Saturday, December 27, 2008

Top Medical Stories of 2008 Challenged 'Lower Is Better' Mantra

By Peggy Peck
27 dec 2008--When it comes to LDLs and glycosylated hemoglobin, the philosophy of lower is better was dealt evidence-based blows this year with a series of surprising findings.

In this year-end review, the editors of present their picks of the medical news events in 2008 that influenced clinical practice or triggered ongoing discussion among clinicians. Among them was a handful of studies that reassessed interpretation of surrogate endpoints such as HbA1c and LDL cholesterol that emerged as a theme.

Take the potent lipid-lowering action of the combination of ezetimibe and simvastatin, marketed as Vytorin. It was reported in January that it brought levels down by 50% or more. But that, it turned out, did not slow or regress the progression of atherosclerosis.

The disappointing bottom-line effect of the dramatic drops in lipids, as revealed in the ENHANCE trial, was supposed to come from findings that had been expected in March 2007 at the American College of Cardiology and then in November 2007 at the American Heart Association, but the data failed to materialize at either venue.

By last January the rumor mill was abuzz, and the word was that that ENHANCE would provide proof that ezetimibe/simvastatin did not slow atherosclerosis as measured by plaque volume in the carotid arteries.

And on Jan. 14 the naysayers were proven correct when Merck/Schering-Plough released the ENHANCE findings in a press release.

(See: ENHANCE Finds No Slowing of Plaque Burden With Ezetimibe/Simvastatin (Vytorin))

That was just the beginning for events focused on this once blockbuster drug. Before the year was out, ENHANCE would be the subject of a controversial session at the ACC meeting, an FDA review, and a congressional investigation.

(See: ACC: ENHANCE Data on Ezetimibe/Simvastatin (Vytorin) Reveal Wavy Bottom Line)

The other shoe dropped in July when the SEAS investigators reported -- again at a press conference -- that the ezetimibe/simvastatin combination reversed aortic stenosis, but use of the drug appeared to be associated with an increase in cancer mortality. The cancer link, they said, appeared to be explained by the play of chance.

(See: ESC: SEAS Data Fail to Quiet Ezetimibe/Simvastatin Controversy)

But lipids aren't everything, and at the start of the year it still seemed logical to argue that if well controlled, low blood glucose levels were good. That being so, aggressive control with a glycosylated hemoglobin target of less than 6% would be even better. So it seemed.

That presumption, it turned out, was not only wrong, but also dangerously so.

On Feb. 6, the National Heart, Lung, and Blood Institute shocked both diabetologists and cardiologists with the news that it was pulling the plug on intensive-glucose-lowering arm of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial because that strategy was associated with excess mortality.

At a press conference, Elizabeth G. Nabel, M.D., director of the NHLBI, said there were 257 deaths in the intensive-treatment group and 203 in the standard-treatment group, an excess of 54 deaths, or three per 1,000 participants each year, since the 10,251-patient trial was started in 2001.

(See: Deaths Force NHLBI to Drop Intensive Glucose-Lowering Strategy in Type 2 Diabetes)

The FDA had more than its share of headaches this year -- and most of them started on foreign shores.

Late last year and continuing well into this year, the FDA began receiving reports that led to a massive recall of heparin that linked to serious and sometimes fatal allergic reactions.

Months of sleuthing, finally identified the contaminant as chemically altered chondroitin-sulfate added to the crude heparin manufactured in plants in China.

(See: Chemically Altered Chondroitin-Sulfate Found in Recalled Heparin)

The FDA had barely caught its breath when the CDC began receiving reports of a salmonella outbreak. The source, initially, was believed to be tomatoes, and the FDA blocked shipments from a number of tomato farms -- most of which were in south central Florida.

But the "DNA fingerprint" identified Salmonella saintpaul in water from an irrigation system at a farm in Nuevo Leon, Mexico, and serrano peppers grown there.

And by that time, almost 400 salmonella cases were reported to the CDC.

(See: More Salmonella Cases Reported as Trail of Infected Tomatoes Goes Cold
FDA Finds Salmonella Saintpaul in Water and Peppers at Mexican Farm)

On top of those import woes, the FDA had to deal with reports of melamine contamination in coffee and tea drinks imported from China and shut down import of generic drugs from two plants located in India.

(See: Chinese Melamine Contamination Triggers U.S. Recall of Instant Coffee and Tea Products
FDA Blocks Imports of 30 Generics from Two Plants in India)

Meanwhile, the mounting toll of traumatic head injury and post traumatic stress disorder was a major medical story this year.

(See: APA: PTSD May Be Major Combat Scar of Iraq Vets
IOM Cites Poor Preparedness for Brain Injuries of Iraq and Afghanistan Vets )

One is never too old for blood pressure control, as was demonstrated in the 3,800-patient Hypertension in the Very Elderly Trial (HYVET), which found that even at age 80 blood pressure-lowering treatments were beneficial.

(See: ACC: Octogenarians and Older Derive Benefits from Hypertension Therapy)

And it might be that one is never too healthy for a statin -- or maybe not.

The results of the 17,800-participant JUPITER trial suggest that patients ages 60 or older who had elevated C-reactive protein but no real evidence of atherosclerosis reduced cardiovascular events -- including deaths due to heart attacks and stroke -- compared with controls.

But cardiologists attending the American Heart Association meeting where the data were released said it was still too early to add statins to the water.

(See: AHA: JUPITER Results Point to Role of Statins for 'Apparently Healthy' Patients )

And rounding out the year, there were a pair of reports dealing with unusual and unique therapies -- the first U.S. face transplantation and an unexpected side effect of a bone marrow transplant for acute myeloid leukemia.

The face transplant took occurred at the Cleveland Clinic, which has been sitting on an IRB approval for the procedure for more than four years. The ideal patient and a suitable donor finally showed up several weeks ago.

The clinic team went public with the news at a press conference December 16.

(See: First U.S. Face Transplant Reported at Cleveland Clinic)

The news of a potential cure for HIV first surfaced last February at the Conference on Retroviruses and Opportunistic Infections, but it wasn't until last month when Gero Hütter, M.D., and colleagues at the Charité-Medical University in Berlin, discussed the results at a press conference that the story really gained traction.

It's now been more than eight months and the 42-year-old American man, who received the bone marrow transplant to treat acute myeloid leukemia, is still free of HIV virus.

FDA Issues Alert on Dangers of Tainted Weight Loss Products

27 dec 2008--Nearly 30 weight loss products sold over the internet and in retail stores are tainted with undeclared, active pharmaceuticals or chemicals, the FDA warned on Tuesday.

An FDA analysis found the following undeclared ingredients:

  • phenytoin;
  • sibutramine, an antiobesity drug that can cause hypertension, seizures, tachycardia, palpitations, heart attack, or stroke;
  • rimonabant, an antiobesity drug not approved for use in the U.S.;
  • phenolphthalein, a possible cancer-causing agent used in chemical experiments.

The agency advises consumers to stop using the products immediately and to consult their physicians. Healthcare providers should report serious side effects to the FDA's MedWatch program.

(The FDA alert includes a complete list of the weight loss products affected by the warning.)

LINK(S):

FDA news release (Free)

FDA Q&A for consumers (Free)

MedWatch program (Free)

Inactivity Increases Heart Failure Risk at All Weight Levels

By Charles Bankhead
BOSTON, 27 dec 2008- Excess weight and physical inactivity can almost triple a man's risk of heart failure, according to data from a large prospective cohort study.

Obese, inactive men had almost a 300% greater risk of heart failure compared with lean, active study participants, Satish Kenchaiah, M.D., of Brigham and Women's Hospital and Harvard, and colleagues reported in the Jan. 6 issue of Circulation: Journal of the American Heart Association.

For a man who is 5' 10" tall, every seven pounds of weight gain increased the risk of heart failure by 11%, the data suggested.

