Friday, November 30, 2007

Cancer Patients Gain From Reporting Symptoms Online

2 hours, 21 minutes ago
FRIDAY, Nov. 30 (HealthDay News) -- Having cancer patients report to doctors on their symptoms and side effects online may improve their care, a new study finds.
Even the sickest cancer patients are willing and capable of reporting their symptoms online, says a team from Memorial Sloan-Kettering Cancer Center in New York City.
"Cancer care has become increasingly complex, causing office visits to become more compressed. This makes it challenging for the clinician to comprehensively assess each patient's symptoms in that brief window of time," study author Dr. Ethan Basch, a medical oncologist, said in a prepared statement.
"Because cancer therapies can be highly toxic, early detection of symptoms and timely treatment is vital. What is exciting to us about online self-reporting is that patients can alert clinicians to crucial symptoms in real time," Basch said.
The study included 107 lung cancer patients receiving outpatient chemotherapy who had access to a secure Internet patient reporting system developed by Basch and his colleagues. The patients were able to access the Symptom Tracking and Reporting (STAR) site using computers in waiting room kiosks and at home to report cancer symptoms and chemotherapy-related side effects.
The patients were followed for up to 16 months and 40 visits. All of the patients used the waiting room kiosks at some or all of their office visits, and an average of 78 percent logged onto the system at any given office visit. Patients were more likely to use STAR if they had prior computer experience.
The study found that 98 percent of patients found STAR easy to use, 90 percent said it was useful, and 77 percent believed it improved the quality of their discussions with clinicians.
The study appears in the Dec. 1 issue of the Journal of Clinical Oncology.
More information
The U.S. National Cancer Institute has more about coping with cancer.
Working the nightshift may cause cancer, say WHO researchers

1 hour, 37 minutes ago
Women who do night work for long periods face a higher risk of breast cancer compared to counterparts who work only in the daytime, according to a World Health Organisation (WHO) cancer report released on Friday.
In an overview of work-related cancer risk, researchers say that "circadian disruption" is "probably carcinogenic" while painters and firefighters are also exposed to carcinogenic hazard through their work.
The report is issued by a working group of the International Agency for Research on Cancer (IARC), a unit of the World Health Organisation (WHO).
Their assessment, based on a review of published epidemiological studies, will appear in the December issue of The Lancet, the IARC said in a press statement.
IARC said that night work is "probably carcinogenic," a term that means there is limited evidence of cancers in humans but sufficient evidence of cancers in lab animals.
The data in this field is based on incidence of breast cancers among nurses and flight attendants, backed by animal studies which show that constant light, dim light at night or simulated jet lag substantially boost tumour development.
One of the authors, Vincent Cogliano, said that the studies among the working women showed that shiftwork posed a less than twofold increase in risk.
"It is a real risk but one that epidemiologists would describe as a modest one," he told AFP.
Cogliano added that the risk for other professions and for other cancers was unclear but noted that nearly 20 percent of the working population in Europe and North America was engaged in shiftwork of some kind.
One possible cause for the increased risk is that the circadian system is disrupted by exposure to light at night.
This alters sleep activity patterns, suppresses production of the hormone melatonin and disregulates genes that control tumour development.
Among painters, occupational exposure to chemical solvents, pigments, additives and fine dust or asbestos is linked to "small but significant" increases in the risk of lung cancer and bladder cancer, the IARC said.
For firefighters, occupational exposure from chemicals, smoke and particles is considered "possibly carcinogenic," meaning that there is limited evidence of carcinogenicity in humans and less than sufficient evidence of this in lab animals.
The paper is published under the IARC's "Monographs Programme," in which the agency identifies environmental factors that boost the risk of cancer, thus providing policymakers and regulators with scientific evidence to support decisions on health and safety.
Long-term improvement seen with hip replacement

Total hip arthroplasty (THA), or hip replacement, is an effective treatment for osteoarthritis (OA), but most studies have only followed patients for up to one year. A new study published in the December issue of Arthritis Care & Research ( examined patients after an average of eight years following hip replacement and found a long-term positive impact on their physical functioning.
Led by Professor Cyrus Cooper and Ms. Janet Cushnaghan of the University of Southampton in Southampton, UK, the study included 282 patients from two English health districts who had OA and were placed on the waiting list for a hip replacement between 1993 and 1995. It also included 295 matched controls from the general population. At the start of the study patients were interviewed about hip injury, pain, physical function, vitality and mental health. In addition, their BMI was calculated, their hands were examined for Heberden’s nodes, an indication of OA, and their hip X-rays were evaluated for severity of OA. Between 2001 and 2004, they completed a self-administered questionnaire asking if and when they had undergone hip replacement, as well as questions about their physical function, vitality and mental health. Follow-up of the patients took place an average of eight years following hip replacement.
The results showed that patients who were waiting for a hip replacement had markedly worse physical functioning than the controls but only small differences in vitality and mental health at the start of the study. By the time of the follow-up, the physical functioning of the OA patients had improved (while that of the controls had deteriorated) but their vitality had deteriorated. In addition, better physical functioning at the start of the study was associated with a greater decline at follow-up, but higher BMI seemed to have no impact. Those with more severe OA according to their X-rays showed the most improvement in physical functioning.
“Our findings are consistent with a sustained beneficial impact on physical functioning following THA for OA, but we found no evidence for parallel improvement in vitality or mental health,” Professor Cooper stated. The researchers noted that the study is limited because it was an observational investigation as opposed to a randomized controlled trial and information about the patients’ disease and surgical procedures was limited. But this weakness was offset by the fact that the study had a long follow-up interval and a relatively large number of patients and controls. “Even when allowance is made for possible confounding effects, the long-term improvement in the physical functioning of the cases is striking when set against the decline that occurred in controls,” the authors note, suggesting that the benefits of hip replacement are substantial and long-lasting.
Although some previous studies have suggested that hip replacement benefits mental health as well, the current study did not find this to be the case, possibly because the mental health status of the patients at the beginning of the study was no different from the control group, even though they had greater physical limitations. Regarding the finding that BMI did not affect long-term physical functioning, the authors suggest that surgeons are perhaps careful in selecting obese patients for this procedure, but in any case a BMI in the range of up to 30 should not be a deterrent to hip replacement as long as the patient is healthy enough to undergo surgery.
The authors conclude that the study adds to the accumulating evidence of the long-term benefits of hip replacement, especially in patients with more severe changes seen on X-rays, and that perhaps these patients should be given higher priority for the procedure.
Osteoarthritis Singled Out as Cause of Meniscal Damage and Knee Pain

