planning what she calls an "in your face" campaign to improve medication adherence. "It's really pretty appalling how badly we do."
This goes far beyond the issue of affording prescriptions. Often people buy their drugs but misunderstand what they're supposed to take, or how. Or forget doses. Or start feeling better and toss the rest of the bottle. Or skip doses for fear of side effects.
It's not just a problem of poverty or poor education. Even the rich and highly educated skip their medicine. Perhaps the most high-profile example is former President Clinton, who stopped taking his cholesterol-lowering statin drug at some point and later needed open-heart surgery to avoid a major heart attack. Statins offer significant heart protection, but about half of patients on statins quit using them within a year.
And remember the globe-trotting tuberculosis patient who was briefly quarantined in May after ignoring doctors' orders not to travel by airplane? He's out of the hospital now but, like all patients with hard-to-treat TB, must take his remaining antibiotics while health workers watch. So many TB patients skip their pills when they feel better — but before all the bacteria are wiped out — that health departments now enforce what's called "directly observed therapy."
For most diseases, however, patients must choose to take their medicines. The new report combs a decade of research to conclude people generally do a lousy job. Among findings from the nonprofit National Council on Patient Information and Education:
_Particularly at risk are people whose diseases are initially symptom-free. Although high blood pressure more than triples the risk of heart disease, for example, just 51 percent of patients stick with their prescribed antidote.
_Also at high risk are the elderly, but adherence is a problem for all ages. As few as 30 percent of teenagers correctly take drugs to prevent asthma attacks, for example.
_Dire consequences aren't always a deterrent. Among patients already blind in one eye from glaucoma, only 58 percent were protecting the other eye. Another study found 18 percent of kidney transplant recipients weren't following instructions to prevent organ rejection.
_Even doctors mess up, acknowledging in one study adhering to their own prescriptions just 79 percent of the time.
_Poor medication adherence can cost an extra $2,000 a year for each patient in extra doctor visits alone, and it's associated with as many as 40 percent of nursing home admissions, even more costly.
_Add preventable hospitalizations and premature death, and the report estimates that poor medication adherence could be costing the country $177 billion in medical bills and lost productivity.
Why is taking medicines correctly so tough? One reason is the general confusion surrounding drugs, says Dr. Ruth Parker of Emory University, a co-author of the new report who has studied the issue for the American College of Physicians Foundation.
When the pharmacy hands over your prescription, there are bunches of papers — stapled to the bag, outside the box, glued to the bottle — that all bear drug information, but often with different wording. Bottles are covered in warning stickers — such as "Take with food" or "Swallow whole" or "Don't use with XYZ other drug" — in so many colors that Parker compares pill containers to Christmas trees.
What in that jumble should patients pay most attention to?
Then there's the wording. Parker recently helped test the seemingly simple instruction "Take two tablets twice daily." Did that mean a total of two, or a total of four? A third of patients who were deemed literate got confused. A more clear instruction would be: "Take two tablets in the morning and two tablets at night."
Beyond literacy, poor eyesight plays a role. Pill-bottle instructions are pretty tiny.
Whatever the cause, Clancy hopes to make "take your medicine" a new priority. Her Agency for Healthcare Research and Quality is starting discussions with the new report's authors, the Food and Drug Administration and health groups about steps to do that. Options range from attention-grabbing ads about the dangers of misusing medicines to better drug labels.
And in October, the National Council on Patient Information and Education will release Web-based videos designed to train seniors about adhering to their meds.
___
EDITOR'S NOTE — Lauran Neergaard covers health and medical issues for The Associated Press in Washington.

Monday, July 30, 2007

Expert: Diabetes drug should be pulled

By ANDREW BRIDGES
The widely used diabetes drug Avandia should be pulled from the market because of heart risks, a federal scientist said Monday.
Those risks, combined with no unique short-term benefits in helping diabetics control blood-sugar levels, fail to justify keeping Avandia on the market, according to a copy of a slide presentation by Food and Drug Administration scientist Dr. David Graham.
The document was distributed at the onset of a daylong meeting of a joint panel of outside experts convened to consider whether the drug should restricted to use in select patients and branded with prominent warnings or removed altogether from sale. Previously, the FDA said information from dozens of studies of the GlaxoSmithKline PLC drug points to an increased risk of heart attack.
Glaxo officials, meanwhile, disputed that conclusion, according to copies of company presentations to be given later Monday.
The FDA isn't required to follow the advice of its advisory committees but usually does.
The FDA moved up the date of Monday's meeting following the May publication of a study by The New England Journal of Medicine that generated new concerns about Avandia's safety. The pooled analysis of 42 studies revealed a 43 percent higher risk of heart attack for those taking Avandia compared with people taking other diabetes drugs or no diabetes medication.
Glaxo, meanwhile, says its own data show no increase in heart risks with Avandia compared with other diabetes drugs, including Actos.
About 1 million Americans with Type 2 diabetes use Avandia to control blood sugar by increasing the body's sensitivity to insulin. That sort of treatment has long been presumed to lessen the heart risks already associated with the disease, which is linked to obesity. News that Avandia, also called rosiglitazone, might actually increase those risks would represent a "serious limitation" of the drug's benefit, according to the FDA.
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On the Net:
Avandia: http://www.avandia.com/
Food and Drug Administration: http://www.fda.gov/
U.S. Cancer Care: Inconsistent and Often Inadequate

