Personality Trait Linked to Risk of Developing Alzheimer's
CHICAGO, Oct. 2 -- A neat orderly mind augmented by a conscientious personality tends to resist Alzheimer's disease, researchers here found.
Self-disciplined and goal-directed persons who scored high on a standard measure of conscientiousness had an 89% lower risk of developing Alzheimer's than those with low scores, Robert S. Wilson, Ph.D., of Rush University, and colleagues, reported in the October issue of the Archives of General Psychiatry.
Conscientiousness was associated with mild cognitive impairment and Alzheimer's, but not with the pathologic hallmarks of these conditions such as neurofibrillary changes, they said.
Epidemiologic research has shown that conscientiousness is associated with a wide range of mental and physical disorders, disability, and death, suggesting that the trait has some general role in health maintenance, the researchers said.
In addition, a number of variables associated with Alzheimer's risk, including educational and occupational attainment, physical exercise, tobacco use, and depressive symptoms, are also associated with conscientiousness, suggesting that the trait may have a more specific link to the development of Alzheimer's, the researchers said.
To test this hypothesis, Dr. Wilson and colleagues studied 997 older Catholic nuns, priests, and brothers without dementia at enrollment in 1994, recruited from more that 40 groups across the U.S.
Participants had standard evaluations that included medical history, neurology examinations, and cognitive testing.
They also completed a standard 12-item measure of conscientiousness. The participants rated agreement on a scale of one to five, with items such as "I am a productive person who always gets the job done."
Conscientiousness scores ranged from 11 to 47, with a higher score indicating a greater degree of conscientiousness. The mean conscientiousness score was 34 out of 48.
Conscientiousness was higher in women than in men and was not related to age or education.
During up to 12 years of annual follow-up by 2006, 176 participants developed Alzheimer's disease.
In a proportional hazards regression model adjusted for age, sex, and education, a high conscientiousness score in the 90th percentile (40 points) was associated with about an 89% reduction in risk of Alzheimer's disease compared with a low score of 28 points (the 10th percentile), the investigators found.
Results were not substantially changed by controlling for other personality traits, activity patterns, vascular conditions, or other risk factors.
Because mild cognitive impairment is increasingly viewed as a state that precedes clinically evident dementia in Alzheimer's, the researchers conducted a further analysis. They found that a higher level of conscientiousness was associated with a reduced risk of mild cognitive impairment (HR, 0.977, 95% CI, 0.956-0.999).
This association remained in subsequent analyses that controlled for physical, cognitive, and social activity or for cardiovascular health, but was no longer significant in analyses that controlled for other personality traits, depressive symptoms, or the ε4 allele.
The researchers also analyzed results from brain autopsies of 324 participants who died during the study. Conscientiousness was unrelated to neuropathologic measures including brain plaques and tangles.
However, conscientiousness did appear to modify the association of neurofibrillary pathologic changes and cerebral infarction with an individual's cognitive abilities before death.
That conscientiousness is associated with a risk of dementia but not with its traditional pathologic features suggests that it may be related to some other neurodeteriorative changes that do not currently leave recognized footprints, the researchers suggested.
There are several ways conscientiousness might protect against Alzheimer's disease, the researchers said. Controlling for cardiovascular health and lifestyle activity patterns did not substantially affect the findings, they found.
It is possible, they said, that conscientious individuals may be likelier to experience educational and occupational success, both of which have been associated with a reduced risk of Alzheimer's disease.
Conscientiousness is also associated with a higher level of resilience and greater reliance on task-oriented coping.
These factors, they said, might decrease the adverse effect of negative life events and chronic psychological distress associated with a risk of dementia in older age.
The main limitation of the study, the researchers said, is that the data were based on a selected group of people who differ from the general population in education and lifestyle so that studying more representative cohorts is important.
Also, they noted that conscientiousness is a somewhat heterogeneous trait complex, but the brief measure used in this study precluded investigation of its subcomponents.
Understanding the mechanisms linking conscientiousness to maintaining cognition in older age may suggest novel strategies for delaying the symptoms of Alzheimer's disease, Dr. Wilson and colleagues wrote.
No financial conflicts were reported.
This research was supported grants from the National Institute on Aging.Primary source: Archives of General PsychiatrySource reference: Wilson RS et al "Conscientiousness and the Incidence of Alzheimer Disease and Mild Cognitive Impairment" Arch Gen Psychiatry. 2007; 64: 1204-1212.
Wednesday, October 03, 2007
Cognitive Reserve Gets More Backing as Dementia Hedge
STOCKHOLM, Oct. 2 -- A healthy cognitive reserve, deposited over a lifetime of learning, appears to protect the better-educated patients from dementia, investigators here suggested.
Among nearly 1,500 adults followed for more than 20 years, those who had at least six years of formal education had a significantly lower risk for any form of dementia and for Alzheimer's disease than adults who had five years of schooling or less, reported Tiia Ngandu, M.D., Ph.D., of the Karolinska Institute, and colleagues.
When they controlled for lifestyle choices such as poor diet or smoking that might contribute to dementia risk, the investigators found that education, or lack of it, remained a strong predictor of cognitive decline, they reported in the Oct. 2 issue of Neurology.
"Our results provide further firm evidence that the low educational level is related to the increased risk of dementia and Alzheimer's disease," they wrote. "We found that the association was independent of a wide range of other vascular and lifestyle related risk factors, and thereby provided evidence against the brain battering hypothesis. Educated persons may have greater cognitive reserve that leads to a postponement of the clinical manifestation of dementia."
The authors noted that many but not all cohort studies that have examined the question have detected an association between level of education and dementia risk, and three basic hypotheses suggesting an explanation for the link have emerged.
The brain reserve hypothesis, for examples, holds that people with higher levels have greater cognitive reserves, and therefore need to experience a higher degree of pathologic changes before dementia becomes evident, they noted.
"This brain reserve could be innate or due to early life factors, and high education would be a consequence of greater reserve," they wrote. "The concept of cognitive reserve adds a functional component to this hypothesis: higher reserve could be a more efficient use of existing networks, and it could be a result of both innate factors and lifelong mental stimulation."
Alternatively, better-educated people may exercise more and eat better than poorly educated people, and therefore be better protected from dementia risk factors such as cerebrovascular infarcts (the brain-battering hypothesis).
A third hypothesis suggests that diagnostic bias may play a role, because more highly schooled patients may score higher on dementia screening tests looking at cognitive ability, the authors noted.
The investigators looked at data on those who took part in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study.
Participants of the CAIDE study came from two towns in eastern Finland. They were chosen at random from population-based samples studied in a survey starting in 1972, with follow-up every five years. In the current study, the authors examined information on 1,449 men and women ranging in age from 65 to 79 who participated in a re-examination in 1998.
They found that compared with people with only five or fewer years of formal education, those who had six to eight years of schooling had an odds ratio for dementia of 0.57 (95% confidence interval 0.29 to 1.13), whereas those with nine years of education or more had an odds ratio of 0.16 (95% CI 0.06 to 0.41).
Similarly, compared with the least well educated group, participants with six to eight years of education had an odds ratio for Alzheimer's disease of 0.49 (95% CI 0.24 to 1.00) and those with nine or more years had an odds ratio of 0.15 (0.05 to 0.40).
In analyses controlling for possible confounders, including demographics and socioeconomic, vascular and lifestyle factors, the authors found that the associations between education and both all-cause dementia and Alzheimer's disease remained, with women and men being equally affected.
In addition, controlling for the presence of the apolipoprotein E4 (ApoE4) allele, a known risk factor for early-onset Alzheimer's disease, did not modify the association. However, "among the ApoE4 noncarriers the risk of dementia was 0.44 (95% CI 0.16 to 1.17) for people with medium education, and 0.05 (0.01 to 0.38) for high education compared with that for low education in the model with full adjustments," the authors noted.
"As vascular factors contribute to the risk of dementia and AD, one of our hypotheses was that these factors could at least partly explain the effect of education on dementia," the authors wrote. "However, adjusting for midlife vascular and lifestyle related risk factors did not change the association between education and dementia."
They noted that in a model that included late-life comorbidities, the association between education and dementia was slightly weakened.
"People with low education also more often had stroke, myocardial infarction, diabetes, and more depressive symptoms," they wrote. "Thus, partly the effect of education could be mediated via these factors, or low education might lead to frailty and thereby increase the risk of both dementing and other late-life disorders."
The large population sample and high-degree of retention (72% of the original sample) are both strengths of the study, the authors said, but they did note a few limitations.
For example, the analyses are based on a sample of participants who survived until the 1998 reexamination, but "it is known that persons with low education also have higher mortality. If those who died between the examinations also were more often demented, then our results would underestimate the true association between education and dementia," they wrote.
They also were unable to determine whether factors that reflect brain maturation could account for at least some of the association between education and dementia (as suggested by the brain reserve hypothesis), because they lacked data on childhood IQ, socioeconomic status of parents, or maximal brain volume, the authors added.
The study was supported by the Alzheimer Association, the Aging Program of the Academy of Finland, and EVO-grants of Kuopio University Hospital, Finland. The authors reported that they had no conflicts of interest.Primary source: NeurologySource reference: Ngandu T et al. "Education and dementia: what lies behind the association?" Neurology 2007; 69: 1442-1450.
STOCKHOLM, Oct. 2 -- A healthy cognitive reserve, deposited over a lifetime of learning, appears to protect the better-educated patients from dementia, investigators here suggested.
Among nearly 1,500 adults followed for more than 20 years, those who had at least six years of formal education had a significantly lower risk for any form of dementia and for Alzheimer's disease than adults who had five years of schooling or less, reported Tiia Ngandu, M.D., Ph.D., of the Karolinska Institute, and colleagues.
When they controlled for lifestyle choices such as poor diet or smoking that might contribute to dementia risk, the investigators found that education, or lack of it, remained a strong predictor of cognitive decline, they reported in the Oct. 2 issue of Neurology.
"Our results provide further firm evidence that the low educational level is related to the increased risk of dementia and Alzheimer's disease," they wrote. "We found that the association was independent of a wide range of other vascular and lifestyle related risk factors, and thereby provided evidence against the brain battering hypothesis. Educated persons may have greater cognitive reserve that leads to a postponement of the clinical manifestation of dementia."
The authors noted that many but not all cohort studies that have examined the question have detected an association between level of education and dementia risk, and three basic hypotheses suggesting an explanation for the link have emerged.
The brain reserve hypothesis, for examples, holds that people with higher levels have greater cognitive reserves, and therefore need to experience a higher degree of pathologic changes before dementia becomes evident, they noted.
"This brain reserve could be innate or due to early life factors, and high education would be a consequence of greater reserve," they wrote. "The concept of cognitive reserve adds a functional component to this hypothesis: higher reserve could be a more efficient use of existing networks, and it could be a result of both innate factors and lifelong mental stimulation."
Alternatively, better-educated people may exercise more and eat better than poorly educated people, and therefore be better protected from dementia risk factors such as cerebrovascular infarcts (the brain-battering hypothesis).
A third hypothesis suggests that diagnostic bias may play a role, because more highly schooled patients may score higher on dementia screening tests looking at cognitive ability, the authors noted.
The investigators looked at data on those who took part in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study.
Participants of the CAIDE study came from two towns in eastern Finland. They were chosen at random from population-based samples studied in a survey starting in 1972, with follow-up every five years. In the current study, the authors examined information on 1,449 men and women ranging in age from 65 to 79 who participated in a re-examination in 1998.
They found that compared with people with only five or fewer years of formal education, those who had six to eight years of schooling had an odds ratio for dementia of 0.57 (95% confidence interval 0.29 to 1.13), whereas those with nine years of education or more had an odds ratio of 0.16 (95% CI 0.06 to 0.41).
Similarly, compared with the least well educated group, participants with six to eight years of education had an odds ratio for Alzheimer's disease of 0.49 (95% CI 0.24 to 1.00) and those with nine or more years had an odds ratio of 0.15 (0.05 to 0.40).
In analyses controlling for possible confounders, including demographics and socioeconomic, vascular and lifestyle factors, the authors found that the associations between education and both all-cause dementia and Alzheimer's disease remained, with women and men being equally affected.
In addition, controlling for the presence of the apolipoprotein E4 (ApoE4) allele, a known risk factor for early-onset Alzheimer's disease, did not modify the association. However, "among the ApoE4 noncarriers the risk of dementia was 0.44 (95% CI 0.16 to 1.17) for people with medium education, and 0.05 (0.01 to 0.38) for high education compared with that for low education in the model with full adjustments," the authors noted.
"As vascular factors contribute to the risk of dementia and AD, one of our hypotheses was that these factors could at least partly explain the effect of education on dementia," the authors wrote. "However, adjusting for midlife vascular and lifestyle related risk factors did not change the association between education and dementia."
They noted that in a model that included late-life comorbidities, the association between education and dementia was slightly weakened.
"People with low education also more often had stroke, myocardial infarction, diabetes, and more depressive symptoms," they wrote. "Thus, partly the effect of education could be mediated via these factors, or low education might lead to frailty and thereby increase the risk of both dementing and other late-life disorders."
The large population sample and high-degree of retention (72% of the original sample) are both strengths of the study, the authors said, but they did note a few limitations.
For example, the analyses are based on a sample of participants who survived until the 1998 reexamination, but "it is known that persons with low education also have higher mortality. If those who died between the examinations also were more often demented, then our results would underestimate the true association between education and dementia," they wrote.
They also were unable to determine whether factors that reflect brain maturation could account for at least some of the association between education and dementia (as suggested by the brain reserve hypothesis), because they lacked data on childhood IQ, socioeconomic status of parents, or maximal brain volume, the authors added.
The study was supported by the Alzheimer Association, the Aging Program of the Academy of Finland, and EVO-grants of Kuopio University Hospital, Finland. The authors reported that they had no conflicts of interest.Primary source: NeurologySource reference: Ngandu T et al. "Education and dementia: what lies behind the association?" Neurology 2007; 69: 1442-1450.
Weight-Based HCV Therapy Brings Better Outcomes
NEW YORK, Oct. 2 -- Giving bigger ribavirin doses to heavier hepatitis C patients appears to result in better outcomes, especially for African Americans, researchers here said.
The finding, from a prospective randomized trial of more than 5,000 treatment-naïve patients, supports the idea of so-called true weight-based dosing of ribavirin, in combination with pegylated interferon alfa-2b, according to Ira M. Jacobson, M.D., of Weill Cornell Medical College, and colleagues.
The combination of the two drugs has been used to treat HCV infection since 2001, with ribavirin given at 1,000 mg a day for patients who weigh less than 75 kg and 1,200 for those who weigh 75 kg or more, Dr. Jacobson and colleagues reported in the October issue of Hepatology.
But in this study, patients were randomized to a flat dose of 800 mg/day, regardless of weight, or to one of several doses adjusted for weight -- 800 mg for patients weighing less than 65 kg, 1,000 mg for patients from 65 to 85 kg, 1,200 mg for those from 85 to 105 kg, and 1,400 mg for patients from 105 to 125 kg.
Patients with genotypes G1, G4, G5, and G6 were treated for 48 weeks and followed for another 24. The primary endpoint was sustained virologic response, defined as less than 125 IU per milliliter of serum of HCV viral RNA, at the end of follow-up.
Patients with genotypes G2 and G3 -- regarded as easier to treat than the other types -- were treated for 24 or 48 weeks.
The study showed that patients in the weight based-arm did better, with a sustained virologic response of 44.2% compared to 40.5% for those in the flat-dose arm. The difference was significant at P=0.008.
Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P<0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P < 0.056). In genotype 2-3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration.
In a post hoc analysis, presented as a separate paper, the researchers analyzed outcomes for the 362 African-American patients in the primary efficacy analysis who had G1 virus, including 188 in the flat-dose arm.
Sustained virologic response was 21% for those getting weight-based dosing, compared with 10% for those in the flat-dose arm - a difference that was significant at P=0.0006.
Relapse rates were also lower -- 22% versus 30% -- in the weight-based arm, the researchers found.
Significant anemia (hemoglobin concentration <10 g/dL) occurred more frequently in the weight-based group (19.3% versus 12.5%). However, only 1% of patients discontinued treatment because of anemia. Mean hemoglobin concentrations were 0.5 g/dL lower throughout treatment in the weight based group than in the fixed dose group, but mean hemoglobin concentration decreases for all ribavirin doses in the weight-based group, including the 1,400-mg dose, were similar.
The issue of treating African Americans is important, the researchers noted, because the prevalence of HCV infection is higher in African Americans than in other ethnic groups, and up to 90% of infected African Americans have genotype G1a or G1b -- both associated with lower response to therapy.
Dr. Jacobson and colleagues noted that even in this study, African Americans had a lower response to treatment, although those in the weight-based arm did better.
Unexpectedly, the researchers said, heavier African Americans in the weight-based arm appeared to do better. The rate of sustained virologic response was 31% for those weighing between 105 and 125 kg, compared with 22% for those between 85 and 015 kg, and 13% for those between 65 and 85 kg.
The researchers said they had no clear explanation for the phenomenon.
The study "adds significantly to our understanding of interferon therapy in African-American patients," commented Steven-Huy Han, M.D., of the University of California Los Angeles and Jason Smith, PharmD, of the Greater Los Angeles Veterans Healthcare Administration Hospital, in an accompanying editorial.
They noted that the findings concerning this "difficult-to-treat population" arise from a secondary evaluation that was not powered for statistical analysis.
Nonetheless, they said, "many of their insights deserve a thoughtful discussion."
On the other hand, they said, the overall study shows that "the traditional notion that ribavirin dosage should be fixed has now been sidelined by the idea that we should tailor ribavirin dosing to our patients."
The study was supported by the Schering-Plough Corp., of Kenilworth, NJ. Among potential conflicts of interest, Dr. Jacobson reports consulting for and/or receiving research support from Schering-Plough, Merck, GlobeImmune, Human Genome Sciences, Coley, Gilead, Vertex, Intermune, Intarcia, Valeant, GlaxoSmithKline, Idenix, Novartis, Bristol-Myers Squibb, Boehringer Ingelheim, and XTL. Nine co-authors also report financial links with Schering-Plough or other pharmaceutical companies, including Roche, Valeant, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Axcan, Wyeth Gilead, and AstraZeneca. Two of the co-authors, Louis Griffel, M.D., and Clifford Brass, M.D., Ph.D., are employees of Schering-Plough.
