Doctors Urged Not to Screen Elderly Men for Prostate Cancer

By TARA PARKER-POPE
05 aug 2008--In a move that could lead to significant changes in medical care for older men, a national task force on Monday recommended that doctors stop screening men ages 75 and older for prostate cancer because the search for the disease in this group was causing more harm than good.
The guidelines, issued by the U.S. Preventive Services Task Force, represent an abrupt policy change by an influential panel that had withheld any advice regarding screening for prostate cancer, citing a lack of reliable evidence. Though the task force still has not taken a stand on the value of screening in younger men, the shift is certain to reignite the debate about the appropriateness of prostate cancer screening at any age.
Screening is typically performed with a blood test measuring prostate-specific antigen, or PSA, levels. Widespread PSA testing has led to high rates of detection. Last year, more than 218,000 men learned they had the disease.
Yet various studies suggest the disease is “overdiagnosed” — that is, detected at a point when the disease most likely would not affect life expectancy — in 29 percent to 44 percent of cases. Prostate cancer often progresses very slowly, and a large number of these cancers discovered through screening will probably never cause symptoms during the patient’s lifetime, particularly for men in their 70s and 80s. At the same time, aggressive treatment of prostate cancer can greatly reduce a patient’s quality of life, resulting in complications like impotency and incontinence.
Past task force guidelines noted there was no benefit to prostate cancer screening in men with less than 10 years left to live. Since it can be difficult to assess life expectancy, it was an informal recommendation that had limited impact on screening practices. The new guidelines take a more definitive stand, however, stating that the age of 75 is clearly the point at which screening is no longer appropriate.
The task force was created by Congress and first convened in 1984 to analyze current medical research and to make recommendations about preventive care for healthy people. Its guidelines are viewed as highly credible and are often relied on by physicians in making decisions about patient care.
“When you look at screening, you have a chance the screening will help you live longer or better, and you have the chance that screening detection and treatment will harm you,” said Dr. Ned Calonge, chairman of the task force and chief medical officer for the Colorado Department of Public Health and Environment. “At age 75, the chances are great that you’ll have negative impacts from the screening.”
It is estimated that one out of every three men 75 and older is now screened for prostate cancer, although some studies suggest the number is even higher. The Journal of the American Medical Association reported in 2006 that in a group of nearly 600,000 older men treated by the Veterans Administration, 56 percent of those ages 75 to 79 had been screened for prostate cancer. Given the large numbers of men over 75 who are being screened, even a small decline in testing may greatly reduce the number of prostate cancer cases detected.
Dr. Calonge said it was important that the guidelines not be viewed as “giving up” on older men. While the new rules should discourage routine testing of older patients, the recommendations will not prevent a man from seeking screening if he desires it, Dr. Calonge said. The new guidelines are not expected to alter Medicare’s current reimbursement for annual PSA screening of older men.
“There will be some men who would say, ‘Let’s do it anyway,’ and other men who say, ‘If we don’t need to do it, let’s not do it,’ ” Dr. Calonge said.
The guidelines focus on the screening of healthy older men without symptoms and will not affect treatment of men who go to the doctor with symptoms of prostate cancer, like frequent or painful urination or blood in the urine or the semen.
Studies of the value of prostate cancer screening for younger men have produced mixed results, but a major clinical trial under way in Europe will try to determine whether there is any value, in terms of longer life expectancy, to screening this group for prostate cancer. Those results may be published as early as next year.
While the verdict is still out on younger men, the data for older men are more conclusive, experts say. The American Cancer Society and the American Urological Association both say annual PSA screening should be offered to average-risk men 50 and older, but only if they have a greater than 10-year life expectancy.
Recently, Swedish researchers collected 10 years of data on men whose cancer was diagnosed after the age of 65 and found no difference in survival among those who were treated for the disease and those whose cancers were monitored but treated only if the cancer progressed. The finding suggests that for most men, stopping screening at 75 is a safe option.
“If someone has made it to the age of 75 and they don’t have an elevated PSA, the likelihood of them developing clinically significant prostate cancer in the last 10 to 15 years of their life is pretty low,” said Dr. Peter C. Albertsen, professor of urology at the University of Connecticut Health Center. “The downside risk begins to outweigh the upside at the age of 75.”
Some studies suggest that as many as half of men 75 and older have clinically insignificant prostate cancer that is unlikely to affect their health but may be found through a biopsy. If the disease is detected as a result of screening, the men may be actively treated with radiation or hormone therapies, or may endure the stress of “watchful waiting” to see if the disease progresses.
Treatments for prostate cancer can cause significant harm, rendering men incontinent or impotent, or leaving them with other urethral, bowel or bladder problems. Hormone treatments can cause weight gain, hot flashes, loss of muscle tone and osteoporosis.
“I’m very pleased the prevention task force has said, at least for the old guys, ‘Leave them alone because our evidence suggests it doesn’t help,’ ” said Dr. Derek Raghavan, director of the Cleveland Clinic Taussig Cancer Institute. “Taking an 80-year-old and telling him he has cancer and telling him he needs radiotherapy or surgery uses up medical resources and puts him at risk. It’s a step toward rational thinking.”

Millions With Chronic Disease Get Little to No Treatment

By REED ABELSON
05 aug 2008--Millions of Americans with chronic disease like diabetes or high blood pressure are not getting adequate treatment because they are among the nation’s growing ranks of uninsured.
That is the central finding of a new study to be published Tuesday in the medical journal Annals of Internal Medicine.
The study, the first detailed look at the health of the uninsured, estimates that about one of every three working-age adults without insurance in the United States has received a diagnosis of a chronic illness. Many of these people are forgoing doctors’ visits or relying on emergency rooms for their medical care, the study said.
The report, based on an analysis of government health surveys of adults ages 18 to 64 years old, estimated that about 11 million of the 36 million people without insurance in 2004 — the latest year of the study — had received a chronic-condition diagnosis.
“These are people who, with modern therapies, can be kept out of trouble,” said Dr. Andrew P. Wilper, the study’s lead author. Therapies for someone with diabetes and hypertension “are routine and widely available, if you have insurance,” said Dr. Wilper, a medical instructor at the University of Washington in Seattle.
The most recent government estimate of the number of people in this country without health insurance is 47 million, which means that if the proportions found in the study have remained constant, there might be nearly 16 million people in this country with a chronic condition but no insurance to pay for medical care.
Nearly a quarter of the uninsured with a chronic illness who were surveyed said they had not visited a health professional within the last year. About 7 percent said they typically went to a hospital emergency room for care.
“A lot of people are suffering from a lack of health insurance,” said Dr. Steffie Woolhandler, another of the study’s authors, who is a physician and associate professor of medicine at Harvard.
People with high blood pressure, for example, are at risk for catastrophic medical events like a stroke if they are not getting the drugs they need or having a doctor monitor their disease, said Karen Davis, the president of the Commonwealth Fund. The fund, a foundation in New York that specializes in health care research, has done its own research into the lack of adequate medical care among the uninsured.
The study, being published Tuesday, may have underestimated exactly how many people who are uninsured have a chronic illness, because it includes only those who have already received such a diagnosis, the authors said. Individuals who have not had their conditions diagnosed because they are not seeing a doctor or nurse are not included.
The study’s authors say that their findings cast doubt on the common assumption that many of the uninsured tend to be young and healthy, requiring little in the way of medical care. Because so many actually have chronic conditions that may be expensive to treat, the cost of covering the uninsured is often underestimated, said Dr. Woolhandler, who advocates a nationalized system of health care.
In Massachusetts, she said, the state’s effort to overhaul its health insurance system to cover more residents is costing much more than expected and has not led to universal coverage because policy makers assumed that more people would be healthy. “The state experiments have all failed because of cost,” she said.
The study describes harsh consequences for neglecting easily treatable diseases in so many people. “For some of the 11.4 million uninsured Americans with serious chronic conditions, access to care seems to be unobtainable; many may face early disability and death as a result,” the study’s authors said.

Erectile dysfunction may be "normal" with age

By Will Boggs
05 aug2008--Erectile dysfunction may be a feature of normal aging in men, while urinary or bowel function doesn't necessarily decline with age, according to a Dutch study.
"I had expected that the association between urological function and age would be stronger," Dr. Ida J. Korfage from Erasmus University Medical Center Rotterdam told Reuters Health.
Using data from more than 3,800 participants in the European Randomized Study on Screening for Prostate Cancer, Korfage and her colleagues assessed whether urinary, bowel, and sexual dysfunction "and the associated bother" were part of the "normal" aging process.
As described in the medical journal Urology, the men -- all of whom were cancer-free -- were divided into five groups by age: 58-61, 62-64, 65-67, 68-70, and 71 years and older.
According to the investigators, the proportion of men with erectile dysfunction was significantly higher among older men, with more of them reporting either that they were sexually active but having problems with erections, or sexually inactive because of erectile problems.
Korfage added, "I like to stress that sexual inactivity is not necessarily the same as erectile dysfunction. Reasons for not being sexually active can also be not being interested (anymore) or not having a partner. Not everybody who is sexually inactive is in need of medication."
Although urinary function was poorer and more bothersome in older age groups, the differences between age groups were not very great.
Bowel problems were uncommon, with no significant differences among age groups, the report indicates.
So, when these problems are seen in older men who have been treated for prostate cancer, they are more likely due to the treatment rather than to age alone, the team points out.
SOURCE: Urology, July 2008.