The data also showed that excess weight and physical activity did not influence each other's effect on heart failure risk.

"Higher [body mass index] increased the risk of heart failure in active and inactive men," Dr. Kenchaiah said. "By the same token, the beneficial effect of vigorous physical activity in reducing the risk of heart failure was observed in lean, overweight, and also obese men."

Although BMI in the obese range (30 kg/m2) is associated with an increased risk of HF, the risk conferred in overweight or preobese (25 to 29.9 kg/m2) individuals had been unclear, the authors said. Numerous health benefits have been ascribed to physical activity, but its influence on the risk of heart failure also had remained unclear, particularly in men. Moreover, the interaction among BMI, physical activity, and heart failure risk had not been examined.

To address the unknowns, Dr. Kenchaiah and colleagues analyzed data from the Physicians' Health Study. The analysis included 21,091 men ages 40 to 84 at enrollment and without known coronary heart disease. They completed annual health surveys since the PHS began in 1982.

The authors examined the individual and combined effects of BMI and vigorous physical activity on heart failure incidence from 1982 to 2007. Vigorous activity was defined as exercise sufficient to cause sweating.

The men were divided into BMI categories of lean (25 kg/m2), overweight (25 to 29.9 kg/m2), and obese (≥30 kg/m2). The authors applied a dichotomous definition to physical activity, defining inactive as rarely or never exercising vigorously and active as vigorous exercise one to three times a month.

During follow-up that averaged 20.5 years, 1,109 participants developed new-onset heart failure. In a multivariate analysis, every 1-kg/m2 increase in BMI increased the risk of heart failure by 11%.

As compared with lean participants, overweight men had a 49% increase in the risk of heart failure, and obese men had a 180% greater risk.

Overall, the data on physical activity showed that men who exercised vigorously five to seven times a week had a 36% reduction in heart failure risk compared with men who reported no physical activity. As compared with men who were both lean and physically active, heart failure risk increased:

  • 19% in the lean and inactive
  • 49% in the overweight and active
  • 78% in the overweight and inactive
  • 168% in the obese and active
  • 293% in the obese and inactive

"Whereas previous studies have established that obese men have a higher likelihood of developing heart failure, the present investigation has extended this knowledge by pointing out that even overweight or pre-obese men are not spared from this increased risk," said Dr. Kenchaiah.

The study was supported in part by the National Heart, Lung and Blood Institute and the National Cancer Institute.

Dr. Kenchaiah reported no potential conflicts of interest.

Coronary Drug-Eluting Stent Safety Diminishes Over Time

By Peggy Peck ,
CALGARY, Alberta, 27 dec 2008 -- Three years after stent placement, the risk of death or revascularization associated with drug-eluting stents was significantly greater than the risk among patients treated with bare metal stents, researchers here reported.

After 12 months, both mortality and repeat revascularization rates were about 25% lower for those receiving drug-eluting stents compared with patients given bare-metal stents, Andrew C. Philpott, M.D., of the University of Calgary, and colleagues, reported online in the Canadian Medical Association Journal.

But, they added, by the end of year three, the relative risk of death or repeat revascularization was more than twice as great for drug-eluting stents.

"The adjusted relative risk of the composite outcome of death or repeat revascularization associated with drug-eluting stents relative to bare-metal stents was 0.73 early in the first year of follow-up," they wrote. "It then rose gradually over time, to a peak of 2.24 at three years."

Dr. Philpott and colleagues used several methods to conduct a time-dependent analysis, and each time "there was an initial pattern of decreased risk of events with drug-eluting stents, followed by a gradual transition over time toward better outcomes with the bare-metal stents."

But despite the increase in relative risk in the time-dependent analysis, the long-term survival for drug-eluting stents was favorable overall, and "we did not detect an overwhelming increase in the risk of death among patients, who received this type of stent," they wrote.

And while the time-dependent analysis revealed an increased risk with drug-eluting stents, "we did not observe any notable survival drops or clusters of deaths."

The findings were derived from data from 6,440 consecutive patients in the APPROACH (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease) registry. All patients were treated from April 1, 2003 through March 31, 2006.

Drug-eluting stents were used in 1,120 patients versus 5,320 patients who received bare-metal stents.

As with other registry studies, patients who received drug-eluting stents were sicker -- 32.8% with diabetes versus 20.8% with bare-metal stent patients (P 0.001) and 7.4% versus 5.0 had kidney disease (P =0.001).

The one-year mortality rate was 3.0% in the drug-eluting stent group versus 3.7% in the bare-metal group, and 12.0% of the drug-eluting stent patients versus 15.8% of the bare-mental stent patients reached the combined endpoint of death or repeat revascularization by 12 months.

Dr. Philpott cautioned that because the comparison was not a randomized, controlled trial the findings might reflect selection bias; thus, they should not be interpreted as an efficacy analysis.

Additionally, the analysis did not include information on long-term medication use, so the investigators could "only speculate on the potential role of discontinuation of antiplatelet therapy on the later onset of adverse outcomes inpatients with drug-eluting stents."

And because they included repeat revascularization in the composite endpoint, "we probably captured procedures done because of disease progression rather than restenosis."

The study was initially funded with a grant from the W. Garfield Weston Foundation. The ongoing operation of the APPROACH registry was funded by the Canadian Cardiovascular Outcomes Research Team, the Canadian Institutes of Health, and the Province Wide Services Committee of Alberta Health and Wellness.

Industry sponsors were Merck Frosst Canada, Roche Canada, Eli Lilly Canada, Bristol-Myers Squibb, Philips Medical Systems Canada, Searle Pharmaceuticals, Boston Scientific, and Cordis, a Johnson & Johnson Company.

Dr. Philpott made no financial disclosures.

New Guidelines Say Needle Lavage Ineffective for Knee Osteoarthritis

By Kristina Fiore
ROSEMONT, Ill.,27 dec 2008- Needle lavage is ineffective and should not be used to treat patients with osteoarthritis of the knee, according to new guidelines released here.

The treatment may be of some benefit, but only in patients who also have mechanical problems such as loose bodies and meniscal tears, according to new guidelines on the treatment of knee osteoarthritis released by the American Academy of Orthopaedic Surgeons.

"The current science shows us that just washing out the joint does not decrease the patient's osteoarthritis symptoms and can expose the patient to additional risk," said John Richmond, M.D., who chaired the work group that penned the guidelines.

Only treatments less invasive than knee replacement surgery were evaluated for the guidelines.

The writing group also recommended against arthroscopy with debridement or lavage, noting that evidence suggested its effects "were not statistically significant on the vast majority of patient-oriented outcome measures for pain and function."

Other interventions getting a thumbs-down were custom foot orthotics, such as lateral heel wedges, and glucosamine, chondroitin, or their combination. The guidelines cited a comprehensive report by the Agency for Healthcare Research and Quality that concluded "glucosamine hydrochloride, chondroitin sulfate, or their combination provide no clinical benefit in patients with primary osteoarthritis of the knee."

These conclusions were all based on level-1 or level-2 rated evidence.

The guidelines do recommend that patients who are overweight, with a body mass index greater than 25, should lose a minimum of 5% of their body weight.

Level-1 evidence found that weight loss results in a significant effect for functional improvement, and it "has the highest potential to actually slow the progression of the disease," Dr. Richmond said.

The guidelines also recommend encouraging patients to participate in low-impact aerobic exercise, because its effect on pain relief and disability are significant.

Sufficient pain treatment, according to the guidelines, includes the analgesics acetaminophen ( 4 g/day) and NSAIDs, as well as intra-articular corticosteroids for short-term relief.

Patients with increased gastrointestinal risks can take the same dose of acetominophen, topical NSAIDs, nonselective oral NSAIDS plus a gastroprotective agent, or cyclooxygenase-2 inhibitors, the guidelines suggest.