BOSTON, Nov. 29 -- In older patients, osteoarthritis causes both knee pain and damage to the meniscus, according to researchers here.
Action Points
Explain to patients that knee stiffness and pain in older individuals are probably caused by osteoarthritis rather than by damage to the meniscus.
Explain that meniscus damage may also be caused by osteoarthritis.
Meniscal damage is not directly linked to knee pain, aching, and stiffness but, rather, both are related to osteoarthritis, Martin Englund, M.D., Ph.D., of Boston University, and colleagues reported in the December issue of Arthritis & Rheumatism.
In the U.S., 11% to 15% of men and women 65 and older have osteoarthritis of the knee manifesting in pain, aching, and stiffness.
Associated with aging, obesity, and sport injuries, tears to the menisci are a common MRI finding, especially in an osteoarthritic knee. However, whether meniscal damage foreshadows knee pain from another source or directly causes it has not been known, the researchers said.
To help improve the early detection of osteoarthritis, researchers with the Multicenter Osteoarthritis Study set out to evaluate the effect of meniscal damage on the development of knee pain, aching, and stiffness in a randomized prospective study of 3,026 individuals ages 50 to 79 who had a high risk of developing osteoarthritis of the knee.
Participants included men and women and white and ethnic minorities recruited from Alabama and Iowa. Knees were studied at baseline and at 15 months.
Case knees (110) were drawn randomly from patients with no frequent symptoms on most days at baseline but who developed frequent pain and stiffness in one or both knees at 15 months.
Control knees (220) were drawn randomly from patients with no frequent symptoms at baseline or at 15 months.
After MRI studies at baseline and 15 months, two musculoskeletal radiologists blinded to the individuals' status assessed meniscal damage using the following scale: 0=intact, 1=minor tear, 2=nondisplaced tear or prior surgical repair, and 3=displaced tear, resection, maceration, or destruction.
Finally, the effect of meniscal damage on the development of frequent knee pain was studied with contingency table and logistic regression analysis.
At baseline, meniscal damage was common in both case knees (38%) and in control knees (29%), with a higher frequency among women.
There was a modest association between the meniscal damage score (range 0-3) and the development of frequent knee pain, aching, or stiffness (odds ratio: 1.21, 95% CI: 0.96 to 1.51), adjusted for age, sex, and body mass index.
However, meniscal damage was present mostly in knees with radiographic evidence of osteoarthritis as measured by Kellgren/Lawrence grade.
For K/L grade 3 or greater, meniscal damage was present in 82%, for grade K/L grade 2, in 39%, and for grade 1, in 26%. Osteoarthritis was considered to be present for grade 2 or greater.
In a stratified analysis, the researchers found no independent association between meniscal damage and the development of frequent knee symptoms.
Meniscal damage in older adults is highly associated with osteoarthritis of the knee, Dr. Englund wrote. However, he added, meniscal damage often seems not to be directly responsible for later pain and stiffness symptoms. Other features of osteoarthritis may be responsible.
It is conceivable, he said, that certain types of meniscal lesion may be directly responsible for knee pain, particularly during the early stages of certain types of tears. Still, he noted, the high prevalence of meniscal damage in the older adult knee and the weak association with knee symptoms suggest that any such discomfort may be self-limited and can be treated conservatively.
The study had certain important limitations, the investigators said, including its limited sample size and the need to collapse various types of meniscal damage into a few categories for statistical analysis.
Also, they said, the relationship between site of damage or type of lesion and knee symptoms requires further study.
Stressing the importance of treating osteoarthritis as a whole-joint disorder, Dr. England said that this study calls attention to the risk of misinterpreting meniscal damage as the direct cause of knee pain.
However, he added, basic prevalence data of meniscal lesions and their association with knee symptoms in the general population of older adults remain to be explained.
This study was supported by grants from the National Institute on Aging. Dr. Englund's work was supported by the Arthritis Foundation.
Primary source: Arthritis & RheumatismSource reference: Englund M, et al "Effect of meniscal damage on the development of frequent knee pain, aching, or stiffness" Arthritis & Rheumatism 2007; 56: 4048-4054.
Insulin-Sensitizing Metformin Treatment Not Linked to Higher Rate of Fractures