Cancer Survivors Often Turn to Complementary Medicine

By Charles Bankhead
ATLANTA, 5 aug 2008-- Complementary medicine, primarily related to faith and spirituality, is used by more than 60% of cancer survivors, according to an American Cancer Society study.
Prayer and spiritual practice were cited by 61.4% of more than 4,000 cancer survivors who participated in a survey, Ted Gansler, M.D., of the society's health promotions division, and colleagues reported online in Cancer.
More than 40% of the survey participants mentioned use of relaxation, faith or spiritual healing, and nutritional supplements or vitamins. By contrast, use of hypnosis, biofeedback, and acupuncture was reported by 1% or fewer of the cancer survivors.
"These findings may be used by clinicians and researchers to inform their decisions regarding which [forms of complementary medicine] to address and research," the authors concluded.
They added that population-based data such as provided by their study "are needed to help focus nationwide research priorities on the most widely used [forms of complementary medicine], to assess their effectiveness in improving survivors' quality of life."
Several studies have documented widespread use of complementary medicine by cancer patients. However, most studies have focused on the treatment period, the authors said. Relatively little data have addressed use of complementary medicine "along the cancer continuum."
The authors examined data from the ACS Study of Cancer Survivors-I database. The study included 4,139 survivors of 10 types of cancer. Breast (24.6%), prostate (19.7%), and colorectal (14.7%) cancer accounted for a majority of the study population.
The patients were surveyed 10 to 24 months after diagnosis. The survey included questions related to the use of 19 different kinds of complementary medicine.
In addition to prayer or spiritual practice, commonly reported forms of complementary medicine included:
Relaxation, 44.3%
Faith/spiritual healing, 42.4%
Nutritional supplements/vitamins, 40.1%
Meditation, 15%
Religious counseling, 11.3%
Massage, 11.2%
Support groups, 9.7%
The authors grouped the 19 complementary medicine practices into five domains and found that mind/body practices accounted for 74.4% of the use of complementary medicine. When the authors subdivided that category, they found that religious/spiritual practices were reported by 64.6% of the study participants and other mind/body practices by 51.9%. Practices in the alternative medicine domain were the least common (2.9%).
Use of complementary medicine differed by type of cancer. Survivors of melanoma and kidney cancer were least likely to use complementary medicine, whereas survivors of breast and ovarian cancer were most likely.
A multivariate logistic regression analysis showed that use of complementary medicine was associated with female sex, younger age, higher income, white race, and more education.
Use of spiritual/religious mind-body complementary methods (faith/spiritual healing, prayer/spiritual practice, and religious counseling) was higher in African Americans than in non-Hispanic whites, Hispanics, and other races (75.8% versus 63.8%, 64.5%, and 64.3%).
This pattern was repeated for nonspiritual/religious mind-body practices (aromatherapy, art therapy, support group attendance, biofeedback therapy, hypnosis, imagery/visualization, meditation, and relaxation); 63% of African Americans reported using at least one of these complementary methods compared with 51.1% of whites and 45.4% of Hispanics.
The authors noted that the results may suffer from response bias and omissions from the list of complementary methods (e.g., exercise and chiropractic) may have led to underestimation of aggregate use.
The authors reported no disclosures.
Primary source: CancerSource reference:Gansler T, et al "A population-based study of prevalence of complementary methods used by cancer survivors. A report from the American Cancer Society's Studies of Cancer Survivors" Cancer 2008; 113: 1048-1057.

Exercise Doesn't Improve Mood

By Crystal Phend
AMSTERDAM, 5 aug 2008 -- Regular exercise does not reduce anxiety and depression in the general population, researchers here found. Genetically identical twins showed no difference in anxious and depressive symptoms when one in the pair exercised more than the other, reported Marleen H. M. De Moor, M.Sc., of VU University Amsterdam, and colleagues in the August issue of the Archives of General Psychiatry. Nor did symptoms decline over time as individuals started exercising more. Although the large, population-based study of twin families confirmed that getting less regular exercise was associated with worse mental health symptoms in the general population as seen in prior studies, the findings show that the effect is not causal, the researchers said.
Genetics may account for much of the link, they said. Up to half of the variation in anxious and depressive symptoms between individuals appears to be heritable while genes also explain about 50% to 60% of differences in exercise behavior.
But the lack of direct benefits for mood shouldn't change physicians' recommendations for the general population, the investigators cautioned.
"These findings do not detract from the beneficial effects of regular exercise on numerous aspects of physical health such as cardiovascular disease and type 2 diabetes mellitus," De Moor and colleagues wrote.
For patients diagnosed with an anxiety or depressive disorder, studies have suggested that prescribed exercise may alleviate symptoms. But that effect may be more environmentally driven, the researchers said.
"The antidepressant effects of exercise may only occur if the exercise is monitored and part of a therapeutic program," they wrote.
To test the causal link suggested by prior studies, De Moor's group analyzed data from 5,952 twins in the Netherlands Twin Register, 1,357 of their other siblings, and 1,249 parents. The analysis included only adults ages 18 to 50.
Overall, there were small but significant correlations between a higher level of leisure-time physical activity and fewer anxious and depressive symptoms (correlation coefficient −0.12, 95% confidence interval −0.14 to −0.09).
Notably, genetics appeared to account for the associations with statistically significant correlation coefficients ranging from −0.16 to −0.24.
Exercise level predicted mental health symptoms in genetically identical monozygotic twin pairs but not in genetically distinct dizygotic twins and sibling pairs.
When genetically identical twins differed from each other in exercise level, the twin who exercised more was not significantly less depressed than the one who exercised less (intrapair difference score range −0.04 to 0.03).
This finding did "not support the hypothesis that exercise causes relief in anxious and depressive symptoms," the researchers said.
Individual environmental correlations -- reflecting level of exercise and other nongenetic factors -- were not significant (coefficients −0.07 to 0.05), "suggesting that the association between exercise behavior and symptoms of anxiety and depression is not explained by a causal effect," the researchers again noted.
In the longitudinal analysis, individual symptom and exercise levels reported periodically from 1991 through 2002 were significantly correlated over time with coefficients comparable to the cross-sectional analysis (−0.07 to −0.14).
Again, genetics were significantly correlated with the longitudinal link between symptoms of anxiety and depression and exercise level whereas environmental correlations were not significant.
Changes over time in the number of metabolic equivalent task (MET) hours of exercise reported were not associated with either significant decrease or increase in anxious and depressive symptoms in the subsequent two-, four-, seven-, nine-, or 11-year intervals.
Which genes might "simultaneously affect the regulation of exercise drive and mood" and thereby account for the association between exercise behavior and risk of anxiety and depression is unknown, the researchers said.
Likely candidates might be those in the dopaminergic, opioidergic, norepinephrenergic, or serotonergic pathways of the brain, they speculated.
They cautioned that the study may have been affected by selection bias, as individuals from families with more participants in the study were less depressed and anxious.
They also noted that the study's power was limited to detect small correlations in men in particular, that the study could not examine more complex causality, and that generalizability could be limited to different age groups and countries.
The study was supported by grants from the Netherlands Organization for Scientific Research. The researchers reported no conflicts of interest.
Primary source: Archives of General PsychiatrySource reference:De Moor MHM, et al "Testing causality in the association between regular exercise and symptoms of anxiety and depression" Arch Gen Psychiatry 2008; 65: 897-905.