Available evidence did not allow recommendations for or against the use of bracing, acupuncture, and intra-articular hyaluronic acid, the committee noted.

The guidelines are available on the AAOS Web site.


Primary source: American Academy of Orthopaedic Surgeons
Source reference:
"Treatment of osteoarthritis of the knee (non-arthroplasty)" AAOS 2008.

Friday, December 26, 2008

Drug adherence poor in women with urinary trouble

Two examples of anticholinergic drugs that are often prescribed for urinary incontinence are oxybutynin (Ditropan) and tolterodine (Detrol).

"Our high discontinuation rates across all anticholinergic drug classes...highlight the need for more effective therapies for lower urinary tract symptoms," Dr. Manish Gopal from Saint Peter's University Hospital, New Brunswick, New Jersey and colleagues conclude.

Using a large database, Gopal and colleagues analyzed 29,369 women aged 18 and older who were initially prescribed an anticholinergic medication, such as Ditropan or Detrol, between 1991 and 2005.

They found that half of women prescribed an anticholinergic stopped taking it by 6 months, and 3 out of 4 women discontinued therapy by 1 year. The median time to discontinuation for all 9 different anticholinergic drugs was about 4 months after initial use.

In a report in the journal Obstetrics and Gynecology, the investigators note that rates of discontinuation increased with duration of use, and "very few women" switched to another drug after initial prescribed treatment before stopping the drug.

Because of the high discontinuation rates of anticholinergic therapy for lower urinary tract symptoms, health care providers "must be vigilant" regarding alternative forms of treatment, such as bladder training and pelvic floor rehabilitation, for overactive bladder "and increase our awareness that this group of women is being treated inadequately," the investigators conclude.

SOURCE: Obstetrics and Gynecology, December 2008.

Surgery improves kidney cancer survival: study

Dr. Pierre I. Karakiewicz from University of Montreal and colleagues determined survival rates for 43,143 patients treated with nephrectomy for advanced renal cell carcinoma that had not spread to other sites and a group of similar patients that did not have the surgery.

Death due to cancer was 5.8-fold higher for nonsurgical therapy than for nephrectomy, the team reports.

In a second analysis, where a subset of patients treated without surgery were matched with up to four surgically treated patients, there was still a 5.1-fold higher rate of cancer-specific mortality (death) in the nonsurgical group than in the nephrectomy group.

Overall, 5- and 10-year estimates of cancer-specific survival were 68.6 percent and 57.5 percent, respectively, for the nephrectomy group, compared with just 14.5 percent and 10.6 percent, respectively, for the nonsurgical therapy group.

This study, the investigators conclude, show that nonsurgical therapy is associated with a 44 percent to 57 percent worse survival than nephrectomy.

"Based on these findings, nephrectomy should be considered as the treatment of choice for patients with locally advanced renal cell carcinoma," they conclude.

SOURCE: BJU (British Journal of Urology) International, December 2008.

Low death rate after obesity surgery in Sweden

"Most published series are from high-volume expert centers," according to lead investigator Dr. Richard Marsk from Danderyd Hospital, Stockholm. "We have shown that bariatric surgery can be performed with low mortality on a national level."

Marsk and colleagues assessed deaths from any cause after weight loss surgery in Sweden using data from 14,768 bariatric procedures conducted between 1980 and 2005.

The early post-surgery death rate ranged from 0.2 percent at 30 days to 0.3 percent at 90 days, they report, with a 1-year cumulative death rate of 0.5 percent.

The 1-year cumulative death rate adjusted for age was higher for men (1.1 percent) than for women (0.4 percent) and higher for patients older than age 50 (1.2 percent) than for patients younger than age 50 (0.4 percent).

Including the entire follow-up period, the age-adjusted death rate was twice as high for men (100 per 10,000 persons per year) than for women (50 per 10,000 persons per year).

"I believe that the increased mortality seen among men is due to increased preoperative co-morbid disease and also later referral to surgery, such that men to a greater extent have established cardiovascular disease at the time of surgery," Marsk said.

"Further studies are needed to explain this in full," he added.

Cumulative mortality did not differ between patients having primary surgery or "revisional" surgery, the researchers note.

The most common causes of death during the first year after weight loss surgery were non-heart related, the investigators report, whereas the most common causes of late death were heart attack and cancer.

SOURCE: Annals of Surgery, November 2008.

Gay and bisexual African-American men have the lowest use of prostate testing

Charles Drew University study examines screening exams for California males

Los Angeles, CA, 26 dec 2008—Gay and bisexual black men are less likely to be tested for prostate cancer than men of any other racial and ethnic backgrounds regardless of their sexual orientation, according to a recent study by a researcher at Charles Drew University of Medicine and Science.

In his study, published in the December issue of Medical Care, Kevin C. Heslin, an assistant professor at Charles Drew University, examined prostate and colorectal testing rates based on sexual orientation, race and ethnicity.

Using data from telephone interviews with 19,410 men who participated in the California Health Interview Survey, the research found no overall difference in the use of the prostate-specific antigen (or PSA) test among gay, bisexual and heterosexual men.

But the percentage of gay and bisexual black men who received the PSA test was 12% to 14% lower than heterosexual blacks and 15% to 28% lower than gay and bisexual whites.

"Gay and bisexual black men had the lowest use of the PSA test, compared with every other group of men in the study," Heslin said. "For blacks, being a member of both racial and sexual minority groups represents a kind of double jeopardy when it comes to getting PSA testing."

The findings are significant because black men are more likely to be diagnosed late with prostate cancer and, as a result, are more likely to die from the disease than any other racial or ethnic group.

Prostate and colorectal cancers are the second and third most common causes of cancer deaths among men in the United States, exceeded only by lung cancer.

Overall, the study found that a greater percentage of gay and bisexual men received colorectal cancer tests compared with heterosexual men, which suggests that gay and bisexual men may have better access to preventive screening than heterosexuals. But the researchers point out that the difference may be partly due to the fact that colorectal cancer tests—such as colonoscopy, sigmoidoscopy, and proctoscopy—are also used to diagnose sexual health problems among gay men.

All the men in the study were age 50 and over, which is the age at which screening for prostate and colorectal cancer is recommended by many professional organizations. The American Cancer Society guidelines recommend that African American males begin receiving the PSA screening test at age 45.

Funded by the National Institutes of Health (NIH), the study, "Sexual Orientation and Testing for Prostate and Colorectal Cancers among Men in California," suggests that health services planners seeking to address racial and ethnic disparities in prostate cancer may need to consider sexual orientation when developing culturally specific screening programs for high-risk subgroups of men, such as African Americans.

Kevin C. Heslin received his Ph.D. in Health Services Research from the University of California, Los Angeles (UCLA). He was a pre-doctoral fellow in the National Institute of Mental Health/UCLA AIDS Research Training Program. He is currently an assistant professor at Charles Drew University of Medicine and Science. His research focuses on access to health services and health outcomes in underserved populations, particularly persons with HIV/AIDS and homeless persons.

Apolipoprotein(a): A natural regulator of inflammation

26 dec 2008--In a study to be published in the January 09 issue of Experimental Biology and Medicine, Hoover-Plow and co-workers in seeking to define a role of apo(a) in leukocyte recruitment have identified a novel activity of apo(a) apolipoprotein that may function as a natural and cell specific suppressor of the inflammatory response in vivo. In addition, a mechanism for this novel function of apo(a) was also identified: its selective regulation of cytokine production. These effects of apo(a) are independent of its molecular mimicry of Plg.

Lipoprotein(a) (Lp(a)) is similar to low density lipoprotein (LDL), but contains an additional apolipoprotein, apo(a). Numerous clinical studies conducted over the past 40 years have identified Lp(a) as a risk factor independent from LDL for a variety of cardiovascular pathologies. Much of the focus of apo(a) pathogenic activities has centered on its strong resemblance to plasminogen, the zymogen for plasmin, the primary enzyme for blood clot degradation. In addition to its important role in clot lysis, plasmin is required for leukocyte recruitment in inflammation. While several in vitro studies have demonstrated the interference of apo(a) in plasminogen leukocyte recruitment, evidence for this in vivo has been lacking.