Many cancer patients are getting inadequate care because the quality of cancer treatment and access to it are inconsistent, the New York Times reports.
An estimated 15% to 25% of women with breast cancer don't get radiation when they should and 20% to 30% don't take antiestrogen drugs. Some women lack prescription drug coverage, fear side effects, or are never told what they need. Only half the patients who should undergo screening for colon cancer actually do so.
Patients in rural areas, small cities, and the poor are often seen by physicians who don't treat enough patients to keep their skills sharp and current. But many patients never seek a second opinion or have the wherewithal to find the kind of specialized care they need.
Some cancer organizations, for example the American College of Surgeons and the National Comprehensive Cancer Network, are addressing the issue by issuing treatment guidelines for various cancers.
VA Hospital Dramatically Lowers Its MRSA Rate

A Veterans Affairs hospital that screens all new patients for methicillin-resistant S. aureus (MRSA) cut infections to 17 cases from an average of 60 in previous years, according to the New York Times.
The paper quotes the hospital's chief of staff as saying that the entire program — added personnel, screening, using disposable blood pressure cuffs, isolating MRSA carriers, leaving a stethoscope in each room — costs about $500,000 while saving some $900,000 annually in treatment costs. Estimated U.S. costs for treating these infections run up to $30 billion annually.
The article quotes an infection-control advocate who criticizes the CDC's 2006 guidelines for infection control as "lax" and giving hospitals "an excuse to do too little."

Sunday, July 29, 2007

Flexner Report

The Flexner Report is a book-length study of medical education in the United States and Canada, written by the professional educator Abraham Flexner and published in 1910 under the aegis of the Carnegie Foundation. Many aspects of the present-day American medical profession stem from the Flexner Report and its aftermath.
The Report (also called Carnegie Foundation Bulletin Number Four) called on American medical schools to enact higher admission and graduation standards, and to adhere strictly to the protocols of mainstream science in their teaching and research. Many American medical schools fell short of the standard advocated in the Report, and subsequent to its publication, nearly half of such schools merged or were closed outright. The Report also concluded that there were too many medical schools in the USA, and that too many doctors were being trained.

History
In the late 19th century, what came to be called allopathic medicine emerged. Allopathic medicine was grounded in antiseptic surgery, the germ theory of infectious disease (which implied a large number of effective public health measures), and the scientific method including clinical trials. The American Medical Association sought to eliminate medical schools that were not fully committed to allopathic medicine. In 1904 the AMA created the Council on Medical Education (CME) whose objective was to restructure American medical education. At its first annual meeting, the CME adopted two standards: one laid down the minimum prior education required for admission to a medical school, the other defined a medical education as consisting of 2 years training in human anatomy and physiology followed by 2 years of clinical work in a teaching hospital. In 1908, the CME asked the Carnegie Foundation for the Advancement of Teaching to survey American medical education, so as to promote the CME's reformist agenda and hasten the elimination of medical schools that failed to meet the CME's standards. The president of the Carnegie Foundation, Henry Pritchett, a staunch advocate of medical school reform, chose Flexner to conduct the survey.
At that time, the 155 medical schools in North America differed greatly in their curricula, methods of assessment, and requirements for admission and graduation. Flexner visited all 155 schools and generalized about them as follows: "Each day students were subjected to interminable lectures and recitations. After a long morning of dissection or a series of quiz sections, they might sit wearily in the afternoon through three or four or even five lectures delivered in methodical fashion by part-time teachers. Evenings were given over to reading and preparation for recitations. If fortunate enough to gain entrance to a hospital, they observed more than participated." The Report became notorious for its harsh description of certain establishments, for example describing Chicago's 14 medical schools as "a disgrace to the State whose laws permit its existence... indescribably foul... the plague spot of the nation."

Recommended changes
When Flexner researched his report, many American medical schools were "proprietary," namely small trade schools owned by one or more doctors, unaffiliated with a college or university, and run to make a profit. A degree was typically awarded after only two years of study. Laboratory work and dissection were not necessarily required. Many of the instructors were local doctors teaching part-time, whose own training left something to be desired. The regulation of the medical profession by state government was minimal or nonexistent. American doctors varied enormously in their scientific understanding of human physiology, and the word "quack" flourished. There is no evidence that the mass of Americans were dissatisfied with this situation.
Flexner looked this situation in the face. Using the Johns Hopkins University School of Medicine as the ideal[1], he boldly recommended that:
Admission to a medical school should require, at minimum, a high school diploma and at least two years of college or university study, primarily devoted to basic science. When Flexner researched his report, only 16 out of 155 medical Schools in the United States and Canada required applicants to have completed two or more years of university education (p 28). According to Hyatt and Stockton, by 1920 92% of USA medical schools required this of applicants.
The length of medical education be four years, and its content should be what the CME agreed to in 1905.
Proprietary medical schools should either close or be incorporated into existing universities. Medical schools should be part of a larger university, because a proper stand-alone medical school would have to charge too much in order to break even.
Less known is Flexner's recommendation that medical schools appoint full-time clinical professors. Holders of these appointments would become "true university teachers, barred from all but charity practice, in the interest of teaching." Flexner pursued this objective for years, despite widespread opposition from existing medical faculty.
Flexner was the child of German immigrants, and had studied and travelled in Europe. He was well aware that one could not practice medicine in continental Europe without having undergone an extensive specialized university education. In effect, Flexner was demanding that USA medical education conform to prevailing practice in continental Europe.
By and large, medical schools in Canada and the United States have followed Flexner's recommendations down to the present day. Recently, however, schools have increased their emphasis on public health matters.