IAC: New Estimate Raises HIV Incidence Sharply

By Michael Smith

MEXICO CITY, 04 aug 2008-- Every 10 minutes, another American becomes infected with HIV.
About a third of them are younger than 30, nearly half are black, and more than half are men who have sex with men.
These startling figures arise from a new CDC analysis of HIV incidence, using a novel method that the agency believes is more accurate than earlier estimates.
In 2006, the CDC now says, about 56,500 people were newly infected in the U.S. The number is sharply higher than the estimate the CDC had been giving for recent years, of about 40,000 a year.
If the estimate is correct, more than 150 people are infected every day, or more than six an hour.
The new analysis "provides the first direct estimates of HIV incidence in the United States using laboratory technologies previously implemented only in clinic-based settings," said Irene Hall, Ph.D., of the CDC, and colleagues.
The study appears in the Aug. 6 issue of the Journal of the American Medical Association and was released here in conjunction with the 17th International AIDS Conference.
The new estimate is not directly comparable to earlier figures, Dr. Hall and colleagues said, and might be higher owing to bias in the new methods, limitations of the older methods, or higher HIV incidence.
But the new method is a "significant breakthrough," said Kevin Fenton, M.D., Ph.D., director of the CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.
Speaking in a telephone press conference, Dr. Fenton said, "We have never before been able to directly measure new infections in the U.S. on a national level."
Previous estimates have been based on newly reported diagnoses, but were not able to establish when the infections took place. "We have not been able to see the leading edge of the epidemic," Dr. Fenton said.
The new figures were also derived initially from reports of new HIV diagnoses in 22 states, part of an expanded HIV surveillance network. The novel aspect of the analysis is the so-called BED HIV-1 capture enzyme immunoassay, which can distinguish recent from long-standing infections.
In 2006, the 22 states reported 39,400 new HIV diagnoses. Of those, 6,864 had specimens available to be tested using the BED assay and 2,133 ( 31%) were classified as recent infections. Extrapolating to the full U.S. yielded the 56,500 figure, whose 95% confidence interval ranged from 48,200 to 64,500. The estimated incidence rate was 22.8 per 100,000 people (with a 95% confidence interval from 19.5 to 26.1).
A statistical back-calculation yielded a similar number -- an estimated 55,400 new infections per year for 2003 through 2006, the researchers said. Dr. Fenton said new infections were probably never as low as the 40,000 figure and have been roughly stable since the late 1990s.
Analysis of the 2006 figures suggests that 34% of the newly infected were younger than 30, that 45% of them were black, and that 53% were men who have sex with men, Dr. Hall and colleagues reported.
"The bottom line is that the HIV epidemic in the U.S. continues to spread, and at a rate greater than was previously thought," according to Julie Davids, executive director of CHAMP, a New York-based advocacy group.
In a statement, Davids called for "the establishment of a comprehensive and accountable national AIDS strategy that will eliminate barriers to effective prevention, generate adequate resources, and hold our government accountable for ending this epidemic."
The implications of the new findings are unacceptable, said CDC director Julie Gerberding, M.D., and more must be done to lower infection rates. Dr. Gerberding, quoted by the New York Times, said "we are not effectively reaching men who have sex with men and African-Americans to lower their risk."
The CDC has been criticized for not releasing its figures earlier, preferring to wait until they could appear in a peer-reviewed journal.
Primary source: Journal of the American Medical AssociationSource reference:Hall HI, et al "Estimation of HIV Incidence in the United States" JAMA 2008; 300(5): 520-529.

IAC: TB Drug Alters Power of HIV Medication

By Michael Smith
MEXICO CITY, 04 aug 2008-- TB patients treated with rifampin (Rifadin, Rimactane) are more likely to fail subsequent HIV therapy if it includes nevirapine (Viramune), researchers said here.
On the other hand, there is less risk of virological failure if TB patients start HIV treatment with a regimen that includes efavirenz (Sustiva), according to Andrew Boulle, M.B.Ch.B., of the University of Cape Town, in South Africa, and colleagues.
But when HIV patients already taking either drug began TB treatment with rifampin, outcomes were comparable to those in patients without TB, Dr. Boulle said.
The finding comes from a study that appears in the Aug. 6 issue of the Journal of the American Medical Association and was released here in conjunction with the 17th International AIDS Conference.
The issue is important in resource-poor countries, where non-nucleoside reverse transcriptase inhibitors such as nevirapine and efavirenz are recommended as components of an initial antiretroviral drug regimen.
Rifampin is a potent inducer of cytochrome P450 enzymes, which metabolize many drugs, including the non-nucleoside reverse transcriptase inhibitors.
Indeed, plasma concentrations of both nevirapine and efavirenz are reduced by the drug, although nevirapine is hardest hit with reductions of between 20% and 55%.
To see what the effects of such reductions might be, the researchers studied HIV treatment-naïve patients in a public sector antiretroviral therapy program in three centers in South Africa.
The analysis included 2,035 individuals who started antiretroviral therapy with efavirenz (including 1,074 who already had TB) and 1,935 who started with nevirapine (including 209 with concurrent TB).
Compared with patients without TB, those with TB (and on rifampin) who started nevirapine were twice as likely to have an elevated viral load six months later. The rate was 16.3%, compared with 8.3%, a difference that was significant at P<0.05.
They were also quicker to develop virological failure -- defined as two consecutive test values of more than 5,000 copies of viral RNA per milliliter of blood. The adjusted hazard ratio was 2.2, with a 95% confidence interval from 1.3 to 3.7, which was significant at P<0.05.
There were no differences between patients starting efavirenz with or without concurrent TB.
And there was no difference in time to virological rebound in patients free of TB compared with those who developed tuberculosis during follow-up while taking either nevirapine or efavirenz.
The latter finding, however, should be taken with a grain of salt, Dr. Boulle said, because the number of patients who developed TB during HIV treatment was relatively small.
Indeed, one of the main limitations of the study as a whole, he said, is that only 209 patients started nevirapine with concurrent TB, which limits the power of the analysis.
Another limitation of the study is that neither survival nor CD4 counts were affected by the antiretroviral regimen in the patients with TB. The assumption made was that virological failure would result in clinical failure.
The study was also observational so the investigators could not exclude confounding by indication for choosing nevirapine as opposed to efavirenz as the initial regimen.
There was no external support for the study.
Dr. Boulle reported no conflicts.
Primary source: Journal of the American Medical AssociationSource reference:Boulle A et al "Outcomes of Nevirapine- and Efavirenz-Based Antiretroviral Therapy When Coadministered With Rifampicin-Based Antitubercular Therapy" JAMA. 2008; 300(5): 530-539

IAC: HIV Care Guidelines Expand Treatment Eligibility

By Michael Smith
MEXICO CITY, 04 aug 2008 - About 100,000 additional HIV-positive patients in the U.S. would be eligible for initiation of antiretroviral therapy under new treatment guidelines issued here.
The 2008 recommendations of the International AIDS Society-USA Panel support initiating therapy even in patients whose immune system remains relatively robust, according to Scott Hammer, M.D., of Columbia.
The guidelines remove the previous upper limit of 500 CD4-positive T cell per microliter of plasma, above which therapy was not recommended, Dr. Hammer said.
He said the changes "substantially increase the eligible group" of HIV-positive people in the U.S., although he was unable to give more than a "ballpark" figure of about 100,000.
The guidelines appear in the Aug. 6 issue of the Journal of the American Medical Association and were released in conjunction with the 17th International AIDS Conference.
The guidelines are intended to guide HIV care in the developed world, Dr. Hammer said, but in the long run, the 14-member panel that developed them hopes they will also guide care in developing countries.
Previously, antiretroviral therapy was recommended if a patient's CD4 cell count fell below 200 cells per microliter of plasma and was recommended for consideration when the count was between 200 and 350.
Therapy was not recommended for patients whose CD4 cell count remained above 350.
In the new guidelines, therapy should begin at 350, and in any case before the count reaches 200, Dr. Hammer said.
Above 350, therapy should be considered on an individual basis, based on co-morbidities, risk factors for progression to AIDS and other diseases, and patient readiness for treatment, he said.
For 2008, the panel also removed the upper limit of 500 cells, suggesting that - depending on the other factors - treatment could begin at any CD4 level, Dr. Hammer said.
The changes came as a result of several factors, he said, including more antiretroviral drugs, a better understanding of the adverse effects of delaying treatment, and more insight into the role of HIV in non-AIDS conditions such as cardiovascular and renal disease.
Currently, Dr. Hammer said, there are 25 individual drugs in seven classes, approved for HIV therapy in the U.S. and - in what he called a sign of "maturation" for the field -- two others have gone out of production.
The range of available drugs has alleviated fears that early therapy would leave patients without options if and when resistance or toxicity developed, he said.
And mounting evidence suggests that a high viral load - regardless of CD4 cell count - is linked to increased morbidity and mortality, he said.
Also, trials of treatment interruptions have suggested that HIV has a role in cardiovascular disease, non-AIDS malignancies, renal disease, and liver disease, he said.
All those factors "support moving forward to earlier initiation of treatment," he said.
The guidelines continue to recommend that initial treatment be based either on a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI), combined with two nucleoside or nucleotide reverse transcriptase inhibitors (nRTI).
The preferred NNRTI is efavirenz (Sustiva), but several PIs are suggested, including lopinavir (Kaletra), atazanavir (Reyataz), fosamprenavir (Lexiva), darunavir (Prezista), and saquinavir (Fortovase, Invirase).
The suggested nRTI combinations are tenofovir/emtricitabine (Viread/Emtriva) and abacavir/lamivudine (Ziagen/3TC).
If abacavir is being considered, the guidelines suggested that patient monitoring should include testing for the immune marker HLA-B*5701, which is associated with abacavir hypersensitivity reactions.
The guidelines also suggest that, before the CCR5 antagonist maraviroc (Selzentry) is used, patients be tested for so-called viral tropism, the type of virus causing their infection.
For all patients, including those experienced with HIV medications, Dr. Hammer said, the goal remains to drive the viral load below the level of 50 copies of viral RNA per milliliter of blood, which is the lower limit of detection for the most sensitive assays.
Primary source: Journal of the American Medical AssociationSource reference:Hammer SM et al. "Antiretroviral Treatment of Adult HIV Infection: 2008 Recommendations of the International AIDS Society-USA Panel." JAMA. 2008;300(5):555-570