In vivo investigation of Lp(a) function has been impeded by the lack of availability of small animal models. Lp(a) is expressed only in humans, nonhuman primates and the European hedgehog. In this study Hoover-Plow's group utilized mice with apo(a) in a plasminogen deficient or replete background to study leukocyte recruitment in three models of inflammation. Hoover-Plow said "In this study apo(a) impeded neutrophil recruitment in two of the models of inflammation, thioglycollate and lipopolysaccharide induced peritonitis. Apo(a) also inhibited neutrophil chemoattractants, and neutrophil recruitment was restored in mice administered neutrophil chemoattractants. The impaired neutrophil recruitment occurred by a mechanism independent of plasminogen. While the clinical studies point to pathogenic functions of apo(a), a physiological role of Lp(a) has been elusive, but must exist to account for its role in humans and non-human primates, but not most other species. Our results indicate for the first time that apo(a), independent of plasminogen interaction, inhibits neutrophil recruitment in vivo and functions as a cell specific suppressor of the inflammatory response."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "Hoover-Plow and colleagues have demonstrated a novel role for apo(a) as a regulator of inflammation. This represents an important contribution to our understanding of the regulation of neutrophil recruitment during the inflammatory response". Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences.

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Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit www.sebm.org. If you are interested in publishing in the journal please visit www.ebmonline.org.

Thursday, December 25, 2008

Older people mixing drugs: study

US researchers found nearly one out of every 25 people aged 57 to 85 took dangerous combinations of drugs with the potential for serious interactions, the study found.

For men ages 75 to 85, it was as high as 1 in 10.

"The public has an awareness that two prescription medications used together might be dangerous," said study author Stacy Tessler Lindau of the University of Chicago Medical Center.

"But what people don't fully appreciate is that non-prescription drugs can interact with prescription drugs and even other non-prescription drugs."

About a third of older adults uses five or more prescriptions and about half use over the counter medications and dietary supplements, the study found.

More than half of older adults used five or more prescription medications, over-the-counter medications or dietary supplements while 29 percent took more than five prescription medications.

More than half of the dangerous drug combinations included the use of aspirin or blood thinners such as warfarin.

The most common dangerous combination of non-prescription drugs was ginkgo biloba and aspirin which can increase the risk of internal bleeding when taken together.

Researchers at the University of Chicago studied the medication use of 3,500 people aged 57 to 85 living independently across the United States to create a representative sample.

When extrapolated to the general population, the study found that some 2.2 million people were at risk from dangerous combinations of medications.

A recent report found that US adults over the age of 65 make are taken to the emergency room more than 175,000 times every year because of bad reactions to medication.

The study was published in this week's edition of the Journal of the American Medical Association.

A Mysterious Link Between Sleeplessness and Heart Disease

The 495 participants in the study filled out sleep questionnaires and kept a log of their hours in bed. At night they also wore motion-sensing devices around their wrists that estimate the number of hours of actual sleep. At the beginning, none of the participants, who were ages 35 to 47, had evidence of coronary artery calcification.

Five years later, 27 percent of those who were sleeping less than five hours a night on average had developed coronary artery calcification for the first time, while only 6 percent of those who were sleeping seven hours or more had developed it. Among those who were sleeping between five and seven hours a night, 11 percent had developed coronary artery calcification, the study found.

After accounting for various other causes, the researchers concluded that one hour more of sleep per night was associated with a 33 percent decrease in the odds of calcification, comparable to the heart benefit gained by lowering one’s systolic blood pressure by 17 millimeters of mercury.

The study was published on Tuesday in the Journal of the American Medical Association. The data were drawn from the ongoing Coronary Artery Risk Development In Young Adults study.

Senior author Diane S. Lauderdale cautioned that the new report does not prove a cause-and-effect relationship between a lack of sleep and heart disease.

“It’s important to say that this is the first report and this does not yet prove the association is causal,” said Dr. Lauderdale, an associate professor of health studies at the University of Chicago Medical Center. “Until we know what the mechanism is -- that it’s really a direct or a causal relationship -- there is no point in making recommendations based on this.”

Although a number of studies have suggested that people who sleep less are at greater risk of heart disease and death, this is the first investigation to measure how much its subjects actually are sleeping, said Dr. Sanjay Patel, assistant professor of medicine at Case Western Reserve University and expert in sleep medicine. Patients’ own self-assessments can be very inaccurate, he added.

What isn’t clear is whether reduced sleep triggers physiological changes that increase heart disease risk, or whether a third, unrelated factor causes both changes, he said.

“It’s possible, for example, that people who are under more stress may be both sleeping less and at higher risk of heart disease,” Dr. Patel said.

If so, he added, “If we got those people to sleep more but they still were under a lot of stress, it wouldn’t change their risk of heart disease.”

Higher education levels are also associated with both a lower risk of heart disease and a tendency to get more sleep, said Dr. Lauderdale.

But it is also possible that lack of sleep leads to certain changes, like increasing blood levels of the stress hormone cortisol, which can raise the risk of coronary artery disease over time, Dr. Lauderdale said.

Another possible mechanism could be through the effect that sleep has on average blood pressure levels over a 24-hour period. Blood pressure usually dips when people are asleep, which could provide health benefits for those who get more sleep, Dr. Lauderdale suggested.

Sleep disorder may be early sign of dementia or Parkinson's disease

ST. PAUL, Minn., 25 dec 2008– People with a sleep disorder that causes them to kick or cry out during their sleep may be at greater risk of developing dementia or Parkinson's disease, according to a study published in the December 24, 2008, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The sleep disorder is called REM sleep behavior disorder. People with the disorder do not have the normal lack of muscle tone that occurs during REM sleep, often known as the dream stage of sleep. Instead, they have excessive muscle activity such as punching, kicking, or crying out, essentially acting out their dreams.

The study involved 93 people with this type of sleep disorder who had no signs of a neurodegenerative disease, such as dementia or Parkinson's disease. The participants were followed for an average of five years. During that time, 26 of the people developed a neurodegenerative disease. Fourteen developed Parkinson's disease, 11 developed dementia and were diagnosed with either Alzheimer's disease or Lewy body dementia. One person developed multiple system atrophy, a rare disorder that affects movement, blood pressure and other body functions.

The estimated five-year risk of developing a neurodegenerative disease was 18 percent, with the 10-year risk at 41 percent and the 12-year risk at 52 percent.

"These results are obviously of great interest to people who have this sleep disorder and their physicians and families," said study author Ronald B. Postuma, MD of McGill University in Montreal, Canada, who carried out the studies at the sleep disorders center at the Sacre Coeur hospital, University of Montreal. Postuma is also a member of the American Academy of Neurology. "The results may help us better understand how these neurodegenerative diseases develop. They also suggest that there may be an opportunity for protecting against the progression to disease, perhaps even preventing it before the symptoms can appear."

Postuma noted that the study involved only people with no known cause for the REM sleep behavior disorder. The disorder can also be caused by narcolepsy or rare brainstem abnormalities. REM sleep disorder from these causes does not necessarily carry the risk of developing a neurodegenerative disease, he said.

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The study was supported by grants from the Canadian Institutes of Health Research and the FRSQ (Fonds de la recherché en santé du Quebec) in Montreal, Canada.

Impaired energy metabolism linked with initiation of plaques in Alzheimer's brain

25 dec 2008--Scientists have identified an initiating molecular mechanism in sporadic Alzheimer's disease (AD). The study, published by Cell Press in the December 26th issue of the journal Neuron, provides new information about generation of damaging amyloid β (Aβ) plaques within the AD brain and underscores the importance of developing new preventative and disease-modifying therapies for AD, especially those aimed at interrupting pathological Aβ-production.