Drs. Han and Smith reported no potential conflicts. Primary source: HepatologySource reference: Jacobson IM et al. "Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients: A Randomized Trial." Hepatology 2007; 46:971-81. Additional source: HepatologySource reference: Jacobson IM et al. "Impact of Weight-Based Ribavirin with Peginterferon alfa-2b in African Americans with Hepatitis C Virus Genotype 1." Hepatology 2007;46:982-90. Additional source: HepatologySource reference: Jason Smith and Steven-Huy Han. "'True' Weight-Based Dosing Versus 'Flat' Dosing of Ribavirin: Will the WIN-R Please Come Forward?" Hepatology 2007;46:953-56.
NEW YORK, Oct. 2 -- Giving bigger ribavirin doses to heavier hepatitis C patients appears to result in better outcomes, especially for African Americans, researchers here said.
The finding, from a prospective randomized trial of more than 5,000 treatment-naïve patients, supports the idea of so-called true weight-based dosing of ribavirin, in combination with pegylated interferon alfa-2b, according to Ira M. Jacobson, M.D., of Weill Cornell Medical College, and colleagues.
The combination of the two drugs has been used to treat HCV infection since 2001, with ribavirin given at 1,000 mg a day for patients who weigh less than 75 kg and 1,200 for those who weigh 75 kg or more, Dr. Jacobson and colleagues reported in the October issue of Hepatology.
But in this study, patients were randomized to a flat dose of 800 mg/day, regardless of weight, or to one of several doses adjusted for weight -- 800 mg for patients weighing less than 65 kg, 1,000 mg for patients from 65 to 85 kg, 1,200 mg for those from 85 to 105 kg, and 1,400 mg for patients from 105 to 125 kg.
Patients with genotypes G1, G4, G5, and G6 were treated for 48 weeks and followed for another 24. The primary endpoint was sustained virologic response, defined as less than 125 IU per milliliter of serum of HCV viral RNA, at the end of follow-up.
Patients with genotypes G2 and G3 -- regarded as easier to treat than the other types -- were treated for 24 or 48 weeks.
The study showed that patients in the weight based-arm did better, with a sustained virologic response of 44.2% compared to 40.5% for those in the flat-dose arm. The difference was significant at P=0.008.
Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P<0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P < 0.056). In genotype 2-3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration.
In a post hoc analysis, presented as a separate paper, the researchers analyzed outcomes for the 362 African-American patients in the primary efficacy analysis who had G1 virus, including 188 in the flat-dose arm.
Sustained virologic response was 21% for those getting weight-based dosing, compared with 10% for those in the flat-dose arm - a difference that was significant at P=0.0006.
Relapse rates were also lower -- 22% versus 30% -- in the weight-based arm, the researchers found.
Significant anemia (hemoglobin concentration <10 g/dL) occurred more frequently in the weight-based group (19.3% versus 12.5%). However, only 1% of patients discontinued treatment because of anemia. Mean hemoglobin concentrations were 0.5 g/dL lower throughout treatment in the weight based group than in the fixed dose group, but mean hemoglobin concentration decreases for all ribavirin doses in the weight-based group, including the 1,400-mg dose, were similar.
The issue of treating African Americans is important, the researchers noted, because the prevalence of HCV infection is higher in African Americans than in other ethnic groups, and up to 90% of infected African Americans have genotype G1a or G1b -- both associated with lower response to therapy.
Dr. Jacobson and colleagues noted that even in this study, African Americans had a lower response to treatment, although those in the weight-based arm did better.
Unexpectedly, the researchers said, heavier African Americans in the weight-based arm appeared to do better. The rate of sustained virologic response was 31% for those weighing between 105 and 125 kg, compared with 22% for those between 85 and 015 kg, and 13% for those between 65 and 85 kg.
The researchers said they had no clear explanation for the phenomenon.
The study "adds significantly to our understanding of interferon therapy in African-American patients," commented Steven-Huy Han, M.D., of the University of California Los Angeles and Jason Smith, PharmD, of the Greater Los Angeles Veterans Healthcare Administration Hospital, in an accompanying editorial.
They noted that the findings concerning this "difficult-to-treat population" arise from a secondary evaluation that was not powered for statistical analysis.
Nonetheless, they said, "many of their insights deserve a thoughtful discussion."
On the other hand, they said, the overall study shows that "the traditional notion that ribavirin dosage should be fixed has now been sidelined by the idea that we should tailor ribavirin dosing to our patients."
The study was supported by the Schering-Plough Corp., of Kenilworth, NJ. Among potential conflicts of interest, Dr. Jacobson reports consulting for and/or receiving research support from Schering-Plough, Merck, GlobeImmune, Human Genome Sciences, Coley, Gilead, Vertex, Intermune, Intarcia, Valeant, GlaxoSmithKline, Idenix, Novartis, Bristol-Myers Squibb, Boehringer Ingelheim, and XTL. Nine co-authors also report financial links with Schering-Plough or other pharmaceutical companies, including Roche, Valeant, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Axcan, Wyeth Gilead, and AstraZeneca. Two of the co-authors, Louis Griffel, M.D., and Clifford Brass, M.D., Ph.D., are employees of Schering-Plough.
Drs. Han and Smith reported no potential conflicts. Primary source: HepatologySource reference: Jacobson IM et al. "Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients: A Randomized Trial." Hepatology 2007; 46:971-81. Additional source: HepatologySource reference: Jacobson IM et al. "Impact of Weight-Based Ribavirin with Peginterferon alfa-2b in African Americans with Hepatitis C Virus Genotype 1." Hepatology 2007;46:982-90. Additional source: HepatologySource reference: Jason Smith and Steven-Huy Han. "'True' Weight-Based Dosing Versus 'Flat' Dosing of Ribavirin: Will the WIN-R Please Come Forward?" Hepatology 2007;46:953-56.
Guidelines Issued for Management of Low Back Pain
October 2, 2007 — The American College of Physicians (ACP) and the American Pain Society (APS) have issued a comprehensive joint clinical practice guideline for the diagnosis and treatment of low back pain, which is published in the October 2 issue of the Annals of Internal Medicine. These guidelines offer recommendations concerning how to categorize patients, when to perform imaging studies, educational information for patients, self-care, when to prescribe medications and what types, and nonpharmacologic therapy. An important caveat is that clinicians should not routinely order imaging and other diagnostic tests.
"There are many options for evaluation and treatment of low back pain," second study author Amir Qaseem, MD, PhD, MHA, senior medical associate in the ACP Department of Clinical Programs and Quality of Care in Philadelphia, Pennsylvania, said in a news release. "We wanted to review all the evidence and develop guidance for clinicians and to give our patients a realistic sense of what they can expect when they visit a clinician for low back pain. It is important to tell patients about their expected course based on evidence-based information and advise them to remain active."
In the United States, several studies suggest that approximately 25% of adults report having had low back pain in the past 3 months, whereas 7.6% report at least 1 episode of severe acute low back pain within the previous year. Clinical evidence suggests that regardless of treatment, most low back pain improves within 1 month. Available treatment options range from watchful waiting to conservative treatment with pharmacologic and nonpharmacologic modalities to invasive procedures such as spinal surgery.
The impetus for the creation of these guidelines was a meeting of a multidisciplinary panel of experts convened in 2006 by ACP and APS. Their mission was to develop questions and the scope of an evidence report on low back pain, to review the available evidence in this field, and to generate recommendations assisting primary care clinicians in diagnosing and treating low back pain.
The joint ACP-APS guidelines target primary care physicians and other clinicians, rather than anesthesiologists, interventional radiologists, orthopaedists, or neurosurgeons. Although these guidelines do not address invasive therapies performed by specialists, the APS plans to publish a separate guideline in 2008 that will describe the use of invasive procedures for low back pain.
The current joint ACP-APS recommendations provide an algorithm to facilitate collection and interpretation of data during the first patient visit and to categorize patients into 1 of 3 general subgroups: (1) nonspecific low back pain (accounts for 85% of patients); (2) back pain potentially associated with spinal conditions, such as spinal stenosis, sciatica, and vertebral compression fracture; and (3) back pain potentially associated with another specific cause, such as cancer.
For patients with nonspecific low back pain, clinicians should not routinely order imaging studies, including radiographs, computerized tomography (CT) scans, magnetic resonance imaging (MRI), or other diagnostic tests. These tests should be used to evaluate only those patients who have severe or progressive neurologic deficits or who are suspected to have cancer, infection, or other underlying condition as the cause of their low back pain.
The guidelines are accompanied by 2 background articles reviewing the evidence underlying the recommendations for pharmacologic and nonpharmacologic treatment options for acute and chronic low back pain.
"Almost all medications reviewed had some benefits, but they have risks," said lead study author Roger Chou, MD, head of the APS Clinical Practice Guidelines Program. "Acetaminophen, for example, is very safe but might not be effective. NSAIDs [nonsteroidal anti-inflammatory drugs] have gastrointestinal and cardiovascular risks."
Specific recommendations in the guidelines are as follows:
Focused history and physical examination should help categorize patients into 1 of 3 broad groups: nonspecific low back pain, back pain potentially associated with radiculopathy or spinal stenosis, or back pain potentially associated with another specific spinal cause. Evaluation of psychosocial risk factors is essential during history taking because these predict the risk for chronic disabling low back pain (strong recommendation; moderate-quality evidence).
For patients with nonspecific low back pain, clinicians should not routinely perform imaging studies, including radiographs, CT scans, and MRI, or other diagnostic tests (strong recommendation; moderate-quality evidence).
Patients with severe or progressive neurologic deficits, or in whom history and physical examination suggest cancer, infection, or other underlying condition as the cause of their low back pain, should undergo imaging studies and other appropriate diagnostic tests (strong recommendation; moderate-quality evidence).
Patients with persistent low back pain and signs or symptoms of radiculopathy or spinal stenosis should undergo MRI or CT only if positive results would potentially lead to surgery or epidural steroid injection for suspected radiculopathy. In choosing an imaging procedure, MRI is preferred to CT (strong recommendation; moderate-quality evidence).
Patient education by clinicians should include provision of evidence-based information on low back pain. Topics that should be covered include expected course and effective self-care options. Clinicians should also counsel their patients to stay physically active (strong recommendation; moderate-quality evidence).
When pharmacotherapy is considered, drugs of choice should be those with proven benefits, and they should be used together with self-care and back care education. Before starting a patient on pharmacotherapy, clinicians should evaluate pain and functional deficits at baseline. They should also review the risk-benefit ratio of specific medications before prescribing them and should consider the relative lack of long-term efficacy and safety data (strong recommendation; moderate-quality evidence). Acetaminophen or NSAIDs are preferred first-line drugs for most patients.
When self-care options do not result in improvement, clinicians should consider adding nonpharmacologic modalities shown to be of benefit. For acute low back pain, the only modality in this category is spinal manipulation. For chronic or subacute low back pain, modalities shown to be of benefit are intensive interdisciplinary rehabilitation, exercise therapy, acupuncture, massage therapy, spinal manipulation, yoga, cognitive-behavioral therapy, or progressive relaxation (weak recommendation; moderate-quality evidence).
"Opioids and muscle relaxers can provide relief for those with severe pain, but their potential benefits and risks should be weighed carefully," Dr. Chou said. "Patients who prefer not to take medication can benefit from non-drug treatments, such as acupuncture, spinal manipulations, and massage therapy. None, however, are proven to be more effective than others to warrant recommendation as first-line therapy."
Dr. Chou has disclosed receiving an honorium from Bayer Healthcare Pharmaceuticals. One of the authors has disclosed financial relationships with Agency for Healthcare Research and Quality, Centers for Disease Control and Prevention, Novo Nordisk, Pfizer, Merck, Bristol-Myers Squibb, Atlantic Philanthropics, and Sanofi-Pasteur.
Ann Intern Med. 2007;147:478-491.
October 2, 2007 — The American College of Physicians (ACP) and the American Pain Society (APS) have issued a comprehensive joint clinical practice guideline for the diagnosis and treatment of low back pain, which is published in the October 2 issue of the Annals of Internal Medicine. These guidelines offer recommendations concerning how to categorize patients, when to perform imaging studies, educational information for patients, self-care, when to prescribe medications and what types, and nonpharmacologic therapy. An important caveat is that clinicians should not routinely order imaging and other diagnostic tests.
"There are many options for evaluation and treatment of low back pain," second study author Amir Qaseem, MD, PhD, MHA, senior medical associate in the ACP Department of Clinical Programs and Quality of Care in Philadelphia, Pennsylvania, said in a news release. "We wanted to review all the evidence and develop guidance for clinicians and to give our patients a realistic sense of what they can expect when they visit a clinician for low back pain. It is important to tell patients about their expected course based on evidence-based information and advise them to remain active."
In the United States, several studies suggest that approximately 25% of adults report having had low back pain in the past 3 months, whereas 7.6% report at least 1 episode of severe acute low back pain within the previous year. Clinical evidence suggests that regardless of treatment, most low back pain improves within 1 month. Available treatment options range from watchful waiting to conservative treatment with pharmacologic and nonpharmacologic modalities to invasive procedures such as spinal surgery.
The impetus for the creation of these guidelines was a meeting of a multidisciplinary panel of experts convened in 2006 by ACP and APS. Their mission was to develop questions and the scope of an evidence report on low back pain, to review the available evidence in this field, and to generate recommendations assisting primary care clinicians in diagnosing and treating low back pain.
The joint ACP-APS guidelines target primary care physicians and other clinicians, rather than anesthesiologists, interventional radiologists, orthopaedists, or neurosurgeons. Although these guidelines do not address invasive therapies performed by specialists, the APS plans to publish a separate guideline in 2008 that will describe the use of invasive procedures for low back pain.
The current joint ACP-APS recommendations provide an algorithm to facilitate collection and interpretation of data during the first patient visit and to categorize patients into 1 of 3 general subgroups: (1) nonspecific low back pain (accounts for 85% of patients); (2) back pain potentially associated with spinal conditions, such as spinal stenosis, sciatica, and vertebral compression fracture; and (3) back pain potentially associated with another specific cause, such as cancer.
For patients with nonspecific low back pain, clinicians should not routinely order imaging studies, including radiographs, computerized tomography (CT) scans, magnetic resonance imaging (MRI), or other diagnostic tests. These tests should be used to evaluate only those patients who have severe or progressive neurologic deficits or who are suspected to have cancer, infection, or other underlying condition as the cause of their low back pain.
The guidelines are accompanied by 2 background articles reviewing the evidence underlying the recommendations for pharmacologic and nonpharmacologic treatment options for acute and chronic low back pain.
"Almost all medications reviewed had some benefits, but they have risks," said lead study author Roger Chou, MD, head of the APS Clinical Practice Guidelines Program. "Acetaminophen, for example, is very safe but might not be effective. NSAIDs [nonsteroidal anti-inflammatory drugs] have gastrointestinal and cardiovascular risks."
Specific recommendations in the guidelines are as follows:
Focused history and physical examination should help categorize patients into 1 of 3 broad groups: nonspecific low back pain, back pain potentially associated with radiculopathy or spinal stenosis, or back pain potentially associated with another specific spinal cause. Evaluation of psychosocial risk factors is essential during history taking because these predict the risk for chronic disabling low back pain (strong recommendation; moderate-quality evidence).
For patients with nonspecific low back pain, clinicians should not routinely perform imaging studies, including radiographs, CT scans, and MRI, or other diagnostic tests (strong recommendation; moderate-quality evidence).
Patients with severe or progressive neurologic deficits, or in whom history and physical examination suggest cancer, infection, or other underlying condition as the cause of their low back pain, should undergo imaging studies and other appropriate diagnostic tests (strong recommendation; moderate-quality evidence).
Patients with persistent low back pain and signs or symptoms of radiculopathy or spinal stenosis should undergo MRI or CT only if positive results would potentially lead to surgery or epidural steroid injection for suspected radiculopathy. In choosing an imaging procedure, MRI is preferred to CT (strong recommendation; moderate-quality evidence).
Patient education by clinicians should include provision of evidence-based information on low back pain. Topics that should be covered include expected course and effective self-care options. Clinicians should also counsel their patients to stay physically active (strong recommendation; moderate-quality evidence).
When pharmacotherapy is considered, drugs of choice should be those with proven benefits, and they should be used together with self-care and back care education. Before starting a patient on pharmacotherapy, clinicians should evaluate pain and functional deficits at baseline. They should also review the risk-benefit ratio of specific medications before prescribing them and should consider the relative lack of long-term efficacy and safety data (strong recommendation; moderate-quality evidence). Acetaminophen or NSAIDs are preferred first-line drugs for most patients.
When self-care options do not result in improvement, clinicians should consider adding nonpharmacologic modalities shown to be of benefit. For acute low back pain, the only modality in this category is spinal manipulation. For chronic or subacute low back pain, modalities shown to be of benefit are intensive interdisciplinary rehabilitation, exercise therapy, acupuncture, massage therapy, spinal manipulation, yoga, cognitive-behavioral therapy, or progressive relaxation (weak recommendation; moderate-quality evidence).
"Opioids and muscle relaxers can provide relief for those with severe pain, but their potential benefits and risks should be weighed carefully," Dr. Chou said. "Patients who prefer not to take medication can benefit from non-drug treatments, such as acupuncture, spinal manipulations, and massage therapy. None, however, are proven to be more effective than others to warrant recommendation as first-line therapy."
Dr. Chou has disclosed receiving an honorium from Bayer Healthcare Pharmaceuticals. One of the authors has disclosed financial relationships with Agency for Healthcare Research and Quality, Centers for Disease Control and Prevention, Novo Nordisk, Pfizer, Merck, Bristol-Myers Squibb, Atlantic Philanthropics, and Sanofi-Pasteur.
Ann Intern Med. 2007;147:478-491.
Psychosocial Factors Predict Hypertension and Coronary Heart Disease
October 2, 2007 —- Trait anger in middle-aged men and long-term stress in men and women predicted the progression from prehypertension to hypertension and incident coronary heart disease (CHD); exercise may reduce trait anger, according to the results of the Atherosclerosis Risk in Communities (ARIC) trial reported in the September/October issue of the Annals of Family Medicine.
"Patients with prehypertension are more likely to progress to frank hypertension," write Marty S. Player, MD, from the Medical University of South Carolina in Charleston, and colleagues. "The role of various psychosocial factors in cardiovascular disease has been of interest for many years.... The objective of this study was to investigate whether psychosocial factors are associated with progression from prehypertension to hypertension and to CHD or CHD mortality after adjustments for traditional risk factors."
The investigators performed a secondary analysis of the ARIC cohort of men and women aged 45 to 64 years at enrollment, including 2334 participants who had prehypertension at the second visit conducted between 1990 and 1992, who had no heart disease or stroke at baseline and who were observed from 1996 to 1998 when the ARIC study was completed. The primary endpoints were progression from prehypertension to hypertension and prehypertension to CHD or death from CHD.