IAC: Injection Drug Use No Bar to HIV Therapy

By Michael Smith
MEXICO CITY, 04 aug 2008-- Injection drug use doesn't change the chance of survival among HIV-positive patients starting highly active antiretroviral therapy (HAART), researchers said here. In a 10-year observational study, injection drug users had death rates that were similar to other HIV-positive patients starting HAART, according to Julio Montaner, M.D., of the University of British Columbia in Vancouver, and colleagues. The finding should quash the common view that people who use injection drugs are inherently unable to benefit from therapy because of their unstable life style, said Dr. Montaner, who is also president-elect of the International AIDS Society.
The study appears in the Aug. 6 issue of the Journal of the American Medical Association and was released here in conjunction with the 17th International AIDS Conference.
The study implies that extending HAART to injection drug users "should be a priority, given that barriers remain" to access, Dr. Montaner said, adding that the Joint United Nations Program on HIV/AIDS has found that -outside of sub-Saharan Africa - a third of all HIV infections are among injection drug users.
The study covered all antiretroviral-naïve residents of the Canadian province of British Columbia who started HAART between Aug. 1, 1996, and June 30, 2006.
The 3,116 patients, with a median age of 39.4, included 915 injection drug users and 579 females. The median duration of follow-up was 5.3 years for the drug users and 4.3 years for others.
Dr. Montaner said previous studies showing worse outcomes for injection drug users on HAART were performed in areas where access to treatment was not free.
He noted that HIV/AIDS care is free in British Columbia, removing a major barrier to care.
A province-wide vital statistics bureau allowed all patients to be followed until death or the end of the study and their causes of death analyzed.
The study found that 622 study participants died during the study period, for a crude mortality rate of 20.0%. Of those, 232 were injection drug users.
The cumulative all-cause mortality rate was similar between the groups -- 26.5% for the drug users and 21.6% for the others - and in a multivariate time-updated Cox regression, the hazard ratio of mortality was also similar (1.09 with a 95% confidence interval from 0.92 to 1.29).
In sub-analyses, Dr. Montaner and colleagues excluded deaths unlikely to be related to HIV, including such things as accidental poisonings, trauma, and suicides.
The drugs users were significantly more likely (P=0.003) than non-users to die of such causes - they accounted for 21.1% of such deaths compared with 9.7%.
However, when accidental deaths were excluded, the death rates again were not statistically different -- 22.4% for the drug users compared 19.1% for the others.
The bottom line, Dr. Montaner said, is that "once barriers are removed, injection drug users can successfully enter treatment."
The study was limited by only having baseline data on injection drug use. So any effect of ongoing drug use could not be ascertained.
The study also only enrolled injection drug users who had HAART prescribed. The authors acknowledged that the overall rate of death might be higher if all injection drug users were counted. Nonetheless, the study demonstrated that injection drug users given HAART had a similar mortality rate to those who did not inject drugs.
The study was supported by the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research. Dr. Montaner receiving educational grants from and serving as an ad hoc advisor to or speaking at various events sponsored by Abbott Laboratories, Agouron Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc., Borean Pharma AS, Bristol-Myers Squibb, DuPont Pharma, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, Immune Response Corp., Incyte, Janssen-Ortho Inc., Kucera Pharmaceutical Company, Merck Frosst Laboratories, Pfizer Canada Inc., Sanofi Pasteur, Shire Biochem Inc., Tibotec Pharmaceuticals Ltd., and Trimeris Inc.
Primary source: Journal of the American Medical AssociationSource reference:Wood E at al. "Highly Active Antiretroviral Therapy and Survival in HIV-Infected Injection Drug Users." JAMA. 2008;300(5):550-554.

IAC: Effects of Growth Hormone Raise Caution Flag

By Michael Smith
MEXICO CITY, 04 aug 2008 -- Low doses of growth hormone reduce abdominal fat deposits in patients with HIV lipodystrophy, researchers said here. In an 18-month, placebo-controlled randomized trial, the hormone also improved blood pressure and triglyceride levels, according to Steven Grinspoon, M.D., of Massachusetts General Hospital and colleagues. On the other hand, the hormone appeared to increase some aspects of blood sugar levels, injecting "a note of caution" into the debate over using growth hormone to treat lipodystrophy, Dr. Grinspoon and colleagues said.
The study appears in the Aug. 6 issue of the Journal of the American Medical Association and was released in conjunction with the 17th International AIDS Conference.
The study is "very informative to the field," Dr. Grinspoon said, noting that off-label use of growth hormone is common.
"Even low-dose growth hormone, albeit effective in reducing cardiovascular risk factors and better tolerated than high-dose growth hormone, may increase specific glucose parameters," Dr. Grinspoon said.
The researchers enrolled 56 patients with HIV, abdominal fat accumulation, and reduced secretion of growth hormone, defined as a peak of less than 7.5 ng/mL of blood.
They were randomized to placebo or growth hormone, starting at 2 mcg/kg of body weight per day, and titrated up to a maximum of 6 mcg/kg over the 18 months of the study.
The study found that the treatment effect - the average difference between the two groups - was:
A reduction by 19 cm2 in visceral adipose tissue, which was significant at P=0.049.
A reduction of 0.8 kg in trunk fat, which was significant at P=0.04.
A drop of 7 mm Hg in diastolic blood pressure, significant at P=0.006.
A 7 mg/dL reduction in triglycerides, significant at P=0.002).
An increase in levels of insulin-like growth factor-1, a marker for growth hormone, by a treatment effect of 129 ng/mL, which was significant at P<0.001.
An increase in two-hour glucose levels (on glucose tolerance testing) of 22 mg/dL, significant at P=0.009.
Adverse events were not significantly different between the groups.
Dr. Grinspoon said that most glucose parameters were unchanged by the growth hormone, but increases on the two-hour test may be an early marker of diabetes.
He said the study showed that those whose two-hour glucose test was worsened by growth hormone were those who had poor glucose tolerance at baseline.
Because of that, he said, "I don't think growth hormone can be recommended for all people with HIV, but it might be quite useful for a subpopulation."
The study was supported by the NIH. EMD Serono provided growth hormone but made no other contribution to the study. Dr. Grinspoon reports research support on an unrelated project from EMD Serono and also serving as a consultant for the company. He also reported financial links with Theratechnologies.
Primary source: Journal of the American Medical AssociationSource reference:Lo J et al. "Low-Dose Physiological Growth Hormone in Patients With HIV and Abdominal Fat Accumulation: A Randomized Controlled Trial." JAMA. 2008;300(5):509-519.

AMPK and PPARδ Agonists Are Exercise Mimetics

Vihang A. Narkar
03 aug 2008--The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test. We found that PPARβ/δ agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1α, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARδ pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.

No time to think?