Consequences of the report
To a remarkable extent, the following present-day aspects of the medical profession in North America are consequences of the Flexner Report:
A physician receives at least 6, and preferably 8, years of post-secondary formal instruction, nearly always in a university setting.;
The quality of medical education is invariably high.
Medical training adheres closely to the scientific method and is thoroughly grounded in human physiology and biochemistry. Medical research adheres fully to the protocols of scientific research;
No medical school can be created without the permission of the state government. Likewise, the size of existing medical schools is subject to state regulation;
Each state branch of the American Medical Association has oversight over the medical schools located within the state;
Medicine in the USA and Canada becomes a highly paid and well-respected profession;
The annual number of medical school graduates sharply declined, and the resulting reduction in the supply of doctors makes the availability and affordability of medical care problematic. The Report led to the closure of the sort of medical schools that trained doctors willing to charge their patients less. Moreover, before the Report, high quality doctors varied their fees according to what they believed their patients could afford, a practice known as price discrimination. The extent of price discrimination in American medicine declined in the aftermath of the Report.
Kessel (1958) argued that the Flexner Report in effect began the cartelization of the American medical profession, a cartelization enforced by the American Medical Association and backed by the police power of each American state. This de facto cartel restricted the supply of physicians, and raised the incomes of the remaining practitioners.
The Report is now remembered because it succeeded in creating a single model of medical education, characterized by a philosophy that has largely survived to the present day. "An education in medicine," wrote Flexner, "involves both learning and learning how; the student cannot effectively know, unless he knows how." Although the report is more than 90 years old, many of its recommendations are still relevant -- particularly those concerning the physician as a "social instrument... whose function is fast becoming social and preventive, rather than individual and curative."

Closure of many medical schools
According to Hyatt and Stockton (p. 8), Flexner sought to shrink the number of medical schools in the USA to 31, and to cut the annual number of medical graduates from 4400 to 2000. A majority of American institutions granting M.D. or D.O. degrees as of the date of the Report (1910) closed within 2-3 decades. (No Canadian medical school was deemed inadequate, and none closed or merged subsequent to the Report.) In 1904, there were 160 M.D. granting institutions with more than 28000 students. By 1920, there were only 85 M.D. granting institution, educating only 13,800 students. By 1935, there were only 66 medical schools operating in the USA.
Between 1910 and 1935, more than half of all American medical schools merged or closed. This dramatic decline was in some part due to the implementation of the Report's recommendation that all "proprietary" schools be closed, and that medical schools should henceforth all be connected to universities. Of the 66 surviving M.D. granting institutions in 1935, 57 were part of a university. An important factor driving the mergers and closures of medical schools was that all state medical boards gradually adopted and enforced the Report's recommendations.

American medicine becomes a less diverse profession
One of the consequences of Flexner's advocacy of university-based medical education was that medical education became much more expensive, putting such education out of reach of all but upper middle class white males. The small "proprietary" schools Flexner condemned, which were contended to be have been based in generations-old folk traditions rather than relatively recent western science, did admit African-Americans, women, and students of limited financial means. These students usually could not afford 6-8 years of university education, and were often simply denied admission to medical schools affiliated with universities. At the same time, the Report tended to delegitimize existing women doctors and doctors of color. While many such doctors continuted to practice, usually within underserviced clienteles, they did so under proscribed circumstances and for less pay. In general, the standardization of medical education advocated in the Report led to the domination of American medicine by well-off white males. It also made it more difficult for people of color, residents of rural areas, and for those of limited means generally to obtain medical care in any form. The Flexner report recommended the closure of several African American Medical schools. Ironically one of the schools was located in his own hometown of Louisville, Kentucky, Louisville National Medical College.

Impact on osteopathic medicine
When Flexner researched his report, allopathic medicine faced vigorous competition from several quarters, including osteopathic medicine, naturopathic medicine, eclectic medicine, physiomedicalism, herbal medicine and homeopathic medicine. Flexner clearly doubted the scientific validity of all forms of medicine other than the allopathic, deeming any approach to medicine that did not employ drugs to help cure the patient as tantamount to quackery and charlatanism. Medical schools that offered courses in bioelectric medicine, eclectic medicine, naturopathy, homeopathy, or "eastern medicine," for example, were told either to drop these courses from their curriculum or lose their accreditation and underwriting support. A few schools resisted for a time, but eventually all complied with the Report or shut their doors.
When Flexner researched his Report, the USA contained a number of medical schools training osteopathic, naturopathic, chiropractic and homeopathic practitioners. Because doctors of osteopathy (D.O.s) often had practices whose scope was similar to that of M.D.s, Flexner insisted that the training of DOs be held to the same standard as that of MDs. Osteopathic medical schools had fought hard over the years for their independence from allopathic medicine, and resented being included in Flexner's report, which concluded that the standards of osteopathic schools were in fact substantially lower. As a result of the Report, the American Medical Association (AMA) expected all osteopathic medical schools to close. Instead, through a series of internal revolutions, the American Osteopathic Association (AOA) brought a number of its schools into compliance with Flexner's recommendations.
Before the Flexner report, osteopathic and allopathic training had little in common. As a result of the Flexner report, American osteopathic medical schools today teach an evidence-based, medicalised, scientific knowledge base. The curricula of osteopathic and allopathic medical schools differ only minimally, the chief difference being the additional instruction in osteopathic schools of manipulative medicine. This dramatic convergence of osteopathic and allopathic training demonstrates the sweeping effect the Flexner report had, not only in the closure of inadequate schools, but also in the standardization of the curricula of surviving schools.