November 29, 2007 — Insulin-sensitizing treatment with metformin is not associated with a higher incidence of bone fractures, but current treatment with insulin increases the risk for fractures, according to the results of a nested case-control study reported in the November 16 Online First issue of Diabetes Care. However, in the long-term, insulin treatment did not affect bone frailty.
"Hypoglycaemic treatments could modulate the risk for fractures in many ways," write Edoardo Mannucci, MD, from the University of Florence and Azienda Ospedaliero-Universitaria Careggi in Florence, Italy, and colleagues. "Most studies have not explored the effect on the incidence of bone fractures of individual oral hypoglycaemic agents, considering all oral treatments only as a whole. Aim of this case-control study, nested within a retrospective cohort, is the assessment of the risk for bone fractures associated with exposure to insulin or different oral hypoglycaemic agents."
Within a cohort of 1945 outpatients with diabetes with a follow-up of 4.1 ± 2.3 years, this nested case-control study compared 83 cases of bone fractures and 249 controls matched for age, sex, duration of diabetes, body mass index, levels of hemoglobin A1c, comorbidity, smoking, and alcohol abuse. The investigators determined exposure to hypoglycemic drugs during the 10 years preceding the event or the matching index date.
A model that included treatment with insulin-secretagogues, metformin, and insulin for at least 36 months during the previous 10 years showed no significant association between bone fractures and medication use. An alternative model considering treatments at the time of fracture showed that insulin treatment was significantly associated with bone fractures in men (odds ratio [OR], 3.20; 95% confidence interval [CI], 1.32 - 7.74) but not in women (OR, 1.41; 95% CI, 0.73 - 2.73).
"Insulin-sensitizing treatment with metformin is not associated with a higher incidence of bone fractures, suggesting that the negative effect of thiazolidinediones is due to a specific action on bone metabolism, rather than to reduction of insulinemia," the study authors write. "Conversely, current treatment with insulin increases the risk of fractures; at the same time, exposure to this agent in the longer term does not appear to affect bone frailty."
Limitations of the study include very few patients receiving thiazolidinediones, preventing separate analysis for each agent; lack of a statistically significant effect of metformin possibly because of insufficient sample size; diagnosis of bone fractures obtained through coded diagnoses at hospital discharge; distinction among spontaneous, traumatic, and indeterminate fractures not considered; lack of data on bone density and frequency of falls; treatments affecting bone metabolism (eg, bisphosphonates, vitamin D, and calcium supplementation) not considered; and possible misclassification of treatments.
"Bone fractures deserve to be considered among treatment outcomes for the choice of hypoglycemic medication, particularly in older patients with type 2 diabetes," the study authors conclude.
Diabetes Care. Published online November 16, 2007.
Diabetes, Low HDL, High Homocysteine Levels Predict Poorer Stroke Recovery