AD, the leading cause of dementia in the elderly, is a devastating neurological disorder characterized by accumulation and deposition of sticky clumps of A? protein. A? protein is generated from amyloid precursor protein (APP) by ?-site APP cleaving enzyme (BACE1). Previous research has suggested that BACE1 activity may play a key role in the initiation of AD pathogenesis and identified BACE1 as a promising target for AD therapeutics.

Recently, BACE1 was linked to cellular stress responses in the brain. Importantly, the AD brain exhibits impaired energy metabolism (a stressful situation) and it has been suggested that diminished cerebral use of glucose and oxygen may be an early event in AD pathogenesis.

Senior study author Dr. Robert Vassar from Northwestern University Feinberg School of Medicine has explored the link between energy inhibition and AD pathogenesis. "We have shown previously, using a pharmacological model of energy metabolism inhibition in pre-plaque transgenic mice with an excess of APP, that BACE1 and Aβ levels are elevated in the brain," says Dr. Vassar.

Dr. Vassar and colleagues expanded on their previous work by using glucose deprivation to examine the molecular mechanisms underlying elevated BACE1 levels in response to energy inhibition. They found that glucose deprivation caused an increase in BACE1 levels and led to the phosphorylation of the stress-inducible translation initiation factor, eIF2?. Further, direct phosphorylation of eIF2? increased BACE1 levels and enhanced Aβ production while inhibition of eIF2? phosphorylation prevented energy-deprivation induced increases in BACE1.

The researchers went on to show that energy inhibition increased eIF2? phosphorylation, BACE1 levels and amyloid plaque formation in APP transgenic mice. In addition, phosphorylated eIF2? and BACE1 were elevated in an aggressive A? plaque-forming mouse model and in humans with AD.

"Here, for the first time we provide evidence linking impaired energy metabolism, an AD-relevant stress, with BACE1 translation mediated by eIF2? phosphorylation," says Dr. Vassar. "Our findings implicate phosphorylated eIF2? in both the initiation and progression of sporadic AD. Future experiments will determine whether inhibition of eIF2? phosphorylation could be an efficacious therapeutic approach for the prevention and treatment of AD."

Brain starvation as we age appears to trigger Alzheimer's

Improving blood flow to brain is a preventive strategy

CHICAGO, 25 dec 2008 --- A slow, chronic starvation of the brain as we age appears to be one of the major triggers of a biochemical process that causes some forms of Alzheimer's disease.

A new study from Northwestern University's Feinberg School of Medicine has found when the brain doesn't get enough sugar glucose -- as might occur when cardiovascular disease restricts blood flow in arteries to the brain -- a process is launched that ultimately produces the sticky clumps of protein that appear to be a cause of Alzheimer's.

Robert Vassar, lead author, discovered a key brain protein is altered when the brain has a deficient supply of energy. The altered protein, called elF2alpha, increases the production of an enzyme that, in turn, flips a switch to produce the sticky protein clumps. Vassar worked with human and mice brains in his research.

The study is published in the December 26 issue of the journal Neuron.

"This finding is significant because it suggests that improving blood flow to the brain might be an effective therapeutic approach to prevent or treat Alzheimer's," said Vassar, a professor of cell and molecular biology at the Feinberg School.

A simple preventive strategy people can follow to improve blood flow to the brain is getting exercise, reducing cholesterol and managing hypertension.

"If people start early enough, maybe they can dodge the bullet," Vassar said. For people who already have symptoms, vasodilators, which increase blood flow, may help the delivery of oxygen and glucose to the brain, he added.

Vassar said it also is possible that drugs could be designed to block the elF2alpha protein that begins the formation of the protein clumps, known as amyloid plaques.

An estimated 10 million baby boomers will develop Alzheimer's in their lifetime, according to the Alzheimer's Association. The disease usually begins after age 60, and risk rises with age. The direct and indirect cost of Alzheimer's and other dementias is about $148 billion a year.

The initial trigger of Alzheimer's has long been a mystery.

Ten years ago, it was Vassar who discovered the enzyme, BACE1, that was responsible for making the sticky, fiber-like clumps of protein that form outside neurons and disrupt their ability to send messages.

But the cause of the high levels of the protein in people with the disease has been unknown. Vassar's study now shows that energy deprivation in the brain might be the trigger starting the process that forms plaques in Alzheimer's.

Vassar said his work suggests that Alzheimer's disease may result from a less severe type of energy deprivation than occurs in a stroke. Rather than dying, the brain cells react by increasing BACE1, which may be a protective response in the short term, but harmful in the long term.

"A stroke is a blockage that prevents blood flow and produces cell death in an acute, dramatic event," Vassar said. "What we are talking about here is a slow, insidious process over many years where people have a low level of cardiovascular disease or atherosclerosis in the brain. It's so mild, they don't even notice it, but it has an effect over time because it's producing a chronic reduction in the blood flow."

Vassar said when people reach a certain age, some may get increased levels of the enzymes that cause a build-up of the plaques. "Then they start falling off the cliff," he said.


Wednesday, December 24, 2008

Study Shows Exercise Shields Against Osteoporosis

Published online Dec. 22 in the British Journal of Sports Medicine, the Japanese study drew its conclusions by looking at the teenage exercise habits of 46 postmenopausal women, now aged 52 or older.

Those who had participated in low-impact, weight-bearing exercise, such as swimming, while younger had significantly greater bone mineral content in both the spine and the thigh bone. The other women in the study had either played more high-impact sports in their youth that involved running or jumping, such as volleyball or tennis, or no sports at all.

Those in the weight-bearing group also had larger outer femoral bone area, which would help protect them more from fracture during pressure from movements, such as bending.

As none of the women with the strongest bones were taking part in any weight-bearing exercise programs at the time of the bone density study, the Suzuka University of Medical Science authors suggest their exercising in their youth helped them more than 40 years later.

More information

The U.S. Department of Health & Human Services has more about preventing osteoporosis.

Even a Little Overweight, Inactivity Hurts the Heart

"What this study shows is that even overweight men who are not obese have an increase in heart failure risk," said Dr. Satish Kenchaiah, lead author of a report on the finding in the Dec. 23 issue of Circulation.

As for exercise, "even a little amount of physical activity appears to decrease the risk of heart failure," said Kenchaiah, who did the research as a epidemiologist at Brigham and Women's Hospital in Boston and is now at the U.S. National Heart, Lung, and Blood Institute.

The study has followed more than 21,000 doctors for two decades, measuring among other factors the influence of overweight and physical activity on development of heart failure, the progressive loss of ability to pump blood, which is often a prelude to major coronary events.

Outright obesity, defined as a body-mass index of 30 or over, has long been known as a risk factor for heart failure. The new report concentrated on men who were borderline overweight, with a body-mass index of 25 to 29.9.

About 5 percent of the doctors were obese, and 40 percent were overweight, when the study began. Adjusting for other risk factors such as high blood pressure and high cholesterol, the study found a 49 percent increased incidence of heart failure in overweight men compared to those with a body-mass index of 25 or less. Incidence of heart failure was 180 percent for the obese men compared to the leaner ones.

It was the same story for physical activity. "Men who engaged in physical activity anywhere from one to three times a month had an 18 percent reduction in heart failure risk," Kenchaiah said. "For those who were active five to seven times a week, the reduction was 36 percent. The more you exercise, the more reduction you achieve."

The association of even minimal physical activity with reduced risk could be explained as an indicator of good habits in general, he said. "It is possible that they have a healthier lifestyle in general," Kenchaiah said.

The study found that doctors who rarely or never exercised were older, smoked cigarettes more often, and were more likely to have high blood pressure or diabetes.