By Alan Connor
03 aug 2008--When Barack Obama met David Cameron, the pair got around to discussing thinking time - and the lack of it. It's not just potential leaders of nations who are short of opportunities to reflect on the bigger picture. How can any of us grab thinking time during the working day?
"These guys just chalk your diary up," lamented Cameron. "We call it the dentist's waiting room."
"The most important thing you need to do," mused Obama, "is to have big chunks of time during the day when all you're doing is thinking."
Apparently unaware of the large fluffy boom mic accompanying their outdoor stroll, David Cameron and Barack Obama swapped fears of getting bogged down in the detail.
If either politician realised he was being recorded, he couldn't have chosen his words better, Obama coming across like the chess-loving contemplative President Bartlet in The West Wing and Cameron balancing work and life more delicately than the workaholic stereotype associated with Gordon Brown.
The political class, being "on" 24/7, may feel in special need of moments to step back from the everyday. But few of us complain of having too much time, whether at work or at home. As a public service, the Magazine asks how to grab yourself some thinking time - from those who've had time to think about it.
CHOOSE YOUR MOMENT No more lunching "al desko"
The most common advice boils down to something that might seem obvious: only work when you're being paid to work. The rest of the day is yours to do with as you wish - and you may wish to devote it to thought.
Obvious, perhaps, but not obvious enough that we do it: various surveys conducted on behalf of food outlets suggest that between 50 and 80% of us skip an actual break for lunch, let alone using the hour for quiet contemplation.
You might not have heard the unspeakable expression "eating al desko", but if you've been in an office, you've probably witnessed the sorry spectacle of a workstation becoming a dining table for seven minutes and a hastily-chomped panino.
"We have to make sure that people in offices go out at lunchtimes," says David Hunter, chief executive of Lifelong Learning UK. "If you leave your desk to wander up the street, you come back refreshed and more able to work."
Tom Hodgkinson, editor of The Idler magazine, speaking from a medieval garden, recommends getting away from your workplace and finding nearby places that will afford you some calm.
"People don't take an hour off for lunch any more. But you can eat in a quarter of an hour and then walk somewhere. Churches are great for this."
He also suggests reclaiming your travel time as an opportunity to take stock rather than worrying about the work that you're either approaching or leaving. "It's good to get off the bus earlier and walk - in London, you can give yourself an hour of pure pleasure."
CHOOSE YOUR LOCATION It doesn't have to be atop a mountain
For the truly dedicated, a dedicated space awaits thinking time. Visuddhimati, a teacher at North London Buddhist centre, says that many non-Buddhists want to study how to be aware and set aside "a little space at home" for meditation: "it could be a corner of the room or a dedicated meditation room."
But what if you're space-poor as well as time-poor?
Tony Buzan, the inventor of graphical "thinking tools" MindMaps, says: "I've asked people where they are physically when they have great ideas, paradigm-shifting epiphanies, or a flood of memories they've been trying to remember.
"Regardless of continent, age, gender, education and race, the answers are the same."
The list that follows is reassuring for those who crave some repose without the need for an ashram. The "oases of thought" Buzan hears about are commonly: the shower; the bath; the loo; shaving; walking in nature; in bed (before sleep, in the middle of the night, or first thing); looking at water; listening to classical music and long-distance travel, such as running or driving.
Happily, these are situations you might find yourself in during your everyday life - and thought may come as long as you're not multi-tasking while you do them. Also, as Hodgkinson points out, adding gardening to the list, "they don't cost anything."
HAVE YOUR PROPS TO HAND Aristotle or Moyles?
In Proust's In Search Of Lost Time, the narrator is prompted to unlock the secrets of memory after some quiet time contemplating a biscuit.
Serendipity is nice when it happens, but you may not wish to risk your precious thinking time hoping for random inspiration.
Tony Buzan recommends that once the time and place are right, you "immediately listen to music you associate with relaxation," preferring piano and baroque. Your musical mileage may vary, even to the CDs of The Smiths, Radiohead, Gorillaz and Lily Allen which Mr Cameron gave to Mr Obama during their chat.
Dr Nigel Warburton of the Open University agrees, again citing the commute as a golden opportunity. "Headphones help people remarkably. You can shut out the distractions on public transport in a way that was impossible a generation ago.
"Podcasting allows people to make far more effective use of their travel - what might have been dead time becomes valuable reflective time."
Practicing what he preaches, Dr Warburton started a series of philosophy podcasts last year and saw them beating Chris Moyles in the iTunes chart - and other contemplative 'casts are, of course, available.
For those who prefer output to input, David Hunter recommends writing down what's on your mind.
"You can gain possession of a problem by writing about it, and looking back over past issues to see how you've dealt with them. That way, you progress your learning as you go along."
And, of course, the prop that prompts your thought doesn't have to be inanimate.
"It's not a given that thought is a solitary rather than a social activity," says Dr Warburton.
"People you disagree with are what gets you going, rather than idly going through an unchallenged stream of consciousness. I think more clearly when I'm challenged."
GIVE YOURSELF LESS TO THINK ABOUT Your mobile has an "off" switch
You may have let a Japanese doctor "train your brain" in a computer game and then filled your brain with the world's knowledge courtesy of Wikipedia - but proper thinking may require you to put these to one side.
"There's a tendency in large organisations to keep us busy," says Hodgkinson, "and when we're not busy, to distract us with a never-ending stream of media like e-mail, Facebook and TV."
Sometimes, even your favourite prompts for thought may get in the way.
"I can say that all great creators, without exception, have taken breaks," says Buzan. "A minimum of two a day." "Leonardo Da Vinci had a bed in his studio and when patrons accused him of wasting time, he said 'If I don't do this, you don't get the work.'"
If your boss might raise an eyebrow or more at the sight of you installing a futon in your cubicle, you can still capture a little of the Leonardo spirit by dedicating time to avoiding the incoming memos, texts and Post-It notes - and the same goes for the homestead, says Hodgkinson.
"You have to disconnect from what stops you thinking - just stop the flow for a bit, not to a hermetic extent. You could unplug the TV or not get a daily paper for a few days."
HAVE THE DESIRE TO THINK You can get it if you really want
"The first step," says Hodgkinson, "is to have an understanding of the importance of thought. Thinking is what makes us human."
These "oases of thought" are not, of course, as scarce for everyone. If your work and life are in perfect balance, if you think that everyone else should work smarter, not harder, or if you can't understand why the rest of the world seems to think it's so busy all the time, you may be one of the lucky ones.
Dr Warburton talks about Open University students who use any means necessary to find the time for thought, getting up two hours before the children or forcing themselves not to nod off at the end of the day.
"Someone who's desperate to do something will find the time," he says. "Everyone can have an hour's less sleep. It's staying alert that's the difficulty."
However, says Hunter, the less tenacious can still reap the benefits. "Everyone needs to make time to think," he says, "not just potential leaders of nations."
Tony Buzan expresses the same idea in the form of an ultimatum.
"If you don't give the brain breaks, it will take them", he says, "in the form of loss of concentration, or what we call a mental breakdown."
Think about that.

Doctor and Patient, Now at Odds

By TARA PARKER-POPE
03 aug 2008--A growing chorus of discontent suggests that the once-revered doctor-patient relationship is on the rocks.
The relationship is the cornerstone of the medical system — nobody can be helped if doctors and patients aren’t getting along. But increasingly, research and anecdotal reports suggest that many patients don’t trust doctors.
About one in four patients feel that their physicians sometimes expose them to unnecessary risk, according to data from a Johns Hopkins study published this year in the journal Medicine. And two recent studies show that whether patients trust a doctor strongly influences whether they take their medication.
The distrust and animosity between doctors and patients has shown up in a variety of places. In bookstores, there is now a genre of “what your doctor won’t tell you” books promising previously withheld information on everything from weight loss to heart disease.
The Internet is bristling with frustrated comments from patients. On The New York Times’s Well blog recently, a reader named Tom echoed the concerns of many about doctors. “I, as patient, say stop acting like you know everything,” he wrote. “Admit it, and we patients may stop distrusting your quick off-the-line, glib diagnosis.”
Doctors say they are not surprised. “It’s been striking to me since I went into practice how unhappy patients are and, frankly, how mistreated patients are,” said Dr. Sandeep Jauhar, director of the heart failure program at Long Island Jewish Medical Center and an occasional contributor to Science Times.
He recounted a conversation he had last week with a patient who had been transferred to his hospital. “I said, ‘So why are you here?’ He said: ‘I have no idea. They just transferred me.’
“Nobody is talking to the patients,” Dr. Jauhar went on. “Everyone is so rushed. I don’t think the doctors are bad people — they are just working in a broken system.”
The reasons for all this frustration are complex. Doctors, facing declining reimbursements and higher costs, have only minutes to spend with each patient. News reports about medical errors and drug industry influence have increased patients’ distrust. And the rise of direct-to-consumer drug advertising and medical Web sites have taught patients to research their own medical issues and made them more skeptical and inquisitive.
“Doctors used to be the only source for information on medical problems and what to do, but now our knowledge is demystified,” said Dr. Robert Lamberts, an internal medicine physician and medical blogger in Augusta, Ga. “When patients come in with preconceived ideas about what we should do, they do get perturbed at us for not listening. I do my best to explain why I do what I do, but some people are not satisfied until we do what they want.”
Others say the problem also stems from a grueling training system that removes doctors from the world patients live in.
“By the time you’re done with your training, you feel, in many ways, that you are as far as you could possibly be from the very people you’ve set out to help,” said Dr. Pauline Chen, most recently a liver transplant surgeon at the University of California, Los Angeles, and the author of “Final Exam: A Surgeon’s Reflections on Mortality” (Knopf, 2007). “We don’t even talk the same language anymore.”
Dr. David H. Newman, an emergency room physician at St. Luke’s-Roosevelt Hospital Center in Manhattan, says there is a disconnect between the way doctors and patients view medicine. Doctors are trained to diagnose disease and treat it, he said, while “patients are interested in being tended to and being listened to and being well.”
Dr. Newman, author of the new book “Hippocrates’ Shadow: Secrets from the House of Medicine” (Scribner), says studies of the placebo effect suggest that Hippocrates was right when he claimed that faith in physicians can help healing. “It adds misery and suffering to any condition to not have a source of care that you trust,” Dr. Newman said.
But these doctors say the situation is not hopeless. Patients who don’t trust their doctor should look for a new one, but they may be able to improve existing relationships by being more open and communicative.
Go to a doctor’s visit with written questions so you don’t forget to ask what’s important to you. If a doctor starts to rush out of the room, stop him or her by saying, “Doctor, I still have some questions.” Patients who are open with their doctors about their feelings and fears will often get the same level of openness in return.
“All of us, the patients and the doctors, ultimately want the same thing,” Dr. Chen said. “But we see ourselves on opposite sides of a divide. There is this sense that we’re facing off with each other and we’re not working together. It’s a tragedy.”

Varenicline versus transdermal nicotine patch for smoking cessation: Results from a randomised, open-label trial

Henri-Jean Aubin
03 aug 2008--Varenicline, a new treatment for smoking cessation, has demonstrated significantly greater efficacy over placebo and sustained release bupropion (bupropion SR). Here we compare a 12-week standard regimen of varenicline with a 10-week standard regimen of transdermal nicotine replacement therapy (NRT) for smoking cessation.
Methods: In this 52-week, open-label, randomised, multicentre, phase 3 trial conducted in Belgium, France, the Netherlands, United Kingdom and United States, participants were randomly assigned (1:1) to receive varenicline up-titrated to 1 mg twice daily for 12 weeks or transdermal nicotine (21 mg/day reducing to 7 mg/day) for 10 weeks. Non-treatment follow-up continued to Week 52. The primary outcome was biochemically confirmed (exhaled carbon monoxide of 10 ppm) self-reported continuous abstinence rate (CAR) for the last 4 weeks of the treatment period in participants who had taken at least one dose of therapy. Secondary outcomes included CAR from the last 4 weeks of treatment through Weeks 24 and 52, and measures of craving, withdrawal and smoking satisfaction.
Results: In total, 376 and 370 participants assigned to varenicline and NRT respectively were eligible for analysis. The CAR for the last 4 weeks of treatment was significantly greater for varenicline (55.9%) than NRT (43.2%; odds ratio [OR] 1.70, 95% confidence interval [CI] 1.26 to 2.28, p<0.001). The Week 52 CAR (NRT,Weeks 8-52; varenicline,Weeks 9-52) was 26.1% for varenicline and 20.3% for NRT (OR 1.40, 95% CI, 0.99 to 1.99, p=0.056). Varenicline significantly reduced craving (p<0.001), withdrawal symptoms (p<0.001) and smoking satisfaction (p<0.001) versus NRT. The most frequent adverse event was nausea (varenicline, 37.2%, NRT, 9.7%).
Conclusions: The outcomes of this registered clinical trial (Clinical Trials Identification Number: NCT00143325) established that abstinence from smoking was greater, and craving, withdrawal symptoms and smoking satisfaction less, at the end of treatment with varenicline than with transdermal nicotine.