Compared with low to moderate levels of trait anger measured by the Spielberger Trait Anger Scale, high levels were associated with progression from prehypertension to hypertension (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.05 - 2.24). Analysis by sex revealed that trait anger was predictive for men but not for women (OR, 1.71; 95% CI, 1.04 - 2.83), and that trait anger in men was associated with progression to CHD, based on survival analysis (hazard ratio [HR], 1.92; 95% CI, 1.07 - 3.54). In both sexes, long-term psychological stress on the Maastricht Questionnaire was associated with risk for incident CHD(HR, 1.68; 95% CI, 1.18 - 2.40).
"High levels of trait anger in middle-aged prehypertensive men were associated with increased risk of progressing to hypertension and incident CHD," the study authors write. "Long-term stress was also associated with increased risk of incident CHD in both men and women."
Limitations of the study include lack of generalizability to patient populations of different ages, observational design precluding causal inference, low incidence (5.8%) of CHD in women in this cohort, and limited duration of follow-up.
"The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure designated prehypertension as a new blood pressure category based on the increased cardiovascular risks and events associated with blood pressures in this range," the study authors conclude. "The findings of this study further support these associations with prehypertension. Additionally, we were able to show that beyond traditional cardiovascular risk factors, anger and psychological stress play a role in development of CHD in participants with prehypertension."
The Health Resources and Services Administration and the National Heart, Lung, and Blood Institute supported this study. The study authors have disclosed no relevant financial relationships.
Ann Fam Med. 2007;5:403-411.
October 2, 2007 —- Trait anger in middle-aged men and long-term stress in men and women predicted the progression from prehypertension to hypertension and incident coronary heart disease (CHD); exercise may reduce trait anger, according to the results of the Atherosclerosis Risk in Communities (ARIC) trial reported in the September/October issue of the Annals of Family Medicine.
"Patients with prehypertension are more likely to progress to frank hypertension," write Marty S. Player, MD, from the Medical University of South Carolina in Charleston, and colleagues. "The role of various psychosocial factors in cardiovascular disease has been of interest for many years.... The objective of this study was to investigate whether psychosocial factors are associated with progression from prehypertension to hypertension and to CHD or CHD mortality after adjustments for traditional risk factors."
The investigators performed a secondary analysis of the ARIC cohort of men and women aged 45 to 64 years at enrollment, including 2334 participants who had prehypertension at the second visit conducted between 1990 and 1992, who had no heart disease or stroke at baseline and who were observed from 1996 to 1998 when the ARIC study was completed. The primary endpoints were progression from prehypertension to hypertension and prehypertension to CHD or death from CHD.
Compared with low to moderate levels of trait anger measured by the Spielberger Trait Anger Scale, high levels were associated with progression from prehypertension to hypertension (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.05 - 2.24). Analysis by sex revealed that trait anger was predictive for men but not for women (OR, 1.71; 95% CI, 1.04 - 2.83), and that trait anger in men was associated with progression to CHD, based on survival analysis (hazard ratio [HR], 1.92; 95% CI, 1.07 - 3.54). In both sexes, long-term psychological stress on the Maastricht Questionnaire was associated with risk for incident CHD(HR, 1.68; 95% CI, 1.18 - 2.40).
"High levels of trait anger in middle-aged prehypertensive men were associated with increased risk of progressing to hypertension and incident CHD," the study authors write. "Long-term stress was also associated with increased risk of incident CHD in both men and women."
Limitations of the study include lack of generalizability to patient populations of different ages, observational design precluding causal inference, low incidence (5.8%) of CHD in women in this cohort, and limited duration of follow-up.
"The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure designated prehypertension as a new blood pressure category based on the increased cardiovascular risks and events associated with blood pressures in this range," the study authors conclude. "The findings of this study further support these associations with prehypertension. Additionally, we were able to show that beyond traditional cardiovascular risk factors, anger and psychological stress play a role in development of CHD in participants with prehypertension."
The Health Resources and Services Administration and the National Heart, Lung, and Blood Institute supported this study. The study authors have disclosed no relevant financial relationships.
Ann Fam Med. 2007;5:403-411.
Raloxifene OK'd for Breast Cancer Prevention
Mon Oct 1, 8:00 PM ET
Older women looking for a medication to help lower their risk of invasive breast cancer now have another option available to them.
The US Food and Drug Administration (FDA) has approved raloxifene (Evista) for breast cancer risk reduction in two groups of postmenopausal women: those with the bone-thinning condition osteoporosis and those at high risk for invasive breast cancer. It joins tamoxifen as just the second so-called chemoprevention drug to be approved for breast cancer.
Under the brand name Evista, raloxifene is already approved, and widely prescribed, for the prevention and treatment of osteoporosis in postmenopausal women. Researchers had previously observed that these women -- roughly half a million at present -- had lower rates of breast cancer than the general population.
Raloxifene is a type of drug known as a selective estrogen receptor modulator, or SERM. In reducing the risk of invasive breast cancer, SERMs may act by blocking estrogen receptors in the breast.
The expanded use of raloxifene -- based on positive clinical studies of approximately 37,000 postmenopausal women over a 10-year period -- "provides an important new option for women at heightened risk of breast cancer," said Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research.
In its announcement, the FDA noted that raloxifene can cause serious side effects, including blood clots in the legs and death due to stroke. Other potential side effects include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating.
The FDA said women with current or prior blood clots in the legs, lungs, or eyes should not take raloxifene. It should not be taken with cholestyramine, a drug used to lower cholesterol levels, or with estrogens.
It also should not be taken by women who are or may become pregnant. At present, tamoxifen remains the drug of choice for women who have not gone through menopause and have a high breast cancer risk. Raloxifene's breast cancer risk reduction effects have not been studied in younger women.
According to American Cancer Society estimates, more than 178,000 women are expected to be diagnosed with invasive breast cancer this year, accounting for more than one-fourth of all cancers in women.
Mon Oct 1, 8:00 PM ET
Older women looking for a medication to help lower their risk of invasive breast cancer now have another option available to them.
The US Food and Drug Administration (FDA) has approved raloxifene (Evista) for breast cancer risk reduction in two groups of postmenopausal women: those with the bone-thinning condition osteoporosis and those at high risk for invasive breast cancer. It joins tamoxifen as just the second so-called chemoprevention drug to be approved for breast cancer.
Under the brand name Evista, raloxifene is already approved, and widely prescribed, for the prevention and treatment of osteoporosis in postmenopausal women. Researchers had previously observed that these women -- roughly half a million at present -- had lower rates of breast cancer than the general population.
Raloxifene is a type of drug known as a selective estrogen receptor modulator, or SERM. In reducing the risk of invasive breast cancer, SERMs may act by blocking estrogen receptors in the breast.
The expanded use of raloxifene -- based on positive clinical studies of approximately 37,000 postmenopausal women over a 10-year period -- "provides an important new option for women at heightened risk of breast cancer," said Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research.
In its announcement, the FDA noted that raloxifene can cause serious side effects, including blood clots in the legs and death due to stroke. Other potential side effects include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating.
The FDA said women with current or prior blood clots in the legs, lungs, or eyes should not take raloxifene. It should not be taken with cholestyramine, a drug used to lower cholesterol levels, or with estrogens.
It also should not be taken by women who are or may become pregnant. At present, tamoxifen remains the drug of choice for women who have not gone through menopause and have a high breast cancer risk. Raloxifene's breast cancer risk reduction effects have not been studied in younger women.
According to American Cancer Society estimates, more than 178,000 women are expected to be diagnosed with invasive breast cancer this year, accounting for more than one-fourth of all cancers in women.
Study Supports Change to Prostate Cancer Biopsy
By Ed EdelsonHealthDay ReporterTue Oct 2, 7:01 PM ET
TUESDAY, Oct. 2 (HealthDay News) -- Adding an extra step to the standard test for prostate cancer might improve treatment for some men, a new study finds.
Doctors now use what's known as the Gleason test -- named for the physician who developed it -- as a major tool in judging how aggressively a prostate cancer should be treated, explained lead researcher Dr. Abhijit A. Patel, a radiation oncologist at Brigham and Women's Hospital in Boston.
His team published its findings in the Oct. 3 issue of the Journal of the American Medical Association.
In the Gleason test, doctors take a biopsy of the cancer and look at the level of disorder displayed by cells in the two largest sections of the sample -- scoring them from 1 (less disorderly) to 5 (more disorderly).
"The less it looks like normal tissue, the more aggressive [the cancer] is," Patel explained. They then add up the two numbers to arrive at a Gleason score. A score of 7 calls for treatment such as radiation therapy, Patel said, while higher scores indicate an even more dangerous tumor.
In the new study, the Brigham and Women's team looked for a third pattern of disorder from another part of the samples. Such disorderly patterns are found in about 5 percent of cases but usually are ignored. The new report included that third pattern in the diagnostic process.
Tests on 2,370 men with prostate cancer showed that men with Gleason score 7 plus this disorderly third pattern had a more rapid increase in prostate-specific antigen (PSA) levels in the blood. PSA indicates prostate tumor growth of the tumor and is the basis of the common PSA diagnostic blood test.
These men should probably receive more aggressive treatment to fight their disease, Patel said, compared to men without this combination of factors.
The time to what physicians call "PSA failure" averaged five years in these men, compared to 6.7 years in men with a Gleason score of 7 but no disorderly third pattern. In fact, the failure time for men with a Gleason score of 7 and the third pattern of disorderly cells was the same as for men whose cancers had a Gleason score of 8 or greater.
"We think these patients should get more therapy," Patel said. "In addition to surgery, they might need hormonal therapy to suppress the activity of testosterone."
Testosterone, the male sex hormone, spurs the growth of prostate cancer.
It's not known yet whether more aggressive treatment for men with the disorderly third pattern will improve their outcomes, since no such study has been done, Patel said.
But the idea does make sense, said Dr. David Berman, an assistant professor of pathology, urology and oncology at the Johns Hopkins University School of Medicine in Baltimore. "In prostate cancer it's difficult to go with things like survival to measure outcome. Biochemical recurrence is the easiest thing you can measure."
The revised Gleason score tested by Patel's group was first proposed several years ago, and has already been adopted by some specialists, Berman noted.
The Hopkins expert is also the lead author of a new report, published in the October issue of Cancer Research, that indicates that the addition of hormone suppression therapy to prostate cancer treatment might bring dangers of its own.
Laboratory studies indicate that hormone suppression therapy could boost the activity of a protein called nestin, which promotes the movement of prostate cancer cells to other parts of the body.
That danger is far from proven, however. "These are early days to make a whole lot of therapeutic recommendations based on it," Berman said.
More information
You can learn more about prostate cancer from the U.S. National Cancer Institute.
By Ed EdelsonHealthDay ReporterTue Oct 2, 7:01 PM ET
TUESDAY, Oct. 2 (HealthDay News) -- Adding an extra step to the standard test for prostate cancer might improve treatment for some men, a new study finds.
Doctors now use what's known as the Gleason test -- named for the physician who developed it -- as a major tool in judging how aggressively a prostate cancer should be treated, explained lead researcher Dr. Abhijit A. Patel, a radiation oncologist at Brigham and Women's Hospital in Boston.
His team published its findings in the Oct. 3 issue of the Journal of the American Medical Association.
In the Gleason test, doctors take a biopsy of the cancer and look at the level of disorder displayed by cells in the two largest sections of the sample -- scoring them from 1 (less disorderly) to 5 (more disorderly).
"The less it looks like normal tissue, the more aggressive [the cancer] is," Patel explained. They then add up the two numbers to arrive at a Gleason score. A score of 7 calls for treatment such as radiation therapy, Patel said, while higher scores indicate an even more dangerous tumor.
In the new study, the Brigham and Women's team looked for a third pattern of disorder from another part of the samples. Such disorderly patterns are found in about 5 percent of cases but usually are ignored. The new report included that third pattern in the diagnostic process.
Tests on 2,370 men with prostate cancer showed that men with Gleason score 7 plus this disorderly third pattern had a more rapid increase in prostate-specific antigen (PSA) levels in the blood. PSA indicates prostate tumor growth of the tumor and is the basis of the common PSA diagnostic blood test.
These men should probably receive more aggressive treatment to fight their disease, Patel said, compared to men without this combination of factors.
The time to what physicians call "PSA failure" averaged five years in these men, compared to 6.7 years in men with a Gleason score of 7 but no disorderly third pattern. In fact, the failure time for men with a Gleason score of 7 and the third pattern of disorderly cells was the same as for men whose cancers had a Gleason score of 8 or greater.
"We think these patients should get more therapy," Patel said. "In addition to surgery, they might need hormonal therapy to suppress the activity of testosterone."
Testosterone, the male sex hormone, spurs the growth of prostate cancer.
It's not known yet whether more aggressive treatment for men with the disorderly third pattern will improve their outcomes, since no such study has been done, Patel said.
But the idea does make sense, said Dr. David Berman, an assistant professor of pathology, urology and oncology at the Johns Hopkins University School of Medicine in Baltimore. "In prostate cancer it's difficult to go with things like survival to measure outcome. Biochemical recurrence is the easiest thing you can measure."
The revised Gleason score tested by Patel's group was first proposed several years ago, and has already been adopted by some specialists, Berman noted.
The Hopkins expert is also the lead author of a new report, published in the October issue of Cancer Research, that indicates that the addition of hormone suppression therapy to prostate cancer treatment might bring dangers of its own.
Laboratory studies indicate that hormone suppression therapy could boost the activity of a protein called nestin, which promotes the movement of prostate cancer cells to other parts of the body.
That danger is far from proven, however. "These are early days to make a whole lot of therapeutic recommendations based on it," Berman said.
More information
You can learn more about prostate cancer from the U.S. National Cancer Institute.
Parkinson's and Alzheimer's dementia very different
Tue Oct 2, 5:07 PM ET
Dementia associated with Parkinson's disease is distinctively different from that seen in Alzheimer's disease, Norwegian researchers report in the Journal of Neurology, Neurosurgery and Psychiatry.
Dr. Kolbjorn Bronnick at Stavanger University Hospital, Norway, and colleagues conducted a neurological assessment of 488 patients with Parkinson's disease dementia and another 488 patients with Alzheimer's disease, using the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-Cognitive Subscale.
The objective of the study by was to assess whether or not a diagnosis could be made based on the results of the cognitive profiles.
"Both groups showed memory impairment, Alzheimer's disease patients performing worse than Parkinson's disease dementia patients," the investigators report. "On the verbal memory tasks in the Alzheimer's Disease Assessment Scale-Cognitive Subscale, however, both groups were clearly impaired relative to a normal control group, with very large effect sizes."
"Poor performance of the Alzheimer's disease patients on the orientation test in Alzheimer's Disease Assessment Scale-Cognitive Subscale best discriminated between the groups, followed by poor performance of the Parkinson's disease dementia patients on the attentional task in Mini-Mental State Examination," Bronnick's team found.
"Diagnosis was predicted from the cognitive profile, with an overall accuracy of 74.7 percent," they report.
"In conclusion," the researchers write, "we found differential cognitive profiles in patients with Parkinson's disease dementia and Alzheimer's disease."
This strongly supports the hypothesis that Parkinson's disease dementia occurs through a mechanism that is quite different than the one associated with Alzheimer's disease, and that there exist pathological and physiological mechanisms specifically related to Parkinson's disease dementia.
SOURCE: Journal of Neurology, Neurosurgery and Psychiatry, October 2007.
Tue Oct 2, 5:07 PM ET
Dementia associated with Parkinson's disease is distinctively different from that seen in Alzheimer's disease, Norwegian researchers report in the Journal of Neurology, Neurosurgery and Psychiatry.
Dr. Kolbjorn Bronnick at Stavanger University Hospital, Norway, and colleagues conducted a neurological assessment of 488 patients with Parkinson's disease dementia and another 488 patients with Alzheimer's disease, using the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-Cognitive Subscale.
The objective of the study by was to assess whether or not a diagnosis could be made based on the results of the cognitive profiles.
"Both groups showed memory impairment, Alzheimer's disease patients performing worse than Parkinson's disease dementia patients," the investigators report. "On the verbal memory tasks in the Alzheimer's Disease Assessment Scale-Cognitive Subscale, however, both groups were clearly impaired relative to a normal control group, with very large effect sizes."
"Poor performance of the Alzheimer's disease patients on the orientation test in Alzheimer's Disease Assessment Scale-Cognitive Subscale best discriminated between the groups, followed by poor performance of the Parkinson's disease dementia patients on the attentional task in Mini-Mental State Examination," Bronnick's team found.
"Diagnosis was predicted from the cognitive profile, with an overall accuracy of 74.7 percent," they report.
"In conclusion," the researchers write, "we found differential cognitive profiles in patients with Parkinson's disease dementia and Alzheimer's disease."
This strongly supports the hypothesis that Parkinson's disease dementia occurs through a mechanism that is quite different than the one associated with Alzheimer's disease, and that there exist pathological and physiological mechanisms specifically related to Parkinson's disease dementia.
SOURCE: Journal of Neurology, Neurosurgery and Psychiatry, October 2007.
Breast cancer survival better after 40: study
Wed Oct 3, 1:04 AM ET
Women stand a better chance of surviving breast cancer if they are over 40 years old when diagnosed, new research released Wednesday showed.
The Australian study confirmed that survival rates are higher for those women who detect the tumour early, and for those with smaller tumours.
Researchers from the Australian Institute of Health and Welfare and the National Breast Cancer Centre looked at the survival rates of more than 10,000 women who were diagnosed with the disease in 1997.
They found that the larger the cancer, the lower the chance of survival.
Women whose cancers were 10 millimetres or less in diameter at diagnosis had a 98 percent chance of being alive five years later.
"This declined to 73 percent for women with cancers 30 millimetres or more in diameter, and to 49 percent for women with advanced cancer where size had not been measured," said the institute's Christine Sturrock.
Survival rates were higher if the cancer was detected before it spread to the lymph nodes while age was also a significant influence, with women under 40 having a lower survival rate, no matter what size the tumour.
For these younger women, those with cancers 10 millimetres or less had a 95 percent survival rate while those whose growths had passed 30 millimetres had only a 67 percent chance of survival.
The director of the National Breast Cancer Centre, Dr Helen Zorbas, said the best outcomes appeared to be for those women diagnosed in their 50s.
"For women who are under 40, they do tend to have a lower survival rate than older women," she told AFP.