November 29, 2007 — Vascular risk factors associated with metabolic stress, including diabetes, low levels of high-density lipoprotein (HDL) cholesterol, and elevated levels of homocysteine predict slower stroke recovery, new research suggests.
The study found that individuals with diabetes, low levels of HDL cholesterol, and high levels of homocysteine who have had a mild to moderate ischemic stroke were twice as likely as their counterparts without these conditions to have poorer cognitive function and greater disability after a stroke.
The researchers also found that recovery was most difficult in individuals older than age 57 years with high total plasma levels of homocysteine.
"The first thing we realized [from the results] is that the dominant influence in the study is recovery, so that in general patients tend to improve after a stroke. However, there were certain factors that significantly slowed the effects of natural recovery, such that not everyone was recovering at the same rate," the study's lead author George C. Newman, MD, PhD, of the Albert Einstein Healthcare Network in Philadelphia, Pennsylvania, told Medscape Neurology & Neurosurgery.
The study is published in the November 27 issue of Neurology.
Mechanism Unclear
Although the mechanism by which these factors impede recovery is not clear, Dr. Newman speculated that oxidative stress may impair endothelial function in the central nervous system or directly affect neuronal function by a complex interaction of several metabolic and inflammatory pathways.
The study is a post hoc analysis of the Vitamin Intervention for Stroke Prevention (VISP), a randomized controlled trial designed to determine whether lowering total plasma levels of homocysteine with large doses of folic acid, pyridoxine, and vitamin B12 would reduce the incidence of recurrent stroke or myocardial infarction.
The original study showed no impact of moderate reductions of levels of homocysteine with vitamin supplementation on recurrent stroke, myocardial infarction, or death at 2-year follow-up. However, the study did establish elevated levels of homocysteine as a vascular risk factor.
"We know it was possible to lower serum homocysteine through large doses of B12, B6, and folate, so the question was would this reduce the risk of heart attack and stroke. The answer was no. The interpretation of this is that it is not the homocysteine itself that injures the blood vessels but that it is a marker for some other process that increases heart attack and stroke risk," said Dr. Newman.
Using the information from the VISP database, the investigators in the current analysis examined the hypothesis that vascular risk factors associated with oxidative stress were also associated with a slower recovery of cognitive function after a stroke.
Rich Database
To conduct the post hoc analysis, Dr. Newman's team mined the VISP trial data, which includes information on 3680 men and women older than age 35 years who have had a mild to moderate ischemic stroke within 90 days of trial enrollment and a fasting level of homocysteine greater than the 25th percentile for patients with stroke.
Participants were recruited from 56 centers in Canada, the United States, and Scotland between 1996 and 2003.
"We wanted to explore whether oxidative stress, which has been associated with vascular dementia in previous studies, would impede recovery of cognitive function following stroke," said Dr. Newman.
The primary outcome variables for the secondary analysis were changes in cognitive function and physical disability as measured by the Mini-Mental State Examination (MMSE) and modified Rankin Scale (mRS), respectively.
To establish potential risk factors for the 2 outcomes, researchers determined MMSE and mRS scores at baseline and at 1 and 2 years after stroke and compared them with vascular risk factor data collected during the 2-year study period.
The researchers looked at several factors that might have an impact on recovery including medication use, race, and age, among others.
Race Linked to Recovery
Medications that individuals took during the study had no impact on either cognitive or physical recovery. These medications included angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, statins, antiplatelet medications, warfarin, and treatment with high-dose or low-dose study vitamins. However, said Dr. Newman, age and race did have an effect.
"Not surprisingly, the older people were, the more difficult it was for them to recover from stroke. However, what was a bit of a surprise was that individuals of nonwhite race had a slower return of their cognitive function."
He added that only African-American race was associated with slower recovery of physical function.
The 3 factors most strongly associated with poorer cognitive function and greater disability after a stroke were diabetes, low levels of HDL cholesterol, and high levels of homocysteine. The investigators also found the factors that influenced recovery of physical function.
According to Dr. Newman, it was not surprising that diabetes impaired physical recovery. However, he added, the magnitude of its effect in slowing recovery of cognitive function was somewhat unexpected but consistent with the oxidative stress hypothesis.
"Diabetes had a very strong influence on cognitive function. This is likely due to its damaging impact on the brain's capillaries and microvessels and that this small-vessel damage is slowing recovery," he said.
The study also showed that higher levels of HDL cholesterol were associated with better cognition, with no significant interaction with age.
Age, Homocysteine Interaction
High levels of homocysteine were also associated with slowed cognitive recovery but only in individuals older than age 57 years. This finding, said Dr. Newman, is consistent with those from the Framingham study, which found a negative effect of high levels of homocysteine on MMSE only in patients older than age 60 years.
"If I were to speculate, I would say this effect is due to the impact of the aging process on natural repair mechanisms and that homocysteine probably puts additional stress on these," said Dr. Newman.
According to Dr. Newman, the study's findings have important implications for clinical practice.
"Patients who have suffered a stroke, have diabetes, low HDL and high homocysteine are much less likely to recover and are also at increased risk of a second stroke. This is a high-risk population that justifies much more aggressive management of their risk factors," said Dr. Newman.
Unfortunately, said Dr. Newman, at this point there are no clear answers about how to manage homocysteine levels because the study showed no benefit of lowering them with folate or vitamin B supplementation. On the other hand, he said, it is important that patients are not B12 deficient.
The study was supported by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. Three of the study authors have received funding for the original VISP trial.
Neurology. 2007;69:2054-2062.

Thursday, November 29, 2007

FDA Panel Urges Stronger Warnings on Flu Drugs

GAITHERSBURG, Md., Nov. 28 -- Labeling for two major flu drugs, oseltamivir (Tamiflu) and zanamivir (Relenza), should be strengthened, an FDA panel has recommended.
In an eight-to-six vote, panel members agreed that package inserts do not adequately address safety concerns surrounding neuropsychiatric events, including delirium and self-injury, that have been associated with the medications.
New language should note that deaths have occurred as a result of those events and may note that flu itself may cause such events, although it remains unclear if the drugs contribute to them, the panel said.
Other recommendations by the panel include explanation that such neuropsychiatric events are rare, occur abruptly, and may result in death, and that patients taking either drug should be monitored closely.
The makers of the drugs -- Roche for oseltamivir and GlaxoSmithKline for zanamivir -- argued that the existing language was adequate.
In its own analysis of more than 150,000 patients, Roche experts argued that the drug is not the cause of the neuropsychiatric events.
"The data increasingly points to the role of influenza in these events," Roche product director David Reddy said. He noted that the disease can cause high fevers, which are associated with "delirium and hallucination."
Nevertheless, the company said it would abide by the FDA's ruling. The agency usually follows the advice of its expert panels, but is not obliged to do so.
The two drugs both aim at blocking the viral enzyme neuraminidase, but they are administered differently. Oseltamivir is available both as an oral capsule and as a suspension, while zanamivir is a dry powder administered in an inhaler.
Neuropsychiatric events have been associated with both drugs, but the majority of cases -- including some deaths -- have been linked to oseltamivir and most of those have taken place in Japan, the FDA said.
The FDA's adverse event reporting system found 596 neuropsychiatric events since oseltamivir was approved, including 16 deaths associated with such an event, according to briefing documents presented to the panel.
The neuropsychiatric events generally had a median onset of 24 hours and resolved quickly in a median of six hours, the agency found.
Zanamivir was associated with 115 events -- 74 of them among patients 21 or younger -- but no deaths, the agency said.
The panel agreed that labeling for two other flu drugs -- the M2 inhibitors amantadine hydrochloride (Symmetrel) and rimantadine hydrochloride (Flumadine) -- does not need to be changed.
Agent Boosts Plateletsin ITP and Thrombocytopenia-Associated HCV

