Screening for Prostate Cancer Recommendation Statement
U.S. Preventive Services Task Force (USPSTF)
10 aug 2008--Prostate cancer is the most common nonskin cancer and the second leading cause of cancer death in men in the United States.
Detection
The USPSTF found convincing evidence that prostate-specific antigen (PSA) screening can detect some cases of prostate cancer.
Benefits of Detection and Early Treatment
In men younger than age 75 years, the USPSTF found inadequate evidence to determine whether treatment for prostate cancer detected by screening improves health outcomes compared with treatment after clinical detection.
In men age 75 years or older, the USPSTF found adequate evidence that the incremental benefits of treatment for prostate cancer detected by screening are small to none.
Harms of Detection and Early Treatment
The USPSTF found convincing evidence that treatment for prostate cancer detected by screening causes moderate-to-substantial harms, such as erectile dysfunction, urinary incontinence, bowel dysfunction, and death. These harms are especially important because some men with prostate cancer who are treated would never have developed symptoms related to cancer during their lifetime.
There is also adequate evidence that the screening process produces at least small harms, including pain and discomfort associated with prostate biopsy and psychological effects of false-positive test results.
USPSTF Assessment
The USPSTF concludes that for men younger than age 75 years, the benefits of screening for prostate cancer are uncertain and the balance of benefits and harms cannot be determined.
For men 75 years or older, there is moderate certainty that the harms of screening for prostate cancer outweigh the benefits.
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Clinical Considerations
Patient Population Under Consideration
This recommendation applies to men in the general U.S. population.
Assessment of Risk
Older men, African-American men, and men with a family history of prostate cancer are at increased risk for diagnosis of and death from prostate cancer.1 Unfortunately, the previously described gaps in the evidence regarding potential benefits of screening also apply to these men.
Screening Tests
The PSA test is more sensitive than the digital rectal examination for detecting prostate cancer. The conventional PSA screening cut-point of 4.0 µg/L detects many cases of prostate cancer; however, some early cases will be missed by this cut-point.2,3 Using a lower cut-point to define an abnormal PSA level detects more cases of cancer.
The proportion of cancer cases detected by lower cutpoints that would ever become clinically apparent is unknown; lower cut-points would label many more men as potentially having cancer. For example, lowering the PSA cut-point to 2.5 µg/L would more than double the number of U.S. men between 40 and 69 years of age with abnormal results.4
Variations of PSA screening, including the use of ageadjusted PSA cut-points, free PSA, PSA density, PSA velocity, PSA slope, and PSA doubling time, have been proposed to improve detection of "clinically important" prostate cancer cases. However, no evidence suggests that any of these testing strategies improves health outcomes.2,5
Suggestions for Practice
Given the uncertainties and controversy surrounding prostate cancer screening in men younger than age 75 years, a clinician should not order the PSA test without first discussing with the patient the potential but uncertain benefits and the known harms of prostate cancer screening and treatment. Men should be informed of the gaps in the evidence and should be assisted in considering their personal preferences before deciding whether to be tested.
Treatment
Because of the uncertainty about the benefits of treating prostate cancer detected by screening men younger than age 75 years, there is no consensus regarding optimal treatment. Current management strategies for localized prostate cancer include watchful waiting (observation with palliative treatment for symptoms only), active surveillance (periodic biochemical monitoring with conversion to curative treatment for signs of disease progression), radical prostatectomy, external-beam radiation therapy, and brachytherapy (or radioactive seed implantation therapy).6
If treatment for prostate cancer detected by screening improves health outcomes, the population most likely to benefit from screening will be men age 50 to 74 years. Even if prostate cancer screening is determined to be effective, the length of time required to experience a mortality benefit is greater than 10 years. Because a 75-year-old man has an average life expectancy of about 10 years, very few men age 75 years or older would experience a mortality benefit. Similarly, men younger than age 75 years who have chronic medical problems and a life expectancy of fewer than 10 years are also unlikely to benefit from screening and treatment.2
Screening Intervals
The yield of screening in terms of cancer cases detected declines rapidly with repeated annual testing. If screening were to reduce deaths, PSA screening as infrequently as every 4 years could yield as much of a benefit as annual screening.7
Useful Resources
Shared decision-making resources specific to prostate cancer screening for clinicians and patients are available from the Centers of Disease Control and Prevention (www.cdc.gov/cancer/prostate/publications/).
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Other Considerations
Research Needs/Gaps
Good-quality randomized, controlled trials (RCTs) are needed to establish the effect, if any, of population-based PSA screening on prostate cancer mortality in men younger than age 75 years. The results of 2 ongoing trials, the U.S. Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the European Study of Screening for Prostate Cancer, should help to clarify the potential benefits of screening.
Future studies should identify testable characteristics of screening-detected prostate cancer that reliably predict poor health outcomes and that therefore may be indications for treatment. Research is needed to compare the long-term benefits of immediate treatment with delayed treatment in men with screening-detected prostate cancer. Two ongoing RCTs, the U.S. Prostate Intervention Versus Observation Trial and the U.K. Prostate Testing for Cancer and Treatment Study, are studying these issues.
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Discussion
Burden of Disease
An estimated 218 890 U.S. men received a prostate cancer diagnosis in 2007, and 1 of 6 men in the U.S. will receive the diagnosis in his lifetime.8 An estimated 27,350 men died of prostate cancer in the United States in 2006.1 The median age of death from prostate cancer from 2000 through 2004 was 80 years, and 71% of deaths occurred in men older than 75 years. African-American men have a substantially higher prostate cancer incidence rate than white men (217.5 vs. 134.5 cases per 100 000 men) and more than twice the prostate cancer mortality rate of white men (56.1 vs. 23.4 deaths per 100 000 men).9
Prostate cancer is a clinically heterogeneous disease. A substantial proportion of prostate cancer cases detected with current screening methods will never cause symptoms during the patients' lifetime. Modeling studies based on U.S. incidence data suggest overdiagnosis rates ranging from 29% to 44% of all prostate cancer cases detected by PSA screening.10 Because patients with "pseudo-disease" receive no benefit from, and may be harmed by, prostate cancer screening and treatment, prostate cancer detection in this population constitutes an important burden.
Scope of USPSTF Review
The previous review, performed for the USPSTF in 2002, found insufficient evidence that screening for prostate cancer improved health outcomes, including mortality. It also found little evidence on the harms of the screening process or the natural history of prostate cancer cases detected with screening.2 The USPSTF determined that a focused evidence update5 should systematically review direct evidence that PSA screening reduces morbidity and mortality, evidence on the magnitude and nature of harms associated with false-positive screening results, and evidence on health outcomes of patients with screeningdetected prostate cancer who did not receive active treatment.
Accuracy of Screening Tests
The 2002 review noted inherent problems with the use of needle biopsy results as a reference standard to assess the accuracy of prostate cancer screening tests. Biopsy detection rates vary according to the number of biopsies performed during a single procedure: The more biopsies performed, the more cancer cases detected. More cancer cases detected with a "saturation" (>20) biopsy procedure tend to increase the apparent specificity of an elevated PSA level; however, many additional cancer cases detected this way are likely to be clinically unimportant. Thus, the accuracy of the PSA test for detecting clinically important prostate cancer cases cannot be determined with precision.
Longitudinal follow-up has also been used as a reference standard. A retrospective study found the sensitivity of a PSA level of 4.0 µg/L or higher to be about 91% for detecting aggressive cases of prostate cancer that developed within 2 years of screening; the sensitivity was about 56% for detecting nonaggressive cancer cases within the same period. Among men who did not receive a prostate cancer diagnosis within 10 years, 9% had an initial PSA level of 4.0 µg/L or greater (which translates to a specificity of 91% for any prostate cancer).11
Effectiveness of Early Detection and Treatment
A meta-analysis of 2 poor-quality RCTs of population-based screening for prostate cancer using PSA and digital rectal examination found no reduction in prostate cancer mortality in men invited versus men not invited for screening (relative risk, 1.01 [95% CI, 0.80 to 1.29]).12 A recent RCT reported that men who received PSA screening had a decreased risk for receiving a diagnosis of metastatic prostate cancer.13 The USPSTF assessed the study as providing inconclusive evidence of benefit from screening because of a high likelihood of unequal outcome ascertainment and small absolute numbers of an imperfect intermediate health outcome (metastatic prostate cancer is an imperfect surrogate of prostate cancer mortality because of both high initial response rates to androgen deprivation therapy and competing causes of death). No RCTs have reported health outcomes from the variations of PSA screening that consist of multiple measurements over time (for example, measurements of PSA velocity, PSA slope, or PSA doubling time).
Randomized, controlled trials comparing prostate cancer treatments with watchful waiting have enrolled few patients with screening-detected prostate cancer. An RCT of 695 men with localized prostate cancer reported a small absolute reduction in all-cause mortality in patients assigned to radical prostatectomy; however, only 5.2% of participants had screening-detected prostate cancer, more than 40% presented with symptoms, and 77.8% of the treatment group had stage T2 (palpable) cancer.14 This stage of cancer is more advanced than cancer typically detected by screening. Yet, after a median of 8.2 years, only 14.4% of men in the control group and 8.6% of men in the treatment group had died of prostate cancer.
Screening-detected cancer is biologically less aggressive, is being detected much earlier in its natural history, or both, so it is unlikely that these results could be obtained in a study of screening-detected cancer in this same time frame. Even if the same disease-specific results could be obtained with a longer time frame, competing causes of death would make any reduction in all-cause mortality less than that found in the study. It is noteworthy that in the 372 men who were at least 65 years of age at the time of diagnosis, the 10-year incidence of death from prostate cancer was similar between the watchful waiting and radical prostatectomy groups, suggesting no benefit from surgery in this age group.14
Estimate of Magnitude of Net Benefit
In men younger than age 75 years, the USPSTF could not determine the net benefit of screening for prostate cancer because of low certainty about the magnitude of benefits of screening and treatment.
In men age 75 years or older, the USPSTF found no direct evidence of benefits of prostate cancer screening. However, the USPSTF was able to establish an upper bound for the potential magnitude of the benefit of treating screening-detected prostate cancer in this age group, by extrapolating from evidence of treatment for clinically detected prostate cancer in this age group.14 For a population of men with an average life expectancy of 10 years or fewer, the USPSTF determined that the benefits of prostate cancer screening and treatment would range from small to none.
Weighing this magnitude of benefit against the moderate-to-substantial psychological and physical harms associated with prostate cancer screening and treatment, the USPSTF concluded that there is at least moderate certainty that the harms of screening for prostate cancer in men age 75 years or older outweigh the benefits.
How Does Evidence Fit with Biological Understanding?
Prostate-specific antigen screening presupposes that most asymptomatic prostate cancer cases will ultimately become symptomatic cases that lead to poor health outcomes. However, the natural history of PSA-detected, nonpalpable, localized prostate cancer is poorly described. No prospective studies have followed a population-based cohort of patients with screening-detected cancer who have had no intervention in order to determine health outcomes resulting from natural progression of the disease. Evidence from small, selected cohorts of men with arbitrarily defined "favorable risk" (that is, with prostate cancer likely to be clinically indolent) suggest a good prognosis for some men with screening-detected cancer; however, the longest of these studies has reported health outcomes from 2 to 10 years after diagnosis only.5
Update of Previous USPSTF Recommendation
This recommendation replaces the 2002 recommendation. The major change in the current recommendation is that the USPSTF now recommends against screening men age 75 years or older for prostate cancer.
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Recommendations of Other Groups
Most major U.S. medical organizations recommend that clinicians discuss the potential benefits and known harms of PSA screening with their patients, consider their patients' preferences, and individualize screening decisions. They generally agree that the most appropriate candidates for screening include men age 50 years or older who have a life expectancy of at least 10 years. These organizations include the American Academy of Family Physicians, American College of Physicians,16 American College of Preventive Medicine,17 and American Medical Association. The American Cancer Society18 and American Urological Association19 recommend offering PSA measurement and digital rectal examination to men annually beginning at age 50 years.
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References
1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43-66. [PMID: 17237035]
2. Harris R, Lohr KN. Screening for prostate cancer: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:917-29. [PMID: 12458993]
3. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4.0 ng per milliliter. N Engl J Med 2004;350:2239-46. [PMID: 15163773]
4. Welch HG, Schwartz LM, Woloshin S. Prostate-specific antigen levels in the United States: implications of various definitions for abnormal. J Natl Cancer Inst 2005;97:1132-7. [PMID: 16077071]
5. Lin K, Lipsitz R, Miller T, Janakiraman S. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med 2008;149:192-9.
6. Wilt TJ, Shamliyan T, Taylor B, MacDonald R, Tacklind J, Rutks I, et al. Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer. (Prepared by Minnesota Evidence-based Practice Center under contract no. 290-02-00009.) Rockville, MD: Agency for Healthcare Research and Quality; 2008. Comparative Effectiveness Review no. 13. AHRQ publication no. 08-EHC010-1. Accessed at http://effectivehealthcare.ahrq.gov/healthInfo.cfm on 3 June 2008.
7. Roobol MJ, Grenabo A, Schröder FH, Hugosson J. Interval cancers in prostate cancer screening: comparing 2- and 4-year screening intervals in the European Randomized Study of Screening for Prostate Cancer, Gothenburg and Rotterdam. J Natl Cancer Inst 2007;99:1296-303. [PMID: 17728218]
8. National Cancer Institute, Surveillance Epidemiology and End Results (SEER). Cancer Stat Fact Sheets: Cancer of the Prostate. Rockville, MD: National Institutes of Health. Accessed at http://seer.cancer.gov/statfacts/html/prost.html on 3 June 2008.
9. U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2004 Incidence and Web-based Report. Atlanta: Centers for Disease Control and Prevention; 2007. Accessed at www.cdc.gov/uscs on 3 June 2008.
10. Etzioni R, Penson DF, Legler JM, di Tommaso D, Boer R, Gann PH, et al. Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends. J Natl Cancer Inst 2002;94:981-90. [PMID: 12096083]
11. Gann PH, Hennekens CH, Stampfer MJ. A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer. JAMA 1995; 273:289-94. [PMID: 7529341]
12. Ilic D, O'Connor D, Green S, Wilt T. Screening for prostate cancer. Cochrane Database Syst Rev 2006;3:CD004720. [PMID: 16856057]
13. Aus G, Bergdahl S, Lodding P, Lilja H, Hugosson J. Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer—results from a prospective, population-based randomized controlled trial. Eur Urol 2007;51:659-64. [PMID: 16934392]
14. Bill-Axelson A, Holmberg L, Ruutu M, Häggman M, Andersson SO, Bratell S, et al. Scandinavian Prostate Cancer Group Study No. 4. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005;352:1977-84. [PMID: 15888698]
15. American Academy of Family Physicians. Summary of Recommendations for Clinical Preventive Services, Revision 6.5, March 2008, Order No. 1968. Leawood, KS: American Academy of Family Physicians; 2007. Accessed at www.aafp.org. on 17 June 2008.
16. American College of Physicians. Screening for prostate cancer. Ann Intern Med 1997;126:480-4. [PMID: 9072936]
17. Lim LS, Sherin K. ACPM Prevention Practice Committee. Screening for prostate cancer in U.S. men ACPM position statement on preventive practice. Am J Prev Med 2008;34:164-70. [PMID: 18201648]
18. Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin 2006;56:11-25; quiz 49-50. [PMID: 16449183]
19. American Urological Association. Prostate-specific antigen (PSA) best practice policy. Oncology (Williston Park) 2000;14:267-72, 277-8, 280 passim. [PMID: 10736812]
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Members of the U.S. Preventive Services Task Force
Members of the U.S. Preventive Services Task Force* are Ned Calonge, MD, MPH, Chair (Colorado Department of Public Health and Environment, Denver, Colorado); Diana B. Petitti, MD, MPH, Vice Chair (Keck School of Medicine, University of Southern California, Sierra Madre, California); Thomas G. DeWitt, MD (Children’s Hospital Medical Center, Cincinnati, Ohio); Allen J. Dietrich, MD (Dartmouth Medical School, Lebanon, NH); Kimberly D. Gregory, MD, MPH (Cedars- Sinai Medical Center, Los Angeles, California); Russell Harris, MD, MPH (University of North Carolina School of Medicine, Chapel Hill, North Carolina); George J. Isham, MD, MS (HealthPartners, Minneapolis, MN); Michael L. LeFevre, MD, MSPH (University of Missouri School of Medicine, Columbia, Missouri); Roseanne Leipzig, MD, PhD, (Mount Sinai School of Medicine, New York, New York): Carol Loveland-Cherry, PhD, RN (University of Michigan School of Nursing, Ann Arbor, Michigan); Lucy N. Marion, PhD, RN (Medical College of Georgia, Augusta, Georgia); Bernadette Melnyk, PhD, RN (Arizona State College of Nursing and Healthcare Innovation, Phoenix, Arizona); Virginia A. Moyer, MD, MPH (University of Texas Health Science Center, Houston, Texas); Judith K. Ockene, PhD (University of Massachusetts Medical School, Worcester, Massachusetts); George F. Sawaya, MD (University of California, San Francisco, San Francisco, California); and Barbara P. Yawn, MD, MSPH, MSc (Olmsted Medical Center, Rochester, Minnesota).
*This list includes members of the Task Force at the time this recommendation was finalized. For a list of current Task Force members, go to http://www.ahrq.gov/clinic/uspstfab.htm
Sunday, August 10, 2008
U.S. Panel Questions Prostate Screening'Dramatic' Risks For Older Men Cited
By Rob Stein
10 aug 2008--The blood test that millions of men undergo each year to check for prostate cancer leads to so much unnecessary anxiety, surgery and complications that doctors should stop testing elderly men, and it remains unclear whether the screening is worthwhile for younger men, a federal task force concluded yesterday.