"The tumours seem to behave differently in younger women," she said, adding that they tended to display larger and more aggressive tumours.
Zorbas said the research should encourage women diagnosed with breast cancer in Australia because of the high rates of survival but that it also underlined the importance of early detection.
"The overall survival rate in Australia is 87 percent, taking into account all sizes and all stages of the disease," she said. "Twenty years ago, this was around 70 to 71 percent."
Wed Oct 3, 1:04 AM ET
Women stand a better chance of surviving breast cancer if they are over 40 years old when diagnosed, new research released Wednesday showed.
The Australian study confirmed that survival rates are higher for those women who detect the tumour early, and for those with smaller tumours.
Researchers from the Australian Institute of Health and Welfare and the National Breast Cancer Centre looked at the survival rates of more than 10,000 women who were diagnosed with the disease in 1997.
They found that the larger the cancer, the lower the chance of survival.
Women whose cancers were 10 millimetres or less in diameter at diagnosis had a 98 percent chance of being alive five years later.
"This declined to 73 percent for women with cancers 30 millimetres or more in diameter, and to 49 percent for women with advanced cancer where size had not been measured," said the institute's Christine Sturrock.
Survival rates were higher if the cancer was detected before it spread to the lymph nodes while age was also a significant influence, with women under 40 having a lower survival rate, no matter what size the tumour.
For these younger women, those with cancers 10 millimetres or less had a 95 percent survival rate while those whose growths had passed 30 millimetres had only a 67 percent chance of survival.
The director of the National Breast Cancer Centre, Dr Helen Zorbas, said the best outcomes appeared to be for those women diagnosed in their 50s.
"For women who are under 40, they do tend to have a lower survival rate than older women," she told AFP.
"The tumours seem to behave differently in younger women," she said, adding that they tended to display larger and more aggressive tumours.
Zorbas said the research should encourage women diagnosed with breast cancer in Australia because of the high rates of survival but that it also underlined the importance of early detection.
"The overall survival rate in Australia is 87 percent, taking into account all sizes and all stages of the disease," she said. "Twenty years ago, this was around 70 to 71 percent."
Tuesday, October 02, 2007
Maintenance Antidepressant Treatment Improves Well-Being in Late-Life Depression
October 1, 2007 — Maintenance antidepressant pharmacotherapy is superior to placebo in preserving improvements in overall health-related quality of life (HR-QOL) achieved with treatment response in late-life depression, according to the results of a study reported in the September issue of the Journal of the American Geriatrics Society.
"Depression is one of the major causes of decline in the health-related quality of life (HR-QOL) of elderly persons," write Alexandre Y. Dombrovski, MD, from the University of Pittsburgh in Pennsylvania, and colleagues. "Because HR-QOL matters to patients and families and is a crucial outcome of depression treatment beyond improvement in symptomatic status, clinicians need to know whether treatment improves and maintains it. To the authors' knowledge, only two randomized, controlled trials have examined the long-term effect of treatment on various domains of HR-QOL."
The hypothesis of this study was that paroxetine would be superior to placebo and that interpersonal psychotherapy would be superior to clinical management, after controlling for the effects of the other treatment.
Open combined treatment with paroxetine and interpersonal psychotherapy identified patients aged 70 years and older with major depression who responded to dual therapy. Responders were randomized to a 2 (paroxetine vs placebo) by 2 (monthly, manual-based interpersonal psychotherapy vs clinical management) double-blind, maintenance trial in which HR-QOL outcomes were evaluated during 1 year of maintenance treatment at a university-based clinic.
Of 363 persons with late-life depression referred for study, 210 gave consent. Of 195 patients who began acute, open-label treatment, 116 met criteria for recovery, were randomized to maintenance treatment, and were included in this analysis.
Outcome measures were overall HR-QOL measured with the Quality of Well-Being Scale (QWB), as well as 6 specific HR-QOL domains derived from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) subscales.
Except for physical functioning, all domains of HR-QOL improved with successful acute and continuation treatment. After controlling for effects of psychotherapy, treatment with paroxetine was superior to placebo in preserving overall well-being (P = .04; effect size [r] = 0.23), social functioning (P =.02; r = 0.27), and role limitations as a result of emotional problems (P =.007; r = 0.30). Compared with supportive clinical management, interpersonal psychotherapy was no better at preserving HR-QOL, after controlling for the effects of treatment with paroxetine.
"Maintenance antidepressant pharmacotherapy is superior to placebo in preserving improvements in overall well-being achieved with treatment response in late-life depression," the study authors write. "No such benefit was seen with interpersonal psychotherapy."
Limitations of the study include a predominantly white sample with more severe depressive symptoms responsive to acute treatment, limiting generalizability.
"Overall, the effects of pharmacotherapy on HR-QOL observed in this study range from modest (0.23) for overall quality of life and social functioning (0.27) to moderate for emotional role functioning (0.30), the domain most directly affected by depression," the study authors conclude. "These effects compare favorably with small or nonsignificant effects of secondary prevention programs in coronary heart disease, angiotensin-converting enzyme inhibitors, and calcium channel blockers in congestive heart failure and with the effects of various antihypertensive agents."
The National Institute of Mental Health and the John A. Hartford Foundation supported this study. GlaxoSmithKline provided paroxetine tablets for use in this study. Some of the authors have disclosed various financial relationships with Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, GSK, Janssen, Lundbeck, Pfizer, Johnson & Johnson, Organon, and Sepracor.
J Am Geriatr Soc. 2007;55:1325-1332.
October 1, 2007 — Maintenance antidepressant pharmacotherapy is superior to placebo in preserving improvements in overall health-related quality of life (HR-QOL) achieved with treatment response in late-life depression, according to the results of a study reported in the September issue of the Journal of the American Geriatrics Society.
"Depression is one of the major causes of decline in the health-related quality of life (HR-QOL) of elderly persons," write Alexandre Y. Dombrovski, MD, from the University of Pittsburgh in Pennsylvania, and colleagues. "Because HR-QOL matters to patients and families and is a crucial outcome of depression treatment beyond improvement in symptomatic status, clinicians need to know whether treatment improves and maintains it. To the authors' knowledge, only two randomized, controlled trials have examined the long-term effect of treatment on various domains of HR-QOL."
The hypothesis of this study was that paroxetine would be superior to placebo and that interpersonal psychotherapy would be superior to clinical management, after controlling for the effects of the other treatment.
Open combined treatment with paroxetine and interpersonal psychotherapy identified patients aged 70 years and older with major depression who responded to dual therapy. Responders were randomized to a 2 (paroxetine vs placebo) by 2 (monthly, manual-based interpersonal psychotherapy vs clinical management) double-blind, maintenance trial in which HR-QOL outcomes were evaluated during 1 year of maintenance treatment at a university-based clinic.
Of 363 persons with late-life depression referred for study, 210 gave consent. Of 195 patients who began acute, open-label treatment, 116 met criteria for recovery, were randomized to maintenance treatment, and were included in this analysis.
Outcome measures were overall HR-QOL measured with the Quality of Well-Being Scale (QWB), as well as 6 specific HR-QOL domains derived from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) subscales.
Except for physical functioning, all domains of HR-QOL improved with successful acute and continuation treatment. After controlling for effects of psychotherapy, treatment with paroxetine was superior to placebo in preserving overall well-being (P = .04; effect size [r] = 0.23), social functioning (P =.02; r = 0.27), and role limitations as a result of emotional problems (P =.007; r = 0.30). Compared with supportive clinical management, interpersonal psychotherapy was no better at preserving HR-QOL, after controlling for the effects of treatment with paroxetine.
"Maintenance antidepressant pharmacotherapy is superior to placebo in preserving improvements in overall well-being achieved with treatment response in late-life depression," the study authors write. "No such benefit was seen with interpersonal psychotherapy."
Limitations of the study include a predominantly white sample with more severe depressive symptoms responsive to acute treatment, limiting generalizability.
"Overall, the effects of pharmacotherapy on HR-QOL observed in this study range from modest (0.23) for overall quality of life and social functioning (0.27) to moderate for emotional role functioning (0.30), the domain most directly affected by depression," the study authors conclude. "These effects compare favorably with small or nonsignificant effects of secondary prevention programs in coronary heart disease, angiotensin-converting enzyme inhibitors, and calcium channel blockers in congestive heart failure and with the effects of various antihypertensive agents."
The National Institute of Mental Health and the John A. Hartford Foundation supported this study. GlaxoSmithKline provided paroxetine tablets for use in this study. Some of the authors have disclosed various financial relationships with Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, GSK, Janssen, Lundbeck, Pfizer, Johnson & Johnson, Organon, and Sepracor.
J Am Geriatr Soc. 2007;55:1325-1332.
Too Much Sleep or Too Little Increases Mortality Risk
HELSINKI, Finland, Oct. 1 -- Sleep excesses one way or the other can carry a roughly 20% greater mortality risk over two decades, investigators here found.
Men, in particular, had a significant increase in the associations between natural death and both stable long and stable short sleep, Christer Hublin, M.D., Ph.D., of the Finnish Institute of Occupational Health, and colleagues, reported in issue of Sleep.
The findings add to evidence of sleep's impact on health and mortality but also show that the association is complicated. "The exact mechanisms [of the association] remain unclear, and they should be assessed in experimental settings and other longitudinal studies," Dr. Hublin and colleagues concluded.
"Although the effect of sleep on mortality is fairly modest compared to . . . smoking or components of the metabolic syndrome, it is still of considerable significance as it is associated with several common disorders such as cardiovascular diseases and diabetes," they added.
Studies published over the past 20 years have generally revealed a U-shaped curve association between sleep length and mortality, with the lowest mortality associated with about seven hours of sleep, the authors stated.
Multiple studies have revealed an increased mortality risk in association with prolonged sleep (eight hours or more). In contrast, the impact of short sleep on mortality has tended to decrease after adjustment for other factors known to be associated with mortality, such as smoking, alcohol use, and physical inactivity.
Dr. Hublin and colleagues reviewed data from the Finnish Twin Cohort, involving 21,268 twins ages 18 and older who completed questionnaires between 1975 and 1981. The questionnaires included items related to sleep habits.
On the basis of the survey responses, participants were categorized as:
Short sleepers (less than seven hours)
Average sleepers
Long sleepers (more than eight hours)
Sleeping well
Sleeping fairly well
Sleeping fairly poorly or poorly
Nonusers, infrequent users, or frequent users of hypnotics or tranquilizers
Proportional hazard models were used to calculate hazard ratios for mortality during 1982 to 2003 by sleep-related variables and their combinations. The primary findings were increased mortality risks associated with:
Short sleep-men +26% and women +21%
Long sleep-men +24% and women +17%
Frequent hypotnotic use-men +31%, women +39%
Snoring as a covariate did not change the results. The effect of sleep on mortality varied by age, and the strong effects were seen in young men.
Overall, sleep length and quality changed in about a third of participants in the study during the period reviewed. The change in sleep patterns manifested in an impact on mortalilty. Among men stable short sleep was associated with a 34% increase in natural deaths and stable long sleep with a 29% increase. During 1975 to 1981, stable short sleepers had a 62% increase in the risk of death from external causes.
The authors reported no disclosures. The study was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics. Primary source: SleepSource reference: Hublin C et al. "Sleep and mortality: a population-based 22-year follow-up study." Sleep 2007;30:epub.
HELSINKI, Finland, Oct. 1 -- Sleep excesses one way or the other can carry a roughly 20% greater mortality risk over two decades, investigators here found.
Men, in particular, had a significant increase in the associations between natural death and both stable long and stable short sleep, Christer Hublin, M.D., Ph.D., of the Finnish Institute of Occupational Health, and colleagues, reported in issue of Sleep.
The findings add to evidence of sleep's impact on health and mortality but also show that the association is complicated. "The exact mechanisms [of the association] remain unclear, and they should be assessed in experimental settings and other longitudinal studies," Dr. Hublin and colleagues concluded.
"Although the effect of sleep on mortality is fairly modest compared to . . . smoking or components of the metabolic syndrome, it is still of considerable significance as it is associated with several common disorders such as cardiovascular diseases and diabetes," they added.
Studies published over the past 20 years have generally revealed a U-shaped curve association between sleep length and mortality, with the lowest mortality associated with about seven hours of sleep, the authors stated.
Multiple studies have revealed an increased mortality risk in association with prolonged sleep (eight hours or more). In contrast, the impact of short sleep on mortality has tended to decrease after adjustment for other factors known to be associated with mortality, such as smoking, alcohol use, and physical inactivity.
Dr. Hublin and colleagues reviewed data from the Finnish Twin Cohort, involving 21,268 twins ages 18 and older who completed questionnaires between 1975 and 1981. The questionnaires included items related to sleep habits.
On the basis of the survey responses, participants were categorized as:
Short sleepers (less than seven hours)
Average sleepers
Long sleepers (more than eight hours)
Sleeping well
Sleeping fairly well
Sleeping fairly poorly or poorly
Nonusers, infrequent users, or frequent users of hypnotics or tranquilizers
Proportional hazard models were used to calculate hazard ratios for mortality during 1982 to 2003 by sleep-related variables and their combinations. The primary findings were increased mortality risks associated with:
Short sleep-men +26% and women +21%
Long sleep-men +24% and women +17%
Frequent hypotnotic use-men +31%, women +39%
Snoring as a covariate did not change the results. The effect of sleep on mortality varied by age, and the strong effects were seen in young men.
Overall, sleep length and quality changed in about a third of participants in the study during the period reviewed. The change in sleep patterns manifested in an impact on mortalilty. Among men stable short sleep was associated with a 34% increase in natural deaths and stable long sleep with a 29% increase. During 1975 to 1981, stable short sleepers had a 62% increase in the risk of death from external causes.
The authors reported no disclosures. The study was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics. Primary source: SleepSource reference: Hublin C et al. "Sleep and mortality: a population-based 22-year follow-up study." Sleep 2007;30:epub.
Elevated White Blood Cell Counts May Signal Higher Cancer Risk
Roxanne Nelson
October 1, 2007 — Postmenopausal women with elevated white blood cell (WBC) counts appear to be at a higher risk of developing certain malignancies, including incident invasive breast, colorectal, endometrial, and lung cancers. The study, which appears in the September 24 issue of the Archives of Internal Medicine, also found that higher levels of WBCs in this population conferred a higher risk of breast, lung, and overall cancer mortality.
"The mechanisms through which inflammation leads to carcinogenesis are incompletely understood," write Hemant K. Roy, MD, and Janardan D. Khandekar, MD, from Evanston Hospital in Illinois, in an accompanying editorial. "Most of the attention in carcinogenesis has focused on adaptive immunity, especially derangements in humoral and cell-mediated immunity."
However, they note, the role of the innate immune system, which includes WBCs, is just beginning to be explored, and recent data demonstrate that in the presence of precancerous tissue, leukocyte antibody receptors become activated and might serve as signals for both growth factors and angiogenesis.
"These findings suggest that leukocytes may be involved in the progression phases of carcinogenesis," they write. "Therefore, it is biologically plausible that WBCs may be involved in cancer development."
However, the editorialists point out that even though the study authors found it statistically significant, the correlation between the WBC count and cancer risk was weak. However, although a WBC count is clearly inadequate for cancer detection, they note, this paper presents compelling support for inflammation as a biomarker.
"The observation that the peripheral WBC count appears to be inadequate for cancer screening does not diminish the promise of probing the immune system," and "this finding foreshadows the use of more sophisticated technologies to exploit the inflammation-cancer link," write Drs. Roy and Khandekar.
Considering the fact that it is an inexpensive test commonly used in clinical practice, the WBC count has been surprisingly infrequently evaluated in epidemiologic studies, explained senior author Karen Margolis, MD, MPH, a senior clinical investigator at HealthPartners Research Foundation, in Minneapolis, Minnesota. "One problem is that it has to be measured right away, whereas many other biomarkers can be measured in stored specimens."
Dr. Margolis and colleagues sought to determine whether there is an independent association between WBC count and incident cancer in postmenopausal women. Their analysis included data on 143,748 postmenopausal women enrolled in the Women's Health Initiative (WHI). At baseline, between 1993 and 1998, the women were between the ages of 50 and 79 years and were free of cancer.
"What the WHI data brings to this topic is the ability to look at cancer incidence and not just cancer mortality, and to compare the association with several types of incident cancer," Dr. Margolis told Medscape Oncology. "The large size of WHI allows us to find relatively small effect sizes."
Upon examining patient demographics, the researchers observed that higher WBC counts were associated with factors that included older age, current tobacco use, aspirin use, higher parity, hypertension, diabetes mellitus, current use of hormones, and a greater body mass index. Conversely, lower counts were associated with factors such as physical activity, months of breastfeeding, increased alcohol use, and ethnic background.
When the analysis was adjusted for age, they noted a graded association between WBC count and incident invasive breast cancer (4639 cases), colorectal cancer (1341 cases), endometrial cancer (766 cases), and lung cancer (1237 cases). After adjustment for possible confounders, the strength of the associations was lessened, but the significant trends with increasing WBC quartile remained.
Women in the highest quartile of WBC count (6.80-15.00 x 109 cells/L) had a 15% higher risk for invasive breast cancer, a 19% higher risk for colorectal cancer, a 42% higher risk for endometrial cancer, and a 63% higher risk for lung cancer than patients in the lowest quartile of WBC count (2.50-4.79 x 109 cells/L).
The results were similar when cancers that developed during the first 2 years of follow-up were excluded from the data. When current smokers were removed from the multivariate analyses, the association between WBC count and invasive breast cancer and endometrial cancer was almost identical. However, the association with colorectal cancer was weaker and statistically nonsignificant.
The researchers also found that there was a strong association between WBC count and mortality related to invasive breast cancer and lung cancer, and between WBC count and overall death from cancer. Even after age and multivariate adjustments, the incidence of mortality from invasive breast cancer remained more than 2 times higher among patients in the highest WBC quartile. Age-adjusted analysis for lung cancer mortality showed a more than 3-fold risk for women in the highest WBC quartile, although after adjustment for smoking, the association was weakened. However, the relationship was still statistically significant, showing a 65% increase in lung cancer mortality in the highest WBC quartile.
Although previous studies have shown mixed results, the preponderance of the evidence was in favor of an association between WBC and cancer before the publication of this study, said Dr. Margolis, and between WBC and C-reactive protein.
"I think the results are likely to apply to men and younger populations, keeping in mind that cancer rates generally go up quite steeply with age," she said. "Younger populations are harder to study."
Although the results of this study are not ready to be applied clinically, physicians should take note of an elevated WBC, even one in the upper range of normal, Dr. Margolis pointed out. "I do think a WBC in the upper range of normal — above 7 or so — should be on clinicians' radar, especially if it is persistent and unrelated to any known cause."