References
^ UNMC's Flexner's Impact on American Medicine

Further Readings
Beck, Andrew H., 2004, "The Flexner Report and the Standardization of American Medical Education," Student JAMA 291: 2139-40.
Bonner, Thomas Neville, 2002. Iconoclast: Abraham Flexner and a Life in Learning. Johns Hopkins Univ. Press.
Flexner, A., 1910. Medical Education in the United States and Canada. Carnegie Foundation for Higher Education.
Gevitz, Norman, and Grant, U. S., 2004. The D.O.s (2nd ed.). Baltimore: The Johns Hopkins University Press. ISBN 0-8018-7834-9.
Goodman and Musgrave, "How The Cost-Plus System Evolved."
Hyatt, M. D., and Stockton, C. G., "The Impact of the Flexner Report on the Fate of Medical Schools in North America After 1909."
Kessel, Reuben, 1958, "Price Discrimination in Medicine," Journal of Law and Economics 1:
Starr, Paul, 1982. The social transformation of American medicine. Basic Books.
Wheatley, S. C., 1989. The Politics of Philanthropy: Abraham Flexner and Medical Education. Univ. of Wisconsin Press.
Dale Steinreich, 2004, "100 Years of Medical Robbery"

Retrieved from "http://en.wikipedia.org/wiki/Flexner_Report"
The Functioning Brains of Us Physicians Should Be "Guidance Systems," Not "Books of Knowledge"

"We are a guidance system, not a book of knowledge," Dr. Lawrence Weed wrote in 1968.[1,2] Then, as now, medical information was expanding exponentially. Each of us physicians needs information sources for an accurate, complete differential diagnosis and for specific diseases.
As physicians, we do not need to carry information about lab tests, medications, or dosages in our heads. We need a reliable ready source of information to consult, and we need to be in charge of providing the patient with excellent quality of care by being a guidance system.
For continuing education and recertification, specific information is usually requested. I classify that as "book of knowledge" information, but a more relevant avenue would be to test the thought-planning process, which is the "guidance system.[3]"
In today's world of readily available information, we are at times assisted by the patient.[4,5] It is not uncommon, once a diagnosis has been made, for the patient to present to us reams of paper that include information about diagnostic tests, disease manifestations, medications, nutritional supplements, and alternative treatments. Since we are now "partners" with the patient in terms of diagnosis and treatment, we need to honor the patient's book of knowledge and provide our best guidance system. This can only increase the quality of care to the patient.[6]
With better sources of information for the patient and the doctor and a better understanding of disease processes, I feel medical care will continue to improve mostly as our guidance systems improve.
SEE LINK BELOW :
http://www.medscape.com/viewarticle/548125
Schools of doctors' dreams

E B Peile, general practioner a, G P Easton, broadcaster b, S Olney, general practitioner c.
a Aston Clinton Surgery, Alesury HP22 5LB, b Science Department, BBC Radio Science Unit,, c The Surgery, 1 Glebe Road, London SW13 0DR

We asked three people with an interest in education to speculate on what a medical school of the future might look like. Here Ed Peile and colleagues describe their Renaissance School; then Jeremy Anderson (p 1456) and Cindy Lam (p 1458) outline their visions.
The Renaissance School will produce broadly educated doctors who think in terms of patients rather than organs and are strong, multiprofessional team players.
The irresistible swing towards medical specialisation has brought advantages for patients, but arguably it has gone too far.1 As Horder puts it, "people are whole units who go wrong as a whole, and do not take kindly to being divided into organ systems."2 Now more than ever, patients need generalist doctors who can put their individual problems in context and provide continuity.

The return of the generalist
In the Renaissance School of General Medicine students will learn only what they need to learn to be supremely effective generalists. From day one the focus of the course will be on "whole patient medicine," which is to be based on holistic consultations with patients in their real contexts.3 There will be no preclinical-clinical divide, and gone will be the days of freestanding courses in biochemistry, physiology, and anatomy. The modular nature of the course will provide a common pathway to careers across the whole spectrum of the health professionfrom medicine and nursing to management and health promotion. Having learnt together as students in a range of disciplines, our graduates will be well equipped to learn both with and from each other and to continue lifelong interprofessional learning.4

Key features of the Renaissance course
Focus on medical generalism in hospital and community
Common course with different exit points for allied health professionals as well as doctors
Learning that is based on problems in real patients from day one
Lay public involved in selection, assessment, and teaching of students
Encounters with patients organised through general practices, community based learning centres attached to practices, general hospital clinics, the internet, and patient partners (patients trained to help train doctors)
Hand held computers to help in assessment of students and self directed learning
Rolling programme of workshops and tutorials

More information see link below :
http://www.bmj.com/cgi/content/full/323/7327/1454
UPTODATE FOR YOUR CLINICAL PRACTICE

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From Physicians for PhysiciansUpToDate is a cooperative effort of thousands of expert clinicians at leading academic centers and is an official educational program of, or offered in cooperation with a number of major medical associations. These include: the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, the American College of Rheumatology, the American Gastroenterological Association, the American Society of Nephrology, the American Thoracic Society, the Endocrine Society, the Society of General Internal Medicine, and the American Academy of Nurse Practitioners. UpToDate is also recommended by the American Academy of Family Physicians. The editorial board for each subspecialty is comprised of the most eminent physicians in the field. UpToDate is from physicians for physicians.
No Commercial Support AcceptedWe have long held the principle that our program be free of commercial bias and as such have accepted no commercial support for our activities or products.
Serving Clinicians since 1989Started in 1989 by Dr. Burton D. Rose along with Dr. Joseph Rush, UpToDate is now available in most internal medicine subspecialties as well as adult primary care, family medicine, ob-gyn and pediatrics. With tens of thousands of subscribers in more than 100 countries, we serve the needs of clinicians around the world.