In the first update of its recommendations for prostate cancer screening in five years, the panel that sets government policy on preventive medicine said that the evidence that the test reduces the cancer's death toll is too uncertain to endorse routine use for men at any age, and that the potential harm clearly outweighs any benefits for men age 75 and older.
"The benefit of screening at this time is uncertain, and if there is a benefit, it's likely to be small," said Ned Calonge, who chairs the 16-member U.S. Preventive Services Task Force. It published the new guidelines today in the Annals of Internal Medicine. "And on the other side, the risks are large and dramatic."
The task force and other groups concluded previously that it was unclear whether the benefits of the prostate-specific antigen, or PSA, test outweigh the risks. The new review of the scientific literature found no evidence to alter that assessment for younger men. It did find enough new data to recommend for the first time against screening for older men.
"We felt with sufficient certainty that your risk of being harmed exceeded your potential benefits starting at age 75," Calonge said.
The recommendations come at a time when doctors are increasingly questioning whether many tests, drugs and procedures are being overused, unnecessarily driving up health-care costs and exposing patients to the risks of unneeded treatment.
"There is this idea that more is always better, and if a test is available we should use it," said Howard A. Brody, a professor of family medicine at the University of Texas Medical Branch at Galveston. "A lot of times, we're doing more harm than good."
The guidelines address perhaps the most important and contentious issue in men's health, and were praised by officials at several leading medical groups, including the National Cancer Institute and the American Cancer Society. But they drew strong criticism from others who are convinced that routine screening is necessary.
"I think they're really missing the boat," said William J. Catalona, a professor of urology at Northwestern University. "It's a disservice to patients. A lot of men die from prostate cancer, and there's just an overwhelming amount of evidence that screening saves lives."
Each year, prostate cancer is diagnosed in more than 218,000 U.S. men. About 28,000 die of it, making it the most common cancer and second-leading cancer killer among men.
The PSA test, which measures a protein in the blood produced by prostate tissue, has significantly increased the number of prostate cancer cases being diagnosed at very early stages. But it remains unclear whether that translates into a reduction in the death rate from the disease. Prostate cancer often grows so slowly that many men die from something else without ever knowing they had it.
Because it is not clear precisely what PSA level signals the presence of cancer, many men experience stressful false alarms that lead to unnecessary surgical biopsies to make a definitive diagnosis, which can be painful and in rare cases can cause serious complications.
Even when the test picks up a real cancer, doctors are uncertain what, if anything, men should do about it. Many men simply are monitored closely to see if the tumor shows signs of growing or spreading. Others undergo surgery, radiation and hormone treatments, which often leave them incontinent, impotent and experiencing other complications.
"People say, 'What's the harm in screening?' In fact, there are several ways in which screening can actually be harmful," said Howard L. Parnes of the National Cancer Institute.
Since the task force issued its previous recommendations in 2002, at least eight new studies have been published. Among them was a large Swedish review that found that men age 65 and older who were treated for prostate cancer were no more likely to survive than those who were not.
"If therapy isn't providing meaningful benefit, then how could screening provide benefit?" Calonge said. "And we know that the therapy produces significant harms."
Men younger than 75 should be carefully counseled about the potential risks associated with the test and the lack of evidence about any benefit before getting it, the panel said.
Men at high risk for prostate cancer, such as African Americans and those with a family history of the disease, are the most likely to benefit from PSA screening. But the panel concluded that the evidence remains inconclusive for those men as well.
Several other experts said that the new recommendations strike a careful balance, and that they hope they might discourage large-scale screenings where the risks and benefits are not carefully laid out.
"I think they are right on target," Parnes said.
Others were highly critical, noting that prostate cancer death rates have plummeted in many countries after they instituted widespread PSA screening.
"We have seen a dramatic drop in mortality," said J. Brantley Thrasher, chairman of the urology department at the University of Kansas and a spokesman for the American Urological Association. "They're not paying attention to that."
Others objected to setting an age cutoff, saying men should be evaluated individually.
"Men are living a lot longer and healthier these days. I play golf with 84-year-old guys who beat me all the time," said E. David Crawford, a professor of surgery and radiation at the University of Colorado at Denver. "You have to individualize treatment. If a 75-year-old man is found to have high-grade prostate cancer, it's going to kill him, and we can intervene and do something for him."
Two large studies are underway -- one in the United States and one in Europe -- to answer the question of whether screening reduces mortality.
"If it turns out that PSA screening and aggressive treatment saves lives, maybe all the harm that it has caused is worth it," said Otis W. Brawley, chief medical officer at the American Cancer Society. "If PSA screening does not save lives, then it's clearly not worth it. We just don't know yet."
By Rob Stein
10 aug 2008--The blood test that millions of men undergo each year to check for prostate cancer leads to so much unnecessary anxiety, surgery and complications that doctors should stop testing elderly men, and it remains unclear whether the screening is worthwhile for younger men, a federal task force concluded yesterday.
In the first update of its recommendations for prostate cancer screening in five years, the panel that sets government policy on preventive medicine said that the evidence that the test reduces the cancer's death toll is too uncertain to endorse routine use for men at any age, and that the potential harm clearly outweighs any benefits for men age 75 and older.
"The benefit of screening at this time is uncertain, and if there is a benefit, it's likely to be small," said Ned Calonge, who chairs the 16-member U.S. Preventive Services Task Force. It published the new guidelines today in the Annals of Internal Medicine. "And on the other side, the risks are large and dramatic."
The task force and other groups concluded previously that it was unclear whether the benefits of the prostate-specific antigen, or PSA, test outweigh the risks. The new review of the scientific literature found no evidence to alter that assessment for younger men. It did find enough new data to recommend for the first time against screening for older men.
"We felt with sufficient certainty that your risk of being harmed exceeded your potential benefits starting at age 75," Calonge said.
The recommendations come at a time when doctors are increasingly questioning whether many tests, drugs and procedures are being overused, unnecessarily driving up health-care costs and exposing patients to the risks of unneeded treatment.
"There is this idea that more is always better, and if a test is available we should use it," said Howard A. Brody, a professor of family medicine at the University of Texas Medical Branch at Galveston. "A lot of times, we're doing more harm than good."
The guidelines address perhaps the most important and contentious issue in men's health, and were praised by officials at several leading medical groups, including the National Cancer Institute and the American Cancer Society. But they drew strong criticism from others who are convinced that routine screening is necessary.
"I think they're really missing the boat," said William J. Catalona, a professor of urology at Northwestern University. "It's a disservice to patients. A lot of men die from prostate cancer, and there's just an overwhelming amount of evidence that screening saves lives."
Each year, prostate cancer is diagnosed in more than 218,000 U.S. men. About 28,000 die of it, making it the most common cancer and second-leading cancer killer among men.
The PSA test, which measures a protein in the blood produced by prostate tissue, has significantly increased the number of prostate cancer cases being diagnosed at very early stages. But it remains unclear whether that translates into a reduction in the death rate from the disease. Prostate cancer often grows so slowly that many men die from something else without ever knowing they had it.
Because it is not clear precisely what PSA level signals the presence of cancer, many men experience stressful false alarms that lead to unnecessary surgical biopsies to make a definitive diagnosis, which can be painful and in rare cases can cause serious complications.
Even when the test picks up a real cancer, doctors are uncertain what, if anything, men should do about it. Many men simply are monitored closely to see if the tumor shows signs of growing or spreading. Others undergo surgery, radiation and hormone treatments, which often leave them incontinent, impotent and experiencing other complications.
"People say, 'What's the harm in screening?' In fact, there are several ways in which screening can actually be harmful," said Howard L. Parnes of the National Cancer Institute.
Since the task force issued its previous recommendations in 2002, at least eight new studies have been published. Among them was a large Swedish review that found that men age 65 and older who were treated for prostate cancer were no more likely to survive than those who were not.
"If therapy isn't providing meaningful benefit, then how could screening provide benefit?" Calonge said. "And we know that the therapy produces significant harms."
Men younger than 75 should be carefully counseled about the potential risks associated with the test and the lack of evidence about any benefit before getting it, the panel said.
Men at high risk for prostate cancer, such as African Americans and those with a family history of the disease, are the most likely to benefit from PSA screening. But the panel concluded that the evidence remains inconclusive for those men as well.
Several other experts said that the new recommendations strike a careful balance, and that they hope they might discourage large-scale screenings where the risks and benefits are not carefully laid out.
"I think they are right on target," Parnes said.
Others were highly critical, noting that prostate cancer death rates have plummeted in many countries after they instituted widespread PSA screening.
"We have seen a dramatic drop in mortality," said J. Brantley Thrasher, chairman of the urology department at the University of Kansas and a spokesman for the American Urological Association. "They're not paying attention to that."
Others objected to setting an age cutoff, saying men should be evaluated individually.
"Men are living a lot longer and healthier these days. I play golf with 84-year-old guys who beat me all the time," said E. David Crawford, a professor of surgery and radiation at the University of Colorado at Denver. "You have to individualize treatment. If a 75-year-old man is found to have high-grade prostate cancer, it's going to kill him, and we can intervene and do something for him."
Two large studies are underway -- one in the United States and one in Europe -- to answer the question of whether screening reduces mortality.
"If it turns out that PSA screening and aggressive treatment saves lives, maybe all the harm that it has caused is worth it," said Otis W. Brawley, chief medical officer at the American Cancer Society. "If PSA screening does not save lives, then it's clearly not worth it. We just don't know yet."
Treadmill test has limited usefulness
It won't detect some heart problems.
By Jane E. Brody
10 aug 2008--Each year hundreds of thousands of Americans, including some 700,000 Medicare recipients, get on a treadmill not for exercise but to try to determine if their hearts are healthy.
Tim Russert, the NBC journalist, had such an exam, called an exercise or treadmill stress test, six weeks before he died of a heart attack in June at age 58. His results had been deemed normal, prompting people to question how worthwhile this test could be.
Two weeks before Russert died, Dr. Todd Miller, a cardiologist and co-director of the Mayo Clinic's Nuclear Cardiology Laboratory in Rochester, Minn., published an assessment of the test's ability to detect potentially life-threatening cardiac problems.
The test is meant to be used “almost exclusively” for people who have symptoms of heart disease, Miller said in an interview.
“But in the real world,” he said, “it is often used as a screening test for people without symptoms who are worried about their risk. The accuracy of the test depends on whom it is used. It is most accurate among populations with a high prevalence of coronary disease.”
Limitations and advantages
In fact, this test is unable to detect the kind of problem that caused Russert's death – a plaque within the wall of a coronary artery that ruptured, resulting in a clot that set off a rapidly fatal heart rhythm abnormality. If not for the rhythm disturbance, Russert would have had a far greater chance of surviving his heart attack, said Miller, who was his doctor.
“Maybe three patients in 1,000 with a low-risk test will die from heart disease within a year,” he said. “Among those deemed at high risk, more than three patients in 100 would die within a year.”
The stress test's main advantages are its rapidity and low cost – one-fifth to one-quarter the cost of more definitive and often more time-consuming tests like a nuclear stress test, CT coronary angiogram or standard angiogram. Medicare pays about $150 for a standard stress test, though hospitals typically charge three to four times that when the test is done on younger patients.
The test has no value unless its findings are interpreted in the context of a person's other risk factors for heart disease: age, sex and heart disease symptoms, as well as smoking, being overweight, hypertension, high cholesterol, diabetes and family history.
Interpreting the results
During a treadmill test, patients are hooked up to an electrocardiogram machine (often abbreviated EKG, for the German spelling) that records the workings of the heart as the duration, speed and difficulty of the exercise increase.
Measurements taken during and immediately after the workout are indicators of cardiovascular fitness and how well a person's autonomic nervous system is functioning. Doctors used to rely mainly on an EKG finding to indicate heart trouble. But scores of studies have zeroed in on other, more reliable findings. Exercise duration has the strongest prognostic value, Miller said.
Even people who have three diseased coronary arteries can be expected to survive four years or more if they can stay on the treadmill for 12 or more minutes, a study in the 1980s of 4,083 patients with symptoms of heart disease showed.
But duration on the treadmill may be limited by lack of physical fitness, back problems or other unrelated disorders, leading to other, more expensive evaluations.
“When a middle-age couch potato is done in after only three minutes on the treadmill, you scratch your head,” Miller said. “Is this heart disease or just deconditioning?”
It won't detect some heart problems.
By Jane E. Brody
10 aug 2008--Each year hundreds of thousands of Americans, including some 700,000 Medicare recipients, get on a treadmill not for exercise but to try to determine if their hearts are healthy.
Tim Russert, the NBC journalist, had such an exam, called an exercise or treadmill stress test, six weeks before he died of a heart attack in June at age 58. His results had been deemed normal, prompting people to question how worthwhile this test could be.
Two weeks before Russert died, Dr. Todd Miller, a cardiologist and co-director of the Mayo Clinic's Nuclear Cardiology Laboratory in Rochester, Minn., published an assessment of the test's ability to detect potentially life-threatening cardiac problems.
The test is meant to be used “almost exclusively” for people who have symptoms of heart disease, Miller said in an interview.
“But in the real world,” he said, “it is often used as a screening test for people without symptoms who are worried about their risk. The accuracy of the test depends on whom it is used. It is most accurate among populations with a high prevalence of coronary disease.”
Limitations and advantages
In fact, this test is unable to detect the kind of problem that caused Russert's death – a plaque within the wall of a coronary artery that ruptured, resulting in a clot that set off a rapidly fatal heart rhythm abnormality. If not for the rhythm disturbance, Russert would have had a far greater chance of surviving his heart attack, said Miller, who was his doctor.
“Maybe three patients in 1,000 with a low-risk test will die from heart disease within a year,” he said. “Among those deemed at high risk, more than three patients in 100 would die within a year.”
The stress test's main advantages are its rapidity and low cost – one-fifth to one-quarter the cost of more definitive and often more time-consuming tests like a nuclear stress test, CT coronary angiogram or standard angiogram. Medicare pays about $150 for a standard stress test, though hospitals typically charge three to four times that when the test is done on younger patients.
The test has no value unless its findings are interpreted in the context of a person's other risk factors for heart disease: age, sex and heart disease symptoms, as well as smoking, being overweight, hypertension, high cholesterol, diabetes and family history.
Interpreting the results
During a treadmill test, patients are hooked up to an electrocardiogram machine (often abbreviated EKG, for the German spelling) that records the workings of the heart as the duration, speed and difficulty of the exercise increase.
Measurements taken during and immediately after the workout are indicators of cardiovascular fitness and how well a person's autonomic nervous system is functioning. Doctors used to rely mainly on an EKG finding to indicate heart trouble. But scores of studies have zeroed in on other, more reliable findings. Exercise duration has the strongest prognostic value, Miller said.
Even people who have three diseased coronary arteries can be expected to survive four years or more if they can stay on the treadmill for 12 or more minutes, a study in the 1980s of 4,083 patients with symptoms of heart disease showed.
But duration on the treadmill may be limited by lack of physical fitness, back problems or other unrelated disorders, leading to other, more expensive evaluations.
“When a middle-age couch potato is done in after only three minutes on the treadmill, you scratch your head,” Miller said. “Is this heart disease or just deconditioning?”
Saturday, August 09, 2008
Lack of Energy May Signal Health Problems in Older Patients
By Todd Neale
NEW YORK, 09 aug 2008Although anergia is common in older patients, it may not be just a normal part of aging, but a sign of more serious health problems, researchers here said. In addition to being more likely to have several health problems, including impaired physical function, patients who lacked energy had higher rates of death at 18 months (12.2% versus 5.9%) and six years (31.1% versus 22.3%) of follow-up (P=0.00 for both), Mathew Maurer, M.D., of Columbia, and colleagues reported in the July issue of the Journal of Gerontology: Medical Sciences. Among 2,130 patients 65 and older who participated in their study, 18% met criteria for anergia.
According to Dr. Maurer, when older patients complain about being tired, most physicians "tell their patients that feeling listless is an expected part of aging, but there are reasons people are tired and they need to be investigated."
Frailty as a geriatric syndrome has received much attention from clinicians and researchers, according to the researchers, with lack of energy or exhaustion as a major component.
However, they said, it's unknown whether lack of energy alone has any clinical relevance in older patients.
So they turned to the Northern Manhattan Aging Project, which surveyed a multiethnic population of Medicare beneficiaries (mean age 74; 33.4% black, 47% Hispanic, and 19.6% white; 68.8% female) living north of 150th Street in New York. They were followed every 18 months from 1989 through 1995.
Participants were classified as having anergia if they said they "sat around a lot for lack of energy" and met at least two of six other criteria for low energy levels.
Overall, 66% of the participants had at least one complaint consistent with a lack of energy and 18% had anergia.
The condition was more common in women than in men (22% versus 12%, P<0.01) and in unmarried versus married participants (21% versus 13%, P<0.001) and with advancing age.
Those with anergia were more likely to rate their health as fair or poor compared with excellent, could walk fewer blocks without resting, reported more physical impairment on basic and instrumental activities of daily living, and were more likely to use an assistive device (P=0.00 for all).
Compared with those who did not have anergia, those with the condition were hospitalized more, and used more office visits, emergency room visits, and home care services (P=0.00 for all).
In a multivariate analysis, anergia was significantly associated with female gender, impaired physical function and instrumental activities of daily living, depression, pain, respiratory symptoms, urinary incontinence, hearing difficulty, feeling dizzy or weak, and social isolation and disengagement (P<0.05 for all).
"These factors could be the initial candidates for clinical investigation of anergia of undetermined origin," the researchers said.
Among participants with anergia at baseline, the condition persisted in 48.1% through 18 months.