"This new report reinforces what we've said in the past," said Dr. Gerald Fletcher, a preventive cardiologist at the Mayo Clinic in Jacksonville, Fla. "Not being obese but being overweight is definitely a risk factor for heart failure."

While Fletcher said he would have liked a more definitive indicator of physical activity -- the report described it as simply breaking a sweat -- he said the study showed again that "vigorous exercise makes the difference. The more you do, the better it is for you."

Two-thirds of Americans have excess body weight, and only about 30 percent exercise regularly, Kenchaiah said. About 660,000 new cases of heart failure are diagnosed each year in the United States, he said, and 80 percent of the men and 75 percent of the women aged 65 and older who are diagnosed with heart failure die within eight years.

FDA warns against some diet pills sold on the Web

The pills are advertised as "natural" fat busters and have intriguing names like Imelda Perfect Slim and Zhen de Shou. Some are touted as new versions of "ancient remedies" from Asia.

They may promise an easy fix to weight problems, but the Food and Drug Administration on Monday said the concoctions contain unlisted ingredients, including high doses of a powerful anti-obesity drug, as well as a suspected carcinogen.

"When consumers are buying these products online, we're telling them that if it sounds too good to be true, it is likely to be too good to be true," said Michael Levy, an FDA lawyer who works on enforcement issues.

FDA lab testing found 28 dietary supplements that could land unsuspecting users in the emergency room. Most of the diet pills appear to be coming from China. They are mainly sold on the Internet.

Nearly all of the pills contain sibutramine, a powerful appetite suppressant that's a chemical cousin of amphetamines. It can cause heart attacks, strokes and heart palpitations, especially in people with a history of high blood pressure or heart problems.

Sibutramine is also the chemical ingredient in the prescription drug Meridia, which is used to treat obesity. But FDA testing found that some of the diet pills contain nearly three times the recommended daily dose.

Several of the pills contain phenolphthalein, a chemical long used as a laxative, but which is now being withdrawn from the market because of cancer risks.

None of the supplements lists the dangerous ingredients on the label. "Consumers have no way of knowing that these products contain powerful drugs that can cause serious health consequences," said Dr. Janet Woodcock, head of the FDA's drug evaluation center.

The FDA is considering criminal charges against some of the companies, because they have not responded to requests for recalls.

The products are:

Fatloss Slimming, 2 Day Diet, 3x Slimming Power, 5x Imelda Perfect Slimming, 3 Day Diet Japan Lingzhi, 24 Hours Diet, 7 Diet Day/Night Formula, 7 Day Herbal Slim, 8 Factor Diet, 999 Fitness Essence, Extrim Plus and GMP.

Also:

Imelda Perfect Slim, Lida DaiDaihua, Miaozi Slim Capsules, Perfect Slim, Perfect Slim 5x, Phyto Shape, ProSlim Plus, Royal Slimming Formula, Slim 3 in 1, Slim Express 360, Slimtech, Somotrin, Superslim, TripleSlim, Zhen de Shou, Venom Hyperdrive 3.0

Some Hidden Choices in Breast Reconstruction

24 dec 2008--For many cancer patients undergoing mastectomies, reconstructive breast surgery can seem like a first step to reclaiming their bodies.

But even as promising new operations are gaining traction at academic medical centers, plastic surgeons often fail to tell patients about them. One reason is that not all surgeons have trained to perform the latest procedures. Another reason is money: some complex surgeries are less profitable for doctors and hospitals, so they have less of an incentive to offer them, doctors say.

“It is clear that many reconstruction patients are not being given the full picture of their options,” said Diana Zuckerman, the president of the National Research Center for Women and Families, a nonprofit group in Washington.

One patient, Felicia Hodges, a 41-year-old magazine publisher in Newburgh, N.Y., chose a double mastectomy after she was found to have cancer of the right breast in 2004. She consulted a plastic surgeon, who offered her only reconstruction with breast implants, she said.

Ms. Hodges chose implants filled with saline, a procedure for which more than a third of reconstruction patients underwent a follow-up operation, studies show.

Ms. Hodges developed wound-healing problems that required her surgeon to remove her right implant, and she was left with a concave chest with a quarter-size hole in it, she said; she described the experience as “worse than the mastectomy.”

Then Ms. Hodges discovered a chat room on the patient-information Web site breastcancer.org, where women share detailed information about breast reconstruction beyond what they may have heard from their doctors.

Ms. Hodges learned of newer, more complex procedures that involve transplanting a wedge of fat and blood vessels from the abdomen or buttocks, which would be refashioned to form new breasts.

“It’s unfortunate that a lot of general surgeons, breast surgeons and plastic surgeons don’t mention it,” said Ms. Hodges, who underwent one of the surgeries, known as a GAP flap, last year. A lifelong athlete and a karate enthusiast, she is now back at her dojo.

To raise awareness of breast reconstruction and to market it to patients, the American Society of Plastic Surgeons has adopted the vocabulary of the movement to support a woman’s freedom to choose an abortion, adjusting it for women with breast cancer. Although women “don’t choose their diagnosis, they can choose to go ahead with reconstruction or not, and with the aid of a knowledgeable plastic surgeon they can choose what their options might be,” Dr. Linda G. Phillips, a plastic surgeon in Galveston, Tex., said in a telephone news conference organized by the plastic surgery society to mark Breast Cancer Awareness Month in October. “Then they have that much more power over their lives if they have that power to choose.”

But for many patients, the options may be limited because their doctors are not proficient in the latest procedures. Dr. Michael F. McGuire, the president-elect of the American Society of Plastic Surgeons, said it is not unusual for surgeons to omit telling patients about operations they do not perform. He compared the rise of more complex breast reconstruction to the advent in the late 1980s of minimally invasive laparoscopic surgery of the gallbladder.

“At the time, only a small percentage of surgeons were doing them and doing them well,” said Dr. McGuire, who is chief of plastic surgery at St. Johns Hospital in Santa Monica, Calif. “If you were not familiar with laparoscopic gallbladder surgery, you were still doing it the traditional way with an open great big scar across the abdomen.”

Uneven information about reconstructive options is a subset of a larger problem, said Dr. Amy K. Alderman, an assistant professor of plastic surgery at the University of Michigan Medical School in Ann Arbor. Only one third of women undergoing operations for breast cancer said their general surgeons had discussed reconstruction at all, according to a study by Dr. Alderman of 1,844 women in Los Angeles and Detroit that was published in February in the journal Cancer.

“In the big picture, it would be great if we could just get doctors to tell people they have an option of reconstruction,” Dr. Alderman said.

Once patients are so informed, she added, plastic surgeons should tell them of options beyond implants. “The next hurdle would be letting them know that using their own tissue is an option, because my guess is that they are not even getting that far in the discussion,” Dr. Alderman said.

About 66,000 women in the United States had mastectomies in 2006, the latest figures available, according to the federal government. And about 57,000 women had reconstructive breast surgery last year, according to estimates from the plastic surgery society.

For many of these women, the operations were more about feeling whole again than about restoring their appearance.

Implant surgery is the most popular reconstruction method in the United States. Often performed immediately after a mastectomy, it initially involves the least surgery — usually a short procedure to insert a temporary balloonlike device called an expander — and the shortest recovery time.

But implants come with the likelihood of future operations. Within four years of implant reconstruction, more than one third of reconstruction patients in clinical studies had undergone a second operation, primarily to fix problems like ruptures and infections, and a few for cosmetic reasons, according to studies submitted by implant makers to the Food and Drug Administration. (Reconstructive patients are more likely to develop complications after implant surgery than cosmetic patients with healthy breast tissue.)

Complication rates for newer flap procedures like the one Ms. Hodges had have not been well studied, though many surgeons say they are less likely to require follow-up operations. The most common flap procedure, named a TRAM flap, for the rectus abdominis muscle, cuts away a portion of abdominal fat, as well as underlying muscle containing blood vessels, and uses the tissue to rebuild a breast. The vessels provide a blood supply for the new breast mound. The procedure promises a more lifelike look and feel, but it carries a risk of a weaker abdominal wall and hernia.