"Of course," she added, "Most people with a WBC in this range will not develop cancer or cardiovascular disease in the next 5 to 10 years, and the relative risk increase for cancer is quite small."
The WHI program is funded by the National Heart, Lung, and Blood Institute, US Department of Health and Human Services.
Arch Intern Med. 2007;167(17):1837-1844, 1822-1823
Roxanne Nelson
October 1, 2007 — Postmenopausal women with elevated white blood cell (WBC) counts appear to be at a higher risk of developing certain malignancies, including incident invasive breast, colorectal, endometrial, and lung cancers. The study, which appears in the September 24 issue of the Archives of Internal Medicine, also found that higher levels of WBCs in this population conferred a higher risk of breast, lung, and overall cancer mortality.
"The mechanisms through which inflammation leads to carcinogenesis are incompletely understood," write Hemant K. Roy, MD, and Janardan D. Khandekar, MD, from Evanston Hospital in Illinois, in an accompanying editorial. "Most of the attention in carcinogenesis has focused on adaptive immunity, especially derangements in humoral and cell-mediated immunity."
However, they note, the role of the innate immune system, which includes WBCs, is just beginning to be explored, and recent data demonstrate that in the presence of precancerous tissue, leukocyte antibody receptors become activated and might serve as signals for both growth factors and angiogenesis.
"These findings suggest that leukocytes may be involved in the progression phases of carcinogenesis," they write. "Therefore, it is biologically plausible that WBCs may be involved in cancer development."
However, the editorialists point out that even though the study authors found it statistically significant, the correlation between the WBC count and cancer risk was weak. However, although a WBC count is clearly inadequate for cancer detection, they note, this paper presents compelling support for inflammation as a biomarker.
"The observation that the peripheral WBC count appears to be inadequate for cancer screening does not diminish the promise of probing the immune system," and "this finding foreshadows the use of more sophisticated technologies to exploit the inflammation-cancer link," write Drs. Roy and Khandekar.
Considering the fact that it is an inexpensive test commonly used in clinical practice, the WBC count has been surprisingly infrequently evaluated in epidemiologic studies, explained senior author Karen Margolis, MD, MPH, a senior clinical investigator at HealthPartners Research Foundation, in Minneapolis, Minnesota. "One problem is that it has to be measured right away, whereas many other biomarkers can be measured in stored specimens."
Dr. Margolis and colleagues sought to determine whether there is an independent association between WBC count and incident cancer in postmenopausal women. Their analysis included data on 143,748 postmenopausal women enrolled in the Women's Health Initiative (WHI). At baseline, between 1993 and 1998, the women were between the ages of 50 and 79 years and were free of cancer.
"What the WHI data brings to this topic is the ability to look at cancer incidence and not just cancer mortality, and to compare the association with several types of incident cancer," Dr. Margolis told Medscape Oncology. "The large size of WHI allows us to find relatively small effect sizes."
Upon examining patient demographics, the researchers observed that higher WBC counts were associated with factors that included older age, current tobacco use, aspirin use, higher parity, hypertension, diabetes mellitus, current use of hormones, and a greater body mass index. Conversely, lower counts were associated with factors such as physical activity, months of breastfeeding, increased alcohol use, and ethnic background.
When the analysis was adjusted for age, they noted a graded association between WBC count and incident invasive breast cancer (4639 cases), colorectal cancer (1341 cases), endometrial cancer (766 cases), and lung cancer (1237 cases). After adjustment for possible confounders, the strength of the associations was lessened, but the significant trends with increasing WBC quartile remained.
Women in the highest quartile of WBC count (6.80-15.00 x 109 cells/L) had a 15% higher risk for invasive breast cancer, a 19% higher risk for colorectal cancer, a 42% higher risk for endometrial cancer, and a 63% higher risk for lung cancer than patients in the lowest quartile of WBC count (2.50-4.79 x 109 cells/L).
The results were similar when cancers that developed during the first 2 years of follow-up were excluded from the data. When current smokers were removed from the multivariate analyses, the association between WBC count and invasive breast cancer and endometrial cancer was almost identical. However, the association with colorectal cancer was weaker and statistically nonsignificant.
The researchers also found that there was a strong association between WBC count and mortality related to invasive breast cancer and lung cancer, and between WBC count and overall death from cancer. Even after age and multivariate adjustments, the incidence of mortality from invasive breast cancer remained more than 2 times higher among patients in the highest WBC quartile. Age-adjusted analysis for lung cancer mortality showed a more than 3-fold risk for women in the highest WBC quartile, although after adjustment for smoking, the association was weakened. However, the relationship was still statistically significant, showing a 65% increase in lung cancer mortality in the highest WBC quartile.
Although previous studies have shown mixed results, the preponderance of the evidence was in favor of an association between WBC and cancer before the publication of this study, said Dr. Margolis, and between WBC and C-reactive protein.
"I think the results are likely to apply to men and younger populations, keeping in mind that cancer rates generally go up quite steeply with age," she said. "Younger populations are harder to study."
Although the results of this study are not ready to be applied clinically, physicians should take note of an elevated WBC, even one in the upper range of normal, Dr. Margolis pointed out. "I do think a WBC in the upper range of normal — above 7 or so — should be on clinicians' radar, especially if it is persistent and unrelated to any known cause."
"Of course," she added, "Most people with a WBC in this range will not develop cancer or cardiovascular disease in the next 5 to 10 years, and the relative risk increase for cancer is quite small."
The WHI program is funded by the National Heart, Lung, and Blood Institute, US Department of Health and Human Services.
Arch Intern Med. 2007;167(17):1837-1844, 1822-1823
Low Education Level Independently Increases Dementia Risk
Caroline Cassels
October 1, 2007 — Low levels of education appear to independently increase dementia risk regardless of other potential contributors, including demographic, socioeconomic, and vascular factors, new research suggests.
Results from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study showed that, compared with individuals with the lowest levels of education, highly educated individuals had an 80% lower dementia risk.
"Generally speaking, people with low education levels seem to lead unhealthier lifestyles, which could suggest the 2 work concurrently to contribute to dementia or Alzheimer's disease, but our results showed a person's education predicted dementia on its own," said Tiia Ngandu, MD, PhD, of the Karolinska Institute in Stockholm, Sweden.
It might be that highly educated people have a greater cognitive reserve, which is the brain's ability to maintain function in spite of damage, making it easier to postpone the negative effects of dementia. Additionally, unhealthy lifestyles may independently contribute to the depletion of this reserve," Dr. Ngandu added.
The study is published in the October 2 issue of Neurology.
Methods
Derived from 4 separate independent population-based, randomly selected samples (from 1972, 1977, 1982, and 1987), the CAIDE study followed 1388 individuals from middle age to late life (an average of 21 years); they underwent re-examination in 1998.
During the mid-life examination, study participants filled out a self-administered questionnaire covering socioeconomic factors, health behavior, health status, and medical history. In addition, a venous blood sample was taken and systolic and diastolic blood pressure and height and weight were measured.
Information on education level was also gathered at the mid-life examination. Study subjects were categorized into 3 groups: those with 5 years of education or less (low); those with 6 to 8 years of education (medium); and those with 9 or more years of education (high).
Methods for the late-life examination were the same as those used in the mid-life exam. During this phase of the study, participants underwent ApoE genotyping and had their cognitive status assessed. Study subjects who scored 24 or less on the Mini-Mental State Examination (MMSE) were referred for further diagnostic examination.
A total of 61 individuals met the diagnosis of dementia. Of these, 48 had Alzheimer's disease.
Dose-Dependent Effect
"Education was associated with the risk of dementia in a dose-dependent manner. Compared with people with low education, those with medium education had a 40% lower risk of developing dementia, and those with high education had 80% lower risk for dementia," the authors write.
According to the investigators, adjustment for potential confounders/mediators, including demographic, socioeconomic, and vascular factors, as well as mid-life physical activity levels, ApoE status, and depression, did not change the results.
"Our study showed that Finnish people with medium to high education have a lower risk of dementia when compared with persons with a low education level. The confounding/mediating effects related to differences in socioeconomic, vascular, or lifestyle characteristics between people with different levels of education were taken into account. However, none of these factors changed the results, suggesting that the effect of education is independent of other risk factors for dementia," they write.
Investigators found that those in late life those with lower education at midlife had a higher occurrence of dementia and Alzheimer's disease.
The study was funded by the Alzheimer's Association, the Aging Program of the Academy of Finland, and Kuopio University Hospital in Finland.
Neurology. 2007; 69:1442-1450.
Caroline Cassels
October 1, 2007 — Low levels of education appear to independently increase dementia risk regardless of other potential contributors, including demographic, socioeconomic, and vascular factors, new research suggests.
Results from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study showed that, compared with individuals with the lowest levels of education, highly educated individuals had an 80% lower dementia risk.
"Generally speaking, people with low education levels seem to lead unhealthier lifestyles, which could suggest the 2 work concurrently to contribute to dementia or Alzheimer's disease, but our results showed a person's education predicted dementia on its own," said Tiia Ngandu, MD, PhD, of the Karolinska Institute in Stockholm, Sweden.
It might be that highly educated people have a greater cognitive reserve, which is the brain's ability to maintain function in spite of damage, making it easier to postpone the negative effects of dementia. Additionally, unhealthy lifestyles may independently contribute to the depletion of this reserve," Dr. Ngandu added.
The study is published in the October 2 issue of Neurology.
Methods
Derived from 4 separate independent population-based, randomly selected samples (from 1972, 1977, 1982, and 1987), the CAIDE study followed 1388 individuals from middle age to late life (an average of 21 years); they underwent re-examination in 1998.
During the mid-life examination, study participants filled out a self-administered questionnaire covering socioeconomic factors, health behavior, health status, and medical history. In addition, a venous blood sample was taken and systolic and diastolic blood pressure and height and weight were measured.
Information on education level was also gathered at the mid-life examination. Study subjects were categorized into 3 groups: those with 5 years of education or less (low); those with 6 to 8 years of education (medium); and those with 9 or more years of education (high).
Methods for the late-life examination were the same as those used in the mid-life exam. During this phase of the study, participants underwent ApoE genotyping and had their cognitive status assessed. Study subjects who scored 24 or less on the Mini-Mental State Examination (MMSE) were referred for further diagnostic examination.
A total of 61 individuals met the diagnosis of dementia. Of these, 48 had Alzheimer's disease.
Dose-Dependent Effect
"Education was associated with the risk of dementia in a dose-dependent manner. Compared with people with low education, those with medium education had a 40% lower risk of developing dementia, and those with high education had 80% lower risk for dementia," the authors write.
According to the investigators, adjustment for potential confounders/mediators, including demographic, socioeconomic, and vascular factors, as well as mid-life physical activity levels, ApoE status, and depression, did not change the results.
"Our study showed that Finnish people with medium to high education have a lower risk of dementia when compared with persons with a low education level. The confounding/mediating effects related to differences in socioeconomic, vascular, or lifestyle characteristics between people with different levels of education were taken into account. However, none of these factors changed the results, suggesting that the effect of education is independent of other risk factors for dementia," they write.
Investigators found that those in late life those with lower education at midlife had a higher occurrence of dementia and Alzheimer's disease.
The study was funded by the Alzheimer's Association, the Aging Program of the Academy of Finland, and Kuopio University Hospital in Finland.
Neurology. 2007; 69:1442-1450.
Minocycline May Improve Stroke Outcomes Out to 24 Hours
Susan Jeffrey
Medscape Medical News 2007. © 2007 Medscape
October 1, 2007 — Results of a randomized open-label trial suggest that the use of minocycline 6 to 24 hours after an acute ischemic stroke is associated with significantly improved clinical outcomes.
"The improvement was already apparent within a week of the stroke," said study author Yair Lampl, MD, from the Edith Wolfson Medical Center and Tel Aviv University, Israel, in a statement from the American Academy of Neurology. "This is exciting because many people who have had stroke cannot be treated if they don't get to the hospital within 3 hours after symptoms start, which is the time frame for current available treatments."
However, he added, "while these are promising results, a much larger, closed-label study is needed to confirm our findings."
Their report appears in the October 2 issue of Neurology.
Neuroprotective Effects of Minocycline
Minocycline is a semisynthetic, second-generation derivative of tetracycline, and has been shown to have a "clear beneficial protective effect," in animal models of multiple sclerosis, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, as well as in stroke models, the authors write.
The proposed mechanism of benefit is thought to relate not to its antibiotic action but to its anti-inflammatory effects, a reduction in microglial activation, matrix metalloproteinase reduction, nitric oxide production, or inhibition of apoptotic cell death, they note.
To look more closely at the potential benefit of minocycline in stroke, the researchers carried out a randomized, open-label, evaluator-blinded study comparing 200 mg of minocycline given orally for 5 days with placebo. The therapeutic window was from 6 to 24 hours after the onset of stroke.
The primary outcome was change from baseline to day 90 on the National Institutes of Health Stroke Scale (NIHSS) with minocycline treatment vs placebo; secondary outcomes were a comparison of NIHSS scores on day 7 and day 30, and the modified Rankin Scale (mRS) and Barthel Index (BI) scores on days 7, 30, and 90.
Of 152 patients randomized, 74 received minocycline and 77 placebo. NIHSS scores at admission were similar between groups.
The pattern of benefit was apparent by days 7 and 30, they note. Deaths, myocardial infarction, recurrent strokes, and hemorrhagic transformations did not differ by treatment group.
Because there were some baseline differences between the groups, they repeated the primary analysis of NIHSS score at 90 days using an analysis of covariance with patient age, peptic ulcer disease, use of ACE inhibitors, sulfonylureas, and baseline NIHSS score as covariates. "The difference between groups remained significant and, in fact, the difference in means increased slightly after adjustment for the effect of these covariates," they write.
Confirmation of their results in a larger double-blind trial is needed, they conclude, as well as further research to refine the dose of minocycline; it was given in this study at a dosage with proven safety, but it is not known if this is an optimal dose, they note. Minocycline was given orally in this trial, but intravenous treatment might be more effective, the authors speculate. Finally, the time window for treatment was 6 to 24 hours, but earlier treatment may have different efficacy, they write.
Finding a Neuroprotectant That Works
Asked for comment by Medscape Neurology and Neurosurgery, Philip Gorelick, MD, from the University of Illinois College of Medicine at Chicago, said this study by Lampl et al "provides an exciting possibility for neuroprotection" and that "minocycline [is] a multipotential neuroprotectant in acute ischemic stroke. These early-phase study results suggest that this agent may be beneficial."
"It is too early to conclude, however, that the agent is efficacious in acute ischemic stroke; a large-scale study will be needed to prove the point," he adds. "As everyone knows, all prior studies have failed to definitively prove that neuroprotection in acute ischemic stroke is safe and effective. We look forward to the results of further testing of this agent in the hopes of finally finding a neuroprotectant that works."
The authors report no conflict of interest.
Neurology. 2007; 69:1404-1410.
Susan Jeffrey
Medscape Medical News 2007. © 2007 Medscape
October 1, 2007 — Results of a randomized open-label trial suggest that the use of minocycline 6 to 24 hours after an acute ischemic stroke is associated with significantly improved clinical outcomes.
"The improvement was already apparent within a week of the stroke," said study author Yair Lampl, MD, from the Edith Wolfson Medical Center and Tel Aviv University, Israel, in a statement from the American Academy of Neurology. "This is exciting because many people who have had stroke cannot be treated if they don't get to the hospital within 3 hours after symptoms start, which is the time frame for current available treatments."
However, he added, "while these are promising results, a much larger, closed-label study is needed to confirm our findings."
Their report appears in the October 2 issue of Neurology.
Neuroprotective Effects of Minocycline
Minocycline is a semisynthetic, second-generation derivative of tetracycline, and has been shown to have a "clear beneficial protective effect," in animal models of multiple sclerosis, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, as well as in stroke models, the authors write.
The proposed mechanism of benefit is thought to relate not to its antibiotic action but to its anti-inflammatory effects, a reduction in microglial activation, matrix metalloproteinase reduction, nitric oxide production, or inhibition of apoptotic cell death, they note.
To look more closely at the potential benefit of minocycline in stroke, the researchers carried out a randomized, open-label, evaluator-blinded study comparing 200 mg of minocycline given orally for 5 days with placebo. The therapeutic window was from 6 to 24 hours after the onset of stroke.
The primary outcome was change from baseline to day 90 on the National Institutes of Health Stroke Scale (NIHSS) with minocycline treatment vs placebo; secondary outcomes were a comparison of NIHSS scores on day 7 and day 30, and the modified Rankin Scale (mRS) and Barthel Index (BI) scores on days 7, 30, and 90.
Of 152 patients randomized, 74 received minocycline and 77 placebo. NIHSS scores at admission were similar between groups.
The pattern of benefit was apparent by days 7 and 30, they note. Deaths, myocardial infarction, recurrent strokes, and hemorrhagic transformations did not differ by treatment group.
Because there were some baseline differences between the groups, they repeated the primary analysis of NIHSS score at 90 days using an analysis of covariance with patient age, peptic ulcer disease, use of ACE inhibitors, sulfonylureas, and baseline NIHSS score as covariates. "The difference between groups remained significant and, in fact, the difference in means increased slightly after adjustment for the effect of these covariates," they write.
Confirmation of their results in a larger double-blind trial is needed, they conclude, as well as further research to refine the dose of minocycline; it was given in this study at a dosage with proven safety, but it is not known if this is an optimal dose, they note. Minocycline was given orally in this trial, but intravenous treatment might be more effective, the authors speculate. Finally, the time window for treatment was 6 to 24 hours, but earlier treatment may have different efficacy, they write.
Finding a Neuroprotectant That Works
Asked for comment by Medscape Neurology and Neurosurgery, Philip Gorelick, MD, from the University of Illinois College of Medicine at Chicago, said this study by Lampl et al "provides an exciting possibility for neuroprotection" and that "minocycline [is] a multipotential neuroprotectant in acute ischemic stroke. These early-phase study results suggest that this agent may be beneficial."
"It is too early to conclude, however, that the agent is efficacious in acute ischemic stroke; a large-scale study will be needed to prove the point," he adds. "As everyone knows, all prior studies have failed to definitively prove that neuroprotection in acute ischemic stroke is safe and effective. We look forward to the results of further testing of this agent in the hopes of finally finding a neuroprotectant that works."
The authors report no conflict of interest.
Neurology. 2007; 69:1404-1410.