ICAD: Pondering Over Woes in Middle Age May Save the Brain in Later Life

By Peggy Peck
CHICAGO, 02 aug 2008-- Men who spend their 40s and 50s focusing on the difficulties of daily life may be rewarded with a dementia-free old age, researchers reported here.
A study of Israeli men found that those who ruminated -- going over and over worrisome details -- during midlife were about 30% to 40% less likely to develop dementia in their 80s, Ramit Ravona-Springer, M.D., of Sheba Medical Center in Ramat Gan, Israel, told attendees at the International Conference on Alzheimer's Disease.
The cohort were 9,000 participants in the Israeli Ischemic Heart Disease study, which is a longitudinal look at incidence and risk factors for cardiovascular disease among Jewish male civil service workers, who were assessed for "rumination" in 1963.
At the initial assessment, the men ranged in age from 40 to 60. The mean age at follow-up in 1999 was 82.
Rumination was defined as the "unintentional process of repetitively focusing attention on one's depressed mood and potential causes and implications of it," said Dr. Ravona-Springer.
To gauge rumination, men were asked, "when your wife/ children/peer/superior hurts you, do you forget this, tend to forget, tend to ruminate, or usually ruminate."
Men who said they forgot or tended to forget scored low on the rumination scale with a one (forget) or two (tended to forget), while those who said they tend to ruminate received a three, and those who usually ruminate were given a four.
In 1999, the researchers conducted follow-up examinations on 1,715 of the 2,600 survivors of the original cohort.
At follow-up, 24% of the men who forgot about hurts inflicted by co-workers or superiors and 21% of those who forgot a hurt by a child or wife had developed dementia.
But only 14% of the men who usually ruminated over hurts inflicted by spouses or children and 15% of those who ruminated about hurts inflicted by peers and bosses had developed dementia.
There were no differences in blood pressure, cholesterol levels, diabetes, or tobacco use by rumination status.
Men with the highest rumination score had a slightly higher survival rate after age 70 -- 63% -- but it was not significantly different from the survival rate for men with low rumination scores.
Dr. Ravona-Springer said that, on first glance, the findings differ from other studies that have linked rumination with depression, and neuroticism, both of which are believed to increase the risk of dementia.
One possible explanation would be the type of rumination -- reflection or brooding.
Reflection, she said, "consists of contemplation, which is proposed to be adaptive, and not associated with increased risk of depression."
Brooding, by contrast, consists of what she called "moody pondering" and it is considered a maladaptive tendency that does increase the risk of depression.
The ruminating men in this study may have been men who were given to reflective pondering, "leading to problem solving, a cognitive activity that may be protective."
No funding source was disclosed. Dr. Ravona-Springer disclosed no financial conflicts.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Ravona-Springer R, et al "Tendency for rumination as a psychological cognitive style in midlife is associated with decreased risk for dementia three decades later" ICAD 2008; Abstract O8-A-2763_ALZ.

Sleep apnea linked to increased risk of death

02 aug 2008--Sleep-disordered breathing (also known as sleep apnea) is associated with an increased risk of death, according to new results from the Wisconsin Sleep Cohort, an 18-year observational study supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. Researchers found that adults (ages 30 to 60) with sleep-disordered breathing at the start of the study were two to three times more likely to die from any cause compared to those who did not have sleep-disordered breathing. The risk of death was linked to the severity of sleep-disordered breathing and was not attributable to age, gender, body mass index (an indicator of overweight or obesity), or cardiovascular health status.
"Sleep-Disordered Breathing and Mortality: Eighteen-Year Follow-Up of the Wisconsin Sleep Cohort," is published August 1 in the journal Sleep.
Researchers followed 1522 generally healthy men and women for an average of 13.8 years after testing them for sleep-disordered breathing using a standard overnight sleep test. Participants with severe sleep-disordered breathing were three times more likely to die during the study than those without breathing problems during sleep. Those who were not treated were at even greater risk. Participants with untreated severe sleep-disordered breathing were four times more likely to die from any cause and five times more likely to die from cardiovascular conditions.
The Wisconsin Sleep Cohort is the most comprehensive assessment yet of mortality risks associated with sleep-disordered breathing and the first to study a randomly selected population of adults in the United States. The findings suggest that the treatment of severe sleep-disordered breathing may be protective, especially against cardiovascular deaths. Further studies are needed to determine whether the findings are applicable across the United States, and how treatment may improve survival, quality of life, and the overall health status of affected individuals.
Michael J. Twery, PhD, director of the NHLBI National Center on Sleep Disorders Research, is available to comment on these findings, as well as on associated health risks of sleep-disordered breathing, and the importance of diagnosing and treating the condition.
An estimated 12-18 million Americans have moderate to severe sleep-disordered breathing. Periodically during sleep, the upper airway becomes narrowed or blocked, and air has trouble reaching the lungs; in some cases, breathing stops completely (called apnea) for seconds to minutes at a time. The frequent pauses in breathing disrupt sleep and prevent adequate amounts of oxygen from entering the bloodstream. Interruptions in breathing are potentially serious medical conditions and should be evaluated by a physician to determine whether treatment is needed.
Because affected individuals are asleep and typically unaware of the breathing problems, and the condition cannot be diagnosed during routine physician office visits, most people with sleep-disordered breathing are undiagnosed.
Untreated sleep-disordered breathing has been linked to a greater risk of cardiovascular disease and risk factors – including high blood pressure, stroke, and diabetes -- as well as to excessive daytime sleepiness, which can impair quality of life and performance on the job or in school, and increase the risk of injury or death from work-related accidents and vehicular crashes.
Common signs that should be discussed with a physician include complaints of snoring from bed partners, excessive daytime sleepiness, and morning headache. Sleep-disordered breathing occurs in people of all ages, but is more common in men, the elderly, and overweight individuals. With the growing prevalence of overweight and obesity in the United States and the aging population, the number of individuals with sleep-disordered breathing is likely to rise.
###
NOTE: On July 28, 2008, the first joint Scientific Statement on Sleep Apnea and Cardiovascular Disease by the American Heart Association (AHA) and the American College of Cardiology was published online in the Journal of the American College of Cardiology and Circulation. Written in collaboration with the NHLBI National Center on Sleep Disorders Research, the statement describes the types and prevalence of sleep disordered breathing (apnea), and its relevance to individuals who either are at risk for or already have established cardiovascular disease. The committee issued the statement recommending that sleep disordered breathing be evaluated in patients with cardiovascular disease because of the increasing evidence, the widespread prevalence of sleep apnea, and its association with the rising levels of obesity.
For more information:
Sleep apnea, http://www.nhlbi.nih.gov/health/public/sleep/sleep_apnea.htm
Your Guide to Healthy Sleep, http://www.nhlbi.nih.gov/health/public/sleep/healthy_sleep.htm
The National Center on Sleep Disorders Research, http://www.nhlbi.nih.gov/about/ncsdr/index.htm
Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at www.nhlbi.nih.gov.
The National Institutes of Health — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

No substitute for hard work: Creatine supplementation does not improve exercise outcomes in COPD