Another flap method, the DIEP free flap, is the newest and most intricate, named for the abdomen’s deep inferior epigastric perforator vessels. It involves moving abdominal fat and blood vessels, but no muscle. The DIEP flap theoretically holds out the promise of a reduced likelihood of abdominal problems. But Dr. Alderman cautioned that researchers have not yet conducted rigorous national studies that would establish a complication rate. Sometimes the flaps fail and need to be surgically removed.

All breast reconstructions involve a tradeoff, said Dr. Scott L. Spear, the chief of plastic surgery at Georgetown University Hospital in Washington. “The implants have a lower investment in the short term and a longer-term higher risk of having to redo it,” said Dr. Spear, who is a paid consultant to the implant maker Allergan. “The flaps have a bigger investment in the short run, but you are less likely to revise it in the long run.”

Dr. Spear said plastic surgeons sometimes fail to mention the flap options for the simple reason that implant surgery can be more profitable. “It’s really embarrassing to say so, but, from a purely selfish point of view, if you are looking at insurance reimbursement for TRAM and DIEP flaps, it’s a loss leader,” Dr. Spear said. “They really require so much time and effort that a surgeon thinks, ‘Man, I can’t afford to do this.’ ”

Nevertheless, Georgetown, long a center of expertise for implant reconstruction, recently hired a plastic surgeon who specializes in the more complicated tissue flaps.

A typical surgeon in Manhattan charges insurers about $7,000 for a one-hour implant reconstruction, but for a DIEP procedure that takes 6 to 12 hours, the going rate is $15,500.

Although health insurers are required by federal law to cover reconstructive breast surgery after mastectomies, the government does not set private insurance rates. Flap reconstruction typically requires a higher out-of-pocket co-payment than implant surgery.

“In certain geographical areas where it is badly reimbursed, it’s a disincentive for plastic surgeons even to do the work,” said Dr. Richard A. D’Amico, a past president of the American Society of Plastic Surgeons, speaking of the flap procedures.

Dr. Stephen R. Colen, the chairman of plastic surgery at Hackensack University Medical Center in New Jersey, said plastic surgeons might also not inform patients about the flap procedures because they lacked the advanced training in microvascular surgery needed to perform them.

“A lot of patients are offered implants because the surgeon does not know how to do the flap, and then the implant fails and they need the flap anyway,” Dr. Colen said.

To counter doctors who might routinely steer patients to implants, Dr. Colen started a program at his hospital in which women can meet directly with an impartial physician’s assistant, who goes over the benefits and drawbacks of reconstruction methods.

“We sort of wanted to take the flow of the patient out of the control of the physician and put it in the hands of a medical person who has no personal or financial interest,” Dr. Colen said.

Dotti Campbell, a retired nurse in Crossville, Tenn., said the plastic surgeon who performed her breast reconstruction after a mastectomy offered her only an implant. “That was his procedure,” said Ms. Campbell. Her first implant developed hardened scar tissue and required replacement. Her replacement implant ruptured. Now she is going to have an operation to replace the second implant, she said.

The DIEP flap was developed by Dr. Robert J. Allen, a plastic surgeon in New York, New Orleans and Charleston, S.C., in 1992. Now surgeons at hospitals including the University of Pennsylvania Health System in Philadelphia and Beth Israel Deaconess Medical Center in Boston specialize in the procedure.

Dr. Allen and Dr. Joshua L. Levine, who operate together in Manhattan, often recommend a prospective patient talk at length with patients of theirs who have had a successful flap procedure, like Ms. Hodges, the magazine publisher and karate student, as well as with those whose first flap reconstructions failed and required a second procedure.

“Patients should not necessarily accept the first thing they hear as the end-all, because that is not necessarily the full story,” Dr. Allen said.

From a Place of Fire and Weeping, Lessons on Memory, Aging and Hope

24 dec 2008--The forest still stands, but the people are gone. Only a stone memorial guards their place, surrounded by tall grasses that hide bits of ash and bone deep beneath their roots.

On this spot on Feb. 4, 1942, more than 920 Jewish men, women and children from the town of Rakov in what is now Belarus were rounded up by the Nazis and herded into the synagogue. Several shrieking children were stabbed with bayonets and thrown over the heads of the weeping Jews just before the doors and windows were sealed and the building was doused with kerosene.

An unspeakable scene of wailing ensued as the once vibrant Jewish community was annihilated in the fire. My patient, now 98, still weeps when he describes witnessing this horror from a hidden perch in a tree. He gasps audibly when he recalls watching his father being pummeled by a Nazi soldier before he was thrust into the doomed crowd.

When this survivor first told me his story, I was speechless. He held tight to my arm, and I imagined myself as the branches of the tree that supported him during this trauma. I was now a witness.

As his psychiatrist I am obliged to ease his suffering, but no medicine of mine can touch such a memory. I have tried hard to understand how he and others managed to mentally survive such traumatic experiences. These aging Holocaust survivors, in particular, have taught me what I have come to call “lessons from fire.”

Lesson 1 is the most difficult for a doctor. Sometimes the perpetual sadness of many older survivors is not to be healed but shared. Over time, as memories fade and the voices of lost loved ones grow quieter, all that remains is a closely guarded sadness, persisting as a substitute for the losses. Any attempt to ease this emotion may be a threat to painful but beloved remnants of memory. What some survivors seek is not medicine or therapy: it is the attentive presence of a doctor and others to serve as the next generation of witnesses.

Lesson 2 brings a paradox. Surviving a grueling trauma does not inoculate one against the stresses of aging. A patient once told me that the small daily indignities she faced in the nursing home felt worse than her experiences in a Siberian labor camp. I realized that she could not bear feeling like a victim again, even in small measure.

Lesson 3 gives me hope. One patient, a survivor of Auschwitz, recently lost her husband of 60 years. She came to me severely depressed, with thoughts of suicide.

I asked her, “How did you have any hope in the camp, knowing that each day could be your last?” She smiled briefly and told me a story (I reconstruct her words from memory):

“My dear doctor, I believe in God, and he was with me in the camp. But I also had several young women from my town with me in the barracks.

“When we had to stand at attention for hours, we stood together, propping up one another when weak. When we dug ditches we did it together, one holding and moving the arms and shovel for another who didn’t have strength that day. We were desperate, but never alone.”

I referred her to a social club we created for older people with mild memory problems, and one day I crept into the room during a discussion group and hid behind a corner to listen.

One women spoke disparagingly of her memory. “I am losing my mind,” she said. “It is so painful.”

Then I heard my patient respond in a resolute voice: “You must have hope. We are all in the same boat here, together.”

As I listened I could feel tears welling in my eyes, but I kept myself hidden, afraid to let the group see their doctor weeping. From my hiding place I witnessed a beloved patient begin to heal herself.

These lessons from fire are not the only points of clinical knowledge that one needs to work with aging victims of trauma, but they’re a good start. When facing the last generation of Holocaust survivors, I offer my presence as a doctor and I feel strengthened by their words.

“Faith — I still have faith,” I hear a survivor say. “Doctor, hope for me!” another commands. These are the primal gifts of life that we share.

Marc E. Agronin is a geriatric psychiatrist in Miami.

Tuesday, December 23, 2008

Sex no longer a taboo subject at nursing homes

"Nobody was talking about it; it was a really hush-hush subject," said Gayle Doll, director of the university's Center on Aging. "I guess it's hard enough for people to think about their parents having sex, let alone their grandparents."

In response, the researchers have produced seminars and training aids to encourage nursing home caregivers to discuss and accommodate sexual desires.

The effort brings Kansas into a national discussion that advocates say will only grow as baby boomers age and take their beliefs about sexual freedom and civil rights into the nation's nursing homes.