Bigger Is Better, Except When It’s Not
By GINA KOLATA
LOOKING back, Dr. Michael Joyner thinks he chose the wrong sport when he became a distance runner. He should have been a swimmer or a rower.
Dr. Joyner, an anesthesiologist and exercise researcher at the Mayo Clinic, was fast — he ran a marathon in 2 hours 25 minutes. But, at 6-foot-5, and 175 pounds at his lightest, he was simply too big to be great.
It turns out that there are rules governed by physics to explain why the best distance runners look so different from the best swimmers or rowers and why being big is beneficial for some sports and not others.
That does not mean that parents should push their children into a sport based on their body type, exercise physiologists say. Most people who run or swim or do other sports, even competitively, do it because they love the sport, not because they are aiming for the Olympic Games. Many also choose a sport because they discover they are good at it.
For example, Dr. Niels H. Secher, an anesthesiologist, exercise researcher and rower at the University of Copenhagen, started rowing when he was 14. He always was big — he weighs 205 pounds — and he immediately loved to row and went with it. “If it works well, you think you are great and you follow up on your success,” he said.
But understanding why body size matters in certain sports can open your eyes to other possibilities, exercise researchers say.
“I’ve told people: ‘You’re tall. Why not try swimming?’” Dr. Joyner said. “Anything worth doing is worth doing well and anything worth keeping a score is worth posting a good score.”
The rules of physics say that distance cycling and distance running are for small people. Rowing and swimming are for people who are big. The physics is so exact that when Dr. Secher tried to predict how fast competitive rowers could go, based only on their sizes and the weights of their boats, he was accurate to within 1 percent.
At first glance, a big rower (and elite male rowers can weigh as much as 250 pounds) may seem to be at a disadvantage trying to row hard enough to push a boat through the water. But because water buoys the boat, weight becomes less of an issue compared with the enormous benefits of having strong muscles.
Their bigger muscles allow bigger people to use more oxygen, giving them more power. It’s like having a bigger motor, Dr. Secher said. Bigger muscles, with their larger cross-section, also are stronger. And bigger muscles can store more glycogen, their fuel for short intense spurts.
The same reasoning explains why elite swimmers are big. Great male swimmers often are 6 feet 4 inches tall, and muscular. And because of the advantage that large muscles give for sprints over short distances, the shorter the distance an athlete must swim, the greater the advantage it is to be big.
Tall swimmers also have another advantage: because swimmers are horizontal in the water, their long bodies give them an automatic edge. “It’s the difference between long canoes and short canoes,” Dr. Joyner said.
Distance running is different. Tall people naturally have longer strides, but stride length, it turns out, does not determine speed. Running requires that you lift your body off the ground with each step, propelling yourself forward. The more you weigh, the harder you have to work to lift your body and the slower you will be.
The best runners are small and light, with slim legs. “If you have large legs, you have to move a big load,” Dr. Secher said. “The smaller you are, the better you are.”
Of course, there are a few exceptions to the scaling rules. There was the Australian runner Derek Clayton, who weighed 160 pounds and set a world marathon mark in 1969.
And there is Tom Fleming (my coach) who won the New York City Marathon in 1973 and 1975. He is 6-foot-1, and while he ran his fastest marathon, 2 hours 12 minutes, weighing 159 pounds, he ran the Boston Marathon in 2 hours 14 minutes weighing 179 pounds. “I tell people that’s the fat-man record of Boston,” he said.
The tallest elite marathoner today, Robert Cheruiyot, is 6-foot-2. But he weighs only 143 pounds. Most elite male marathoners, Dr. Joyner notes, are between 5-foot-7 and 5-foot-11 and weigh between 120 and 140 pounds. In distance running, he said, “you just don’t find many big people.”
The situation is more complicated for triathletes, who must run and cycle and swim. The size that is best for running and cycling is not good for swimming. Yet in general, swimmers have an advantage, Dr. Secher said. It is easier for a great swimmer to learn cycling and running than for a good runner or cyclist to learn to be a good swimmer. Swimming, he says, is so dependent on technique that it is hard to become proficient as an adult.
The decision for high school coaches, said Hayden Smith, a cross-country coach at Albion College, is whether to say anything when a young teenager seems set on the wrong sport. He said he kept mum when he was coaching in high school. But, he added, the best high school athlete he ever coached initially went out for football. The football coach refused to let him join the team — he would not give the boy the equipment.
“He told the kid, ‘You’ll be a great runner,’” Mr. Smith recalled.
The coach was right. The boy started running and ended up one of the top 10 in the nation.
No one ever told Dr. Joyner not to run. Injuries, though, finally forced him to look for another sport. He chose swimming, knowing that his size would be to his advantage.
Dr. Joyner got a coach, worked hard on his technique, and recently ranked 15th swimming a mile in a United States Masters swimming championship race (for people over age 25) . He started too late, he said, to know what he might have been as a swimmer.
But that is O.K., Dr. Joyner said. He loved running. And there is more to performance than simply having the right sort of body for the sport. There is hard work and rigorous training, and, of course, there is motivation.
“I always remember something the late Bill Bowerman said at a clinic I attended in the late 1970s,” he added, referring to the legendary distance running coach. “Sometimes what matters is not what dog is in the fight but how much fight is in the dog.”
By GINA KOLATA
LOOKING back, Dr. Michael Joyner thinks he chose the wrong sport when he became a distance runner. He should have been a swimmer or a rower.
Dr. Joyner, an anesthesiologist and exercise researcher at the Mayo Clinic, was fast — he ran a marathon in 2 hours 25 minutes. But, at 6-foot-5, and 175 pounds at his lightest, he was simply too big to be great.
It turns out that there are rules governed by physics to explain why the best distance runners look so different from the best swimmers or rowers and why being big is beneficial for some sports and not others.
That does not mean that parents should push their children into a sport based on their body type, exercise physiologists say. Most people who run or swim or do other sports, even competitively, do it because they love the sport, not because they are aiming for the Olympic Games. Many also choose a sport because they discover they are good at it.
For example, Dr. Niels H. Secher, an anesthesiologist, exercise researcher and rower at the University of Copenhagen, started rowing when he was 14. He always was big — he weighs 205 pounds — and he immediately loved to row and went with it. “If it works well, you think you are great and you follow up on your success,” he said.
But understanding why body size matters in certain sports can open your eyes to other possibilities, exercise researchers say.
“I’ve told people: ‘You’re tall. Why not try swimming?’” Dr. Joyner said. “Anything worth doing is worth doing well and anything worth keeping a score is worth posting a good score.”
The rules of physics say that distance cycling and distance running are for small people. Rowing and swimming are for people who are big. The physics is so exact that when Dr. Secher tried to predict how fast competitive rowers could go, based only on their sizes and the weights of their boats, he was accurate to within 1 percent.
At first glance, a big rower (and elite male rowers can weigh as much as 250 pounds) may seem to be at a disadvantage trying to row hard enough to push a boat through the water. But because water buoys the boat, weight becomes less of an issue compared with the enormous benefits of having strong muscles.
Their bigger muscles allow bigger people to use more oxygen, giving them more power. It’s like having a bigger motor, Dr. Secher said. Bigger muscles, with their larger cross-section, also are stronger. And bigger muscles can store more glycogen, their fuel for short intense spurts.
The same reasoning explains why elite swimmers are big. Great male swimmers often are 6 feet 4 inches tall, and muscular. And because of the advantage that large muscles give for sprints over short distances, the shorter the distance an athlete must swim, the greater the advantage it is to be big.
Tall swimmers also have another advantage: because swimmers are horizontal in the water, their long bodies give them an automatic edge. “It’s the difference between long canoes and short canoes,” Dr. Joyner said.
Distance running is different. Tall people naturally have longer strides, but stride length, it turns out, does not determine speed. Running requires that you lift your body off the ground with each step, propelling yourself forward. The more you weigh, the harder you have to work to lift your body and the slower you will be.
The best runners are small and light, with slim legs. “If you have large legs, you have to move a big load,” Dr. Secher said. “The smaller you are, the better you are.”
Of course, there are a few exceptions to the scaling rules. There was the Australian runner Derek Clayton, who weighed 160 pounds and set a world marathon mark in 1969.
And there is Tom Fleming (my coach) who won the New York City Marathon in 1973 and 1975. He is 6-foot-1, and while he ran his fastest marathon, 2 hours 12 minutes, weighing 159 pounds, he ran the Boston Marathon in 2 hours 14 minutes weighing 179 pounds. “I tell people that’s the fat-man record of Boston,” he said.
The tallest elite marathoner today, Robert Cheruiyot, is 6-foot-2. But he weighs only 143 pounds. Most elite male marathoners, Dr. Joyner notes, are between 5-foot-7 and 5-foot-11 and weigh between 120 and 140 pounds. In distance running, he said, “you just don’t find many big people.”
The situation is more complicated for triathletes, who must run and cycle and swim. The size that is best for running and cycling is not good for swimming. Yet in general, swimmers have an advantage, Dr. Secher said. It is easier for a great swimmer to learn cycling and running than for a good runner or cyclist to learn to be a good swimmer. Swimming, he says, is so dependent on technique that it is hard to become proficient as an adult.
The decision for high school coaches, said Hayden Smith, a cross-country coach at Albion College, is whether to say anything when a young teenager seems set on the wrong sport. He said he kept mum when he was coaching in high school. But, he added, the best high school athlete he ever coached initially went out for football. The football coach refused to let him join the team — he would not give the boy the equipment.
“He told the kid, ‘You’ll be a great runner,’” Mr. Smith recalled.
The coach was right. The boy started running and ended up one of the top 10 in the nation.
No one ever told Dr. Joyner not to run. Injuries, though, finally forced him to look for another sport. He chose swimming, knowing that his size would be to his advantage.
Dr. Joyner got a coach, worked hard on his technique, and recently ranked 15th swimming a mile in a United States Masters swimming championship race (for people over age 25) . He started too late, he said, to know what he might have been as a swimmer.
But that is O.K., Dr. Joyner said. He loved running. And there is more to performance than simply having the right sort of body for the sport. There is hard work and rigorous training, and, of course, there is motivation.
“I always remember something the late Bill Bowerman said at a clinic I attended in the late 1970s,” he added, referring to the legendary distance running coach. “Sometimes what matters is not what dog is in the fight but how much fight is in the dog.”
Artificial-Joint Makers Settle Kickback Case
By BARNABY J. FEDER
Four of the nation’s biggest makers of artificial hips and knees have agreed to pay a total of $310 million in penalties to settle federal accusations that they used fake consulting agreements and other tactics to get surgeons to use their products.
Under the settlements, which were announced yesterday by the United States attorney in Newark, the four companies were charged with criminal conspiracy to violate anti-kickback laws. But they will not be prosecuted if they follow new compliance procedures under federal monitoring for 18 months.
“This industry routinely violated anti-kickback statutes by paying physicians for the purpose of exclusively using their products,” said Christopher J. Christie, the United States attorney in Newark. “Prior to our investigation, many orthopedic surgeons in this country made decisions predicated on how much money they could make — choosing which device to implant by going to the highest bidder.”
The fines will settle potential civil charges against the companies and preserve their ability to receive federal Medicare reimbursements. None of the companies admitted any wrongdoing.
A fifth big maker of orthopedic devices, Stryker Orthopedics, accepted federal supervision for 18 months. But the Justice Department agreed not to file criminal charges because Stryker was the first company to cooperate in the investigation, according to the government. The company admitted no wrongdoing.
Stryker Orthopedics, which is based in Mahwah, N.J., and is a unit of the Stryker Corporation of Kalamazoo, Mich., did not reach any settlement of potential civil charges. But Dean Bergy, Stryker’s chief financial officer, said the company was not aware of anything in connection with the investigation that might lead to civil charges or any restriction on Medicare reimbursements.
The other companies involved included Biomet; the DePuy Orthopaedics unit of Johnson & Johnson; and Zimmer Holdings, all based in Warsaw, Ind. The fourth was Smith & Nephew, a British company whose orthopedics subsidiary has headquarters in Memphis.
The government said the five companies represented 95 percent of the hip and knee implant market.
Although no doctors were cited in the settlements, the investigation is continuing, Mr. Christie said.
The inquiry began in March 2005 when Mr. Christie’s office sent subpoenas to the companies, requesting documents related to their consulting and “professional service” agreements with doctors from 2002 on. Later, the inquiry expanded backward into relationships with doctors starting in the late 1990s and included matters like the terms of research grants. Wall Street learned the investigation had reached the stage of preliminary settlement negotiations in a Biomet filing with the Securities and Exchange Commission in July.
Relationships between orthopedics companies and their customers are among the most complicated — and potentially conflicted — in health care. In contrast to drugs, which are typically developed in company laboratories, many orthopedic devices and related tools originate from inventions by doctors, who often retain a financial stake in their market success.
Even when devices are invented by companies, they are often extensively modified during development in consultation with leading doctors, whom the device companies then turn to for help in commercial application of the products and training other doctors to use them.
The costs of the devices are usually charged to a hospital or clinic rather than the surgeons, even though the surgeons have control over which are used. And while some orthopedic devices are highly specialized, others are mature products that vary little from company to company.
As a result, as surgeons select among devices, companies have strong incentive to court them with paid consulting agreements or other financial inducements.
The settlements allow the companies to continue to enter into product development agreements with doctors that reward them with royalties based on future sales. But the companies will be required to pay for consulting and other services on an hourly basis, with a cap of $500 an hour. Zimmer, the market leader in hips and knees, is paying $169.5 million to settle the civil charges. “Importantly, the resolution agreements clearly define how we and our key competitors will interact with physician collaborators, thereby establishing a standard of conduct across the industry,” said David Dvorak, Zimmer’s president and chief executive.
DePuy, which is paying $84.7 million, said in a news release that it “supports this agreement and the government’s efforts to further positive change throughout the industry.”
Smith & Nephew, paying $28.9 million, issued a statement from David Illingworth, its chief executive. “We are satisfied that the industrywide compliance program made uniform by this settlement will ensure continued, appropriate use of consultants,” Mr. Illingworth said.
Shares of all four public companies rose after the settlement announcement.
Biomet, which was fined $26.9 million, was acquired by private equity investors in an $11.4 billion deal that closed Tuesday. It no longer trades as a public stock.
“The dollar figures were a little higher than expected, but this is being viewed as a speeding ticket for these companies,” said Robin Young, a consultant and publisher of Orthopedics This Week, a newsletter.
Mr. Young said he happened to be running a panel at a conference in Warsaw on innovations in orthopedics when news of the settlement arrived. He said one theme in the ensuing discussion was that the government might now turn attention to smaller orthopedics companies. Those companies have been taking market share from the industry leaders and often have more extensive financial relationships with their customers than the industry leaders. Government scrutiny of those relationships could make it harder to snatch business from the bigger companies.
By BARNABY J. FEDER
Four of the nation’s biggest makers of artificial hips and knees have agreed to pay a total of $310 million in penalties to settle federal accusations that they used fake consulting agreements and other tactics to get surgeons to use their products.
Under the settlements, which were announced yesterday by the United States attorney in Newark, the four companies were charged with criminal conspiracy to violate anti-kickback laws. But they will not be prosecuted if they follow new compliance procedures under federal monitoring for 18 months.
“This industry routinely violated anti-kickback statutes by paying physicians for the purpose of exclusively using their products,” said Christopher J. Christie, the United States attorney in Newark. “Prior to our investigation, many orthopedic surgeons in this country made decisions predicated on how much money they could make — choosing which device to implant by going to the highest bidder.”
The fines will settle potential civil charges against the companies and preserve their ability to receive federal Medicare reimbursements. None of the companies admitted any wrongdoing.
A fifth big maker of orthopedic devices, Stryker Orthopedics, accepted federal supervision for 18 months. But the Justice Department agreed not to file criminal charges because Stryker was the first company to cooperate in the investigation, according to the government. The company admitted no wrongdoing.
Stryker Orthopedics, which is based in Mahwah, N.J., and is a unit of the Stryker Corporation of Kalamazoo, Mich., did not reach any settlement of potential civil charges. But Dean Bergy, Stryker’s chief financial officer, said the company was not aware of anything in connection with the investigation that might lead to civil charges or any restriction on Medicare reimbursements.
The other companies involved included Biomet; the DePuy Orthopaedics unit of Johnson & Johnson; and Zimmer Holdings, all based in Warsaw, Ind. The fourth was Smith & Nephew, a British company whose orthopedics subsidiary has headquarters in Memphis.
The government said the five companies represented 95 percent of the hip and knee implant market.
Although no doctors were cited in the settlements, the investigation is continuing, Mr. Christie said.
The inquiry began in March 2005 when Mr. Christie’s office sent subpoenas to the companies, requesting documents related to their consulting and “professional service” agreements with doctors from 2002 on. Later, the inquiry expanded backward into relationships with doctors starting in the late 1990s and included matters like the terms of research grants. Wall Street learned the investigation had reached the stage of preliminary settlement negotiations in a Biomet filing with the Securities and Exchange Commission in July.
Relationships between orthopedics companies and their customers are among the most complicated — and potentially conflicted — in health care. In contrast to drugs, which are typically developed in company laboratories, many orthopedic devices and related tools originate from inventions by doctors, who often retain a financial stake in their market success.
Even when devices are invented by companies, they are often extensively modified during development in consultation with leading doctors, whom the device companies then turn to for help in commercial application of the products and training other doctors to use them.
The costs of the devices are usually charged to a hospital or clinic rather than the surgeons, even though the surgeons have control over which are used. And while some orthopedic devices are highly specialized, others are mature products that vary little from company to company.
As a result, as surgeons select among devices, companies have strong incentive to court them with paid consulting agreements or other financial inducements.
The settlements allow the companies to continue to enter into product development agreements with doctors that reward them with royalties based on future sales. But the companies will be required to pay for consulting and other services on an hourly basis, with a cap of $500 an hour. Zimmer, the market leader in hips and knees, is paying $169.5 million to settle the civil charges. “Importantly, the resolution agreements clearly define how we and our key competitors will interact with physician collaborators, thereby establishing a standard of conduct across the industry,” said David Dvorak, Zimmer’s president and chief executive.
DePuy, which is paying $84.7 million, said in a news release that it “supports this agreement and the government’s efforts to further positive change throughout the industry.”
Smith & Nephew, paying $28.9 million, issued a statement from David Illingworth, its chief executive. “We are satisfied that the industrywide compliance program made uniform by this settlement will ensure continued, appropriate use of consultants,” Mr. Illingworth said.
Shares of all four public companies rose after the settlement announcement.