SEE LINK BELOW :
http://patients.uptodate.com/
Study finds 30-minute CPR classes just as effective as multihour courses

Dr. Lynn Roppolo (right), assistant professor of emergency medicine, and Dr. Ahamed Idris, professor of emergency medicine, were part of a group of researchers who have found that a user-friendly,...
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DALLAS – July 25, 2007 -- UT Southwestern Medical Center researchers have found that a user-friendly, 30-minute, video-based cardiopulmonary resuscitation training session is just as effective as the traditional three- to four-hour course in teaching basic life-saving techniques to laypersons. In addition, at six months after the training – a critical point for CPR skill retention – those who took the shorter course performed CPR and used an automated external defibrillator (AED) just as well or better than those who take the traditional training.
These findings, published in the August issue of the journal Resuscitation, are the first to evaluate and document the effectiveness of long-term retention of the new 30-minute CPR-AED training.
“The results of this formal investigation should not only facilitate more widespread training and frequent re-training in CPR techniques, but it also diminishes some of the inefficiencies and labor-intensity inherent in traditional CPR training,” said Dr. Paul Pepe, chief of emergency medicine at UT Southwestern.
Traditional CPR courses last half a day, as six to eight people take turns practicing their skills on a shared manikin. The remainder of the time is spent listening to instruction, leaving little time for skills practice, the researchers report.
“Using individualized kits, the trainees can focus on uninterrupted skills practice and develop muscle memory from more intensive, focused and reiterative practice,” said Dr. Pepe.
The shorter course is much more convenient and easily accessible, said Dr. Lynn Roppolo, assistant professor of emergency medicine and lead author of the study.
“Individuals practice while they learn, allowing more time to perform and retain the critical hands-on skills required to provide more effective CPR,” Dr. Roppolo said. “All of these factors will likely translate into more people knowing what to do – and doing it right – whenever CPR is needed. As a result, hopefully, many more lives will be saved in years to come.”
For the study, volunteers recruited in Fort Worth were selected randomly to take either the 30-minute course or a traditional three-hour session.
The short course consisted of a 23-minute digital video disc program, developed by the American Heart Association, which covers basic adult CPR skills, including recognition of signs of life, calling for help, opening the airway, rescue breaths and chest compressions.
As two dozen or more students watched the video in each session simultaneously, they practiced the CPR techniques almost continuously for nearly 20 minutes on their own personal mini-manikin, supervised by a “facilitator” who generally only needed to answer an occasional question from the trainees once the DVD was started.
Also included was a three-minute discussion and demonstration on the recognition of and best procedures for choking, as well as a five-minute demonstration of the use of an AED.
In the traditional course, students attended a three-hour session consisting of lectures supplemented by related video-based instruction, practice of basic CPR skills, choking procedures and instruction and hands-on practice in the use of an AED. During this course, there was one certified instructor for every six to eight students during the skills practice.
After their respective training, the students from both groups were tested using a life-sized manikin, which was connected to a laptop computer that objectively measured parameters such as the rate and depth of ventilations and chest compressions.
In addition to the computer measurements, overall CPR performance and AED use were videotaped and later judged as being appropriate by CPR training experts, who graded each study participant without knowing whether the he or she had taken the half-hour course or the traditional training.
Immediately after taking the class, there were no significant differences in CPR performance between the students who took the three-hour course as compared to those who took the 30-minute course.
After six months, however, trainees who took the 30-minute course called 9-1-1 and provided adequate ventilation more frequently than those who took the longer course. Also, both at the initial and six-month follow-up test, the students who took the traditional course took 30 percent longer to assess for signs of life, and they took significantly more time to pause between chest compressions to perform ventilations.
In grading AED use immediately after the courses, the trainees who took the 30-minute course placed the AED pads and delivered a shock correctly in 98 percent of the cases, compared to 92 percent of those who took the longer course. Moreover, at the critical six-month follow-up, 93 percent of those in the half-hour course still operated the AED well and 93 percent were still judged to be performing chest compressions adequately.
“The results of this investigation were very compelling. This study suggests that hands-on practice is not necessary to learn how to operate an AED, a device that directly provides the rescuer with vocal instructions once it is turned on,” said Dr. Roppolo. “Thus, training tools that utilize cognitive modes, such as the Internet and DVD demonstrations, may be just as effective.”
A new century of Alzheimer's disease research
Mayo Clinic scientists aim to improve risk prediction, diagnosis and treatment