One of the first Kansas seminars was held at Schowalter Villa in Hesston, where many staff first reacted with, "We're going to talk about WHAT?" said Lillian Claassen, vice president of health services at the villa.

Claassen said residents' sexuality had always been a difficult subject for nursing homes and the Kansas State training affirmed her earlier efforts to address the topic.

"It wasn't like we hadn't cared for these needs in the past, but it was liberating to some folks to have an open discussion with university researchers," Claassen said. "It empowered people to think about how they could help folks."

Doll said the training focuses on explaining what sexuality means for older adults, identifying barriers to fulfilling the sexual needs, finding strategies to help residents and how to discern appropriate from inappropriate sexual behaviors.

Solutions can be as simple as providing "do not disturb" signs or making sure staffers don't barge into residents' rooms without knocking. Claassen said her nursing home provides a discreet room for residents and has staff work through possible scenarios they may encounter.

Sometimes, it's as simple as arranging a bed for someone who needs physical therapy in a way that also allows that patient to be with his or her companion, she said.

"My greatest interest is to promote dignity in a situation that can be very challenging," Claassen said. "We all need touch, kindness and companionship. We try to enable that in this setting, which can be very public but where there is still a need for privacy."

Sexuality doesn't always mean intercourse. Many lonely or depressed residents are simply looking for ways to relieve loneliness and depression, Doll said.

For example, she told of one resident who had asked for pornography but dropped the request when the staff started spending more time with him.

"The staff can help with the loneliness and need for connection that residents often have," Doll said. "Some sexual expressions that might be seen as inappropriate will go away when they simply get the attention they deserve."

When the need does include sexual activity, the issue becomes more difficult if one of the residents is suffering from dementia, advocates say. That can manifest itself in a resident making passes at a staff member.

Claassen said her staff is trained to respond politely and to understand that the impaired resident may be mistaking the staff member for a spouse or reacting as he or she has in the past, which is often more vivid than the present for those suffering from dementia.

If a resident with dementia becomes involved with another resident, the issue becomes determining if the sexual activity is consensual, said Robin Dessel, a national expert on dementia who is the director of memory care at Hebrew Home in Riverdale, N.Y.

Dessel said people with dementia, even those who can no longer speak, have wants and desires and the ability to express them. It takes a trained and educated staff to recognize if a sexual overture or relationship involves abuse or is borne of real need, she said.

Dessel said she has seen a growing awareness that the aging do not forfeit their rights as they become infirm, and that includes the right to express sexuality. She expects that trend to increase as baby boomers, with more liberal attitudes toward sex than their parents, continue to age.

"No matter what we see, even if someone needs total care or is incontinent, they still feel," Dessel said. "If there's a bonding with someone else, I think it's a time of celebration at that point that there's something left, something good and pleasurable for that person."

To meet that challenge, clinicians and providers need some standardized parameters to use to assess patients' consent, Dessel said.

The Kansas State researchers say federal guidelines should be developed to help nursing homes deal with sexuality in a positive way.

"Nursing homes are the second most regulated industry in the country, behind nuclear power plants," Doll said. "But none of those regulations address sexuality. So, consequently, no one knows how to handle it."

___

On the Net:

http://www.humec.k-state.edu/aging

Experts identify gene variants linked to lung cancer

Their finding involves two genes, ABCB1 and ABCC1, which were previously thought to be linked to eliminating carcinogens from the lungs and protecting them against inhaled toxins.

In their study, the researchers analyzed the genes of 500 patients with lung cancer and 517 cancer-free participants in southeastern China.

"The investigators found that certain (gene) variants were found much more often in individuals with lung cancer than in cancer-free controls," they wrote in a statement.

Among those with cancer, 31 percent were found with a certain mutation of the ABCB1 gene, while 27 percent were found with a variant of the ABCC1 gene.

But those same mutations were found in only 15 percent and 12 percent of participants in the cancer-free group.

"The variant (of ABCB1) was particularly associated with an increased risk of cancer in women and in individuals under age 60 years. It also was linked to a major type of lung cancer called adenocarcinoma," the researchers said.

Another study published in the Lancet in October predicted that China would see 65 million deaths from chronic obstructive pulmonary disease (COPD) and 18 million deaths from lung cancer between 2003 and 2033 from smoking and biomass burning at home.

Those figures would account for 19 and 5 percent respectively of all deaths in China during that period, said the researchers at the Harvard School of Public Health (HSPH).

Respiratory diseases are among the 10 leading causes of deaths in China. About half of Chinese men smoke. In more than 70 percent of homes, Chinese cook and heat their homes with wood, coal and crop residues.

(Reporting by Tan Ee Lyn; Editing by Jeremy Laurence)

A simple questionnaire to replace a doctor's exam

23 dec 2008--The good news — you've been offered the perfect job. The not-so-good news — it's contingent on a medical exam.

For the disabled, people with diseases like HIV, or those who are simply mega-stressed at the thought of a doctor's waiting room, undergoing a medical exam to qualify for a job can be daunting. For them, new research from Tel Aviv University brings excellent news.

Medical exams are often not an accurate predictor of competency or job performance, says Tel Aviv University researcher Dr. Shlomo Moshe, an occupational physician from the Sackler Faculty of Medicine. Thanks to his new research, unnecessary and uncomfortable medical and psychological tests can now be replaced with a pencil and paper — and can provide a much more accurate forecast.

"A questionnaire can effectively rule out those who are not fit for white collar and non-hazardous blue collar positions," Dr. Moshe says, "and with our test, more people are actually found fit for work than those assessed by a medical exam."

A Win-Win for the Workplace

The research is excellent news for employers, too.

The potential savings in medical costs are enormous ― as are the costs of litigation after a rescinded offer. Currently, the Americans with Disabilities Act means employers can't order medical tests for prospective hires until after a job offer has been made. Since the act went into effect, a number of complicated lawsuits have arisen from companies rescinding job offers.

"It's only natural that an employer wants to be sure he won't be affected by an employee's medical problems, and that a disability won't affect job performance," says Dr. Moshe. "He wants a certificate of health. Now we can give that without extracting a drop of blood or urine."

Based on data collected during his experience as an occupational physician and from insurance companies, Dr. Moshe's non-invasive "medical test" can be performed in an office or online. The predictive power of the test is so strong, results indicate, that it can not only eliminate unnecessary medical exams, but can help those previously deemed unemployable find suitable work. The test is already used widely in Israel.

Extremely High Accuracy

Researchers in the study show that 98% of all people who take the questionnaire are correctly deemed suitable for employment. The test is so effective that occupational experts in America have been asking for a copy of the questionnaire. It's now available in the Occupational Medicine journal which reports on Dr. Moshe's study.

Israeli employers have been using the questionnaire since 2000. It includes several dozen questions, including: Are you taking medications regularly? Have you ever filed a disability claim? Do you have allergies to any food and medications? Have you ever been injured in an accident?

Antiquated Tests Are Costly and Irrelevant

Most of the medical tests currently used to screen prospective employees were developed decades ago, when workers were frequently exposed to dangerous substances such as lead and asbestos. Because new safety standards limit the incidence of exposure to such toxins, a majority of traditional medical tests are completely redundant, Dr. Moshe indicates. And major communicable diseases like tuberculosis, formerly common, are found quite rarely today.

"Obviously, employers, are afraid of lawsuits and poor performance on the job," Dr. Moshe concludes. "Our test gives everyone in the system job security."

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Dr. Moshe is an occupational physician, working in Maccabi Healthcare Services. The organization supports and encourages clinical research taking place in the community in cooperation with Tel Aviv University and other University-affiliated medical centres.

American Friends of Tel Aviv University (www.aftau.org) supports Israel's leading and most comprehensive center of higher learning. In independent rankings, TAU's innovations and discoveries are cited more often by the global scientific community than all but 20 other universities worldwide.