02 aug 2008--Creatine, a popular nutritional supplement renowned for enhancing athletic performance and muscle strength, does not improve exercise outcomes in patients with chronic obstructive pulmonary disease (COPD), according to a new study. The randomized, placebo-controlled, double-blind study provided the most powerful evidence to date that the effect of creatine (Cr) supplementation was negligible at best among these patients.
"We have evidence to suggest Cr uptake into muscles [in COPD patients] but are unable to explain why an increase in muscle Cr did not enhance training," wrote the study's lead author, Sarah Deacon, M.D., specialist registrar at the Institute for Lung Health at Glenfield Hospital in Leicester, England.
The results were published in the first issue for August of the American Journal of Respiratory and Critical Care Medicine by the American Thoracic Society (ATS).
Cr supplementation has been shown to improve short-burst, high-intensity exercise function in athletes, as well as enhancing isometric muscle strength, lower body endurance and lean body mass in the elderly. To determine whether Cr supplementation could similarly enhance the physical condition of COPD patients, Dr. Deacon and co-researchers recruited 100 patients with COPD to either receive Cr or a placebo over the course of a seven week pulmonary rehabilitation program.
Those who were randomized to the placebo group were give lactose supplements that appeared identical to the Cr-containing supplements. Following a five-day loading period (22g/d Cr or 24 g/d lactose) each subject followed maintenance dosing of 3.76 or 4 g of Cr or lactose respectively.
Of the original 100 subjects, 80 successfully completed the study. In both control and Cr groups, there were statistically significant improvements in functional and muscular performance during the loading phase, but no differences were seen between the groups. The Cr group also showed a greater, but non-significant percentage of improvement in the incremental shuttle walking test with loading and after pulmonary rehabilitation, but additional analysis still showed no overall effect between it and the placebo group.
"The most likely explanation is that any benefits of creatine have been submerged by the large training effect of physical training alone," wrote Dr. Deacon.
This study, therefore, further validates that there is no substitute for the old-fashioned hard work that is an essential element of pulmonary rehabilitation. "Those of us interested in pulmonary rehabilitation are happy to see confirmation of the beneficial effects of exercise training…. This information indicates that creatine supplementation not be viewed as a good substitute for exercise training—good news for adepts of pulmonary rehabilitation," wrote Francoise Maltais, M.D., Didier Saey, Ph.D., and Richard Debigare, Ph.D., all of the Centre de Recherche de l'Hospital Laval Quebec in Canada.
"Without minimizing the importance of the quest to optimize the results of pulmonary rehabilitation, we had to appreciate that only a small portion of patients with COPD actually engage in pulmonary rehabilitation….so improved [access] is important for PR to achieve its full potential from a public health perspective."
Dr. John Heffner, past president of the ATS, commented that "these and other studies are finally gaining recognition that pulmonary rehabilitation is an essential element of comprehensive care for patients with COPD. The weight of the evidence has succeeded in gaining Medicare payment for rehabilitation services, which has been one of our major hurdles to access."

Flu Vaccine Doesn't Protect Seniors From Pneumonia

By Steven Reinberg
02 aug 2008 -- Flu vaccine may not protect older people from pneumonia once they get the disease, researchers report.
Older, frail adults are more susceptible to getting the flu, even if they have been vaccinated, and once getting the flu, they are more susceptible to such complications as pneumonia. It had been thought that flu vaccine would prevent flu -- and pneumonia -- across all groups of seniors, but this benefit appears to be largely confined to younger, healthier seniors.
"In seniors, flu vaccine was not linked to a reduced risk of pneumonia," said lead researcher Michael L. Jackson, a postdoctoral fellow at the Group Health Center for Health Studies in Seattle.
Jackson still recommends that seniors get flu vaccine, however. "There have been good randomized trials that show, at least in healthy seniors, that the vaccine reduces the risk of influenza," he said. "However, earlier studies have overestimated how well the vaccine works in reducing complications of influenza. So, the vaccine may not reduce the risk of complications as much as previously thought," he said.
Among young healthy seniors, the vaccine reduces the risk of flu, Jackson said. "When you look at the total population of seniors, which includes people over 75 and people that have chronic health diseases -- lung disease, heart disease, diabetes, and things like that -- we don't know if the vaccine is effective in the seniors," he said. "People with these chronic diseases are more susceptible to getting the flu, and they are more likely to develop pneumonia if they do get influenza."
The report is published in the Aug. 2 issue of The Lancet.
For the study, Jackson's team collected data on 1,173 people between the ages of 65 and 94 who developed pneumonia They compared these individuals with 2,346 people who did not get pneumonia. Both groups had similar rates of flu vaccination over the three seasons of studies, the researchers say.
The researchers found that vaccinated seniors who got the flu were as likely to develop pneumonia as unvaccinated seniors who got the flu.
Dr. Pascal James Imperato, dean of the master of public health program at the State University of New York Downstate Medical Center in New York City, was not surprised by these results.
"We know that elderly people do not form sufficient antibodies to certain vaccines, the flu vaccine included," Imperato said. "In addition, people in their 70s and 80s and 90s are more prone to pneumonia with or without influence. A number of these pneumonias may be secondary to other causes aside from influenza."
Even though many of the elderly will not develop sufficient antibodies to the flu vaccine, getting the shot is still worthwhile, Imperato said. "Having many people vaccinated builds up a herd immunity to disease, and you create barriers to transmission," he added.
Dr. Marc Siegel, a clinical associate professor of medicine at New York University School of Medicine in New York City, said the results of this study fly in the face of prevailing wisdom.
Siegel noted that 36,000 people in the United States die each year from the flu. "Over 90 percent of them are elderly," he said. "We give the flu shot primarily to prevent elderly deaths.
The effectiveness of the flu vaccine varies year to year, however, depending on how good a match it is for the circulating strains of influence. "In the best years, the flu vaccine is really only 40 to 60 percent effective," Siegel added.
In addition, Siegel thinks that the flu vaccine protects against other complication including respiratory diseases, which can also be fatal. "There are plenty of flu-related complications that are life-threatening besides pneumonia," he said.
"This study is a reminder that flu vaccines are not a panacea, but they are valuable, because they cut down on the incidence of influenza," Siegel said. "Flu shots definitely cut down on the number of flu-related deaths."

Alzheimer's Research Holds Promise

By ALICE PARK

01 aug 2008--When it comes to Alzheimer's disease, there hasn't been much to celebrate in recent years. Efforts to develop a vaccine against the brain disorder have stalled, and no drugs have been able to reverse the slow death of neurons that robs people of their memories and thoughts. For the first time in many years, however, researchers in the field are genuinely excited about the potential for effective drug treatments and helpful new risk factors.
Scientists gathered this week at the Alzheimer's Association's International Conference on Alzheimer's Disease in Chicago, presenting a slew of promising results from drug trials, a new understanding of how the neurological disease works and insights into the way social and lifestyle factors may affect its progression. "On the one hand, Alzheimer's disease is a complex pathologic process, and that is daunting," says Dr. Ronald Petersen, chair of the Alzheimer's Association's medical and scientific advisory council and director of the Mayo Clinic Alzheimer's Disease Research Center. "But now we are beginning to segregate out different therapeutic targets and develop drugs that have an impact on each target, so in combination they may handle the disease better than any single approach."
The potential success of the combination strategy was borne out in some of the conference's most exciting papers. Researchers from Mount Sinai School of Medicine reported, for example, that compared with other Alzheimer's patients, those who had diabetes and took insulin plus another anti-diabetes medication to control blood sugar had 80% fewer amyloid plaques - the sticky brain-clogging masses that, together with protein tangles, are the hallmarks of Alzheimer's disease. Although the mechanism wasn't entirely clear, researchers think the drugs may work by normalizing the brain's communication network of insulin receptors, which goes awry in the Alzheimer's brain, while clearing away the damaging plaques.
In a separate trial, an experimental drug called rember, developed by a Singapore-based company, also showed some promise in a safety study. Among 321 patients, rember appeared to stall advancement of the disease, degrading the protein tangles that build up in Alzheimer's brains. Potentially, a combination of drug therapies - designed to prevent both plaques and tangles - may prove effective in slowing the progression of the disease.
But future approaches won't stop with drug treatments. Petersen notes that researchers are also forging ahead with innovative screening tests to identify Alzheimer's patients sooner - before too much deterioration occurs in the brain. Better screens could also potentially identify patients by the specific type of brain buildup - plaques vs. tangles - that is causing them the most severe problems. That kind of triage early on could help doctors target the right patients with the most effective therapies.
Alzheimer's doctors also reported new discoveries about certain lifestyle factors that may accelerate or slow the dementia that often precedes Alzheimer's. Swedish psychologists studied rates of the disease in a sample of 1,449 people over a period of 21 years. They found, as previous research has suggested, that single people have up to twice the risk of developing Alzheimer's as their married counterparts. But what was unexpected was the finding that the reason for a person's singlehood impacts his or her risk. Compared with other singletons, people who were single as a result of divorce or widowing had a three times and six times greater risk, respectively. "This was quite unexpected," says Krister Hakansson, who led the study and is a lecturer in psychology and a Ph.D. candidate at Vaxjo University and the Karolinska Institute. "We established the association, but when it comes to explaining it, we can only speculate at this state."
One reason for the higher risk could be that those who had the cognitive protection and social benefits of a relationship but lost them may be worse off than those who never enjoyed those benefits at all; or perhaps the emotional toll of losing a close partner damages cognitive functions in a way that puts these people at greater risk for dementia and Alzheimer's down the line. Either way, says Hakansson, the results suggest that "if you are looking for interventions to prevent Alzheimer's, one way may be to identify people who have been divorced or widowed, and who haven't adapted or gotten back into the social circle, and give them support with the aim of giving them new structure and social networks in their lives."
As more discoveries are made, researchers hope they'll develop a better understanding of who is most at risk of Alzheimer's disease, how each patient's case is unique, and how best to treat specific patients with the drug and lifestyle changes that will be most effective for them. Taken together, these approaches could one day make the long goodbye of Alzheimer's a thing of the past.