"Collectively," the researchers said, "these findings would suggest that anergia warrants consideration as a geriatric syndrome."
They said that "in clinical settings, anergia, being recognizable as a 'chief complaint or concern,' is a more readily identifiable condition than frailty is."
Accordingly, "further investigations for potentially effective interventions targeted at anergia in older persons appear warranted," they said
In addition, they said, the condition could be a useful outcome measure in clinical trials.
The authors acknowledged several limitations of the study: the results were derived from a single data set, response rates were low, the data were predominantly self-reported, the survey did not include information on comorbidities such as renal failure or congestive heart failure, some participants were lost to follow-up, the criteria for anergia were preliminary, and the cross-sectional analyses could not establish causality.
The authors made no disclosures.
Primary source: Journal of Gerontology: Medical SciencesSource reference:Cheng H, et al "Self-reported lack of energy (anergia) among elders in a multiethnic community" J Gerontol A Biol Sci Med Sci 2008; 63: 707-714.
According to Dr. Maurer, when older patients complain about being tired, most physicians "tell their patients that feeling listless is an expected part of aging, but there are reasons people are tired and they need to be investigated."
Frailty as a geriatric syndrome has received much attention from clinicians and researchers, according to the researchers, with lack of energy or exhaustion as a major component.
However, they said, it's unknown whether lack of energy alone has any clinical relevance in older patients.
So they turned to the Northern Manhattan Aging Project, which surveyed a multiethnic population of Medicare beneficiaries (mean age 74; 33.4% black, 47% Hispanic, and 19.6% white; 68.8% female) living north of 150th Street in New York. They were followed every 18 months from 1989 through 1995.
Participants were classified as having anergia if they said they "sat around a lot for lack of energy" and met at least two of six other criteria for low energy levels.
Overall, 66% of the participants had at least one complaint consistent with a lack of energy and 18% had anergia.
The condition was more common in women than in men (22% versus 12%, P<0.01) and in unmarried versus married participants (21% versus 13%, P<0.001) and with advancing age.
Those with anergia were more likely to rate their health as fair or poor compared with excellent, could walk fewer blocks without resting, reported more physical impairment on basic and instrumental activities of daily living, and were more likely to use an assistive device (P=0.00 for all).
Compared with those who did not have anergia, those with the condition were hospitalized more, and used more office visits, emergency room visits, and home care services (P=0.00 for all).
In a multivariate analysis, anergia was significantly associated with female gender, impaired physical function and instrumental activities of daily living, depression, pain, respiratory symptoms, urinary incontinence, hearing difficulty, feeling dizzy or weak, and social isolation and disengagement (P<0.05 for all).
"These factors could be the initial candidates for clinical investigation of anergia of undetermined origin," the researchers said.
Among participants with anergia at baseline, the condition persisted in 48.1% through 18 months.
"Collectively," the researchers said, "these findings would suggest that anergia warrants consideration as a geriatric syndrome."
They said that "in clinical settings, anergia, being recognizable as a 'chief complaint or concern,' is a more readily identifiable condition than frailty is."
Accordingly, "further investigations for potentially effective interventions targeted at anergia in older persons appear warranted," they said
In addition, they said, the condition could be a useful outcome measure in clinical trials.
The authors acknowledged several limitations of the study: the results were derived from a single data set, response rates were low, the data were predominantly self-reported, the survey did not include information on comorbidities such as renal failure or congestive heart failure, some participants were lost to follow-up, the criteria for anergia were preliminary, and the cross-sectional analyses could not establish causality.
The authors made no disclosures.
Primary source: Journal of Gerontology: Medical SciencesSource reference:Cheng H, et al "Self-reported lack of energy (anergia) among elders in a multiethnic community" J Gerontol A Biol Sci Med Sci 2008; 63: 707-714.
Eat oily fish at least once a week to protect your eyesight in old age
09 aug 2008--Eating oily fish once a week may reduce age-related macular degeneration (AMD) which is the major cause of blindness and poor vision in adults in western countries and the third cause of global blindness, according to a study published today in the American Journal of Clinical Nutrition.
There are two types of AMD, wet and dry. Of the two, wet AMD is the main cause of vision loss. A team of researchers across seven European countries and co-ordinated by the London School of Hygiene & Tropical Medicine sought to investigate the association between fish intake and omega 3 fatty acids with wet AMD, comparing people with wet AMD with controls. Participants were interviewed about their dietary habits including how much fish they ate and what type. Information on the main omega 3 fatty acids (docosahexaenoicacid (DHA) and eicosapentaenoic acid (EPA) was obtained by linking dietary data with food composition tables.
The findings show that people who habitually consume oily fish at least once a week compared with less than once a week are 50% less likely to have wet AMD. There was no benefit from consumption of non oily white fish. There was a strong inverse association between levels of DHA and EPA and wet AMD. People in the top 25% of DHA and EPA levels (300 mg per day and above) were 70% less likely to have wet AMD.
Astrid Fletcher, Professor of Epidemiology at the London School of Hygiene & Tropical Medicine, who led the study, commented: "This is the first study in Europeans to show a beneficial association on wet AMD from the consumption of oily fish and is consistent with results from studies in the USA and Australia. Two 3oz servings a week of oily fish, such as salmon, tuna or mackerel, provides about 500 mg of DHA and EPA per day".
The research team is not, however, recommending omega 3 supplements as the study did not investigate whether supplements would have the same benefit as dietary sources.
###
The EUREYE study was funded by the European Commission with additional support from the Macular Disease Society UK and the Thomas Pocklington Trust.
To contact Astrid Fletcher, please call the London School of Hygiene & Tropical Medicine on 0207 927 2802 / 07828 617 901 or email gemma.howe@lshtm.ac.uk
09 aug 2008--Eating oily fish once a week may reduce age-related macular degeneration (AMD) which is the major cause of blindness and poor vision in adults in western countries and the third cause of global blindness, according to a study published today in the American Journal of Clinical Nutrition.
There are two types of AMD, wet and dry. Of the two, wet AMD is the main cause of vision loss. A team of researchers across seven European countries and co-ordinated by the London School of Hygiene & Tropical Medicine sought to investigate the association between fish intake and omega 3 fatty acids with wet AMD, comparing people with wet AMD with controls. Participants were interviewed about their dietary habits including how much fish they ate and what type. Information on the main omega 3 fatty acids (docosahexaenoicacid (DHA) and eicosapentaenoic acid (EPA) was obtained by linking dietary data with food composition tables.
The findings show that people who habitually consume oily fish at least once a week compared with less than once a week are 50% less likely to have wet AMD. There was no benefit from consumption of non oily white fish. There was a strong inverse association between levels of DHA and EPA and wet AMD. People in the top 25% of DHA and EPA levels (300 mg per day and above) were 70% less likely to have wet AMD.
Astrid Fletcher, Professor of Epidemiology at the London School of Hygiene & Tropical Medicine, who led the study, commented: "This is the first study in Europeans to show a beneficial association on wet AMD from the consumption of oily fish and is consistent with results from studies in the USA and Australia. Two 3oz servings a week of oily fish, such as salmon, tuna or mackerel, provides about 500 mg of DHA and EPA per day".
The research team is not, however, recommending omega 3 supplements as the study did not investigate whether supplements would have the same benefit as dietary sources.
###
The EUREYE study was funded by the European Commission with additional support from the Macular Disease Society UK and the Thomas Pocklington Trust.
To contact Astrid Fletcher, please call the London School of Hygiene & Tropical Medicine on 0207 927 2802 / 07828 617 901 or email gemma.howe@lshtm.ac.uk
Fat Cell Protein Boosts Heart Attack Risk in Elderly
09 aug 2008-- A protein produced by fat cells may play a pivotal role in increasing an older American's risk for a heart attack even if they are losing weight, a new report says.
Levels of adiponectin increase in the bloodstream when people lose weight and appear to endanger the cardiovascular health of older people, according to the new study to be published in The Journal of Clinical Endocrinology & Metabolism.
This finding, though, appears odd, because past studies have shown high adiponectin concentration is associated with lower risks of diabetes and cholesterol abnormalities.
"This study is significant because previous findings have been contradictory, and the present investigation includes the largest number of heart attacks in an elderly group to date," Dr. Jorge Kizer, an associate professor of medicine and public health at Weill Cornell Medical College in New York City, said in a news release issued by the journal's publisher. "Our findings make a persuasive case that adiponectin is in fact associated with an increase in heart disease risk in older persons."
The new study looked at a sample of 1,386 adults, aged 65 to 100, from around the country. Of these, 604 had heart disease, with those with the highest adiponectin levels being most likely to suffer a heart attack.
The researchers theorized that higher adiponectin levels may indicate underlying disease, or even have direct harmful effects especially in the elderly. Previous studies show adiponectin increases energy expenditure in the central nervous system of mice -- something that could be significantly harmful if also occurring in older adults by accelerating the loss of skeletal muscle.
The findings are consistent, though, with other recent studies tying high adiponectin to mortality in the elderly.
"This study shows that this abundant product of fat cells is a marker and perhaps even a mediator of worsened outcomes in persons aged 65 years and older," Kizer said.
More information
The National Institute of Health has more about healthy aging.
09 aug 2008-- A protein produced by fat cells may play a pivotal role in increasing an older American's risk for a heart attack even if they are losing weight, a new report says.
Levels of adiponectin increase in the bloodstream when people lose weight and appear to endanger the cardiovascular health of older people, according to the new study to be published in The Journal of Clinical Endocrinology & Metabolism.
This finding, though, appears odd, because past studies have shown high adiponectin concentration is associated with lower risks of diabetes and cholesterol abnormalities.
"This study is significant because previous findings have been contradictory, and the present investigation includes the largest number of heart attacks in an elderly group to date," Dr. Jorge Kizer, an associate professor of medicine and public health at Weill Cornell Medical College in New York City, said in a news release issued by the journal's publisher. "Our findings make a persuasive case that adiponectin is in fact associated with an increase in heart disease risk in older persons."
The new study looked at a sample of 1,386 adults, aged 65 to 100, from around the country. Of these, 604 had heart disease, with those with the highest adiponectin levels being most likely to suffer a heart attack.
The researchers theorized that higher adiponectin levels may indicate underlying disease, or even have direct harmful effects especially in the elderly. Previous studies show adiponectin increases energy expenditure in the central nervous system of mice -- something that could be significantly harmful if also occurring in older adults by accelerating the loss of skeletal muscle.
The findings are consistent, though, with other recent studies tying high adiponectin to mortality in the elderly.
"This study shows that this abundant product of fat cells is a marker and perhaps even a mediator of worsened outcomes in persons aged 65 years and older," Kizer said.
More information
The National Institute of Health has more about healthy aging.
Pleasure from Smoking -- and Addiction to It -- Is a Genetic Thing
By Charles Bankhead
ANN ARBOR, Mich., 09 aug 2008-- The nicotine "buzz" that leads to addiction in some people arises from a genetic mutation that enhances pleasurable responses, investigators here reported. The mutation in a subunit of the neuronal acetylcholine receptor (CHRNA5) increased the odds of nicotine dependence by 50%, and Caucasians with the mutation were 60% more likely to feel a pleasurable rush or "buzz" when they smoked their first cigarette, Ovide Pomerleau, Ph.D., of the University of Michigan, and colleagues reported in the August issue of Addiction. "The findings suggest that phenotypes related to subjective experiences upon smoking experimentation may mediate the development of nicotine dependence," the authors said.
Many studies have underscored the genetic influence on smoking habits, including initiation, persistence, and addiction, and recently, several common variants have been shown to be associated with nicotine dependence in Caucasians, the authors said.
The variants, or single nucleotide polymorphisms (SNPs), had several effects with functional significance, including effects on nicotine metabolism, they continued. Additional research showed that an SNP in exon 4 of CHRNA5 altered the nicotine receptor.
Subsequently, a highly correlated CHRNA5/CHRNA3 haplotype was found to have a strong influence on smoking behavior, specifically the number of cigarettes smoked per day, the authors said.
In an attempt to expand on the previous work, Dr. Pomerleau and colleagues focused on phenotype associations for the top 25 SNPs associated with nicotine dependence. They began with the SNP previously shown to alter the nicotine receptor (rs16969968) and then examined the other 24.
Their case-control study involved 203 smokers and 232 controls between ages 25 and 65 and included 72 African Americans among the 435 total participants. The smokers had at least a five-year history of smoking five or more cigarettes a day, including six months at their current level. Cases had smoked as many as 100 cigarettes in their lifetime but never regularly.
The study participants retrospectively rated pleasurable and unpleasurable sensations they felt when they smoked a cigarette for the very first time.
Of the 25 SNPs evaluated, only the rs16969968 variant demonstrated a significant association with smoking behavior (OR 1.48, 95% CI 1.08 to 2.03).
Caucasians accounted entirely for the significant effect (OR 1.51 versus OR 0.68 for African Americans).
The variant significantly predicted smoking behavior in the combined analysis and the analysis by race (P=0.01).
Minor alleles at rs16969968 were significantly associated with a pleasurable rush or buzz during early smoking in Caucasians (OR 1.61, P=0.01).
The sensations correlated strongly with current smoking (OR 8.2, P<0.0001), a correlation that persisted in a combined analysis of both races (OR 6.2, P<0.0001).
"No other initial smoking experience was associated significantly with the rs16969968 genotype," the authors said.
"The gene-association analysis in the present study indicates that minor alleles at rs16969968 may have contributed to smoking by enhancing the reinforcing effects of nicotine in nicotine-naive individuals who went on to become regular smokers," they added.
The findings, combined with those of previous studies, "implicate initial sensitivity as a key variable in smoking development," they concluded.
They pointed out that the study of relationships in the African-American sample was inconclusive because of the small number of participants available.
They also indicated that the data suggested that African Americans may be more reactive to initial cigarettes than Caucasians but it is unlikely that this particular polymorphism is involved in the differences observed.
The study was supported by the National Institutes of Health.
Dr. Pomerleau and two co-authors have served as consultants to Pfizer. Two co-authors invented a patented process used to evaluate SNPs in diagnosis and treatment of addiction.
Primary source: AddictionSource reference:Sherva R, et al "Association of a single nucleotide polymorphism inneuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with 'pleasurable buzz' during early experimentation with smoking" Addiction 2008; 103: 1544-1552.
By Charles Bankhead
ANN ARBOR, Mich., 09 aug 2008-- The nicotine "buzz" that leads to addiction in some people arises from a genetic mutation that enhances pleasurable responses, investigators here reported. The mutation in a subunit of the neuronal acetylcholine receptor (CHRNA5) increased the odds of nicotine dependence by 50%, and Caucasians with the mutation were 60% more likely to feel a pleasurable rush or "buzz" when they smoked their first cigarette, Ovide Pomerleau, Ph.D., of the University of Michigan, and colleagues reported in the August issue of Addiction. "The findings suggest that phenotypes related to subjective experiences upon smoking experimentation may mediate the development of nicotine dependence," the authors said.
Many studies have underscored the genetic influence on smoking habits, including initiation, persistence, and addiction, and recently, several common variants have been shown to be associated with nicotine dependence in Caucasians, the authors said.
The variants, or single nucleotide polymorphisms (SNPs), had several effects with functional significance, including effects on nicotine metabolism, they continued. Additional research showed that an SNP in exon 4 of CHRNA5 altered the nicotine receptor.
Subsequently, a highly correlated CHRNA5/CHRNA3 haplotype was found to have a strong influence on smoking behavior, specifically the number of cigarettes smoked per day, the authors said.
In an attempt to expand on the previous work, Dr. Pomerleau and colleagues focused on phenotype associations for the top 25 SNPs associated with nicotine dependence. They began with the SNP previously shown to alter the nicotine receptor (rs16969968) and then examined the other 24.
Their case-control study involved 203 smokers and 232 controls between ages 25 and 65 and included 72 African Americans among the 435 total participants. The smokers had at least a five-year history of smoking five or more cigarettes a day, including six months at their current level. Cases had smoked as many as 100 cigarettes in their lifetime but never regularly.
The study participants retrospectively rated pleasurable and unpleasurable sensations they felt when they smoked a cigarette for the very first time.
Of the 25 SNPs evaluated, only the rs16969968 variant demonstrated a significant association with smoking behavior (OR 1.48, 95% CI 1.08 to 2.03).
Caucasians accounted entirely for the significant effect (OR 1.51 versus OR 0.68 for African Americans).
The variant significantly predicted smoking behavior in the combined analysis and the analysis by race (P=0.01).
Minor alleles at rs16969968 were significantly associated with a pleasurable rush or buzz during early smoking in Caucasians (OR 1.61, P=0.01).
The sensations correlated strongly with current smoking (OR 8.2, P<0.0001), a correlation that persisted in a combined analysis of both races (OR 6.2, P<0.0001).
"No other initial smoking experience was associated significantly with the rs16969968 genotype," the authors said.
"The gene-association analysis in the present study indicates that minor alleles at rs16969968 may have contributed to smoking by enhancing the reinforcing effects of nicotine in nicotine-naive individuals who went on to become regular smokers," they added.
The findings, combined with those of previous studies, "implicate initial sensitivity as a key variable in smoking development," they concluded.
They pointed out that the study of relationships in the African-American sample was inconclusive because of the small number of participants available.
They also indicated that the data suggested that African Americans may be more reactive to initial cigarettes than Caucasians but it is unlikely that this particular polymorphism is involved in the differences observed.
The study was supported by the National Institutes of Health.
Dr. Pomerleau and two co-authors have served as consultants to Pfizer. Two co-authors invented a patented process used to evaluate SNPs in diagnosis and treatment of addiction.
Primary source: AddictionSource reference:Sherva R, et al "Association of a single nucleotide polymorphism inneuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with 'pleasurable buzz' during early experimentation with smoking" Addiction 2008; 103: 1544-1552.