Biomet, which was fined $26.9 million, was acquired by private equity investors in an $11.4 billion deal that closed Tuesday. It no longer trades as a public stock.
“The dollar figures were a little higher than expected, but this is being viewed as a speeding ticket for these companies,” said Robin Young, a consultant and publisher of Orthopedics This Week, a newsletter.
Mr. Young said he happened to be running a panel at a conference in Warsaw on innovations in orthopedics when news of the settlement arrived. He said one theme in the ensuing discussion was that the government might now turn attention to smaller orthopedics companies. Those companies have been taking market share from the industry leaders and often have more extensive financial relationships with their customers than the industry leaders. Government scrutiny of those relationships could make it harder to snatch business from the bigger companies.
More Hollywood Studios Say ‘No Smoking’
By MICHAEL CIEPLY
LOS ANGELES, Sept. 30 — In the movie musical “Dreamgirls” last year, James “Thunder” Early, Eddie Murphy’s soul-singing, chain-smoking character, was so infuriated by a fumbled food order that he mashed his cigarette into a chicken sandwich that was supposed to have no mayonnaise.
That portrayal and scene could still fly these days at DreamWorks, which made the movie. But if Universal Pictures were to produce the movie today, Mr. Murphy might consider having his character switch to chewing gum.
The biggest studios are usually like-minded when it comes to what is fit to portray on screen. But they have become divided lately in confronting one of the entertainment industry’s touchiest issues: smoking in movies that reach the young.
Under pressure from an antismoking lobby unsatisfied by a promise that the industry’s trade group made in May to consider tobacco use as a factor in film ratings, the six largest studio owners have been patching together individual responses to those who want cigarettes out of films rated G, PG or PG-13.
Smoking opponents view the result as surprising progress toward a virtual ban on tobacco images in all but films with R or NC-17 ratings.
Yet Hollywood is also waking to the realization that a committed band of advocates is rapidly changing what is permissible in the movies. And that precedent could embolden other groups campaigning to rid movies of portrayals of gun use, transfat consumption or other behavior that can be proved harmful to the public.
“It’s a chilling idea,” said Bill Condon, who wrote and directed “Dreamgirls” for the DreamWorks and Paramount Pictures units of Viacom.
General Electric, the corporate parent of Universal Pictures, decided last April that, with few exceptions, “no smoking incidents should appear in any youth-rated film” produced by the studio or its sister units, Focus, Rogue and Working Title Films.
“Movies are supposed to reflect reality,” Mr. Condon said. “You’re taking away a detail that is one of the more defining aspects of a lifestyle.”
The extent to which depictions of smoking actually spur the young to smoke remains a subject of debate. Widely cited research by Dr. James A. Sargent of the Dartmouth Medical School showed a connection between adolescent exposure to smoking in movies and addiction to tobacco. But Dr. Deborah Glik, director of the Health and Media Research Group at the University of California, Los Angeles, said the connection appeared strongest among those who were already predisposed by other factors to smoke.
In any case, corporate Hollywood is in a hurry to find the right side of the issue. The companies are being prodded by a network of antismoking campaigners, some of them flush from Big Tobacco’s settlement with various state attorneys general, and already successful in much of the country in banning smoking in bars, restaurants and other public places.
The Rev. Michael Crosby, who coordinates antismoking efforts for the Interfaith Center on Corporate Responsibility, compared the state of play to a horse-race game in a carnival, with each company leaping past the other in recent months. “G.E. is now ahead,” said Mr. Crosby, who has been pressing the studios on the issue via shareholder resolutions and executive meetings for the last decade.
Before G.E. moved with what is widely regarded as the toughest antismoking policy to date, Time Warner had said it “strongly discourages” smoking in youth films produced by its Warner Brothers and New Line units, and seeks to limit smoking depictions in films marketed to what it called mixed audiences.
In July, the Walt Disney Company said it would ban smoking in its Disney-branded movies, like the “Pirates of the Caribbean” series, while trying to discourage tobacco use in youth-rated movies from its Miramax and Touchstone units. A spokesman for the Sony Corporation’s Sony Pictures Entertainment said the studio — which showed tobacco use in all three of its PG-13 rated “Spider-Man” films — has a policy under which it tries to discourage the depiction of tobacco products in youth-oriented films.
Viacom is meanwhile scrambling to devise a smoking policy of its own, having been assured two weeks ago by Mr. Crosby and his allies that it was increasingly out of step with its studio brethren. That warning came about because antismoking groups had recently discovered that the News Corporation and its 20th Century Fox Film division were already on the bandwagon, thanks to a strict though intentionally unpublicized policy of rooting tobacco out of youth-friendly films for the last three years.
Since 2004, the studio’s production manual has mandated that no principal character can be seen to smoke in a film set in contemporary times and to be rated G, PG or PG-13 unless the studio’s president of production signs off on the scene. Tobacco ads and promotions are not supposed to be visible in Fox movies. Even antismoking messages on screen are not to have been provided by tobacco companies.
The reduction of on-screen smoking is a pet project of the studio’s co-chairman, Tom Rothman, according to both Mr. Crosby and industry executives who requested anonymity because they did not want to offend a competitor or were not authorized to discuss the policy.
Yet Mr. Rothman has been reluctant to make a public issue of the studio’s policy, for fear that it might open the door to demands from groups with other causes, or put the studio at a competitive disadvantage with filmmakers who see blanket restrictions on smoking as threatening the credibility of their work.
Indeed, James L. Brooks, one of the most powerful filmmakers in Hollywood, was not stopped by that policy last year. His Gracie Films delivered the animated PG-13 rated “Simpsons Movie,” featuring enough tobacco (even in the trailer) to earn a “black lung” rating from the scenesmoking.org Web site, which monitors smoking impressions in movies.
Mr. Brooks and Fox executives did not respond to queries about why the smoking portrayals were allowed despite the policy.
Even the most aggressive studios have built wiggle room into their policies. To date, no company has said that it would bar smoking in the many films that are produced independently and later acquired for distribution by a studio. Thus, the hard-bitten, soft-hearted table server played by Cheryl Hines in the PG-13 rated “Waitress,” picked up by Mr. Rothman’s Fox Searchlight at the last Sundance Film Festival, can still wield a cigarette near the pregnant character played by Keri Russell.
Neither has any studio figured out how to deal with directors who may rely on their contractual right of “final cut” to include such scenes. Sony’s guidelines allow for exceptions if the scenes are needed for historical authenticity or to deliver an antismoking message. And even at G.E. and Universal, the policy says the presumption against a smoking scene can be “rebutted” based on its importance to the film, the difficulty of removing it, and whether or not the picture will be marketed to adolescents.
Advocates are naturally suspicious that such loopholes will only delay what they see as progress. “In about five years, they’ll live up to promises they’re making now,” said Michael Passoff, associate director of As You Sow, a socially responsible investment group based in San Francisco that has pressed studio owners on the smoking issue.
Eventually, the approach of the industry’s trade group, the Motion Picture Association of America — which relies on the ratings system to reduce tobacco impressions reaching the young — may diminish the need for individual solutions.
“This is still a new policy, and it’s going to take time to develop,” said Seth Oster, the association’s executive vice president and chief communications officer. Mr. Oster said 22 films have had warnings about smoking attached to their ratings since the system went into effect. And at least one film, “Saving Sarah Cain,” released by the News Corporation’s FoxFaith unit, has had its rating bumped to PG from G because it depicted tobacco use.
Some opponents of smoking on film see a chaos of individual policies as the prelude to an inevitable broad agreement to banish tobacco from all but adult-rated films.
“I think success is going to come very suddenly,” said Stanton A. Glantz, director of the Center for Tobacco Research and Education at the University of California, San Francisco, and whose proposal would led to an R rating for virtually all tobacco use in movies. “It will take the monkey off the individual companies’ backs.”
Edward J. Markey, Democrat of Massachusetts who is chairman of the House subcommittee on telecommunications and the Internet, said he would prefer to see an industrywide antismoking initiative, perhaps like the agreement in 2000 to limit the marketing of violent films, though he did not expect that to happen without further hearings.
Should an industrywide policy happen, of course, some young viewers might turn to entertainment they find less pinched, and more authentic. Not incidentally, the pilot episode of “quarterlife,” a new series about recent college graduates planned for direct distribution on the Web, concludes with a soulful discussion between two friends on a cigarette break.
Or, as Mr. Condon pointed out, the push for tobacco prohibition in film for the young might simply add new cachet to what is forbidden. “If they succeed, they may well glamorize smoking again,” he said.
By MICHAEL CIEPLY
LOS ANGELES, Sept. 30 — In the movie musical “Dreamgirls” last year, James “Thunder” Early, Eddie Murphy’s soul-singing, chain-smoking character, was so infuriated by a fumbled food order that he mashed his cigarette into a chicken sandwich that was supposed to have no mayonnaise.
That portrayal and scene could still fly these days at DreamWorks, which made the movie. But if Universal Pictures were to produce the movie today, Mr. Murphy might consider having his character switch to chewing gum.
The biggest studios are usually like-minded when it comes to what is fit to portray on screen. But they have become divided lately in confronting one of the entertainment industry’s touchiest issues: smoking in movies that reach the young.
Under pressure from an antismoking lobby unsatisfied by a promise that the industry’s trade group made in May to consider tobacco use as a factor in film ratings, the six largest studio owners have been patching together individual responses to those who want cigarettes out of films rated G, PG or PG-13.
Smoking opponents view the result as surprising progress toward a virtual ban on tobacco images in all but films with R or NC-17 ratings.
Yet Hollywood is also waking to the realization that a committed band of advocates is rapidly changing what is permissible in the movies. And that precedent could embolden other groups campaigning to rid movies of portrayals of gun use, transfat consumption or other behavior that can be proved harmful to the public.
“It’s a chilling idea,” said Bill Condon, who wrote and directed “Dreamgirls” for the DreamWorks and Paramount Pictures units of Viacom.
General Electric, the corporate parent of Universal Pictures, decided last April that, with few exceptions, “no smoking incidents should appear in any youth-rated film” produced by the studio or its sister units, Focus, Rogue and Working Title Films.
“Movies are supposed to reflect reality,” Mr. Condon said. “You’re taking away a detail that is one of the more defining aspects of a lifestyle.”
The extent to which depictions of smoking actually spur the young to smoke remains a subject of debate. Widely cited research by Dr. James A. Sargent of the Dartmouth Medical School showed a connection between adolescent exposure to smoking in movies and addiction to tobacco. But Dr. Deborah Glik, director of the Health and Media Research Group at the University of California, Los Angeles, said the connection appeared strongest among those who were already predisposed by other factors to smoke.
In any case, corporate Hollywood is in a hurry to find the right side of the issue. The companies are being prodded by a network of antismoking campaigners, some of them flush from Big Tobacco’s settlement with various state attorneys general, and already successful in much of the country in banning smoking in bars, restaurants and other public places.
The Rev. Michael Crosby, who coordinates antismoking efforts for the Interfaith Center on Corporate Responsibility, compared the state of play to a horse-race game in a carnival, with each company leaping past the other in recent months. “G.E. is now ahead,” said Mr. Crosby, who has been pressing the studios on the issue via shareholder resolutions and executive meetings for the last decade.
Before G.E. moved with what is widely regarded as the toughest antismoking policy to date, Time Warner had said it “strongly discourages” smoking in youth films produced by its Warner Brothers and New Line units, and seeks to limit smoking depictions in films marketed to what it called mixed audiences.
In July, the Walt Disney Company said it would ban smoking in its Disney-branded movies, like the “Pirates of the Caribbean” series, while trying to discourage tobacco use in youth-rated movies from its Miramax and Touchstone units. A spokesman for the Sony Corporation’s Sony Pictures Entertainment said the studio — which showed tobacco use in all three of its PG-13 rated “Spider-Man” films — has a policy under which it tries to discourage the depiction of tobacco products in youth-oriented films.
Viacom is meanwhile scrambling to devise a smoking policy of its own, having been assured two weeks ago by Mr. Crosby and his allies that it was increasingly out of step with its studio brethren. That warning came about because antismoking groups had recently discovered that the News Corporation and its 20th Century Fox Film division were already on the bandwagon, thanks to a strict though intentionally unpublicized policy of rooting tobacco out of youth-friendly films for the last three years.
Since 2004, the studio’s production manual has mandated that no principal character can be seen to smoke in a film set in contemporary times and to be rated G, PG or PG-13 unless the studio’s president of production signs off on the scene. Tobacco ads and promotions are not supposed to be visible in Fox movies. Even antismoking messages on screen are not to have been provided by tobacco companies.
The reduction of on-screen smoking is a pet project of the studio’s co-chairman, Tom Rothman, according to both Mr. Crosby and industry executives who requested anonymity because they did not want to offend a competitor or were not authorized to discuss the policy.
Yet Mr. Rothman has been reluctant to make a public issue of the studio’s policy, for fear that it might open the door to demands from groups with other causes, or put the studio at a competitive disadvantage with filmmakers who see blanket restrictions on smoking as threatening the credibility of their work.
Indeed, James L. Brooks, one of the most powerful filmmakers in Hollywood, was not stopped by that policy last year. His Gracie Films delivered the animated PG-13 rated “Simpsons Movie,” featuring enough tobacco (even in the trailer) to earn a “black lung” rating from the scenesmoking.org Web site, which monitors smoking impressions in movies.
Mr. Brooks and Fox executives did not respond to queries about why the smoking portrayals were allowed despite the policy.
Even the most aggressive studios have built wiggle room into their policies. To date, no company has said that it would bar smoking in the many films that are produced independently and later acquired for distribution by a studio. Thus, the hard-bitten, soft-hearted table server played by Cheryl Hines in the PG-13 rated “Waitress,” picked up by Mr. Rothman’s Fox Searchlight at the last Sundance Film Festival, can still wield a cigarette near the pregnant character played by Keri Russell.
Neither has any studio figured out how to deal with directors who may rely on their contractual right of “final cut” to include such scenes. Sony’s guidelines allow for exceptions if the scenes are needed for historical authenticity or to deliver an antismoking message. And even at G.E. and Universal, the policy says the presumption against a smoking scene can be “rebutted” based on its importance to the film, the difficulty of removing it, and whether or not the picture will be marketed to adolescents.
Advocates are naturally suspicious that such loopholes will only delay what they see as progress. “In about five years, they’ll live up to promises they’re making now,” said Michael Passoff, associate director of As You Sow, a socially responsible investment group based in San Francisco that has pressed studio owners on the smoking issue.
Eventually, the approach of the industry’s trade group, the Motion Picture Association of America — which relies on the ratings system to reduce tobacco impressions reaching the young — may diminish the need for individual solutions.
“This is still a new policy, and it’s going to take time to develop,” said Seth Oster, the association’s executive vice president and chief communications officer. Mr. Oster said 22 films have had warnings about smoking attached to their ratings since the system went into effect. And at least one film, “Saving Sarah Cain,” released by the News Corporation’s FoxFaith unit, has had its rating bumped to PG from G because it depicted tobacco use.
Some opponents of smoking on film see a chaos of individual policies as the prelude to an inevitable broad agreement to banish tobacco from all but adult-rated films.
“I think success is going to come very suddenly,” said Stanton A. Glantz, director of the Center for Tobacco Research and Education at the University of California, San Francisco, and whose proposal would led to an R rating for virtually all tobacco use in movies. “It will take the monkey off the individual companies’ backs.”
Edward J. Markey, Democrat of Massachusetts who is chairman of the House subcommittee on telecommunications and the Internet, said he would prefer to see an industrywide antismoking initiative, perhaps like the agreement in 2000 to limit the marketing of violent films, though he did not expect that to happen without further hearings.
Should an industrywide policy happen, of course, some young viewers might turn to entertainment they find less pinched, and more authentic. Not incidentally, the pilot episode of “quarterlife,” a new series about recent college graduates planned for direct distribution on the Web, concludes with a soulful discussion between two friends on a cigarette break.
Or, as Mr. Condon pointed out, the push for tobacco prohibition in film for the young might simply add new cachet to what is forbidden. “If they succeed, they may well glamorize smoking again,” he said.
Doctor’s Gender May Be Factor in Heart Diagnoses
By NICHOLAS BAKALAR
Conventional wisdom holds that coronary heart disease is an illness of older men, and that may be why doctors have difficulty diagnosing it in women. But do female doctors at least do a better job than male doctors? Apparently not, a new study finds.
The study, published online on Aug. 30 in Sociology of Health and Illness, did find significant differences in the ways male and female doctors diagnosed the illness. It reported that male doctors might be less biased by the gender and age of the patient being examined.
“We’re not trying to say that one group of doctors is better than another,” John B. McKinlay, the principal investigator said. “What we’re trying to do is for the first time describe and explain how much variability there is in doctors’ behavior when they look at exactly the same clinical presentation in different patients.”
The scientists videotaped professional actors portraying patients of varying gender, age, race and socioeconomic status who all had medically apparent symptoms of heart disease.
Then 112 male and female primary care doctors, half in Massachusetts and the rest in Britain, watched the videos. The physicians were asked to think of the patient as one of their own, make a diagnosis and suggest a treatment plan. Finally, they were asked to describe what factors they considered in arriving at their decisions.
Both male and female doctors picked up more psychological cues from female patients than from male patients. A characterization like “seemed very low" or “very depressed” was more likely to be made about a female patient than a male one.
Comments about a patient’s self-presentation like, “He doesn’t give a very cogent history,” or, “She’s a passive victim,” were more common among female doctors, and they made significantly more such observations of female patients.
Male doctors noticed fewer such cues in general, and only slightly more from male than female patients. This suggests that doctors, and especially female doctors, may be more sensitive to such information in patients of their own gender.
Even though older age is a significant risk factor for heart disease in both men and women, female doctors paid significantly less attention to female patients’ ages than those of males.
Dr. Alexandra J. Lansky, an associate professor of clinical medicine in cardiology at the Columbia University Medical Center who was not involved in the study, found the paper revealing.
“The old statement that female docs are better prepared to take care of female patients does not stand,” Dr. Lansky said. “Female docs are missing one big point that the male docs don’t miss, and that’s the age-related factor.”
Not all experts found the report convincing. “This study clearly says that female and male doctors approach the patient interview differently,” said Dr. Elizabeth A. Jackson, an assistant professor of medicine at the University of Michigan. “But they appear to have a similar knowledge base. This was not a real-life situation, and you can’t take conclusions from one study in isolation. I’d like to see if these results can be replicated.”
Dr. McKinlay, who is head of the New England Research Institutes in Watertown, Mass., said the study offered a new way to look at the disparities between men and women in treating coronary heart disease.