JACKSONVILLE, Fla. -- Imagine the day when a routine visit to the family doctor includes a simple blood test to predict the risk for developing Alzheimer’s disease (AD). If the test returns a worrisome result -- too many sticky brain proteins that might begin to gum up memory and thought in 10 to 15 years -- a person could be offered an aspirin-like pill to keep those proteins in check.
That is the future a visionary team of researchers at Mayo Clinic’s campus in Jacksonville aims to reach.
“It will be very straightforward, like today’s blood cholesterol test to gauge risk of developing heart disease,” says Steve Younkin, M.D., Ph.D., a Mayo Clinic neuroscientist. “If your cholesterol profile is out of whack, treatment with a simple statin drug can reduce that risk. Our goal is to develop a similar kind of testing and treatment to keep the brain in balance.”
Researchers and physicians at Mayo Clinic’s sites in Florida, Minnesota and Arizona are studying various aspects of Alzheimer’s. When combined, the elements provide a comprehensive approach to unraveling the mystery of the disease: from understanding why it develops, to how it can be diagnosed early, treated effectively and, ultimately, prevented.
Much of the basic lab, animal research and drug discovery occurs in Jacksonville. Mayo researchers in Jacksonville, Rochester, Minn., and Scottsdale, Ariz., are studying aging’s effects in thousands of elderly individuals. Researchers want to know how aging changes brain structure, thought processes and blood chemistry, so they can model and predict progression to Alzheimer’s disease.
“Whether it is working with people or doing lab science, we have really tried to focus our research on ways in which we can make a difference in the lives of our patients, both today and tomorrow,” says Todd Golde, M.D., an Alzheimer’s disease researcher who chairs the Department of Neurosciences at Mayo Clinic Jacksonville.
And, by all accounts, that focus will likely begin to pay off in this second century of Alzheimer’s research. Until 1986, some 80 years after German physician Alois Alzheimer discovered the brain abnormalities associated with the disease, physicians understood little about Alzheimer’s disease. But several decades ago, the pace of discovery began to accelerate, says Ronald Petersen, M.D., Ph.D., a Mayo physician in Rochester who directs the Mayo Clinic Alzheimer’s Disease Research Center (ADRC), encompassing the research programs in Jacksonville and Rochester.
“We have moved a great distance forward in understanding what might be the key, or, in the least, an important aspect of this disease,” Dr. Petersen says. “And we are at the threshold of developing therapies that we hope will eventually impact Alzheimer’s disease.”
“We are not slogging through a fog anymore,” says Dr. Younkin, who has helped define the direction that Alzheimer’s research has taken in many of the world’s research labs. “We can see the top of the hill for the first time, and while we probably won’t get where we want to be for many years, it is really exciting.” Dr. Younkin helped discover that a single brain protein, known as amyloid-beta 42 (AB42), appears to be the central player in the disorder. And much of Alzheimer’s drug research is focused on different ways to attack Aâ42, believed to be the most vulnerable target -- the Achilles’ heel -- of Alzheimer’s disease.
“We know AB42 is always on the scene and is clearly important,” says Richard Caselli, M.D., who heads Alzheimer’s disease research at Mayo Clinic in Arizona. “So the prevailing model is that AB42 is it, and if you can somehow control AB42, you can control Alzheimer’s disease.”
Enoxaparin Dosing in ACS Often Varies From Labeling, Can Raise Bleeding Risk

July 27, 2007 — Almost half of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) who received enoxaparin (Lovenox, Sanofi-Aventis) were given doses that were either higher or lower than what the labeling recommends, in a US registry analysis that also tied "excess" dosing to an increased in-hospital risk of serious bleeding.
Evidence-based guidelines for anticoagulation in acute coronary syndromes (ACS) tend to spend more time on choice of agent than on appropriate dosing, observed lead author Dr Nancy M Allen LaPointe (Duke University Medical Center, Durham, NC). But, she told heartwire, "It's important that we not just look at getting the appropriate drugs into the patients, but also that we try to get the most appropriate dose into the patients so we can maximize both efficacy and safety." The analysis, based on the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) registry, appears in the July 23 Archives of Internal Medicine.
"Lower-than-recommended" enoxaparin dosing didn't significantly affect the adjusted in-hospital risks of bleeding or death in the analysis, but that doesn't mean it was without cost. The analysis, Allen LaPointe observed, didn't look at reinfarction or other endpoints with more relevance to inadequate anticoagulation.
Of the 10,687 CRUSADE patients who received enoxaparin for NSTE-ACS, 47.3% received a dosage that varied from the recommended 2 mg/kg/day (or 1 mg/kg/day if creatinine clearance <30 mL/min) by more than 10 mg; the dosage was excessive in 18.7% and lower-than-recommended in 29.2% of the total.
The increased major-bleeding risk among patients getting excessive enoxaparin was significant at p<0.001 after adjusting for patient history, features, and drug and procedure-based therapies. All-cause mortality was also raised, but the difference fell short of significance at p=0.06. Lower-than-recommended dosing appeared to increase the all-cause mortality risk, but the difference wasn't significant after adjustment for patient characteristics and therapies.
Odds ratios* (95% CI) for major bleeding and death among patients receiving excess and lower-than-recommended enoxaparin dosing in CRUSADE
*Adjusted for age; sex; body-mass index; history of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft (CABG), heart failure, and stroke; smoking status, hematocrit, renal function, acutely received medications; and procedures performed.† Major bleeding defined as intracranial or retroperitoneal bleeding, a >12% reduction in hematocrit, red blood cell transfusion when hematocrit is increased or decreased. Cohort excludes patients transferred to other hospitals or who underwent CABG.‡ Cohort excludes patients transferred to other hospitals.
Although the analysis doesn't address why dosing was often excessive, one possible reason, Allen LaPointe said, may have been that some practitioners failed to appropriately consider creatinine clearance. In the analysis, about 58% patients who received excessive enoxaparin had an initial creatinine clearance <30 mL/min, the threshold for going from a full dose to a half dose. As for the remaining 42%, she speculated, perhaps the practitioners didn't have an accurate weight for the patient, or they didn't adjust the dosage in response to changes in creatinine clearance over time.
The analysis was partially supported by Millennium Pharmaceuticals. The CRUSADE initiative "is funded by Schering-Plough Corporation and Bristol-Myers Squibb/Sanofi-Aventis Pharmaceuticals partnership." Allen LaPointe reports receiving a research funding or support from Pfizer and Merck and an honorarium from Sanofi-Aventis for speaking. Disclosures for other coauthors appear in the report.
Arch Intern Med. 2007;167:1539-1544.
FDA Issues Approvable Letter For Wyeth's Experimental Drug Pristiq To Treat Menopause Symptoms