FDA Issues Alert on Rhabdomyolysis Risk When Combining Simvastatin with Amiodarone
By Peggy Peck
ROCKVILLE, Md., 09 aug 2008-- The FDA has again warned of a dose-dependent increased risk of rhabdomyolysis when simvastatin (Zocor) at more than 20 mg is used in combination with amiodarone (Cordarone, Pacerone).
The simvastatin label was modified in 2002 to add a warning about the increased risk, but the FDA said today that it continues "to receive reports of rhabdomyolysis in patients treated concurrently with amiodarone and simvastatin, particularly with simvastatin doses greater than 20 mg daily."
The FDA said the precise mechanism was unknown, but was related to the fact that amiodarone inhibits the cytochrome P450 3A4 (CYP3A4) enzyme. This is the same enzyme that metabolizes simvastatin.
Physicians should consider use of another statin for patients taking amiodarone, particularly if they require simvastatin doses greater than 20 mg daily to meet their lipid goals.
The agency said it did "not have data on how varying the dose of amiodarone in patients taking simvastatin affects the risk of developing rhabdomyolysis."
The FDA said it was working with the manufacturer of Cordarone to revise the prescribing information to warn of an increased risk of rhabdomyolysis when amiodarone is taken with simvastatin in doses exceeding 20 mg daily.
By Peggy Peck
ROCKVILLE, Md., 09 aug 2008-- The FDA has again warned of a dose-dependent increased risk of rhabdomyolysis when simvastatin (Zocor) at more than 20 mg is used in combination with amiodarone (Cordarone, Pacerone).
The simvastatin label was modified in 2002 to add a warning about the increased risk, but the FDA said today that it continues "to receive reports of rhabdomyolysis in patients treated concurrently with amiodarone and simvastatin, particularly with simvastatin doses greater than 20 mg daily."
The FDA said the precise mechanism was unknown, but was related to the fact that amiodarone inhibits the cytochrome P450 3A4 (CYP3A4) enzyme. This is the same enzyme that metabolizes simvastatin.
Physicians should consider use of another statin for patients taking amiodarone, particularly if they require simvastatin doses greater than 20 mg daily to meet their lipid goals.
The agency said it did "not have data on how varying the dose of amiodarone in patients taking simvastatin affects the risk of developing rhabdomyolysis."
The FDA said it was working with the manufacturer of Cordarone to revise the prescribing information to warn of an increased risk of rhabdomyolysis when amiodarone is taken with simvastatin in doses exceeding 20 mg daily.
Friday, August 08, 2008
Scientists produce stem cells for 10 diseases
By STEPHANIE NANO
08 aug 2008--Harvard scientists say they have created stems cells for 10 genetic disorders, which will allow researchers to watch the diseases develop in a lab dish.
This early step, using a new technique, could help speed up efforts to find treatments for some of the most confounding ailments, the scientists said.
The new work was reported online Thursday in the journal Cell, and the researchers said they plan to make the cell lines readily available to other scientists.
Dr. George Daley and his colleagues at the Harvard Stem Cell Institute used ordinary skin cells and bone marrow from people with a variety of diseases, including Parkinson's, Huntington's and Down syndrome to produce the stem cells.
The new cells will allow researchers to "watch the disease progress in a dish, that is, to watch what goes right or wrong," Doug Melton, co-director of the institute, said during a teleconference.
"I think we'll see in years ahead that this opens the door to a new way to treating degenerative diseases," he said.
The new technique reprograms cells, giving them the chameleon-like qualities of embryonic stem cells, which can morph into all kinds of tissue, such as heart, nerve and brain. As with embryonic stem cells, the hope is to speed medical research.
Research teams in Wisconsin and Japan were the first to report last November that they had reprogrammed skin cells, and that the cells had behaved like stem cells in a series of lab tests. Just last week, another Harvard team of scientists said they reprogrammed skin cells from two elderly patients with ALS, or Lou Gehrig's disease, and grew them into nerve cells.
Melton said the new disease-specific cell lines "represent a collection of degenerative diseases for which there are no good treatments and, more importantly, no good animal models for the most part in studying them."
A new laboratory has been created to serve as a repository for the cells, and to distribute them to other scientists researching the diseases, Melton said.
"The hope is that this will accelerate research and it will create a climate of openness," said Daley.
He expects stem cell lines to be developed for many more diseases, noting, "this is just the first wave of diseases." Other diseases for which they created stem cells are Type 1, or juvenile, diabetes; two types of muscular dystrophy, Gaucher disease and a rare genetic disorder known as the "bubble boy disease."
Daley stressed that the reprogrammed cells won't eliminate the need or value of studying embryonic stem cells.
"At least for the foreseeable future, and I would argue forever, they are going to be extremely valuable tools," he said.
The reprogramming work was funded by the National Institutes of Health and private contributions to the Harvard Stem Cell Institute.
This early step, using a new technique, could help speed up efforts to find treatments for some of the most confounding ailments, the scientists said.
The new work was reported online Thursday in the journal Cell, and the researchers said they plan to make the cell lines readily available to other scientists.
Dr. George Daley and his colleagues at the Harvard Stem Cell Institute used ordinary skin cells and bone marrow from people with a variety of diseases, including Parkinson's, Huntington's and Down syndrome to produce the stem cells.
The new cells will allow researchers to "watch the disease progress in a dish, that is, to watch what goes right or wrong," Doug Melton, co-director of the institute, said during a teleconference.
"I think we'll see in years ahead that this opens the door to a new way to treating degenerative diseases," he said.
The new technique reprograms cells, giving them the chameleon-like qualities of embryonic stem cells, which can morph into all kinds of tissue, such as heart, nerve and brain. As with embryonic stem cells, the hope is to speed medical research.
Research teams in Wisconsin and Japan were the first to report last November that they had reprogrammed skin cells, and that the cells had behaved like stem cells in a series of lab tests. Just last week, another Harvard team of scientists said they reprogrammed skin cells from two elderly patients with ALS, or Lou Gehrig's disease, and grew them into nerve cells.
Melton said the new disease-specific cell lines "represent a collection of degenerative diseases for which there are no good treatments and, more importantly, no good animal models for the most part in studying them."
A new laboratory has been created to serve as a repository for the cells, and to distribute them to other scientists researching the diseases, Melton said.
"The hope is that this will accelerate research and it will create a climate of openness," said Daley.
He expects stem cell lines to be developed for many more diseases, noting, "this is just the first wave of diseases." Other diseases for which they created stem cells are Type 1, or juvenile, diabetes; two types of muscular dystrophy, Gaucher disease and a rare genetic disorder known as the "bubble boy disease."
Daley stressed that the reprogrammed cells won't eliminate the need or value of studying embryonic stem cells.
"At least for the foreseeable future, and I would argue forever, they are going to be extremely valuable tools," he said.
The reprogramming work was funded by the National Institutes of Health and private contributions to the Harvard Stem Cell Institute.
People with heart disease still have trouble controlling blood lipid levels
08 aug 2008— Despite some improvements to lower "bad" cholesterol levels, people with cardiovascular diseases still need to do a better job controlling overall blood lipid levels, according to a UC Irvine Heart Disease Prevention Program study.
Researchers found that 37 percent of Americans with diseases that affect the heart and vascular system had reached recommended levels of LDL-C (bad cholesterol), but only 17 percent were at recommended levels for all lipids – LDL-C, HDL-C ("good" cholesterol) and triglycerides. In contrast, 85 percent of those without cardiovascular diseases were at recommended LDL-C levels, while 67 percent were at recommended levels for all lipids.
The study reveals that many adults, particularly those with known cardiovascular diseases, inadequately control these key lipids. Proper diet, exercise, and more appropriate use of therapies to target all lipids are needed, especially for those most at risk, said Nathan D. Wong, study leader and Heart Disease Prevention Program director.
The researchers analyzed data from the nearly 3,000 adults older than 20 who participated in the National Health and Nutrition Examination Survey in 2003-04 and published their findings in the American Heart Journal.
"While national treatment recommendations have focused on aggressive management of LDL-C levels, mainly through statin therapy, we have found little change in HDL-C levels and an actual increase in triglyceride levels," Wong said. "This is not good news, as these factors are important components of cardiovascular risk."
Persons with known cardiovascular diseases should have LDL-C levels below 100 mg (or below 130 mg for most other adults). For all adults, HDL-C levels should be 40 mg or higher for men and 50 mg or higher for women. Triglyceride levels should be below 150 mg.
Obesity and an increasingly sedentary lifestyle are controllable factors that can lead to low HDL-C and elevated LDL-C and triglycerides. High blood pressure, smoking and diabetes can further compound risks associated with high lipid levels.
Wong recommends that all adults have a lipid profile done and speak to their healthcare provider about lifestyle measures and appropriate medications to improve their levels.
Cardiovascular disease is the leading killer of Americans, taking nearly 500,000 lives each year. To decrease risk, doctors recommend that people control their weight, blood pressure and blood lipid levels through good lifestyle habits and minimal stress.
###
Heli Ghandehari of UCI and Sachin Kamal-Bahl of Merck & Co., Inc. also participated in the study, which was supported by a contract from Merck & Co., Inc. to UC Irvine.
The UCI Heart Disease Prevention Program in the School of Medicine strives for excellence in scholarly research, education and healthcare aimed at the prevention and early detection of coronary heart disease. For more information, visit www.heart.uci.edu.
About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 27,000 undergraduate and graduate students and nearly 2,000 faculty members. The third-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3.6 billion. For more UCI news, visit www.today.uci.edu.
News Radio: UCI maintains on campus an ISDN line for conducting interviews with its faculty and experts. The use of this line is available free-of-charge to radio news programs/stations who wish to interview UCI faculty and experts. Use of the ISDN line is subject to availability and approval by the university.
08 aug 2008— Despite some improvements to lower "bad" cholesterol levels, people with cardiovascular diseases still need to do a better job controlling overall blood lipid levels, according to a UC Irvine Heart Disease Prevention Program study.
Researchers found that 37 percent of Americans with diseases that affect the heart and vascular system had reached recommended levels of LDL-C (bad cholesterol), but only 17 percent were at recommended levels for all lipids – LDL-C, HDL-C ("good" cholesterol) and triglycerides. In contrast, 85 percent of those without cardiovascular diseases were at recommended LDL-C levels, while 67 percent were at recommended levels for all lipids.
The study reveals that many adults, particularly those with known cardiovascular diseases, inadequately control these key lipids. Proper diet, exercise, and more appropriate use of therapies to target all lipids are needed, especially for those most at risk, said Nathan D. Wong, study leader and Heart Disease Prevention Program director.
The researchers analyzed data from the nearly 3,000 adults older than 20 who participated in the National Health and Nutrition Examination Survey in 2003-04 and published their findings in the American Heart Journal.
"While national treatment recommendations have focused on aggressive management of LDL-C levels, mainly through statin therapy, we have found little change in HDL-C levels and an actual increase in triglyceride levels," Wong said. "This is not good news, as these factors are important components of cardiovascular risk."
Persons with known cardiovascular diseases should have LDL-C levels below 100 mg (or below 130 mg for most other adults). For all adults, HDL-C levels should be 40 mg or higher for men and 50 mg or higher for women. Triglyceride levels should be below 150 mg.
Obesity and an increasingly sedentary lifestyle are controllable factors that can lead to low HDL-C and elevated LDL-C and triglycerides. High blood pressure, smoking and diabetes can further compound risks associated with high lipid levels.
Wong recommends that all adults have a lipid profile done and speak to their healthcare provider about lifestyle measures and appropriate medications to improve their levels.
Cardiovascular disease is the leading killer of Americans, taking nearly 500,000 lives each year. To decrease risk, doctors recommend that people control their weight, blood pressure and blood lipid levels through good lifestyle habits and minimal stress.
###
Heli Ghandehari of UCI and Sachin Kamal-Bahl of Merck & Co., Inc. also participated in the study, which was supported by a contract from Merck & Co., Inc. to UC Irvine.
The UCI Heart Disease Prevention Program in the School of Medicine strives for excellence in scholarly research, education and healthcare aimed at the prevention and early detection of coronary heart disease. For more information, visit www.heart.uci.edu.
About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 27,000 undergraduate and graduate students and nearly 2,000 faculty members. The third-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3.6 billion. For more UCI news, visit www.today.uci.edu.
News Radio: UCI maintains on campus an ISDN line for conducting interviews with its faculty and experts. The use of this line is available free-of-charge to radio news programs/stations who wish to interview UCI faculty and experts. Use of the ISDN line is subject to availability and approval by the university.
IAC: More HIV Treatment May Reduce Transmission Risk
By Michael Smith
MEXICO CITY, 08 aug 2008-- There is growing evidence that highly active anti-retroviral therapy (HAART) has an added benefit -- it may reduce the rate of sexual transmission of HIV, researchers at the International AIDS Conference say.
If that's so -- and all the data are not in -- it will add weight to the argument that HIV treatment, now being scaled up around the world, should be rolled out more quickly.
"The wind is behind the sails for this idea," said Myron Cohen, M.D., of the University of North Carolina in Chapel Hill.
In a press conference, Dr. Cohen said there is evidence from physiological studies of HIV-positive men that HAART can reduce to undetectable the level of HIV in the genital tract.
It's not much of a leap, Dr. Cohen said, to think that with low levels of HIV in semen "the probability of sexual transmission would be greatly reduced."
Retrospective and prospective observational studies of discordant couples -- in which one partner is HIV-positive and the other is not -- also support the idea, he said.
Better data will come from a phase III randomized trial now being conducted by the HIV Prevention Trials Network, which is studying the effect of HAART on transmission in discordant couples, according to Dr. Cohen.
In Thailand, a 50% increase in the number of HIV-positive people getting HAART resulted in a 53% reduction in new infections, according to Julio Montaner, M.D., of the British Columbia Centre of Excellence in HIV/AIDS.
Dr. Montaner, a passionate advocate of universal HIV treatment, is the incoming president of the International AIDS Society, which organizes this biennial meeting.
With colleagues, Dr. Montaner developed a mathematical model, published last month in the Journal of Infectious Diseases, that suggested increasing HAART coverage would cut new infections dramatically.
For instance, the model suggested, an increase in coverage from 50% to 75% would cut new infections by 30%.
"Treatment is not enough to solve this problem, and no one here is saying we can treat our way out of this epidemic," Dr. Montaner said.
From the political point of view, one important implication of the prevention theory is the "tremendously real and psychological boost it would give to the roll-out of treatment everywhere," said Stephen Lewis, the former United Nations Ambassador to Africa for HIV/AIDS.
Lewis said the world is in a "desperate race against time in the search for prevention that works."
As U.N. ambassador, he said, he often got resistance from a country's leaders to the notion of increasing treatment. Had he been able to add that treatment would prevent future HIV infections, he said, "it would have been a huge inducement to roll out treatment more quickly."
A side effect of more treatment is that more people are willing to talk about other forms of prevention, said Elly Katabira, M.D., of Makarere University in Uganda, who is the incoming president-elect of the society.
The availability of HIV care gives health officials "credibility to discuss prevention," he said.
Among the clues that suggest HAART may reduce transmission is the success of treatment in cutting mother-to-child transmission, said Cal Cohen, M.D., research director of the Boston-based treatment and research group CRI of New England.
Including all the other lines of evidence, "the data are consistent," Dr. Cohen said.
Dr. Cohen noted some interventions -- such as condom use or male circumcision -- are known to prevent or reduce viral transmission. Yet, after 25 years of the HIV/AIDS pandemic, "we still see transmission everywhere we look."
"Is treatment the next piece of the puzzle?" he said.
Dr. Cohen said that prevention methods such as condoms only work when they are used. In the same way, "treatment is prevention only if treatment works."
The theory that HAART will help prevent infections remains controversial, with critics pointing out that in some heavily treated populations -- such as gay men in Amsterdam -- HIV incidence continues to rise.
But the bottom line, Dr. Cohen said, is that treatment is its own reward. Even if the prevention theory turns out to be incorrect, "we should still treat people because they need to be treated."
Primary source: Journal of Infectious DiseasesSource reference:Lima VD, et al "Expanded access to highly active antiretroviral therapy: a potentially powerful strategy to curb the growth of the HIV epidemic" JID 2008; 198: 59.
By Michael Smith
MEXICO CITY, 08 aug 2008-- There is growing evidence that highly active anti-retroviral therapy (HAART) has an added benefit -- it may reduce the rate of sexual transmission of HIV, researchers at the International AIDS Conference say.
If that's so -- and all the data are not in -- it will add weight to the argument that HIV treatment, now being scaled up around the world, should be rolled out more quickly.
"The wind is behind the sails for this idea," said Myron Cohen, M.D., of the University of North Carolina in Chapel Hill.
In a press conference, Dr. Cohen said there is evidence from physiological studies of HIV-positive men that HAART can reduce to undetectable the level of HIV in the genital tract.
It's not much of a leap, Dr. Cohen said, to think that with low levels of HIV in semen "the probability of sexual transmission would be greatly reduced."
Retrospective and prospective observational studies of discordant couples -- in which one partner is HIV-positive and the other is not -- also support the idea, he said.
Better data will come from a phase III randomized trial now being conducted by the HIV Prevention Trials Network, which is studying the effect of HAART on transmission in discordant couples, according to Dr. Cohen.
In Thailand, a 50% increase in the number of HIV-positive people getting HAART resulted in a 53% reduction in new infections, according to Julio Montaner, M.D., of the British Columbia Centre of Excellence in HIV/AIDS.
Dr. Montaner, a passionate advocate of universal HIV treatment, is the incoming president of the International AIDS Society, which organizes this biennial meeting.