NEW YORK, Nov. 28 -- Eltrombopag (Promacta), an investigative thrombopoietin-receptor agonist, has boosted platelets in both immune thrombocytopenic purpura and hepatitis C-related cirrhosis, according to early trials.Higher daily doses elevated platelet counts to at least 50,000 per mm3 within two weeks in more than 80% of patients with relapsed or refractory chronic immune (or idiopathic) thrombocytopenic purpura, reported James B. Bussel, M.D., of Weill Cornell Medical College here, and colleagues.
Action Points
Caution interested patients that the early results for this investigative agent reported in these studies need to be confirmed in larger, longer-term phase III studies.
Inform interested patients that there is no FDA-approved treatment for thrombocytopenia in HCV-infected patients, although several options are available for treating chronic immune thrombocytopenic purpura.
A significant increase in platelets was also seen in 74% to 95% of eltrombopag-treated HCV patients with cirrhosis-related thrombocytopenia, a major reason why patients cannot endure antiviral treatments, reported John G. McHutchison, M.D., of Duke in Durham, N.C., and colleagues.
Results of both trials were reported in the Nov. 29 issue of the New England Journal of Medicine. Robert S. Schwartz, M.D., an NEJM editor, cautioned in an accompanying editorial, "The results reported for thrombopoietin-receptor agonists are too preliminary for any definitive statement about applications in clinical practice."
However, for hematologists thwarted by failure of every treatment for patients with ITP, he said, "a new, safe way of treating the disease would be a considerable advance."
Dr. Bussel's group conducted a multicenter phase I trial comparing oral eltrombopag and placebo. Patients were randomized to once-daily placebo or 30, 50, or 75 mg of eltrombopag for six weeks or until platelet counts reached 200,000 per mm3.
The trial included 118 adults with chronic ITP and platelet counts below 30,000 per mm3 who had failed at least one standard treatment, typically glucocorticoids or IV immunoglobulins. Among them, 47% had undergone splenectomy and 32% were receiving concomitant medication for the disease.
The trial was stopped at the first interim analysis when the two highest dose groups met predefined stopping criteria for efficacy.
Most patients on the higher doses reached the primary endpoint, a platelet count of 50,000 or more per mm3 on day 43. This included 81% on the 75-mg dose and 70% on the 50-mg dose but only 28% on the 30-mg dose and 11% of controls (P0.001).
The same results were seen without the last-observation-carried-forward analysis (73%, 56%, 22%, and 10%, respectively, P=0.002 for 50 mg versus placebo and P=0.001 for 75 mg versus placebo).
Median platelet counts approached the normal 150,000 to 400,000 per mm3 range by day 15 in both of the higher dose eltrombopag groups but returned almost to baseline within two weeks of the last dose.
Platelet counts rose above 200,000 per mm3 during the study in 4% of placebo group patients compared with 14% of those on 30 mg, 37% on 50 mg, and 50% on 75 mg of eltrombopag.
Bleeding events decreased during treatment with the higher doses. Adverse events were similar in incidence and severity to those in the placebo group.
For HCV-related cirrhosis, Dr. McHutchison's multicenter phase II trial randomized 74 patients with platelet counts of 20,000 to less than 70,000 per mm3 (median 55,000) to the same three dosages or placebo once daily for four weeks.
Patients who reached a platelet count of 70,000 or 100,000 per mm3 by week four could start HCV treatment with peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron), respectively, plus ribavirin. Eltrombopag or placebo continued during the 12-week regimen.
This trial was also discontinued early when a predetermined criterion was met.
Platelet counts rose to 100,000 per mm3 or more at week four -- the primary endpoint -- with eltrombopag in a dose-dependent manner (P0.001 overall and versus placebo for each dose group).
Among the patients who could receive antiviral treatment were 22% of those on placebo, 71% on 30 mg of eltrombopag, 74% on 50 mg of eltrombopag, and 91% on 75 mg of the agent.
During the antiviral treatment phase, platelet counts were consistently higher with eltrombopag than with placebo. Despite a drop in platelet counts in all three eltrombopag groups during antiviral treatment, "perhaps owing to the antiplatelet effect of peginterferon," levels remained above the 50,000 per mm3 threshold at which a reduction in the peginterferon dose is recommended.
The most common side effects of eltrombopag were headache, dry mouth, abdominal pain, and nausea, but they did not cause treatment discontinuation.
Both research groups said their findings require confirmation in phase III trials with longer duration.
Primary source: New England Journal of MedicineSource reference: McHutchison JG, et al "Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C"N Engl J Med 2007; 357: 2227-36. Additional source: New England Journal of MedicineSource reference: Bussel JB, et al "Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura"N Engl J Med 2007; 357: 2237-47. Additional source: New England Journal of MedicineSource reference: Schwartz RS, "Immune thrombocytopenic purpura -- from agony to agonist"N Engl J Med 2007; 357: 2299-2301.
Radiation Threat of CT Scans Cited