“A lot of the time,” he said, “health disparities have been explained by characteristics of the patient — race or economics, women versus men, older versus younger. But here the variability is explained by characteristics of the doctor.”
By NICHOLAS BAKALAR
Conventional wisdom holds that coronary heart disease is an illness of older men, and that may be why doctors have difficulty diagnosing it in women. But do female doctors at least do a better job than male doctors? Apparently not, a new study finds.
The study, published online on Aug. 30 in Sociology of Health and Illness, did find significant differences in the ways male and female doctors diagnosed the illness. It reported that male doctors might be less biased by the gender and age of the patient being examined.
“We’re not trying to say that one group of doctors is better than another,” John B. McKinlay, the principal investigator said. “What we’re trying to do is for the first time describe and explain how much variability there is in doctors’ behavior when they look at exactly the same clinical presentation in different patients.”
The scientists videotaped professional actors portraying patients of varying gender, age, race and socioeconomic status who all had medically apparent symptoms of heart disease.
Then 112 male and female primary care doctors, half in Massachusetts and the rest in Britain, watched the videos. The physicians were asked to think of the patient as one of their own, make a diagnosis and suggest a treatment plan. Finally, they were asked to describe what factors they considered in arriving at their decisions.
Both male and female doctors picked up more psychological cues from female patients than from male patients. A characterization like “seemed very low" or “very depressed” was more likely to be made about a female patient than a male one.
Comments about a patient’s self-presentation like, “He doesn’t give a very cogent history,” or, “She’s a passive victim,” were more common among female doctors, and they made significantly more such observations of female patients.
Male doctors noticed fewer such cues in general, and only slightly more from male than female patients. This suggests that doctors, and especially female doctors, may be more sensitive to such information in patients of their own gender.
Even though older age is a significant risk factor for heart disease in both men and women, female doctors paid significantly less attention to female patients’ ages than those of males.
Dr. Alexandra J. Lansky, an associate professor of clinical medicine in cardiology at the Columbia University Medical Center who was not involved in the study, found the paper revealing.
“The old statement that female docs are better prepared to take care of female patients does not stand,” Dr. Lansky said. “Female docs are missing one big point that the male docs don’t miss, and that’s the age-related factor.”
Not all experts found the report convincing. “This study clearly says that female and male doctors approach the patient interview differently,” said Dr. Elizabeth A. Jackson, an assistant professor of medicine at the University of Michigan. “But they appear to have a similar knowledge base. This was not a real-life situation, and you can’t take conclusions from one study in isolation. I’d like to see if these results can be replicated.”
Dr. McKinlay, who is head of the New England Research Institutes in Watertown, Mass., said the study offered a new way to look at the disparities between men and women in treating coronary heart disease.
“A lot of the time,” he said, “health disparities have been explained by characteristics of the patient — race or economics, women versus men, older versus younger. But here the variability is explained by characteristics of the doctor.”
Dengue fever surges in Latin America
By MICHAEL MELIA, Associated Press WriterSun Sep 30, 3:51 AM ET
Dengue fever is spreading across Latin America and the Caribbean in one of the worst outbreaks in decades, causing agonizing joint pain for hundreds of thousands of people and killing nearly 200 so far this year.
The mosquitoes that carry dengue are thriving in expanded urban slums scattered with water-collecting trash and old tires. Experts say dengue is approaching record levels this year as many countries enter their wettest months.
"If we do not slow it down, it will intensify and take a greater social and economic toll on these countries," said Dr. Jose Luis San Martin, head of anti-dengue efforts for the Pan American Health Organization, a regional public health agency.
The U.S. Centers for Disease Control and Prevention in Atlanta has posted advisories this year for people visiting Latin American and Caribbean destinations to use mosquito repellant and stay inside screened areas whenever possible.
"The danger is that the doctors at home don't recognize the dengue," said Dr. Wellington Sun, the chief of the CDC's dengue branch in San Juan. "The doctors need to raise their level of suspicion for any traveler who returns with a fever."
Dengue has already damaged the economies of countries across the region by driving away tourists, according to a document prepared for a PAHO conference beginning Monday in Washington.
Some countries have focused mosquito eradication efforts on areas popular with tourists. Mexico sent hundreds of workers to the resorts of Puerto Vallarta, Cancun and Acapulco this year to try to avert outbreaks.
Health ministers from across the region meet at the PAHO conference and San Martin said he will urge them to devote more resources to dengue fever.
The tropical virus was once thought to have been nearly eliminated from Latin America, but it has steadily gained strength since the early 1980s. Now, officials fear it could emerge as a pandemic similar to one that became a leading killer of children in Southeast Asia following World War II.
Officials say the virus is likely to grow deadlier in part because tourism and migration are circulating four different strains across the region. A person exposed to one strain may develop immunity to that strain — but subsequent exposure to another strain makes it more likely the person will develop the hemorrhagic form.
"The main concern is what's happening in the Americas will recapitulate what has happened in Southeast Asia, and we will start seeing more and more severe types of cases of dengue as time progresses," Sun said.
The disease — known as "bonebreak fever" because of the pain — can incapacitate patients for as long as a week with flu-like symptoms. A deadly hemorrhagic form, which also causes internal and external bleeding, accounts for less than 5 percent of cases but has shown signs of growing.
So far this year, 630,356 dengue cases have been reported in the Americas — most in Brazil, Venezuela, or Colombia — with 12,147 cases of hemorrhagic fever and 183 deaths, according to the Pan American Health Organization. With the spread expected to accelerate during the upcoming rainy season in many countries, cases this year could exceed the 1,015,000 reported in 2002, according to San Martin.
In Puerto Rico, where 5,592 suspected cases and three deaths have been reported, some lawmakers called this week for the health secretary to resign.
In the Dominican Republic, which has reported 25 deaths this year, the health department announced Thursday that it would train 2.5 million public school students to encourage parents and neighbors to eliminate standing water.
Researchers have not yet developed a vaccine against dengue and Sun said that for now, the only way to stop the virus is to contain the mosquito population — a task that relies of countless, relentless individual efforts including installing screen doors and making sure mosquitoes are not breeding in garbage.
"It's like telling people to stop smoking," he said. "They may do it for a while, but they don't do it on a consistent basis and without doing that, it's not effective."
While dengue is increasing around the developing world, the problem is most dramatic in the Americas, according to the CDC.
Health officials believe the resurgence of the malaria-like illness is due partly to a premature easing of eradication programs in the 1970s.
Migration and tourism also have carried new strains of the virus across national borders, even into the United States, which had largely wiped out the disease after a 1922 outbreak that infected a half-million people.
Mexico has been struggling with an alarming increase in the deadly hemorrhagic form of dengue, which now accounts for roughly one in four cases. The government has confirmed 3,249 cases of hemorraghic dengue for the year through Sept. 15, up from 1,924 last year.
The CDC says there is no drug to treat hemorrhagic dengue, but proper treatment, including rest, fluids and pain relief, can reduce death rates to about 1 percent.
San Martin said he use the meetings starting Monday to urge enforcement of trash disposal regulations, more investment in mosquito control and new incentives for communities to participate.
"It is a battle of every government, every community and every individual," he said.
By MICHAEL MELIA, Associated Press WriterSun Sep 30, 3:51 AM ET
Dengue fever is spreading across Latin America and the Caribbean in one of the worst outbreaks in decades, causing agonizing joint pain for hundreds of thousands of people and killing nearly 200 so far this year.
The mosquitoes that carry dengue are thriving in expanded urban slums scattered with water-collecting trash and old tires. Experts say dengue is approaching record levels this year as many countries enter their wettest months.
"If we do not slow it down, it will intensify and take a greater social and economic toll on these countries," said Dr. Jose Luis San Martin, head of anti-dengue efforts for the Pan American Health Organization, a regional public health agency.
The U.S. Centers for Disease Control and Prevention in Atlanta has posted advisories this year for people visiting Latin American and Caribbean destinations to use mosquito repellant and stay inside screened areas whenever possible.
"The danger is that the doctors at home don't recognize the dengue," said Dr. Wellington Sun, the chief of the CDC's dengue branch in San Juan. "The doctors need to raise their level of suspicion for any traveler who returns with a fever."
Dengue has already damaged the economies of countries across the region by driving away tourists, according to a document prepared for a PAHO conference beginning Monday in Washington.
Some countries have focused mosquito eradication efforts on areas popular with tourists. Mexico sent hundreds of workers to the resorts of Puerto Vallarta, Cancun and Acapulco this year to try to avert outbreaks.
Health ministers from across the region meet at the PAHO conference and San Martin said he will urge them to devote more resources to dengue fever.
The tropical virus was once thought to have been nearly eliminated from Latin America, but it has steadily gained strength since the early 1980s. Now, officials fear it could emerge as a pandemic similar to one that became a leading killer of children in Southeast Asia following World War II.
Officials say the virus is likely to grow deadlier in part because tourism and migration are circulating four different strains across the region. A person exposed to one strain may develop immunity to that strain — but subsequent exposure to another strain makes it more likely the person will develop the hemorrhagic form.
"The main concern is what's happening in the Americas will recapitulate what has happened in Southeast Asia, and we will start seeing more and more severe types of cases of dengue as time progresses," Sun said.
The disease — known as "bonebreak fever" because of the pain — can incapacitate patients for as long as a week with flu-like symptoms. A deadly hemorrhagic form, which also causes internal and external bleeding, accounts for less than 5 percent of cases but has shown signs of growing.
So far this year, 630,356 dengue cases have been reported in the Americas — most in Brazil, Venezuela, or Colombia — with 12,147 cases of hemorrhagic fever and 183 deaths, according to the Pan American Health Organization. With the spread expected to accelerate during the upcoming rainy season in many countries, cases this year could exceed the 1,015,000 reported in 2002, according to San Martin.
In Puerto Rico, where 5,592 suspected cases and three deaths have been reported, some lawmakers called this week for the health secretary to resign.
In the Dominican Republic, which has reported 25 deaths this year, the health department announced Thursday that it would train 2.5 million public school students to encourage parents and neighbors to eliminate standing water.
Researchers have not yet developed a vaccine against dengue and Sun said that for now, the only way to stop the virus is to contain the mosquito population — a task that relies of countless, relentless individual efforts including installing screen doors and making sure mosquitoes are not breeding in garbage.
"It's like telling people to stop smoking," he said. "They may do it for a while, but they don't do it on a consistent basis and without doing that, it's not effective."
While dengue is increasing around the developing world, the problem is most dramatic in the Americas, according to the CDC.
Health officials believe the resurgence of the malaria-like illness is due partly to a premature easing of eradication programs in the 1970s.
Migration and tourism also have carried new strains of the virus across national borders, even into the United States, which had largely wiped out the disease after a 1922 outbreak that infected a half-million people.
Mexico has been struggling with an alarming increase in the deadly hemorrhagic form of dengue, which now accounts for roughly one in four cases. The government has confirmed 3,249 cases of hemorraghic dengue for the year through Sept. 15, up from 1,924 last year.
The CDC says there is no drug to treat hemorrhagic dengue, but proper treatment, including rest, fluids and pain relief, can reduce death rates to about 1 percent.
San Martin said he use the meetings starting Monday to urge enforcement of trash disposal regulations, more investment in mosquito control and new incentives for communities to participate.
"It is a battle of every government, every community and every individual," he said.
Panic attacks may hike heart attack risk
By CARLA K. JOHNSON, Associated Press WriterMon Oct 1, 4:06 PM ET
The rapid pulse and shortness of breath of a panic attack can feel like a heart attack, and it may signal heart trouble down the road, a study of more than 3,000 older women suggests.
Women who reported at least one full-blown panic attack during a six-month period were three times more likely to have a heart attack or stroke over the next five years than women who didn't report a panic attack.
The researchers took into account other risk factors such as smoking, high blood pressure, inactivity and depression and still found that panic attacks raised risk.
The findings add panic attacks to a list of mental health issues — depression, fear, hostility and anxiety — already linked in previous research to heart problems, said study co-author Dr. Jordan Smoller of Boston's Massachusetts General Hospital.
"Postmenopausal women who are experiencing panic attacks may be a subgroup with elevated risk," Smoller said. "Monitoring them and reducing their cardiovascular risk may be important."
The study, published in Monday's Archives of General Psychiatry, wasn't designed to explain the link, Smoller said. He speculated that a panic attack may trigger heart rhythm problems or that stress hormones released during an attack may harm the heart.
The findings don't surprise Susie Rissler, 51, of Terre Haute, Ind. A panic attack sufferer since childhood, she's also has had three mini-strokes.
"You feel like the whole world is caving in," Rissler said of her panic attacks, which can include a racing heartbeat and chest pains. "I've had shaking, sweating, curling up in a ball totally afraid to even look around. Panic attacks can really destroy a person in a lot of different ways."
Some of the reported panic symptoms may have been heart problems in disguise, Smoller said. Symptoms such as racing heart, chest pain or shortness of breath, experienced as a panic attack, may have been caused by an undiagnosed heart problem.
"One study doesn't settle a question," he cautioned. "The number of events seen in this sample is still relatively small." Forty-one of the 3,243 women in the analysis had a heart attack or death from a heart problem. An additional 40 had strokes.
The study, which enrolled women from 1997-2000 and followed them for five years, was funded by the drug company Glaxo Wellcome, which is now GlaxoSmithKline PLC. The company makes Paxil, an anti-anxiety drug. Some of the study's co-authors reported financial ties to that company and others.
The research relied on the women's memories, rather than doctors' diagnoses, which could be considered a weakness of the study, said Dr. JoAnn Manson of Harvard's Brigham and Women's Hospital. But Manson, who wasn't involved in the study, said it's likely the findings point to a real connection between panic and heart problems.
"It does tie together very well with what we know about the biology and physiology of the stress hormones," Manson said. "I think it does suggest that this is something to discuss with your doctor" for women prone to panic attacks.
Previous research has found that panic attacks are more common in women than in men. The researchers found that 330 of the women, ages 51 to 83 years at the start of the study, reported a full-blown panic attack during the previous six months. Of those, about 4 percent, went on to have a heart attack or stroke. That compares with 2 percent of the women who reported no panic attacks but who had heart attacks or strokes.
Once the researchers adjusted for other health factors, they found the heart and stroke risk three times greater among women who had panic attacks.
A full-blown attack was defined as a sudden attack of fear, anxiety or discomfort accompanied by at least four of 12 symptoms, such as shortness of breath.
Laura Kubzansky of the Harvard School of Public Health, who wasn't involved in the new study but does similar research, said stress hormones may cause immediate heart damage or wear-and-tear over time. During panic, "the body is flooded with hormones that in the short run help the body cope with an emergency, but in the long run take a toll," she said.
While treating panic with medication may help some people with the psychological distress, there's no evidence yet that medication alone reduces heart risk, Kubzansky said.
"We still don't know how best to address this or how reversible these effects are," Kubzansky said.
___
On the Net:
Archives of General Psychiatry: http://archpsyc.ama-assn.org/
By CARLA K. JOHNSON, Associated Press WriterMon Oct 1, 4:06 PM ET
The rapid pulse and shortness of breath of a panic attack can feel like a heart attack, and it may signal heart trouble down the road, a study of more than 3,000 older women suggests.
Women who reported at least one full-blown panic attack during a six-month period were three times more likely to have a heart attack or stroke over the next five years than women who didn't report a panic attack.
The researchers took into account other risk factors such as smoking, high blood pressure, inactivity and depression and still found that panic attacks raised risk.
The findings add panic attacks to a list of mental health issues — depression, fear, hostility and anxiety — already linked in previous research to heart problems, said study co-author Dr. Jordan Smoller of Boston's Massachusetts General Hospital.
"Postmenopausal women who are experiencing panic attacks may be a subgroup with elevated risk," Smoller said. "Monitoring them and reducing their cardiovascular risk may be important."
The study, published in Monday's Archives of General Psychiatry, wasn't designed to explain the link, Smoller said. He speculated that a panic attack may trigger heart rhythm problems or that stress hormones released during an attack may harm the heart.
The findings don't surprise Susie Rissler, 51, of Terre Haute, Ind. A panic attack sufferer since childhood, she's also has had three mini-strokes.
"You feel like the whole world is caving in," Rissler said of her panic attacks, which can include a racing heartbeat and chest pains. "I've had shaking, sweating, curling up in a ball totally afraid to even look around. Panic attacks can really destroy a person in a lot of different ways."
Some of the reported panic symptoms may have been heart problems in disguise, Smoller said. Symptoms such as racing heart, chest pain or shortness of breath, experienced as a panic attack, may have been caused by an undiagnosed heart problem.
"One study doesn't settle a question," he cautioned. "The number of events seen in this sample is still relatively small." Forty-one of the 3,243 women in the analysis had a heart attack or death from a heart problem. An additional 40 had strokes.
The study, which enrolled women from 1997-2000 and followed them for five years, was funded by the drug company Glaxo Wellcome, which is now GlaxoSmithKline PLC. The company makes Paxil, an anti-anxiety drug. Some of the study's co-authors reported financial ties to that company and others.
The research relied on the women's memories, rather than doctors' diagnoses, which could be considered a weakness of the study, said Dr. JoAnn Manson of Harvard's Brigham and Women's Hospital. But Manson, who wasn't involved in the study, said it's likely the findings point to a real connection between panic and heart problems.
"It does tie together very well with what we know about the biology and physiology of the stress hormones," Manson said. "I think it does suggest that this is something to discuss with your doctor" for women prone to panic attacks.
Previous research has found that panic attacks are more common in women than in men. The researchers found that 330 of the women, ages 51 to 83 years at the start of the study, reported a full-blown panic attack during the previous six months. Of those, about 4 percent, went on to have a heart attack or stroke. That compares with 2 percent of the women who reported no panic attacks but who had heart attacks or strokes.
Once the researchers adjusted for other health factors, they found the heart and stroke risk three times greater among women who had panic attacks.
A full-blown attack was defined as a sudden attack of fear, anxiety or discomfort accompanied by at least four of 12 symptoms, such as shortness of breath.
Laura Kubzansky of the Harvard School of Public Health, who wasn't involved in the new study but does similar research, said stress hormones may cause immediate heart damage or wear-and-tear over time. During panic, "the body is flooded with hormones that in the short run help the body cope with an emergency, but in the long run take a toll," she said.
While treating panic with medication may help some people with the psychological distress, there's no evidence yet that medication alone reduces heart risk, Kubzansky said.
"We still don't know how best to address this or how reversible these effects are," Kubzansky said.
___
On the Net:
Archives of General Psychiatry: http://archpsyc.ama-assn.org/
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