With colleagues, Dr. Montaner developed a mathematical model, published last month in the Journal of Infectious Diseases, that suggested increasing HAART coverage would cut new infections dramatically.
For instance, the model suggested, an increase in coverage from 50% to 75% would cut new infections by 30%.
"Treatment is not enough to solve this problem, and no one here is saying we can treat our way out of this epidemic," Dr. Montaner said.
From the political point of view, one important implication of the prevention theory is the "tremendously real and psychological boost it would give to the roll-out of treatment everywhere," said Stephen Lewis, the former United Nations Ambassador to Africa for HIV/AIDS.
Lewis said the world is in a "desperate race against time in the search for prevention that works."
As U.N. ambassador, he said, he often got resistance from a country's leaders to the notion of increasing treatment. Had he been able to add that treatment would prevent future HIV infections, he said, "it would have been a huge inducement to roll out treatment more quickly."
A side effect of more treatment is that more people are willing to talk about other forms of prevention, said Elly Katabira, M.D., of Makarere University in Uganda, who is the incoming president-elect of the society.
The availability of HIV care gives health officials "credibility to discuss prevention," he said.
Among the clues that suggest HAART may reduce transmission is the success of treatment in cutting mother-to-child transmission, said Cal Cohen, M.D., research director of the Boston-based treatment and research group CRI of New England.
Including all the other lines of evidence, "the data are consistent," Dr. Cohen said.
Dr. Cohen noted some interventions -- such as condom use or male circumcision -- are known to prevent or reduce viral transmission. Yet, after 25 years of the HIV/AIDS pandemic, "we still see transmission everywhere we look."
"Is treatment the next piece of the puzzle?" he said.
Dr. Cohen said that prevention methods such as condoms only work when they are used. In the same way, "treatment is prevention only if treatment works."
The theory that HAART will help prevent infections remains controversial, with critics pointing out that in some heavily treated populations -- such as gay men in Amsterdam -- HIV incidence continues to rise.
But the bottom line, Dr. Cohen said, is that treatment is its own reward. Even if the prevention theory turns out to be incorrect, "we should still treat people because they need to be treated."
Primary source: Journal of Infectious DiseasesSource reference:Lima VD, et al "Expanded access to highly active antiretroviral therapy: a potentially powerful strategy to curb the growth of the HIV epidemic" JID 2008; 198: 59.
XDR-TB Succumbs to Multi-Drug Regimen
By John Gever
BOSTON, 08 aug 2008--Most patients in one large-scale program were cured of extensively drug-resistant tuberculosis (XDR-TB) with individualized outpatient regimens of second-line antibiotics, researchers here said. Among 48 HIV-negative patients with XDR-TB in Lima, Peru, 29 achieved cure with regimens involving cycloserine, a fluoroquinolone drug, and at least one other drug including an injectable agent, for a cure rate of 60.4%, reported Carole Mitnick, Sc.D., and colleagues in the Aug. 7 issue of the New England Journal of Medicine. The patients were among 810 with drug-resistant TB who were referred for therapy from 1999 through 2002 under a program organized by the Peruvian government, Dr. Mitnick said in an interview.
Drug susceptibility testing was conducted in 651 patients, with 48 deemed to have extensive drug resistance. The remaining 603 cases were classed as multi-drug resistant (MDR).
The cure rate for the MDR-TB patients was 66.3%, the researchers said.
Before entering the program, those with XDR-TB had received a mean of 4.2 earlier treatment regimens with a mean total duration of treatment of 34.7 months.
In the program, drug-susceptibility testing was performed for each patient in a U.S. lab to guide treatment. The goal was to find at least five drugs likely to be effective. While susceptibility results were pending, patients received empirical therapy.
Oral drug treatment lasted at least 18 months and injectables were given for at least eight months after sputum cultures became negative.
If it was impossible to identify five drugs likely to be effective, a smaller number were given for longer periods. All regimens included a fluoroquinolone and an injectable agent.
The same approach was used for XDR- and MDR-TB.
A total of 18 drugs were available in the program. They included oral agents such as ethambutol and pyrazamide, first- or second-line injectables, first- or later-generation fluoroquinolones, and a variety of other drugs.
The XDR-TB patients received a mean of 5.3 anti-TB drugs for which susceptibility had been shown or that patients had not received for more than a month.
Median time for sputum culture conversion from positive to negative was 90 days in the XDR-TB patients, significantly longer than the median 61 days for MDR-TB cases.
But the median time to cure was nearly the same: 26.0 months (95% CI 24.6 to 27.8) for XDR-TB compared with 24.8 months (95% CI 24.5 to 25.2) in the MDR-TB cases.
Fewer than 10% of patients in both groups failed to comply with therapy, reflecting daily supervision of the outpatient therapy by program workers.
A few patients in each category showed positive bacteriological results following cure or completion of therapy (two patients with XDR-TB and 15 with MDR-TB). Dr. Mitnick and colleagues had no information on the results of follow-up treatment in those patients.
Dr. Mitnick said the findings were simultaneously encouraging and discouraging.
"The good news is that community-based treatment was able to cure more than 60% of patients with XDR-TB in a resource-poor setting in South America," she said. "The bad news is that this program was able to cure only 60% of those patients."
She said the previous, extensive therapy failures that preceded the patients' treatment in the program were a significant problem in both groups.
The XDR-TB patients were resistant to a mean of 8.4 drugs according to the susceptibility testing, while the MDR-TB isolates resisted a mean of 5.3 drugs, Dr. Mitnick said.
On the plus side, she said, the 60% cure was achieved with outpatient treatment, whereas earlier programs elsewhere had confined XDR-TB patients in "prison-like" conditions with much poorer results.
In an accompanying editorial, Mario C. Raviglione, M.D., of the World Health Organization's Stop TB department, agreed that such efforts to treat XDR-TB had largely failed.
The report from the Peruvian program, he wrote, "reveals a new and brighter perspective: even in developing countries, extensively drug-resistant tuberculosis may be cured in the majority of cases when management is aggressive and appropriate."
He said the program's outpatient basis may have contributed to its success. "It was community-based in the majority of patients, thus avoiding the additional stress of prolonged hospitalizations [and] it included psychological support for people taking potentially toxic drugs," he noted.
"If every national program put this strategy in place with equal vigor and assertiveness, as in the metropolitan Lima project, drug resistance would be minimized and, when already present, effectively managed," he added.
The study was funded by the Bill and Melinda Gates Foundation, Thomas J. White, Partners in Health, the Peruvian Ministry of Health, the David Rockefeller Center for Latin American Studies at Harvard University, the Francis Family Foundation, the Pittsfield Anti-tuberculosis Association, the Eli Lilly Foundation, and the Hatch Family Foundation, and by career development awards from the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute.
Study authors and Dr. Raviglione reported no potential conflicts of interest.
Additional source: New England Journal of MedicineSource reference: Mitnick C, et al "Comprehensive treatment of extensively drug-resistant tuberculosis" N Engl J Med 2008; 359: 563-74. Additional source: New England Journal of MedicineSource reference: Raviglione M, et al "Facing extensively drug-resistant tuberculosis -- a hope and a challenge" N Engl J Med 2008; 359: 636-37.
By John Gever
BOSTON, 08 aug 2008--Most patients in one large-scale program were cured of extensively drug-resistant tuberculosis (XDR-TB) with individualized outpatient regimens of second-line antibiotics, researchers here said. Among 48 HIV-negative patients with XDR-TB in Lima, Peru, 29 achieved cure with regimens involving cycloserine, a fluoroquinolone drug, and at least one other drug including an injectable agent, for a cure rate of 60.4%, reported Carole Mitnick, Sc.D., and colleagues in the Aug. 7 issue of the New England Journal of Medicine. The patients were among 810 with drug-resistant TB who were referred for therapy from 1999 through 2002 under a program organized by the Peruvian government, Dr. Mitnick said in an interview.
Drug susceptibility testing was conducted in 651 patients, with 48 deemed to have extensive drug resistance. The remaining 603 cases were classed as multi-drug resistant (MDR).
The cure rate for the MDR-TB patients was 66.3%, the researchers said.
Before entering the program, those with XDR-TB had received a mean of 4.2 earlier treatment regimens with a mean total duration of treatment of 34.7 months.
In the program, drug-susceptibility testing was performed for each patient in a U.S. lab to guide treatment. The goal was to find at least five drugs likely to be effective. While susceptibility results were pending, patients received empirical therapy.
Oral drug treatment lasted at least 18 months and injectables were given for at least eight months after sputum cultures became negative.
If it was impossible to identify five drugs likely to be effective, a smaller number were given for longer periods. All regimens included a fluoroquinolone and an injectable agent.
The same approach was used for XDR- and MDR-TB.
A total of 18 drugs were available in the program. They included oral agents such as ethambutol and pyrazamide, first- or second-line injectables, first- or later-generation fluoroquinolones, and a variety of other drugs.
The XDR-TB patients received a mean of 5.3 anti-TB drugs for which susceptibility had been shown or that patients had not received for more than a month.
Median time for sputum culture conversion from positive to negative was 90 days in the XDR-TB patients, significantly longer than the median 61 days for MDR-TB cases.
But the median time to cure was nearly the same: 26.0 months (95% CI 24.6 to 27.8) for XDR-TB compared with 24.8 months (95% CI 24.5 to 25.2) in the MDR-TB cases.
Fewer than 10% of patients in both groups failed to comply with therapy, reflecting daily supervision of the outpatient therapy by program workers.
A few patients in each category showed positive bacteriological results following cure or completion of therapy (two patients with XDR-TB and 15 with MDR-TB). Dr. Mitnick and colleagues had no information on the results of follow-up treatment in those patients.
Dr. Mitnick said the findings were simultaneously encouraging and discouraging.
"The good news is that community-based treatment was able to cure more than 60% of patients with XDR-TB in a resource-poor setting in South America," she said. "The bad news is that this program was able to cure only 60% of those patients."
She said the previous, extensive therapy failures that preceded the patients' treatment in the program were a significant problem in both groups.
The XDR-TB patients were resistant to a mean of 8.4 drugs according to the susceptibility testing, while the MDR-TB isolates resisted a mean of 5.3 drugs, Dr. Mitnick said.
On the plus side, she said, the 60% cure was achieved with outpatient treatment, whereas earlier programs elsewhere had confined XDR-TB patients in "prison-like" conditions with much poorer results.
In an accompanying editorial, Mario C. Raviglione, M.D., of the World Health Organization's Stop TB department, agreed that such efforts to treat XDR-TB had largely failed.
The report from the Peruvian program, he wrote, "reveals a new and brighter perspective: even in developing countries, extensively drug-resistant tuberculosis may be cured in the majority of cases when management is aggressive and appropriate."
He said the program's outpatient basis may have contributed to its success. "It was community-based in the majority of patients, thus avoiding the additional stress of prolonged hospitalizations [and] it included psychological support for people taking potentially toxic drugs," he noted.
"If every national program put this strategy in place with equal vigor and assertiveness, as in the metropolitan Lima project, drug resistance would be minimized and, when already present, effectively managed," he added.
The study was funded by the Bill and Melinda Gates Foundation, Thomas J. White, Partners in Health, the Peruvian Ministry of Health, the David Rockefeller Center for Latin American Studies at Harvard University, the Francis Family Foundation, the Pittsfield Anti-tuberculosis Association, the Eli Lilly Foundation, and the Hatch Family Foundation, and by career development awards from the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute.
Study authors and Dr. Raviglione reported no potential conflicts of interest.
Additional source: New England Journal of MedicineSource reference: Mitnick C, et al "Comprehensive treatment of extensively drug-resistant tuberculosis" N Engl J Med 2008; 359: 563-74. Additional source: New England Journal of MedicineSource reference: Raviglione M, et al "Facing extensively drug-resistant tuberculosis -- a hope and a challenge" N Engl J Med 2008; 359: 636-37.
Americans Opt by Landslide for Wholesale Revision of Healthcare System
By Emily P. Walker
NEW YORK, 08 aug 2008--An overwhelming proportion of Americans believes the nation's healthcare system needs a fundamental change or a complete overhaul, according to the results of a survey released today.
And the next president is just the person to stimulate such reforms, said nine of every 10 respondents in the survey of a geographically representative sample of 1,004 adults, conducted on May 23 through May 27 by Harris Interactive for the Commonwealth Fund. Democrats support major changes more than Republicans do, the survey found.
"A majority of adults look to the next president to lead by proposing reforms that could improve the quality of healthcare, ensure affordable care, and decrease the number of uninsured," the survey report said. "Across income levels, region, and political affiliation, adults want presidential candidates to focus on health reforms in each of these areas.
"About nine of 10 adults say it is important for presidential candidates to have reform proposals that would improve the quality of care (90%), ensure care and insurance are affordable (93%), and decrease the number of uninsured (88%). In fact, a majority think these policy priorities are very important."
Irrespective of income, 32% of the respondents called for a completely rebuilt health system and another 50% percent thought it required fundamental changes.
Eighty-one percent of respondents who were insured all year and 89% who were uninsured at some point during the year called for fundamental change or complete rebuilding.
About nine out of 10 respondents think the next president should take steps to improve healthcare quality, reduce the cost of healthcare and decrease the number of uninsured people.
The majority of respondents (73%) expressed frustration with their recent healthcare encounters including difficulty getting regular doctor's appointments, receiving advice and seeing a clinician during non-office hours.
Part of that dissatisfaction stems from the fragmented state of the healthcare system, said Stephen C. Schoenbaum, M.D., executive vice president for programs at the Commonwealth Fund. Dr. Shoenbaum said patients "see the system as not well-organized and not well-coordinated."
About half of the respondents reported organization-related problems, such as having to call numerous times to retrieve a test result, or getting to an appointment before their test results arrived.
Respondents also expressed frustration with the amount of medical paperwork, duplicative tests, and what they deemed to be unnecessary treatments.
Patients cited electronic medical records and better collaboration between providers as possible fixes. The survey found that nearly nine out of 10 adults think doctors should use computerized medical records, access test results electronically, and share results with other doctors electronically. More than half of respondents would also like to be able to schedule appointments and communicate with their physician via the Internet.
"Strong public support for the use of health information technology stands in stark contrast to actual practice in the United States," researchers said, citing an earlier study that found just 23% of primary care physicians use electronic medical records.
Most respondents (91%) answered that it is "important," or "very important," to have one place or person responsible for managing their care.
By Emily P. Walker
NEW YORK, 08 aug 2008--An overwhelming proportion of Americans believes the nation's healthcare system needs a fundamental change or a complete overhaul, according to the results of a survey released today.
And the next president is just the person to stimulate such reforms, said nine of every 10 respondents in the survey of a geographically representative sample of 1,004 adults, conducted on May 23 through May 27 by Harris Interactive for the Commonwealth Fund. Democrats support major changes more than Republicans do, the survey found.
"A majority of adults look to the next president to lead by proposing reforms that could improve the quality of healthcare, ensure affordable care, and decrease the number of uninsured," the survey report said. "Across income levels, region, and political affiliation, adults want presidential candidates to focus on health reforms in each of these areas.
"About nine of 10 adults say it is important for presidential candidates to have reform proposals that would improve the quality of care (90%), ensure care and insurance are affordable (93%), and decrease the number of uninsured (88%). In fact, a majority think these policy priorities are very important."
Irrespective of income, 32% of the respondents called for a completely rebuilt health system and another 50% percent thought it required fundamental changes.
Eighty-one percent of respondents who were insured all year and 89% who were uninsured at some point during the year called for fundamental change or complete rebuilding.
About nine out of 10 respondents think the next president should take steps to improve healthcare quality, reduce the cost of healthcare and decrease the number of uninsured people.
The majority of respondents (73%) expressed frustration with their recent healthcare encounters including difficulty getting regular doctor's appointments, receiving advice and seeing a clinician during non-office hours.
Part of that dissatisfaction stems from the fragmented state of the healthcare system, said Stephen C. Schoenbaum, M.D., executive vice president for programs at the Commonwealth Fund. Dr. Shoenbaum said patients "see the system as not well-organized and not well-coordinated."
About half of the respondents reported organization-related problems, such as having to call numerous times to retrieve a test result, or getting to an appointment before their test results arrived.
Respondents also expressed frustration with the amount of medical paperwork, duplicative tests, and what they deemed to be unnecessary treatments.
Patients cited electronic medical records and better collaboration between providers as possible fixes. The survey found that nearly nine out of 10 adults think doctors should use computerized medical records, access test results electronically, and share results with other doctors electronically. More than half of respondents would also like to be able to schedule appointments and communicate with their physician via the Internet.
"Strong public support for the use of health information technology stands in stark contrast to actual practice in the United States," researchers said, citing an earlier study that found just 23% of primary care physicians use electronic medical records.
Most respondents (91%) answered that it is "important," or "very important," to have one place or person responsible for managing their care.
Thursday, August 07, 2008
Exercise Lowers Risk of Colon Cancer
07 aug 2008-- Physical activity can reduce the risk of colon cancer, but few American adults are aware of this, a new study shows.
A sedentary lifestyle accounts for as many as 14 percent of all colon cancer cases in the United States. People who get lots of exercise have a 30 percent to 40 percent lower risk of developing colon cancer, according to study co-author Elliott Coups, of the Division of Population Science at the Fox Chase Cancer Center in Cheltenham, Pa., and colleagues.
But their analysis of survey data from 1,932 adults who answered questions about colon cancer risk found that only 15 percent said they used physical activity as a way of reducing their colon cancer risk. The findings were published in the August issue of Patient Education and Counseling.
Several factors may contribute to this lack of knowledge about the link between exercise and colon cancer risk.
"Patients may not be learning this information from their health-care providers and information regarding colon cancer prevention is not as well publicized as it could be," Coups said in a new release from the Center for the Advancement of Health.