ICAD: Investigational Alzheimer's Drug Found Beneficial in Extension Trial

By Todd Neale
CHICAGO, 01 aug 2008 -- For patients with mild to moderate Alzheimer's disease, the investigational drug dimebon continued to show benefits and safety in a six-month, open-label extension of a placebo-controlled trial, researchers reported here. Earlier this month, Rachelle Doody, M.D., of Baylor College of Medicine in Houston, and colleagues reported in The Lancet that after one year, Alzheimer's patients who received dimebon had significantly improved cognitive function, memory, activities of daily living, and behavior compared with those on placebo, who progressively worsened. Participants in both groups were then eligible to enroll in the six-month open-label extension and 104 patients -- 54 who had been taking dimebon and 50 who had received placebo -- entered the study.
As expected, those who had originally been taking dimebon began to decline to below baseline values on the various measures through the extension phase, but the declines were delayed compared with the estimated drop in function with placebo.
"We did not arrest the disease permanently," said co-author Jeffrey Cummings, M.D., of the University of California Los Angeles, at the International Conference on Alzheimer's Disease. "Eventually the mechanisms of the disease, whatever they are, overwhelm the benefits of dimebon."
Patients who had been on placebo stabilized when they crossed over to treatment with dimebon for the extension phase, but at a lower level of function than those who were originally taking the active treatment.
"This emphasizes the benefit of earlier treatment, and suggests the possibility that dimebon may slow the progression of Alzheimer's," Dr. Cummings said.
"However," he added, "open-label extensions are not the same as placebo-controlled trials, and extrapolation of the treatment results should be done with caution."
The researchers are currently enrolling patients for a phase III clinical trial to be conducted in multiple countries, including the U.S.
According to Dr. Cummings, the FDA has said that the trial will provide enough evidence to move forward with a new drug application. He said that dimebon could be on the market by 2011.
Dimebon works by repairing mitochondrial function at sites of cellular stress, such as beta-amyloid plaques. The repair might help prevent cell death and increase signaling between neurons, according to Dr. Cummings.
In the six-month extension phase, the 104 participants were all given 20 mg of dimebon three times a day; 92 (88.5%) completed treatment.
The mean age of the participants at the beginning of the extension phase was 69. Those who had been taking dimebon in the one-year study had a higher mean score on the Mini-Mental State Examination compared with those who had been taking placebo (19 versus 17).
The projected decline on various assessments if a patient was to take placebo was estimated using a linear regression analysis of data from the one-year study.
Those who received dimebon in the one-year study preserved function close to baseline values after 18 months and continued to show an advantage over the predicted decline with placebo.
On the Alzheimer's Disease Assessment Scale -- cognitive subscale (ADAS-cog), patients who had received dimebon for 18 months had a significantly smaller decline than those who had crossed over from placebo (P<0.05).
On the Alzheimer's Disease Cooperative Study -- Activities of Daily Living (ADCS-ADL) scale, patients who were on dimebon dropped 2.40 points through 18 months, compared with a 4.3-point decline in those who had been taking placebo.
On the Neuropsychiatric Inventory (NPI), patients who were taking dimebon declined by 0.68 points at 18 months, compared with 3.2 points in those who were taking placebo.
On the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), 57.4% of patients on dimebon improved or showed no change at 18 months, compared with 39.1% of placebo patients.
Dr. Cummings said that dimebon was well tolerated, although dry mouth, sweating, and depressed mood and sadness were more common in patients taking active treatment compared with placebo.
He said that the rates of depression with active treatment (about 15%) were not high enough to halt the phase III trial that is being planned.
The study was funded by Medivation, maker of dimebon.
Dr. Cummings and three of his co-authors reported serving as consultants for Medivation. Two of his co-authors are employees, shareholders, and board members of Medivation.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Cummings J, et al "18-month data from an open-label extension of a one-year controlled trial of dimebon in patients with mild-to-moderate Alzheimer's disease" ICAD 2008; Abstract P4-334.

ICAD: Monoclonal Antibody that Binds to Amyloid Found Safe in Alzheimer's

By Todd Neale
CHICAGO,01 aug 2008-- An investigational monoclonal antibody that binds to beta-amyloid was well tolerated by Alzheimer's patients in a 12-week phase II study that was too short to establish meaningful clinical efficacy endpoints.
With a goal of enabling the body to more easily clear beta-amyloid42, from which plaques are predominantly made, LY2062430 was given IV to 52 Alzheimer's patients, said Eric Siemers, M.D., of Eli Lilly in Indianapolis, maker of the antibody, at the International Conference on Alzheimer's Disease here.
Dr. Siemers said the increased clearance of beta-amyloid could potentially slow the progression of Alzheimer's by preventing the build-up of plaques.
The antibody was well tolerated, he said, with no infusion reactions or evidence in the cerebrospinal fluid or on MRI scans of meningoencephalitis, microhemorrhage, or edema through 112 days of follow-up.
There was a slight immune response to the antibody in five patients, but it did not affect the pharmacokinetics or binding of beta-amyloid, Dr. Siemers said.
On the basis of the results, a phase III trial will be conducted starting in 2009.
Dr. Siemers and colleagues recruited patients diagnosed with mild-to- moderate Alzheimer's disease (mean age 71.2, mean baseline Mini-Mental State Examination score 20.2).
They were given infusions of the antibody for 12 weeks at one of four doses -- 100 mg per week (10), 100 mg every four weeks (11), 400 mg per week (11), or 400 mg every four weeks (10) -- or placebo (10).
All doses of antibody increased mean plasma concentrations of beta-amyloid to about 100,000 pg/mL for beta-amyloid40 and 10,000 pg/mL for beta-amyloid42.
About a 10th of a percent of the antibody entered the cerebrospinal fluid and similar increases in beta-amyloid concentration were found.
Surprisingly, as the dose increased, the amount of beta-amyloid42 -- the form of the protein found primarily in plaques -- that was not bound to the antibody also increased in the cerebrospinal fluid.
According to Dr. Siemers, that finding suggested that the antibody was not simply binding free beta-amyloid, which would cause the amount of the protein to decrease, but was also dissolving plaques in the brain.
Two other types of protein found primarily in plaques also increased in the plasma and cerebrospinal fluid with higher doses of the antibody, further strengthening the evidence that plaques were dissolving, he said.
However, MRI scans did not show any reduction in the amyloid plaque load in the brain through 12 weeks. The scans and the tracer used may not have been sensitive enough to detect the changes, Dr. Siemers said.
As expected, he said, there were no significant differences between the treatment groups or the placebo group in cognitive function measured using the Alzheimer's Disease Assessment Scale -- cognitive subscale.
The study was funded by Eli Lilly, maker of the antibody.
Dr. Siemers and four of his co-authors are employees of Eli Lilly. The other four co-authors have received grants or research support from the company.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Siemers E, et al "Safety, tolerability, and biomarker effects of an Abeta monoclonal antibody administered to patients with Alzheimer's disease" ICAD 2008; Abstract P4-346.

Advances Made Against Alzheimer's Disease

By Ed Edelson
01 aug 2008--New reports on very different approaches to treating Alzheimer's disease could one day lead to better therapies for the mind-robbing condition, experts say.
A trio of studies that were presented Wednesday at the Alzheimer's Association 2008 International Conference on Alzheimer's Disease in Chicago noted progress made on three different treatment fronts.
The first involves a drug called Dimebon, with positive results being reported from tests in Russia. Dimebon is an antihistamine, and data from the Russian trials indicated that Dimebon might have value in treating Alzheimer's.
This buttressed American research reported earlier this year that showed improvements in Alzheimer's patients given Dimebon in a controlled study. The drug is believed to prevent the death of brain cells.
Researchers at the University of California, Los Angeles, studied 183 people who had mild to moderate Alzheimer's disease. Mental function remained stable in those taking the drug, while it declined in those given a placebo. Mental function also stabilized in people who were first given a placebo after they began taking Dimebon.
Another trial used the body's immune system to prevent the mental deterioration suffered by people with Alzheimer's disease. The immune attack is aimed at the deposits of beta-amyloid protein that accumulate in the brains of patients.
"The idea has been around for almost a decade now," Nixon. "The initial notion was to use the vaccine approach to prevent amyloid deposition, injecting amyloid so the body would attack the deposits. Now we are into phase two, injecting the antibody itself."
Researchers at Eli Lilly & Co. reported on 52 people with mild to moderate Alzheimer's. Some were given weekly injections of a monoclonal antibody that binds to beta amyloid, while others were injected with a placebo.
Detailed measurements showed an increased level of beta amyloid in both blood and cerebrospinal fluid after 12 weeks in those getting the antibody, an indication that the beta amyloid in the brain might be starting to dissolve, the researchers said. New studies of the therapy are planned.
Nixon viewed the results with "tempered optimism." One interesting finding was the response to the therapy was greatest in people who did not have a known genetic marker for Alzheimer's risk, he said. "What is the significance of this? Why do carriers not respond?" Nixon asked. The answer might help explain Alzheimer's disease better, he said.
A third study using a broad spectrum of antibodies was reported by a team at Weill Cornell Medical College in New York City. The treatment, originally developed by Baxter International to treat autoimmune conditions, was given to 24 people with mild to moderate Alzheimer's disease in a set of trials extending as long as 18 months. Statistically significant increases in mental function were seen in those getting the treatment, the researchers said. A large-scale, 18-month follow-up trial will be done.