NEW YORK, Nov. 28 -- Dramatic growth in the use of computed tomography has brought with it an equally dramatic increase in radiation exposure and associated risk of radiation-induced malignancy, investigators here asserted.
Action Points
Explain to interested patients that increased use of computed tomography and the technology's higher radiation dose may pose a cancer risk that patients should discuss with their physicians.
In an effort to quantify those risks, David J. Brenner, Ph.D., D.Sc., and Eric J. Hall, D.Phil., D.Sc., of Columbia University, cited studies indicating that 0.4% of all cancers in the U.S. might be attributed to radiation exposure. However, they stated in the Nov. 29 issue of the New England Journal of Medicine, those estimates were based on CT-scan volume in 1991 and 1996.
Extrapolating those results to current CT use, the authors said, the current proportion of cancers attributable to CT-associated radiation could be as great as 1.5% to 2%.
Of particular concern, they said, is increased use of CT in pediatric diagnosis, which has exposed children to adult radiation protocols that only recently were modified for pediatric applications.
The cancer risk posed by CT-associated radiation might not be fully appreciated by health care professionals or the public, they said.
They pointed out that "part of the issue is that physicians often view CT studies in the same light as other radiologic procedures, even though radiation doses are typically much higher with CT than with other radiologic procedures.
In a recent survey of radiologists and emergency room physicians, they said, "about 75% of the group significantly underestimated the radiation dose from a CT scan, and 53% of radiologists and 91% of emergency room physicians did not believe that CT scans increased the lifetime risk of cancer."
"Although the individual risk estimates … are small, the concern about the risks from CT is related to the rapid increase in its use -- small individual risks applied to an increasingly large population may create a public health issue some years in the future," Drs. Brenner and Hall stated.
Fueled by advances that have made the technology more accessible, the estimated number of CT scans in the United States has increased from three million in 1980 to 62 million, the authors noted. The total scan volume includes at least four million studies in children.
CT involves larger radiation doses than conventional X-ray imaging. For example, a conventional abdominal X-ray delivers a radiation dose of 0.25 mSv (or mGy) to the stomach; an abdominal CT exposes the stomach to a dose of 10 mSv. That dose increases to 20 mSv with neonatal abdominal CT.
As the radiation dose increases, so do the risks of radiation-induced DNA damage, the authors said.
"Most radiation-induced damage is rapidly repaired by various systems within the cell, but DNA double-strand breaks are less easily repaired, and occasional misrepair can lead to induction of point mutations, chromosomal translocations, and gene fusions, all of which are linked to the induction of cancer," the authors stated.
Epidemiologic studies have provided evidence suggesting an increased cancer risk from radiation doses corresponding to common CT protocols. Studies of atomic-bomb survivors in Japan revealed a significant increase in overall cancer risk in the subgroup of survivors exposed to low doses of radiation in the range of 5 to 150 mSv. The mean dose exposure in the subgroup was 40 mSv, similar to the relevant organ dose of a typical adult CT involving two or three scans.
A study of workers in the nuclear energy industry demonstrated an increased risk of cancer mortality in workers exposed to an average radiation dose of about 20 mSv. Consistent with the study of atomic-bomb survivors, the increased cancer mortality risk remained significant across the range of radiation exposures of 5 to 150 mSv.
"The situation is even clearer for children, who are at greater risk than adults from a given dose of radiation, both because they are inherently more radiosensitive and because they have more remaining years of life during which a radiation-induced cancer could develop," the authors noted.
"Despite the fact that most diagnostic CT scans are associated with very favorable ratios of benefit to risk, there is a strong case to be made that too many CT studies are being performed in the United States," the authors concluded. "There is considerable literature questioning the use of CT, or the use of multiple CT scans, in a variety of contexts, including management of blunt trauma, seizures, and chronic headaches, and particularly questioning its use as a primary diagnostic tool for acute appendicitis in children."
Beyond these clinical issues, other problems arise when CT scans are used to practice defensive medicine or when an initially justified CT scan is repeated as a patient passes through the medical system, often because of a lack of communication, they added. Still another problem pertains to widespread underestimation of CT-related radiation doses by physicians.
To minimize the CT-associated radiation dose and risk, Drs. Brenner and Hall offer three suggestions:
Reduce the CT-related dose in individual patients by use of automatic exposure control and other technologic developments.
Replace CT with other imaging modalities when appropriate.
Decrease the number of prescribed CT studies.
The authors reported no relevant conflicts. Dr. Brenner disclosed grant support from the National Cancer Institute and National Institute of Allergy and Infectious Diseases, and Dr. Hall disclosed grant support from the Department of Energy.Primary source: New England Journal of MedicineSource reference: Brenner DJ, Hall EJ, "Computed tomography -- an increasing source of radiation exposure"N Engl J Med 2007; 357: 2277-2284.
Minority Women More Likely to Experience Severe Pain Related to Metastatic Breast Cancer