Doctors may find it easier to tell patients about the general health benefits of exercise, rather than specifically referring to colon cancer, even if a patient has a family history of colon cancer or other risk factors for the disease.
"In the context of busy clinic visits, it is, in some ways, efficient for patients to be reminded that physical activity is good for their health in general. Going through each specific health benefit of physical activity would take considerable time," said Coups.
Sedentary people can greatly benefit from starting a modest exercise program, such as gardening or walking two to three hours a week, according to Dr. Edward Giovannucci, a professor at the Harvard School of Public Health.
"Sedentary people should first set such moderate, achievable goals. More benefits could accrue from higher levels and more intense exercise, such as jogging, running or tennis. To some extent, more may be better, but it is important to note that a little is much better than nothing," Giovannucci said in the news release.
Perceived Medical Discrimination May Discourage Cancer Screening
By Charles Bankhead
PALO ALTO, Calif., 07 aug 2008 -- Perceived discrimination in medical care translated into lower rates of screening for breast and colorectal cancer in minority patients, investigators here found.
Patients who perceived discrimination in the healthcare setting were up to 70% less likely to be screened, LaVera M. Crawley, M.D., of Stanford, and colleagues, reported in the August issue of Cancer Epidemiology Biomarkers and Prevention.
Overall, women were influenced more than men by the perception of discrimination.
However, the lowest screening rates were among men who had a usual source of care and sensed discrimination.
"These findings of a significant association between perceived racial or ethnic-based medical discrimination and cancer screening behaviors have serious implications for cancer health disparities," the authors concluded.
However, they cautioned that "we cannot know whether the reported events represented actual discriminatory acts or if perception of discrimination was accurate. Clearly, more research is needed to confirm these initial findings and to explain the gender differences as well as to explore important subgroup differences."
In a 2002 report on unequal treatment in American health care, the Institute of Medicine expressed concern that racial and ethnic discrimination may play a major role in health-care disparities.
Although difficult to measure directly, discrimination, either real or perceived, has been shown to affect health-seeking behaviors, such as preventive services, the authors said.
Most studies that have examined perceived discrimination and health outcomes have focused on generalized discrimination, rather than medical discrimination (related to the care received), they continued.
To examine the impact of perceived medical discrimination on cancer screening, the investigators reviewed data from the 2003 and 2005 California Health Interview Survey. Both surveys elicited information about minority respondents' perception of discrimination in the healthcare setting.
The study involved a total of 11,245 African-American, American Indian/Alaskan Native, Asian, and Latino adults, comprising 8,051 women ages 40 to 75 and 3,194 men ages 50 to 75.
More than half had at least some college education, about 85% had health insurance, and more than 90% reported a usual source of care.
The primary outcome measures were rates of screening for colorectal cancer in men and women ages 50 to 75 and rates of breast cancer screening in women ages 40 to 75.
The overall screening rate for colorectal cancer (endoscopy within the past five years and/or fecal occult blood testing within the past year) was 41.8% among women and 43.4% among men.
About 60% of the women reported having a mammogram within the past year.
The responses showed that 8.9% of women and 6.2% of men had perceived medical discrimination within the past five years.
As compared with respondents who reported no discrimination, women who perceived medical discrimination were 34% less likely to be screened for colorectal cancer (OR 0.66, 95% CI 0.64 to 0.69) and 48% less likely to be screened for breast cancer (OR 0.52, 95% CI 0.51 to 0.54).
Men who perceived discrimination were just as likely to be screened for colorectal cancer as those who reported no discrimination (OR 1.02, 95% CI 0.97 to 1.07).
However, men who perceived discrimination and reported having a usual source of care were 70% less likely to be screened (OR 0.30, 95% CI 0.28 to 0.32).
The findings suggest that "some persons may delay or avoid getting screened for cancers and that this delay may be associated with racial or ethnic-based experiences they encounter within the medical setting," the authors said.
The authors acknowledged that a cross-sectional survey precludes an examination of causality.
They also noted a potential for sample bias because of low response rates to the surveys (33.5% in 2003 and 26.9% in 2005).
The authors reported no disclosures.
Additional source: Cancer Epidemiology, Biomarkers & PreventionSource reference: Crawley LM, et al "Perceived medical discrimination and cancer screening behaviors of racial and ethnic minority adults" Cancer Epidemiol Biomarkers Prev 2008; 17: OF1-8.
By Charles Bankhead
PALO ALTO, Calif., 07 aug 2008 -- Perceived discrimination in medical care translated into lower rates of screening for breast and colorectal cancer in minority patients, investigators here found.
Patients who perceived discrimination in the healthcare setting were up to 70% less likely to be screened, LaVera M. Crawley, M.D., of Stanford, and colleagues, reported in the August issue of Cancer Epidemiology Biomarkers and Prevention.
Overall, women were influenced more than men by the perception of discrimination.
However, the lowest screening rates were among men who had a usual source of care and sensed discrimination.
"These findings of a significant association between perceived racial or ethnic-based medical discrimination and cancer screening behaviors have serious implications for cancer health disparities," the authors concluded.
However, they cautioned that "we cannot know whether the reported events represented actual discriminatory acts or if perception of discrimination was accurate. Clearly, more research is needed to confirm these initial findings and to explain the gender differences as well as to explore important subgroup differences."
In a 2002 report on unequal treatment in American health care, the Institute of Medicine expressed concern that racial and ethnic discrimination may play a major role in health-care disparities.
Although difficult to measure directly, discrimination, either real or perceived, has been shown to affect health-seeking behaviors, such as preventive services, the authors said.
Most studies that have examined perceived discrimination and health outcomes have focused on generalized discrimination, rather than medical discrimination (related to the care received), they continued.
To examine the impact of perceived medical discrimination on cancer screening, the investigators reviewed data from the 2003 and 2005 California Health Interview Survey. Both surveys elicited information about minority respondents' perception of discrimination in the healthcare setting.
The study involved a total of 11,245 African-American, American Indian/Alaskan Native, Asian, and Latino adults, comprising 8,051 women ages 40 to 75 and 3,194 men ages 50 to 75.
More than half had at least some college education, about 85% had health insurance, and more than 90% reported a usual source of care.
The primary outcome measures were rates of screening for colorectal cancer in men and women ages 50 to 75 and rates of breast cancer screening in women ages 40 to 75.
The overall screening rate for colorectal cancer (endoscopy within the past five years and/or fecal occult blood testing within the past year) was 41.8% among women and 43.4% among men.
About 60% of the women reported having a mammogram within the past year.
The responses showed that 8.9% of women and 6.2% of men had perceived medical discrimination within the past five years.
As compared with respondents who reported no discrimination, women who perceived medical discrimination were 34% less likely to be screened for colorectal cancer (OR 0.66, 95% CI 0.64 to 0.69) and 48% less likely to be screened for breast cancer (OR 0.52, 95% CI 0.51 to 0.54).
Men who perceived discrimination were just as likely to be screened for colorectal cancer as those who reported no discrimination (OR 1.02, 95% CI 0.97 to 1.07).
However, men who perceived discrimination and reported having a usual source of care were 70% less likely to be screened (OR 0.30, 95% CI 0.28 to 0.32).
The findings suggest that "some persons may delay or avoid getting screened for cancers and that this delay may be associated with racial or ethnic-based experiences they encounter within the medical setting," the authors said.
The authors acknowledged that a cross-sectional survey precludes an examination of causality.
They also noted a potential for sample bias because of low response rates to the surveys (33.5% in 2003 and 26.9% in 2005).
The authors reported no disclosures.
Additional source: Cancer Epidemiology, Biomarkers & PreventionSource reference: Crawley LM, et al "Perceived medical discrimination and cancer screening behaviors of racial and ethnic minority adults" Cancer Epidemiol Biomarkers Prev 2008; 17: OF1-8.
Alcohol consumption declining, according to results of new study
New York, 07 aug 2008- Overall alcohol use—particularly consumption of beer—is declining in the US, according to a new study published in the August 2008 issue of The American Journal of Medicine. Researchers examined 50 years of data and found several changes in alcohol intake but no change in alcohol use disorders. Americans are drinking significantly less beer and more wine, while hard liquor use has remained fairly constant. More people now report that they are non-drinkers. People born later in the 20th century drink more moderately than older people. As we age, our individual alcohol consumption goes down.
Researchers examined 8,000 records of the Framingham Heart Study, the longest population-based study of American adults ever conducted, to measure alcohol consumption over 50 years. Because the Framingham study recruited subjects that were born before 1900 until 1959, it gives insights into behavior and medical histories through most of the 20th Century. Subjects, both from the original cohort and from the children of the original cohort, have been interviewed every 4 years, from 1948 until 2003. Since each individual was followed directly, a set of histories of lifetime alcohol use could be captured.
While heavy alcohol use is associated with numerous bad outcomes, moderate consumption has been linked to improved cardiovascular health and to improved morbidity and mortality in the elderly. This study shows that, on the whole, the American population is moving in a healthier direction. Despite more favorable patterns of drinking, risk of alcohol dependence did not show a decrease. The proportion of people who developed alcohol-related disorders, such as alcoholic cardiomyopathy or alcoholic cirrhosis remained nearly constant across all age groups.
Writing in the article, Yuqing Zhang, DSc, Boston University School of Medicine, and his co-investigators state, "The findings in this study may be considered encouraging in many ways: the average amount of alcohol has decreased in more recently born cohorts, the percentage of the population exhibiting 'moderate' alcohol intake has been increasing steadily, and the percentage reporting 'heavy' drinking has decreased over time…While these data suggest the development of more favorable patterns of alcohol consumption over the latter part of the 20th century, that also show that, at the same time, the cumulative incidence of alcohol use disorders has not shown a decrease, and continuing efforts at preventing them are warranted."
###
The article is "Secular Trends in Alcohol Consumption over 50 Years: The Framingham Study" by Yuqing Zhang, DSc, Xinxin Guo, MPH, Richard Saitz, MD, MPH, Daniel Levy, MD, MPH, Emily Sartini, MA, Jingbo Niu, DSc, and R. Curtis Ellison, MD. It appears in The American Journal of Medicine, Volume 121, Issue 8 (August 2008) published by Elsevier.
New York, 07 aug 2008- Overall alcohol use—particularly consumption of beer—is declining in the US, according to a new study published in the August 2008 issue of The American Journal of Medicine. Researchers examined 50 years of data and found several changes in alcohol intake but no change in alcohol use disorders. Americans are drinking significantly less beer and more wine, while hard liquor use has remained fairly constant. More people now report that they are non-drinkers. People born later in the 20th century drink more moderately than older people. As we age, our individual alcohol consumption goes down.
Researchers examined 8,000 records of the Framingham Heart Study, the longest population-based study of American adults ever conducted, to measure alcohol consumption over 50 years. Because the Framingham study recruited subjects that were born before 1900 until 1959, it gives insights into behavior and medical histories through most of the 20th Century. Subjects, both from the original cohort and from the children of the original cohort, have been interviewed every 4 years, from 1948 until 2003. Since each individual was followed directly, a set of histories of lifetime alcohol use could be captured.
While heavy alcohol use is associated with numerous bad outcomes, moderate consumption has been linked to improved cardiovascular health and to improved morbidity and mortality in the elderly. This study shows that, on the whole, the American population is moving in a healthier direction. Despite more favorable patterns of drinking, risk of alcohol dependence did not show a decrease. The proportion of people who developed alcohol-related disorders, such as alcoholic cardiomyopathy or alcoholic cirrhosis remained nearly constant across all age groups.
Writing in the article, Yuqing Zhang, DSc, Boston University School of Medicine, and his co-investigators state, "The findings in this study may be considered encouraging in many ways: the average amount of alcohol has decreased in more recently born cohorts, the percentage of the population exhibiting 'moderate' alcohol intake has been increasing steadily, and the percentage reporting 'heavy' drinking has decreased over time…While these data suggest the development of more favorable patterns of alcohol consumption over the latter part of the 20th century, that also show that, at the same time, the cumulative incidence of alcohol use disorders has not shown a decrease, and continuing efforts at preventing them are warranted."
###
The article is "Secular Trends in Alcohol Consumption over 50 Years: The Framingham Study" by Yuqing Zhang, DSc, Xinxin Guo, MPH, Richard Saitz, MD, MPH, Daniel Levy, MD, MPH, Emily Sartini, MA, Jingbo Niu, DSc, and R. Curtis Ellison, MD. It appears in The American Journal of Medicine, Volume 121, Issue 8 (August 2008) published by Elsevier.
IAC: Raltegravir (Isentress) Matches Standard Initial Care at 96 Weeks
By Michael Smith
MEXICO CITY, 07 aug 2008-- In patients starting HIV therapy, the integrase inhibitor raltegravir (Isentress) had a long-lasting benefit and was well tolerated, a researcher said here. After 96 weeks of treatment, raltegravir had a virological effect that was almost identical to standard therapy with efavirenz (Sustiva), according to Marty Markowitz, M.D., of the Aaron Diamond AIDS Research Center in New York city. The findings extend earlier results from the industry-sponsored phase II randomized trial, Dr. Markowitz told an oral abstract session at the
The drug was approved last year for use in patients whose HIV is resistant to drug therapy and the earlier results from this trial suggested it was of equal benefit in treatment-naive patients.
But clinicians have been watching for the 96-week results to satisfy themselves that the effect is both durable and does not come with any unexpected side effects, said Cal Cohen, M.D., research director of the Boston-based treatment and research group CRI of New England.
"It was good news -- we didn't see a problem" on either front, said Dr. Cohen, who was not part of the study.
The drug is now widely used in treatment-experienced patients, he said, and to some extent in those beginning therapy who can't tolerate efavirenz.
"This will, to some extent, justify that," he said.
The study enrolled 198 treatment-naive patients and randomized them in a blinded fashion to one of four doses of raltegravir -- 100, 200, 400, and 600 milligrams twice a day -- or to 600 milligrams a day of efavirenz.
At week 48, the raltegravir patients were all put on 400 milligrams twice daily.
Dr. Markowitz said that at week 96, 83% of the 160 patients in the raltegravir group had a viral load of fewer than 50 copies of HIV RNA per milliliter of blood.
In the 38 efavirenz patients, the rate was 84%, he said.
The rates were also similar when the researchers considered a higher viral cut-off of 400 copies, he said.
Only two patients relapsed from week 48 through week 96, Dr. Markowitz said, one each in the raltegravir and efavirenz groups.
Interestingly, the patient who relapsed in the raltegravir arm appeared to do so without developing any resistance mutations. "He had wild-type virus on genotyping," Dr. Markowitz said.
On the other hand, the efavirenz patient who relapsed had developed well-known mutations that lead to drug resistance, he said.
Overall, he said, adverse events were generally similar between the two medications, but drug-related adverse events (mainly neuropsychiatric issues) were higher in the efavirenz arm, where 74% of patients reported them, compared with 50% for raltegravir.
There were three malignancies in the raltegravir arm, compared with one among efavirenz patients, but the difference was not significant.
Raltegravir had a generally neutral effect on lipids, he said.
The study was sponsored by Merck & Co. Dr. Markowitz made no disclosures.
Primary source: International AIDS ConferenceSource reference:Markowitz M, et al "Sustained antiretroviral efficacy of raltegravir as part of combination ART in treatment-naive HIV-1 infected patients: 96-week data" IAC 2008; Abstract TUAB0102.
By Michael Smith
MEXICO CITY, 07 aug 2008-- In patients starting HIV therapy, the integrase inhibitor raltegravir (Isentress) had a long-lasting benefit and was well tolerated, a researcher said here. After 96 weeks of treatment, raltegravir had a virological effect that was almost identical to standard therapy with efavirenz (Sustiva), according to Marty Markowitz, M.D., of the Aaron Diamond AIDS Research Center in New York city. The findings extend earlier results from the industry-sponsored phase II randomized trial, Dr. Markowitz told an oral abstract session at the
The drug was approved last year for use in patients whose HIV is resistant to drug therapy and the earlier results from this trial suggested it was of equal benefit in treatment-naive patients.
But clinicians have been watching for the 96-week results to satisfy themselves that the effect is both durable and does not come with any unexpected side effects, said Cal Cohen, M.D., research director of the Boston-based treatment and research group CRI of New England.
"It was good news -- we didn't see a problem" on either front, said Dr. Cohen, who was not part of the study.
The drug is now widely used in treatment-experienced patients, he said, and to some extent in those beginning therapy who can't tolerate efavirenz.
"This will, to some extent, justify that," he said.
The study enrolled 198 treatment-naive patients and randomized them in a blinded fashion to one of four doses of raltegravir -- 100, 200, 400, and 600 milligrams twice a day -- or to 600 milligrams a day of efavirenz.
At week 48, the raltegravir patients were all put on 400 milligrams twice daily.
Dr. Markowitz said that at week 96, 83% of the 160 patients in the raltegravir group had a viral load of fewer than 50 copies of HIV RNA per milliliter of blood.
In the 38 efavirenz patients, the rate was 84%, he said.
The rates were also similar when the researchers considered a higher viral cut-off of 400 copies, he said.
Only two patients relapsed from week 48 through week 96, Dr. Markowitz said, one each in the raltegravir and efavirenz groups.
Interestingly, the patient who relapsed in the raltegravir arm appeared to do so without developing any resistance mutations. "He had wild-type virus on genotyping," Dr. Markowitz said.
On the other hand, the efavirenz patient who relapsed had developed well-known mutations that lead to drug resistance, he said.
Overall, he said, adverse events were generally similar between the two medications, but drug-related adverse events (mainly neuropsychiatric issues) were higher in the efavirenz arm, where 74% of patients reported them, compared with 50% for raltegravir.