26 Jul 2007 FDA on Monday issued an "approvable letter" for Wyeth's experimental drug Pristiq as a nonhormonal treatment for hot flashes and other menopause symptoms, an agency spokesperson said, the Wall Street Journal reports. According to the Journal, an approvable letter means that FDA could approve the drug but also usually means the agency needs more information before granting final approval (Corbett Dooren/Rubenstein, Wall Street Journal, 7/24).Pristiq is a new version of Wyeth's depression treatment Effexor, which will lose patent protection in 2010. Wyeth is seeking approval from FDA to market Pristiq as a depression treatment for older women, as well as a treatment for menopause symptoms (Kaiser Daily Women's Health Policy Report, 4/23). FDA spokesperson Rita Chappelle confirmed that the agency sent Wyeth the approvable letter but declined to provide additional information, the AP/Forbes reports (Perrone, AP/Forbes, 7/23). According to a Wyeth release, FDA in its letter said that before the application could be approved, Wyeth must provide additional data on the potential for serious adverse cardiovascular and hepatic effects associated with the use of Pristiq. The agency requested that these data come from a minimum one-year, randomized, placebo-controlled clinical trial conducted in postmenopausal women. In addition, FDA said that Wyeth must address certain chemistry, manufacturing and controls deficiencies prior to approval. FDA also made additional clinical and chemistry requests, which it said were not approvability issues, according to the release. "Wyeth remains committed to the development of Pristiq as a potential treatment for moderate-to-severe vasomotor symptoms associated with menopause," Gary Stiles, executive vice president and chief medical officer at Wyeth, said, adding, "We will work with the agency to satisfy its requests for additional data and move the medicine forward in the FDA review process" (Wyeth release, 7/24). Wyeth said it plans to submit more data to FDA in the first quarter of 2008 in an effort to gain approval for Pristiq as a depression treatment, the Journal reports (Wall Street Journal, 7/24).
Health Care Literacy Might Affect Mortality Rates Of Elderly U.S. Residents, Study Suggests

27 Jul 2007 People ages 65 and older who have difficulty comprehending basic health-related material such as prescription bottles and appointment slips are more likely to die within six years than people who can understand the information, according to a study published Monday in the Archives of Internal Medicine, the AP/Boston Herald reports (AP/Boston Herald, 7/24). The study, conducted at Northwestern University's Feinberg School of Medicine and led by internist David Baker, involved 3,260 Medicare beneficiaries in managed care plans in five cities. The beneficiaries were interviewed in 1997, and information was collected about their race, ethnicity, education, income, weight, chronic medical conditions and health-related behaviors such as smoking and exercise (USA Today, 7/23). Beneficiaries also were given a test to evaluate their ability to understand appointment slips, prescription labels and instructions on how to prepare for an X-ray. The study found that one-fourth of the beneficiaries were considered medically illiterate. According to the study, nearly 40% of those considered medically illiterate died by the conclusion of the study in 2003, compared with 19% of those in the medically literate group. After factoring in beneficiaries' health at the beginning of the study and other variables, researchers found that medically illiterate beneficiaries were 50% more likely to die than those who were medically literate -- a number "much higher" than the researchers expected, Baker said. According to Baker, the inability to understand medical information and instructions makes it difficult for beneficiaries to manage chronic conditions, which can lead to more serious health problems. Joanne Schwartzberg, director of aging and community health at the American Medical Association, said that evidence shows that as many as 90 million U.S. residents have trouble understanding medical information (AP/Boston Herald, 7/24). An abstract of the study is available online.
New breast cancer gene found

ANN ARBOR, Mich., July 27 (UPI) -- FOXP3, a gene that blocks the HER-2 protein linked to aggressive breast cancer, has been uncovered by U.S. researchers. Yang Liu and his colleagues at the University of Michigan Comprehensive Cancer Center were exploring FOXP3's role in autoimmune disease when they noticed that 90 percent of the female mice they had bred for their experiments and which lacked the FOXP3 gene were developing breast cancer. They also had high levels of ErbB2, the mouse equivalent of HER-2 in humans. Since breast cancer is rare in mice, they thought the gene must be responsible and decided to look at human breast cancer tissue to see if FOXP3 was present or absent. They examined 600 human breast cancer tissue samples and discovered that 80 percent of them did not contain FOXP3 and the gene was mutated in the rest. FOXP3 is located on the X chromosome, which means that a single mutation can effectively silence the gene and allow levels of HER-2 to rise. "FOXP3 defects promote cancer development," said Yang. "We do not know whether this is a genetic defect that puts women at higher risk. For treatment, this gene could be quite important, but for diagnosis, it's too early to tell." A report on the study was published in the current issue of the journal Cell.