Roxanne Nelson

November 28, 2007 — Nonwhite women with metastatic breast cancer are more likely than white women to suffer severe pain associated with their disease, according to a report in the November 26 online issue of Cancer. Even though all the women who participated in the prospective multicenter randomized controlled trial received standard analgesic treatment, nonwhite race was predictive of poorer pain control.
The authors note that adequate analgesia is partially dependent on accurate reporting by the patient, but that patients might be reluctant to report their pain. Social, cultural, and religious issues can interfere with the reporting of pain by minority patients. The authors also point out that oncologists bear the responsibility for providing adequate analgesia and effective pain management over time in minority women with metastatic breast cancer, and that the medical profession in general has an obligation to determine the scope of cancer pain treatment disparities and to devise remedies that address it.
"Our main point is that clinicians should pay attention to risk factors for worsening pain over time when making decisions about pain management in women with breast cancer that has spread to bone," said lead author Liana D. Castel, PhD, from the Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill.
Their study did not address the specific reasons for racial differences in pain management, Dr. Castel told Medscape Oncology, but she pointed to a report from the Institute of Medicine called "Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care," which discusses evidence of possible sources of disparities at system, provider, and patient levels.
"The report led me to believe that the problem of disparities in cancer pain comes from a combination of factors on all 3 of these levels," she said.
Previous studies have noted that factors such as age, race, tumor type, genetics, psychosocial context, and culture have all been found to affect pain and analgesic efficacy. Younger patients with breast cancer also appear to be at a higher risk for posttreatment pain. Previous research has also shown racial disparities in patients with different types of cancer.
In 1 multicenter study that involved patients with a variety of cancers, including breast, gynecologic system, genitourinary tract, lymph nodes, and lung, the researchers found that patients seen at centers that predominantly treat minorities were 3 times more likely than those treated elsewhere to have inadequate pain management, Dr. Castel explained.
Dr. Castel referred to another study, conducted in 2000, that looked at pain in 108 minority patients with different types of cancer and surveyed nurses and physicians. It showed that physicians underestimated pain in 74% of black patients and 64% of Hispanic ones and were more likely to underestimate the pain severity of female patients than male patients.
"I believe that pain control does fit the paradigm of racial disparities that have been seen in healthcare in general," she said.
On the basis of this existing evidence, Dr. Castel and colleagues hypothesized that, compared with white women, minority patients have higher hazards of pain severity and pain interference in daily activities.
In a cohort of 1124 women with metastatic breast cancer and bone metastases, the Brief Pain Inventory (BPI) was administered repeatedly during a 1-year period. The authors defined the outcome as the time to first reach a pain score of 7 or above on the BPI (0–10) pain severity or interference scales.
They found that racial differences were statistically significant for pain severity and pain interference. Nonwhite race presented the greatest hazard for first reaching a BPI severity score of 7 or greater. The same results were seen for the pain interference model; nonwhite race presented the greatest hazard for reaching an interference score of 7 or above.
"In order of magnitude, the 2 biggest factors we found to be associated with risk of pain severity were radiation therapy in the preceding 80 days and non-Caucasian race," Dr. Castel told Medscape Oncology. "For pain interference with daily living, race was among the 4 biggest factors found to be associated with pain risks."
Inactive performance status, radiation therapy in the preceding 80 days, and hospital admission in the preceding 80 days were the most hazardous time-dependent variables for pain interference.
The authors emphasized that future research should explicitly collect and model the longitudinal effects of factors explored in this study, along with other psychological, sociocultural, healthcare-level, and clinical characteristics that are currently known to affect pain.
"Clinicians should use information about known risk factors to inform more aggressive and earlier intervention among non-Caucasian women with metastatic breast cancer," concluded the authors, because minority women are at risk for more pain and greater worsening of pain over the course of this disease.
This study was supported by an AHRQ National Research Service Award Institutional Research Training Grant.
Cancer. Published online November 26, 2007.
Knowing "Cardiovascular Age" May Help Patients Get to Lipid Targets, Follow Medical Advice