There were three malignancies in the raltegravir arm, compared with one among efavirenz patients, but the difference was not significant.
Raltegravir had a generally neutral effect on lipids, he said.
The study was sponsored by Merck & Co. Dr. Markowitz made no disclosures.
Primary source: International AIDS ConferenceSource reference:Markowitz M, et al "Sustained antiretroviral efficacy of raltegravir as part of combination ART in treatment-naive HIV-1 infected patients: 96-week data" IAC 2008; Abstract TUAB0102.
Rituximab Reverses Kidney Damage of Membranous Nephropathy
By Crystal Phend
BERGAMO, Italy, 07 aug 2008-- Kidney damage from refractory idiopathic membranous nephropathy may be reduced or even healed with rituximab (Rituxan), researchers here found.
In a small study, 20% of patients with the autoimmune disease achieved complete remission on rituximab, reported Piero Ruggenenti, M.D., of Negri Bergamo Laboratories here, and colleagues in the November issue of the Clinical Journal of the American Society Nephrology.
Repeat kidney biopsies showed that autoantibodies disappeared over time and glomerular structural damage healed, which the researchers said was "likely to translate into long-term renoprotection."
These findings represent a first step toward selective therapy, they wrote.
Membranous nephropathy, one of the most common immune-mediated kidney diseases, involves immunoglobulins produced by B cells, which are the primary target of rituximab.
Treatment for the disease has traditionally relied on steroids and broader spectrum immune suppression with drugs such as alkylating agents, calcineurin inhibitors, and mycophenolate mofetil (CellCept, Myfortic).
However, these immunosuppressant agents carry severe toxicity risk without much benefit for kidney survival, the researchers noted. Despite therapy, 40% of patients progress to end-stage renal failure.
Following a successful pilot study with rituximab in these patients, the researchers studied the drug in 50 consecutive patients with long-standing, biopsy-proven idiopathic membranous nephropathy refractory to standard treatments.
Participants received four weekly intravenous infusions of rituximab at a dose of 375 mg/m2 each.
The investigators previously reported that the drug reduced the amount of protein lost in the urine due to the disease. Ten patients in the study achieved reduction of 24-hour proteinuria to less than 0.5 g for at least six months.
These patients who had remission of proteinuria after rituximab therapy were more likely to be women (P<0.05) and had lower baseline serum creatinine levels and less severe proteinuria initially.
To see the functional implications and kidney structural effects of this improvement, the researchers followed-up on these patients.
All 10 had a full remission with normalization of serum albumin and cholesterol levels and significant increases in body weight, hematocrit, and hemoglobin concentration, though not in blood pressure or serum creatinine.
GFR was stable over time, whereas the RPF significantly declined. Consequently, the filtration fraction decreased and renal vascular resistance increased at the time of the repeat biopsy compared with baseline. Albumin fractional clearance significantly decreased and sodium fractional clearance significantly increased (by 8.5-fold) compared with baseline.
Rituximab cleared out circulating CD20 and CD19 B cells after the first infusion. After six to nine months, cell counts began to climb toward the normal range. However, proteinuria did not recur.
Seven patients agreed to repeat functional and histological assessment with repeat biopsy at a median of 21 months after rituximab therapy and 11 months after remission of proteinuria.
Histology at baseline showed a typical pattern of diffuse, granular staining for total immunoglobulin G (IgG), IgG4, and C3 along glomerular capillary walls. But after rituximab, all tissue samples had either no staining or "remarkably reduced" staining for IgG4 compared with baseline (P<0.01). There was trend for decrease in C3 staining as well.
Likewise, the stage I to III lesions seen with electron microscopy in all biopsy samples at baseline improved after treatment. The electron-dense deposits disappeared in two of the seven patients' kidney tissue and were almost completely reabsorbed in the rest.
Podocyte changes were also less severe after rituximab. At baseline, patients had substantially fewer filtration slit pores than nonproteinuric controls (0.27 versus 2.04 slits/µm glomerular basement membrane). But this increased significantly after treatment, although still not to the normal range (0.86 slits/µm, P<0.05).
"Finding that these changes largely recovered at repeat biopsies suggests that preventing the immunologically mediated injury allowed progressive restoration of the glomerular epithelial layer," the researchers said.
They noted that the study was limited by the small number of patients and lack of a control group, although the consistent findings in repeat biopsies suggested this wasn't a problem.
"Whether this may apply to other glomerulopathies," they concluded, "and may translate into long-term protection from renal function loss and the potentially life-threatening complications of the nephrotic syndrome remains to be established in properly powered prospective trials."
The researchers reported no conflicts of interest.
Primary source: Clinical Journal of the American Society of NephrologySource reference:Ruggenenti P, et al "Effects of rituximab on morphofunctional abnormalities of membranous glomerulopathy" Clin J Am Soc Nephrol 2008; DOI: 10.2215/CJN.01730408.
By Crystal Phend
BERGAMO, Italy, 07 aug 2008-- Kidney damage from refractory idiopathic membranous nephropathy may be reduced or even healed with rituximab (Rituxan), researchers here found.
In a small study, 20% of patients with the autoimmune disease achieved complete remission on rituximab, reported Piero Ruggenenti, M.D., of Negri Bergamo Laboratories here, and colleagues in the November issue of the Clinical Journal of the American Society Nephrology.
Repeat kidney biopsies showed that autoantibodies disappeared over time and glomerular structural damage healed, which the researchers said was "likely to translate into long-term renoprotection."
These findings represent a first step toward selective therapy, they wrote.
Membranous nephropathy, one of the most common immune-mediated kidney diseases, involves immunoglobulins produced by B cells, which are the primary target of rituximab.
Treatment for the disease has traditionally relied on steroids and broader spectrum immune suppression with drugs such as alkylating agents, calcineurin inhibitors, and mycophenolate mofetil (CellCept, Myfortic).
However, these immunosuppressant agents carry severe toxicity risk without much benefit for kidney survival, the researchers noted. Despite therapy, 40% of patients progress to end-stage renal failure.
Following a successful pilot study with rituximab in these patients, the researchers studied the drug in 50 consecutive patients with long-standing, biopsy-proven idiopathic membranous nephropathy refractory to standard treatments.
Participants received four weekly intravenous infusions of rituximab at a dose of 375 mg/m2 each.
The investigators previously reported that the drug reduced the amount of protein lost in the urine due to the disease. Ten patients in the study achieved reduction of 24-hour proteinuria to less than 0.5 g for at least six months.
These patients who had remission of proteinuria after rituximab therapy were more likely to be women (P<0.05) and had lower baseline serum creatinine levels and less severe proteinuria initially.
To see the functional implications and kidney structural effects of this improvement, the researchers followed-up on these patients.
All 10 had a full remission with normalization of serum albumin and cholesterol levels and significant increases in body weight, hematocrit, and hemoglobin concentration, though not in blood pressure or serum creatinine.
GFR was stable over time, whereas the RPF significantly declined. Consequently, the filtration fraction decreased and renal vascular resistance increased at the time of the repeat biopsy compared with baseline. Albumin fractional clearance significantly decreased and sodium fractional clearance significantly increased (by 8.5-fold) compared with baseline.
Rituximab cleared out circulating CD20 and CD19 B cells after the first infusion. After six to nine months, cell counts began to climb toward the normal range. However, proteinuria did not recur.
Seven patients agreed to repeat functional and histological assessment with repeat biopsy at a median of 21 months after rituximab therapy and 11 months after remission of proteinuria.
Histology at baseline showed a typical pattern of diffuse, granular staining for total immunoglobulin G (IgG), IgG4, and C3 along glomerular capillary walls. But after rituximab, all tissue samples had either no staining or "remarkably reduced" staining for IgG4 compared with baseline (P<0.01). There was trend for decrease in C3 staining as well.
Likewise, the stage I to III lesions seen with electron microscopy in all biopsy samples at baseline improved after treatment. The electron-dense deposits disappeared in two of the seven patients' kidney tissue and were almost completely reabsorbed in the rest.
Podocyte changes were also less severe after rituximab. At baseline, patients had substantially fewer filtration slit pores than nonproteinuric controls (0.27 versus 2.04 slits/µm glomerular basement membrane). But this increased significantly after treatment, although still not to the normal range (0.86 slits/µm, P<0.05).
"Finding that these changes largely recovered at repeat biopsies suggests that preventing the immunologically mediated injury allowed progressive restoration of the glomerular epithelial layer," the researchers said.
They noted that the study was limited by the small number of patients and lack of a control group, although the consistent findings in repeat biopsies suggested this wasn't a problem.
"Whether this may apply to other glomerulopathies," they concluded, "and may translate into long-term protection from renal function loss and the potentially life-threatening complications of the nephrotic syndrome remains to be established in properly powered prospective trials."
The researchers reported no conflicts of interest.
Primary source: Clinical Journal of the American Society of NephrologySource reference:Ruggenenti P, et al "Effects of rituximab on morphofunctional abnormalities of membranous glomerulopathy" Clin J Am Soc Nephrol 2008; DOI: 10.2215/CJN.01730408.
Wednesday, August 06, 2008
Will Older Men Give Up the PSA Test?
06 aug 2008--Men ages 75 and older should not be screened for prostate cancer. This is the important and definitive conclusion of the U.S. Preventive Services Task Force, which for the first time has made a specific recommendation about the value of screening for prostate cancer.
To many doctors, the new guidelines will not come as a shock. Quite a few believe that because prostate cancer often progresses slowly, not causing symptoms for 10 years or longer, it’s inappropriate to look for it in healthy older men. A man aged 75 or older may well die of another cause long before his prostate cancer becomes a problem. And treatment of prostate cancer has significant drawbacks, often leading to impotence, incontinence and a variety of other complications that reduce a patient’s quality of life.
But what doctors know and what happens in practice often are two different things.
Prostate screening involves a simple blood test to check for prostate-specific antigen, or PSA. Many doctors find it easier just to do a PSA test than take the time to explain the pros and cons to a patient. Patients themselves, many accustomed since their late 40s or early 50s to getting tested, aren’t always comfortable with the idea of stopping the screening once they reach older age.
And interestingly, doctors say the wives of many older men, themselves firm believers in screening for cervical cancer and breast cancer, sometimes push their husbands and doctors to continue screening for prostate cancer.
The statistics on inappropriate screening are surprising. In one study of 600,000 men treated by the Veterans Administration, screening rates were 64 percent for men ages 70 to 74, 56 percent for men ages 75 to 80, 45 percent for men ages 80 to 84 — and a surprising 36 percent for men ages 85 and older.
“For some men, it’s a tough issue to face,'’ said Dr. Ned Calonge, chairman of the task force and chief medical officer of the Colorado Department of Public Health and Environment. “It isn’t that we know when you’re going to die, or that it’s all over so don’t worry about anything else…. We’re very poor at predicting how much longer you’re going to live. If you take it from the standpoint of risk versus benefit, the chances are more that screening is going to harm you.'’
Dr. Calonge hopes the new guidelines will trigger another round of discussion about PSA testing between doctors and patients.
“Even before this, we were really trying to recommend to physicians that given the uncertainty about benefit for screening, you should really discuss on an individual basis the pros and cons of screening,'’ Dr. Calonge said. “What we find in practice is that adds additional time and effort that’s not compensated as part of normal clinical care. It’s easier to just draw the blood test. I think what we hope now is that it will be just as easy to not do the blood test.'’
What do you think? Will you be ready to give up PSA testing when you or your spouse reaches the age of 75? To learn more about the new guidelines, click here to read the full story. Then join the discussion by posting your comments below.
Light Exercise Prevents Atrial Fibrillation in Elderly
By Ed Edelson
06 aug 2008 -- Light to moderate exercise -- just walking a few blocks or even dancing -- can help prevent the abnormal heart rhythm called atrial fibrillation in those most vulnerable to it -- older people, a new study finds.
Atrial fibrillation, in which the two upper chambers of the heart tend to twitch rather than beat steadily, is the most common heart rhythm abnormality. It is especially common after age 65. The danger is that blood can pool, causing clots that move to the heart or brain. There have been reports of an increased incidence of the abnormality in younger people who exercise vigorously.
"Prior studies have looked at atrial fibrillation in young and middle-aged and generally healthy people," said study lead author Dr. Dariush Mozaffarian, a cardiologist at Brigham and Women's Hospital in Boston. "They found that, for example, marathon runners have a higher risk of atrial fibrillation. But the vast majority of atrial fibrillation occurs later in life. After 65, about one in five people develops atrial fibrillation over 10 years."
Mozaffarian and his colleagues studied the habits of 5,446 adults, average age 73, comparing their physical activities with the risk of developing atrial fibrillation.
"No one has looked at exercise and atrial fibrillation in these older people," he said. "We found that light to moderate exercise, such as walking 10 blocks a week, was associated with a lower incidence of atrial fibrillation."
Specifically, the researchers found that the incidence of the heart abnormality was 22 percent lower in those walking five to 11 blocks a week than for those walking fewer than five blocks a week. It was 24 percent lower for those walking 12 to 23 blocks weekly, 33 percent lower for those walking 24 to 59 blocks, and 44 percent lower for those walking 60 or more blocks a week.
Overall, there was a 50 percent lower risk of developing atrial fibrillation when comparing people with the highest and lowest levels of walking distance and pace.
The findings were published in the Aug. 5 issue of the journal Circulation.
Meanwhile, a separate trial looking at the effect of exercise on atrial fibrillation from a different angle is being done by Dr. Jorge A. Joglar, an associate professor of internal medicine and director of clinical cardiac physiology at the University of Texas Southwestern Medical Center at Dallas.
"We have enrolled patients who have atrial fibrillation already to see whether exercise improves their quality of life," Joglar said.
The 10 participants in the trial, all in their mid-70s and diagnosed with atrial fibrillation, are doing aerobic exercises 45 minutes a day, three or four days a week, Joglar said. "They are riding stationary bicycles or walking fast," he explained.
The study is ongoing, but "preliminary data appears to be that they feel better and function better," Joglar said.
He and Mozaffarian stressed that light exercise, whatever its effect on atrial fibrillation, has known benefits, such as helping control blood pressure and weight. Other studies have shown that the right exercise -- "not too strenuous but not too light, either" -- is helpful against angina, the chest pain caused by heart artery problems, Joglar said.
"There are additional strong reasons for the public to focus on exercise," Mozaffarian said.
By Ed Edelson
06 aug 2008 -- Light to moderate exercise -- just walking a few blocks or even dancing -- can help prevent the abnormal heart rhythm called atrial fibrillation in those most vulnerable to it -- older people, a new study finds.
Atrial fibrillation, in which the two upper chambers of the heart tend to twitch rather than beat steadily, is the most common heart rhythm abnormality. It is especially common after age 65. The danger is that blood can pool, causing clots that move to the heart or brain. There have been reports of an increased incidence of the abnormality in younger people who exercise vigorously.
"Prior studies have looked at atrial fibrillation in young and middle-aged and generally healthy people," said study lead author Dr. Dariush Mozaffarian, a cardiologist at Brigham and Women's Hospital in Boston. "They found that, for example, marathon runners have a higher risk of atrial fibrillation. But the vast majority of atrial fibrillation occurs later in life. After 65, about one in five people develops atrial fibrillation over 10 years."
Mozaffarian and his colleagues studied the habits of 5,446 adults, average age 73, comparing their physical activities with the risk of developing atrial fibrillation.
"No one has looked at exercise and atrial fibrillation in these older people," he said. "We found that light to moderate exercise, such as walking 10 blocks a week, was associated with a lower incidence of atrial fibrillation."
Specifically, the researchers found that the incidence of the heart abnormality was 22 percent lower in those walking five to 11 blocks a week than for those walking fewer than five blocks a week. It was 24 percent lower for those walking 12 to 23 blocks weekly, 33 percent lower for those walking 24 to 59 blocks, and 44 percent lower for those walking 60 or more blocks a week.
Overall, there was a 50 percent lower risk of developing atrial fibrillation when comparing people with the highest and lowest levels of walking distance and pace.
The findings were published in the Aug. 5 issue of the journal Circulation.
Meanwhile, a separate trial looking at the effect of exercise on atrial fibrillation from a different angle is being done by Dr. Jorge A. Joglar, an associate professor of internal medicine and director of clinical cardiac physiology at the University of Texas Southwestern Medical Center at Dallas.
"We have enrolled patients who have atrial fibrillation already to see whether exercise improves their quality of life," Joglar said.
The 10 participants in the trial, all in their mid-70s and diagnosed with atrial fibrillation, are doing aerobic exercises 45 minutes a day, three or four days a week, Joglar said. "They are riding stationary bicycles or walking fast," he explained.
The study is ongoing, but "preliminary data appears to be that they feel better and function better," Joglar said.
He and Mozaffarian stressed that light exercise, whatever its effect on atrial fibrillation, has known benefits, such as helping control blood pressure and weight. Other studies have shown that the right exercise -- "not too strenuous but not too light, either" -- is helpful against angina, the chest pain caused by heart artery problems, Joglar said.
"There are additional strong reasons for the public to focus on exercise," Mozaffarian said.
Obesity seen protective in cases of heart failure
06 aug 2008--Overweight and obese patients with heart failure seem to have a lower risk of dying than their normal-weight counterparts, according to a review of published studies involving more than 28,000 heart failure patients who were followed for an average of nearly three years.
There is evidence, Dr. Antigone Oreopoulos told Reuters Health, that a normal body mass index (BMI) "is likely not the ideal BMI" in people with heart failure, which occurs when the heart loses its ability to pump blood efficiently.
Oreopoulos, from University of Alberta, Edmonton, Canada, and associates reviewed nine studies that examined the impact of BMI on mortality. They pooled the data to estimate the risk of death in patients who are underweight, overweight or obese compared to patients with a normal body weight.