Saturday, July 28, 2007

Hospitalized elderly get barely enough calories


By Anthony J. Brown, MDFri Jul 27, 3:48 PM ET
The energy input from food taken in by hospitalized elderly patients is only just sufficient to cover their minimal energy output, French researchers estimate. The group believes such patients could benefit from higher caloric intake.
Malnutrition is known to be common among elderly patients hospitalized with acute illness, because they often have little appetite and don't eat much. Exactly how much energy these patients expend and what their calorie requirements are, however, have been unclear.
As reported in the Journal of the American Geriatric Society, Dr. Patrick Ritz, from University Hospital, Angers, and colleagues calculated the energy intake and energy expenditure at rest in 90 acutely ill patients ranging in age from 65 to 99 years.
The resting energy expenditure (REE) was multiplied by the physical activity level constant (1.42) to determine the actual energy input needed to cover normal activity.
The team found that energy intake was 1.29-times higher than the REE, so it fell short of energy requirements by 205 kcal/day, on average.
The results indicate that the energy intake in hospitalized elderly patients is equivalent to the amount needed to sustain vital functions in healthy individuals, the authors conclude. "This is notably inadequate in elderly patients in acute care units," they point out, since people battling illness expend more energy.
"Spontaneous food intake being just sufficient to match minimal requirements, higher calorie intakes are likely to be beneficial for hospitalized elderly patients in acute care units," Ritz's team concludes.
SOURCE: Journal of the American Geriatric Society, July 2007.
IAS: Darunavir Noninferior to Lopinavir in TITAN trial

SYDNEY, July 27 -- HIV treatment with the newly approved protease inhibitor darunavir (Prezista) was noninferior to the standard-of-care treatment lopinavir/ritonavir (Kaletra) in a year-long trial."This is the first time that any drug has been shown to be superior to lopinavir," said Jose Valdez-Madruga, MD, director of clinical trials for the Sao Paulo AIDS Program in Brazil. "Patients with experienced HIV infection now have an option for treatment."
In a presentation at the International AIDS Society meeting, Dr. Valdez-Madruga said that after 48 weeks of treatment, 71% of HIV-infected participants who were taking darunavir, boosted with ritonavir, had undetectable viral loads, using the <50 copies/mL assay. In comparison, 60% of patients on lopinavir, boosted with ritonavir, achieved the undetectable level on that assay.
The 11% difference in being able to suppress the virus to undetectable levels reached statistical significance (P=.005), Dr. Valdez-Madruga said.
In the TITAN (TMC114/r in Treatment-Experienced patients Naïve to lopinavir) trial, investigators screened 785 patients before enrolling 595 into the group given either darunavir at 600 mg and ritonavir at 100 mg or lopinavir at 400 mg and ritonavir at 100 mg on a twice-daily dosing schedule.
In addition to the protease inhibitors, all patients received an optimized background regimen of at least two antiretrovirals from the nucleoside reverse transcriptase or non-nucleoside reverse transcriptase classes. The use of enfuvirtide (Fuzeon) was not allowed in the trial.
Dr. Valdez-Madruga said that the primary endpoint of the trial was to show that the darunavir regimen was non-inferior to the lopinavir regimen.
The researchers assigned 298 patients to darunavir and 297 were given lopinavir. At the start of the trial, the average viral load in each group was about 40,000 copies/mL. The participants had mean CD-4 positive cell counts of about 230. About 30% of patients in each group were naïve to protease inhibitors.
About 21% of patients in the darunavir arm did not finish the trail, but only four participants (1.3%) dropped out because of virological failure. About 29% of lopinavir patients dropped out, 34 because of virologic failure (11.4%).
The most common adverse event in the trial was diarrhea, reported by 31.8% of darunavir patients and 41.8% of lopinavir patients. Twice as many lopinavir patients had Grade 2-4 diarrhea than darunavir patients. About 16.1% of patients on darunavir reported any kind of rash, compared with 6.7% of patients on lopinavir.
"We also found that darunavir appears to protect the other drugs classes better than lopinavir," Dr. Valdez-Madruga said. He explained that fewer resistance mutations in the nucleoside reverse transcriptase class and in the protease inhibitor class appeared while patients were being treated with darunavir.
"The study shows that darunavir is a better drug than lopinavir," commented Robert Murphy, M.D., of Northwestern in Chicago.
"Whether this trial will change clinical practice, however, may not have anything to do with the science," Dr. Murphy said. He noted that lopinavir/ritonavir can be taken as one pill, but darunavir and ritonavir have to be taken separately. "That means patients have to fill two prescriptions and have two co-pays. Kaletra is a very good drug. I wouldn't switch a patient on the basis of this trial unless there was a reason for doing so."
Dr. Valdez-Madruga concurred. He said that if a patient was experiencing diarrhea on lopinavir, he would consider a switch because diarrhea was less frequent among darunavir patients. Primary source: Abstract Book 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention incorporating the 19th ASHM ConferenceASM ConferenceAJournal
Source reference: Jose Valdez-Madruga et al "TUAB101 - Comparison of 48-week efficacy and safety of darunavir/ritonavir (DRV/r) with lopinavir/ritonavir (LPV/r) in LPV/r-naïve, treatment-experienced patients: a randomised, controlled phase III trial (TITAN)," Abstract Book 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention incorporating the 19th ASHM Conference, 22-25 July 2007, Sydney, Australia; p 91.