According to the researchers, patients who were overweight or obese were less likely to die during follow up compared to their normal-weight peers. Being overweight or obese "remained protective" against death in a "risk-adjusted" analysis.
Heart failure patients who had a normal weight or who were underweight had the highest death rates. "It remains unknown, however, if higher body fat levels are actually the cause of better outcomes in patients with heart failure," the researchers note in the American Heart Journal.
"We believe there is a need for prospective studies to confirm these findings and elucidate potential mechanisms" for the potentially protective effect of increased body weight on heart failure, Oreopoulos and colleagues conclude.
"Our findings," they point out, "are consistent with evidence in other chronic disease populations," including survivors of heart attack and chronic hemodialysis patients, demonstrating lower death rates with higher BMI levels.
SOURCE: American Heart Journal, July 2008.
06 aug 2008--Overweight and obese patients with heart failure seem to have a lower risk of dying than their normal-weight counterparts, according to a review of published studies involving more than 28,000 heart failure patients who were followed for an average of nearly three years.
There is evidence, Dr. Antigone Oreopoulos told Reuters Health, that a normal body mass index (BMI) "is likely not the ideal BMI" in people with heart failure, which occurs when the heart loses its ability to pump blood efficiently.
Oreopoulos, from University of Alberta, Edmonton, Canada, and associates reviewed nine studies that examined the impact of BMI on mortality. They pooled the data to estimate the risk of death in patients who are underweight, overweight or obese compared to patients with a normal body weight.
According to the researchers, patients who were overweight or obese were less likely to die during follow up compared to their normal-weight peers. Being overweight or obese "remained protective" against death in a "risk-adjusted" analysis.
Heart failure patients who had a normal weight or who were underweight had the highest death rates. "It remains unknown, however, if higher body fat levels are actually the cause of better outcomes in patients with heart failure," the researchers note in the American Heart Journal.
"We believe there is a need for prospective studies to confirm these findings and elucidate potential mechanisms" for the potentially protective effect of increased body weight on heart failure, Oreopoulos and colleagues conclude.
"Our findings," they point out, "are consistent with evidence in other chronic disease populations," including survivors of heart attack and chronic hemodialysis patients, demonstrating lower death rates with higher BMI levels.
SOURCE: American Heart Journal, July 2008.
Uninsured Americans Carry Large Chronic Disease Burden
By John Gever
CAMBRIDGE, Mass., 06 aug 2008-- Nearly one-third of uninsured Americans under age 65 reported having cardiovascular disease, diabetes, hypertension, or some other chronic condition, researchers here said.
Data from the National Health and Nutrition Examination Survey (NHANES) showed that percentages of uninsured people reporting a chronic condition ranged from 11.9% for hypercholesterolemia (95% CI 9.3% to 12.6%) to 19.3% for asthma and COPD (95% CI 16% to 22.3%), reported Andrew P. Wilper, M.D., M.P.H., of Cambridge Health Alliance, and colleagues in the Aug. 5 issue of Annals of Internal Medicine.
Percentages for other chronic diseases were:
Cardiovascular disease, 16.1% (95% CI 12.6% to 19.6%)
Hypertension, 15.5% (95% CI 13.4% to 17.6%)
Diabetes mellitus, 16.6% (95% CI 13.2% to 20%)
Previous cancer (excluding non-melanoma skin cancer), 15.4% (95% CI 11.5% to 19.3%)
Some 31.3% of the uninsured had at least one of the six conditions (95% CI 28.7% to 34%), the researchers said.
"These findings counter notions that persons without insurance are a largely healthy population with little need for ongoing medical care," Dr. Wilper and colleagues wrote.
The researchers said 45.4% of insured patients had at least one chronic disease. The higher percentage was likely because they were older on average than the uninsured, they said.
In June, the CDC reported that about 43 million Americans, 14.5% of the overall population, were uninsured in 2007. (See Southwest Lags in Health Insurance Coverage)
According to the NHANES data -- from surveys conducted from 1999 through 2004 -- 20.8% of the non-elderly adult population, or 36.4 million individuals (95% CI 33.1 to 40 million), were without health insurance.
The study was only the second to examine the burden of chronic disease in the uninsured, Dr. Wilper and colleagues said. The earlier research, covering 1997 and 1998 with a different data set, found substantially lower rates of chronic disease, suggesting a trend toward poorer health status among the uninsured.
The NHANES survey obtained data on health insurance status and other health-related information from 12,486 respondents.
Dr. Wilper and colleagues found that, after adjusting for age, sex, and race/ethnicity, lack of insurance significantly predicted a lower likelihood of seeing a health professional in the past year (6.2% versus 22.6% for the insured, P<0.001).
Those without insurance were also more likely to name an emergency department as their standard site of care (7.1% versus 1.1%, P<0.001) and to report not having a standard site of care (22.6% versus 6.2%, P<0.001).
"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," Dr. Wilper and colleagues wrote.
They pointed out that treatments for the six chronic conditions are both standard and a national priority.
The researchers suggested that a healthcare system with a de facto exclusion based on insurance status is unethical.
In an accompanying editorial, Marshall H. Chin, M.D., M.P.H., of the University of Chicago, commented that ensuring good treatment for chronic disease will require more than health insurance reform.
"It will not be sufficient unless it is coupled with quality improvement efforts targeting the reasons that vulnerable populations with access to care often do not receive optimal care," he wrote.
He noted that quality of care varies among facilities and regions. For example, he said, recent budget cuts have hit public clinic and hospital systems in Atlanta and Chicago.
"Healthcare reform must ensure that adequate resources flow to healthcare organizations and providers that serve a disproportionate share of vulnerable patients," Dr. Chin said.
Programs to reduce disparities in care can improve outcomes for the uninsured immediately, even in the absence of insurance reform, he said.
The study was funded by the Health Resources and Services Administration. No potential conflicts of interest were reported.
Primary source: Annals of Internal MedicineSource reference:Wilper A, et al "A national study of chronic disease prevalence and access to care in uninsured U.S. adults" Ann Intern Med 2008; 149: 170-76. Additional source: Annals of Internal MedicineSource reference: Chin M "Improving care and outcomes of uninsured persons with chronic disease ... now" Ann Intern Med 2008; 149: 206-207.
By John Gever
CAMBRIDGE, Mass., 06 aug 2008-- Nearly one-third of uninsured Americans under age 65 reported having cardiovascular disease, diabetes, hypertension, or some other chronic condition, researchers here said.
Data from the National Health and Nutrition Examination Survey (NHANES) showed that percentages of uninsured people reporting a chronic condition ranged from 11.9% for hypercholesterolemia (95% CI 9.3% to 12.6%) to 19.3% for asthma and COPD (95% CI 16% to 22.3%), reported Andrew P. Wilper, M.D., M.P.H., of Cambridge Health Alliance, and colleagues in the Aug. 5 issue of Annals of Internal Medicine.
Percentages for other chronic diseases were:
Cardiovascular disease, 16.1% (95% CI 12.6% to 19.6%)
Hypertension, 15.5% (95% CI 13.4% to 17.6%)
Diabetes mellitus, 16.6% (95% CI 13.2% to 20%)
Previous cancer (excluding non-melanoma skin cancer), 15.4% (95% CI 11.5% to 19.3%)
Some 31.3% of the uninsured had at least one of the six conditions (95% CI 28.7% to 34%), the researchers said.
"These findings counter notions that persons without insurance are a largely healthy population with little need for ongoing medical care," Dr. Wilper and colleagues wrote.
The researchers said 45.4% of insured patients had at least one chronic disease. The higher percentage was likely because they were older on average than the uninsured, they said.
In June, the CDC reported that about 43 million Americans, 14.5% of the overall population, were uninsured in 2007. (See Southwest Lags in Health Insurance Coverage)
According to the NHANES data -- from surveys conducted from 1999 through 2004 -- 20.8% of the non-elderly adult population, or 36.4 million individuals (95% CI 33.1 to 40 million), were without health insurance.
The study was only the second to examine the burden of chronic disease in the uninsured, Dr. Wilper and colleagues said. The earlier research, covering 1997 and 1998 with a different data set, found substantially lower rates of chronic disease, suggesting a trend toward poorer health status among the uninsured.
The NHANES survey obtained data on health insurance status and other health-related information from 12,486 respondents.
Dr. Wilper and colleagues found that, after adjusting for age, sex, and race/ethnicity, lack of insurance significantly predicted a lower likelihood of seeing a health professional in the past year (6.2% versus 22.6% for the insured, P<0.001).
Those without insurance were also more likely to name an emergency department as their standard site of care (7.1% versus 1.1%, P<0.001) and to report not having a standard site of care (22.6% versus 6.2%, P<0.001).
"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," Dr. Wilper and colleagues wrote.
They pointed out that treatments for the six chronic conditions are both standard and a national priority.
The researchers suggested that a healthcare system with a de facto exclusion based on insurance status is unethical.
In an accompanying editorial, Marshall H. Chin, M.D., M.P.H., of the University of Chicago, commented that ensuring good treatment for chronic disease will require more than health insurance reform.
"It will not be sufficient unless it is coupled with quality improvement efforts targeting the reasons that vulnerable populations with access to care often do not receive optimal care," he wrote.
He noted that quality of care varies among facilities and regions. For example, he said, recent budget cuts have hit public clinic and hospital systems in Atlanta and Chicago.
"Healthcare reform must ensure that adequate resources flow to healthcare organizations and providers that serve a disproportionate share of vulnerable patients," Dr. Chin said.
Programs to reduce disparities in care can improve outcomes for the uninsured immediately, even in the absence of insurance reform, he said.
The study was funded by the Health Resources and Services Administration. No potential conflicts of interest were reported.
Primary source: Annals of Internal MedicineSource reference:Wilper A, et al "A national study of chronic disease prevalence and access to care in uninsured U.S. adults" Ann Intern Med 2008; 149: 170-76. Additional source: Annals of Internal MedicineSource reference: Chin M "Improving care and outcomes of uninsured persons with chronic disease ... now" Ann Intern Med 2008; 149: 206-207.
Eating Fish May Protect Against Silent Brain Infarcts
By Todd Neale
KUOPIO, Finland, 06 aug 2008-- Older patients who ate at least three servings of fish a week had a decreased risk of certain subclinical brain abnormalities, researchers found. Patients 65 and older who ate the most tuna or other fish high in omega-3 fatty acids tended to have a 26% reduced risk of silent infarct compared with those eating less than one serving a month (RR 0.74, 95% CI 0.54 to 1.01, P=0.06), Jyrki Virtanen, Ph.D., of the University of Kuopio, and colleagues reported in the Aug. 5 issue of Neurology. In addition, those who ate the most fish had 10.6% better white matter grade scores compared with those who ate the least (P=0.003) after adjusting for various risk factors.
The associations did not apply to consumption of fried fish, most likely because the types of fish usually fried -- for example, cod and pollock -- have low levels of omega-3 fatty acids.
Although fish consumption has been linked to risk of clinical stroke, whether eating fish affects the risk of subclinical brain abnormalities -- which are associated with cognitive and neurobehavioral impairments and risk of future stroke -- is unknown, the researchers said.
To address the question, they turned to the Cardiovascular Health Study, conducted in four U.S. communities. They looked at data for 3,857 participants ages 65 and older who underwent at least one MRI scan; 2,116 of them underwent two scans five years apart.
All were free from clinical transient ischemic attack or stroke.
Fish consumption was measured using food frequency questionnaires, one administered at enrollment in 1989-1990 and the other during follow-up in 1995-1996.
Higher consumption of tuna or other broiled or baked fish was associated with younger age, female sex, higher education, lower systolic blood pressure, higher LDL and HDL cholesterol, higher ankle-arm index, higher energy intake, higher fruit and vegetable consumption, and lower saturated fat intake (P<0.05 for all).
On the first MRI, 23% of the participants showed at least one subclinical infarct, and on the second the prevalence was 23.1%.
For each additional serving of tuna or other non-fried fish consumed per week, the risk of subclinical infarct was reduced by 7% (P=0.03 for trend).
Among patients who had two scans performed, 16.6% had at least one new silent infarct between the two scans.
There was a nonsignificant trend toward a lower incidence of silent infarcts for those who ate the most fish. The lack of statistical significance was possibly related to limited power, the researchers said.
Fish consumption was not associated with sulcal or ventricular grades, markers of brain atrophy (P>0.10 for both).
Because consumption of fish or omega-3 fatty acids has also been associated with reduced risk of dementia and Alzheimer's disease in other studies, the researchers said, "our findings suggest that prevention of subclinical infarcts and white matter abnormalities may be one mechanism whereby fish or [omega-3 fatty acid] consumption may decrease the development of these debilitating conditions."
The authors acknowledged some limitations of the study, including the fact that participants who underwent MRI scans were healthier than those who did not, which might reduce the generalizability of the findings to the entire older population.
In addition, estimates of sulcal grade have high rates of inter-reader variability, the second food frequency questionnaire did not have information on fried fish consumption, estimating omega-3 fatty acid intake by questionnaire could have resulted in some exposure misclassification, and the food frequency questionnaires and MRI were not administered at the same time.
Finally, the associations could have been the result of other factors related to fish consumption, such as a healthier lifestyle.
Nevertheless, the researchers said, "our results support the need for randomized trials of fish or fish oil intake to reduce subclinical ischemic events, which would be feasible and important given the high incidence of such events in older adults."
The study was supported by contracts from the National Heart, Lung, and Blood Institute, by the National Institute of Neurological Disorders and Stroke, and by grants from the Finnish Cultural Foundation, Helsingin Sanomar Centennial Foundation, Finnish Foundation for Cardiovascular Research, Yrjo Jahnsson Foundation, and University of Kuopio.
The authors made no disclosures.
Primary source: NeurologySource reference:Virtanen J, et al "Fish consumption and risk of subclinical brain abnormalities on MRI in older adults" Neurology 2008; 71: 439-446.
By Todd Neale
KUOPIO, Finland, 06 aug 2008-- Older patients who ate at least three servings of fish a week had a decreased risk of certain subclinical brain abnormalities, researchers found. Patients 65 and older who ate the most tuna or other fish high in omega-3 fatty acids tended to have a 26% reduced risk of silent infarct compared with those eating less than one serving a month (RR 0.74, 95% CI 0.54 to 1.01, P=0.06), Jyrki Virtanen, Ph.D., of the University of Kuopio, and colleagues reported in the Aug. 5 issue of Neurology. In addition, those who ate the most fish had 10.6% better white matter grade scores compared with those who ate the least (P=0.003) after adjusting for various risk factors.
The associations did not apply to consumption of fried fish, most likely because the types of fish usually fried -- for example, cod and pollock -- have low levels of omega-3 fatty acids.
Although fish consumption has been linked to risk of clinical stroke, whether eating fish affects the risk of subclinical brain abnormalities -- which are associated with cognitive and neurobehavioral impairments and risk of future stroke -- is unknown, the researchers said.
To address the question, they turned to the Cardiovascular Health Study, conducted in four U.S. communities. They looked at data for 3,857 participants ages 65 and older who underwent at least one MRI scan; 2,116 of them underwent two scans five years apart.
All were free from clinical transient ischemic attack or stroke.
Fish consumption was measured using food frequency questionnaires, one administered at enrollment in 1989-1990 and the other during follow-up in 1995-1996.
Higher consumption of tuna or other broiled or baked fish was associated with younger age, female sex, higher education, lower systolic blood pressure, higher LDL and HDL cholesterol, higher ankle-arm index, higher energy intake, higher fruit and vegetable consumption, and lower saturated fat intake (P<0.05 for all).
On the first MRI, 23% of the participants showed at least one subclinical infarct, and on the second the prevalence was 23.1%.
For each additional serving of tuna or other non-fried fish consumed per week, the risk of subclinical infarct was reduced by 7% (P=0.03 for trend).
Among patients who had two scans performed, 16.6% had at least one new silent infarct between the two scans.
There was a nonsignificant trend toward a lower incidence of silent infarcts for those who ate the most fish. The lack of statistical significance was possibly related to limited power, the researchers said.
Fish consumption was not associated with sulcal or ventricular grades, markers of brain atrophy (P>0.10 for both).
Because consumption of fish or omega-3 fatty acids has also been associated with reduced risk of dementia and Alzheimer's disease in other studies, the researchers said, "our findings suggest that prevention of subclinical infarcts and white matter abnormalities may be one mechanism whereby fish or [omega-3 fatty acid] consumption may decrease the development of these debilitating conditions."
The authors acknowledged some limitations of the study, including the fact that participants who underwent MRI scans were healthier than those who did not, which might reduce the generalizability of the findings to the entire older population.
In addition, estimates of sulcal grade have high rates of inter-reader variability, the second food frequency questionnaire did not have information on fried fish consumption, estimating omega-3 fatty acid intake by questionnaire could have resulted in some exposure misclassification, and the food frequency questionnaires and MRI were not administered at the same time.
Finally, the associations could have been the result of other factors related to fish consumption, such as a healthier lifestyle.
Nevertheless, the researchers said, "our results support the need for randomized trials of fish or fish oil intake to reduce subclinical ischemic events, which would be feasible and important given the high incidence of such events in older adults."
The study was supported by contracts from the National Heart, Lung, and Blood Institute, by the National Institute of Neurological Disorders and Stroke, and by grants from the Finnish Cultural Foundation, Helsingin Sanomar Centennial Foundation, Finnish Foundation for Cardiovascular Research, Yrjo Jahnsson Foundation, and University of Kuopio.
The authors made no disclosures.
Primary source: NeurologySource reference:Virtanen J, et al "Fish consumption and risk of subclinical brain abnormalities on MRI in older adults" Neurology 2008; 71: 439-446.
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