November 28, 2007 — Simple ways of informing patients about their cardiovascular risk can make them more likely to adhere to medical advice and reach lipid goals, a new study suggests [1]. In particular, the easily understandable concept of "cardiovascular age" might strike a chord with patients, particularly those at the highest risk of developing cardiovascular disease (CVD) but who don't yet have overt symptoms.
"We've been doing this for many years at the McGill Cardiovascular Health Improvement Program," lead author on the study, Dr Steven A Grover (McGill University, Montreal, QC), told heartwire. "Over a dozen years ago we started showing patients what their risk profiles were and how much they were changing when they lost weight, exercised, or took drugs for their lipids. So we were quite convinced from our own personal experiences that this was a useful way to guide patients about the progress of their treatments, particularly for asymptomatic conditions like blood pressure and cholesterol, when you're trying to convince the patients that they need to embark on some sort of therapy, whether it's lifestyle or drugs, and yet they don't feel that anything is wrong and they certainly don't notice any differences when you make changes."
Grover and colleagues report the results of their 3053-patient Cardiovascular Health Evaluation to Improve Compliance and Knowledge Among Uninformed Patients (CHECK-UP) study in the November 26, 2007 issue of the Archives of Internal Medicine.
Percent risk and cardiovascular age
For the study, 230 primary-care physicians enrolled more than 3000 patients, of whom 2687 were still in the study after 12 months. All patients underwent risk-factor screening at baseline, which generated a one-page computer printout detailing their probability of developing cardiovascular disease. For people with preexisting CVD, this was calculated using a CV life-expectancy model; for people with no CVD, their risk estimate was expressed as a percent risk of developing CVD over the next eight years, using Framingham risk estimates, and as a CV life expectancy. As the authors describe, this second tool — validated in earlier studies — expresses a patient's risk as their "cardiovascular age," calculated as the patient's age minus the difference between his or her estimated remaining life expectancy, taking into account coronary and stroke risk and the average remaining life expectancy of Canadians of the same age and sex. Study participants were then randomized to either usual care or to be shown the computer printout with their risk-profile results. Over the subsequent 12 months, patients had their lipids and blood pressure measured and met with their physicians at three-month intervals throughout the year. All patients were regularly encouraged to meet and maintain their lipid goals, but only patients in the intervention group were shown their risk-profile printouts during the visits.
After 12 months and after adjustment for baseline lipid levels, patients who had been shown their risk profiles throughout the study had greater, statistically significant, reductions in low-density lipoprotein (LDL) cholesterol levels and total-cholesterol/high-density lipoprotein (HDL) cholesterol ratios, although the differences between the two groups were small. Patients who regularly saw their risk-profile changes were also more likely to reach their lipid goals — a finding particularly marked in patients who had the worst lipid profiles at baseline.
According to Grover, cardiovascular age was one of the strongest predictors of reaching lipid targets, even stronger than Framingham risk. "While we can't say definitively, the thing that came up the most strongly was age gap: in other words, how far was your cardiovascular age from your chronological age? There appeared to be a dose response: the bigger the age gap, the bigger the impact on risk profile. But when we looked at high, medium, or low risk by Framingham, the impact was less. The thing that really seemed to motivate patients was seeing this one line about their cardiovascular age."
Understanding cardiovascular risk
Two editorials accompanying the CHECK-UP study explore the nuanced problem of cardiovascular risk communication. According to Dr Rod Jackson and Sue Wells (University of Auckland, New Zealand) [2], the concept of managing risk, not risk factors, is poorly grasped by doctors, let alone patients. "Most physicians are still taught to diagnose and treat hypertension and hyperlipidemia, whereas risk-based approaches dispense with these entrenched yet clinically irrelevant diagnoses. Also, most treatments are designed to target individual risk factors, so it is difficult for physicians not to focus on measuring and treating blood pressure or blood lipid levels."
A major hurdle, however, is time; the time allotted in the CHECK-UP study to calculate cardiovascular risk and convey it to patients at regular intervals would be difficult for many busy physicians to invest. As such, computerized systems that link risk calculations to patient medical records can expedite the process. In New Zealand, they point out, the PREDICT computerized system is already doing this for 45,000 patients.
Jackson and Wells also suggest that Grover et al's concept of cardiovascular age will prove to be "the right metric to translate predicted cardiovascular risk into something meaningful to patients and physicians" and should be further explored.
In a second editorial [3], Dr Charles B Eaton (Brown University, Pawtucket, RI) points out that the CHECK-UP study also indirectly validates the role of regular physician visits. Indeed, the fact that the difference between the two study groups for the study end points was not larger than that reported by the authors might be due to the fact that even patients in the nonintervention group were in regular contact with a physician urging them to meet treatment goals. Still, Eaton notes, "only 45% to 66% of these high-risk cardiovascular patients had reached their respective lipid targets after one year, and thus, a large treatment gap still persisted."
Hope for the aging heart
Acknowledging the gap, Grover told heartwire that his study is at least a step in the right direction. He believes that finding new ways of involving patients is paramount. "We know for certain that the drugs that work well in clinical trials don't do nearly as well in real life. So clearly, the treatment paradigms for chronic asymptomatic medical conditions have to go beyond what we're doing now," he said. "In a chronic-care situation, patients become their own experts—they know what makes them better and what makes them worse. If we're talking about an asymptomatic condition, they know what behaviors bring their lipids under control and what behaviors make them go out of control. To engage the patient so that you can leverage that knowledge is potentially a very powerful instrument."
In fact, Grover thinks the notion of cardiovascular age also holds profound resonance for doctors. His group has offered cardiovascular-age assessments in the exhibition hall at Canadian Cardiovascular Society meetings for the past 10 years. "Health professionals come back year after year to see how their numbers are changing, which shocks me," he told heartwire. "I always believed health professionals would probably have a gut sense of how they are doing and really weren't interested. But that's really not the case at all; they'll line up to get it done."
Pfizer sponsored the CHECK-UP study. Some of the study authors have disclosed various financial relationships with Pfizer, Sanofi Aventis, AstraZeneca, and Orynx.
Drs. Jackson, Wells, and Eaton have disclosed no relevant financial relationships.
Grover SA, Lowensteyn I, Joseph L, et al. Patient knowledge of coronary risk profile improves the effectiveness of dyslipidemia therapy: the CHECK-UP study: A randomized controlled trial. Arch Intern Med. 2007;167:2296-2303.
Eaton CB. Using cardiovascular age equivalent to close the treatment gap for dyslipidemia. Arch Intern Med. 2007;167:2288.
Jackson R, Wells S. Prediction is difficult, particularly about the future. Arch Intern Med. 2007;167:2286-2287.
New Drug May Help Increase Platelet Counts in Patients With Hepatitis C

Laurie Barclay, MD

November 28, 2007 — Eltrombopag (Promacta, Revolade; GlaxoSmithKline) may help increase platelet counts in patients with hepatitis C virus (HCV) infection, thereby enabling them to take antiviral drugs, according to the results of a randomized controlled trial reported in the November 29 issue of the New England Journal of Medicine. This new, orally active thrombopoietin-receptor agonist also increased platelet counts in patients with idiopathic thrombocytopenic purpura.
"We feel this is an important development for many people infected with [HCV] worldwide," lead author John G. McHutchison, MD, from the Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, says in a news release. "A significant number of patients with HCV infection will at some point develop platelet problems that will compromise their getting the best treatments we have. Anything we can do to prevent that from happening would improve their care."
In this phase 2, multicenter trial, 74 patients with cirrhosis caused by HCV and with platelet counts between 20,000 and 70,000/mm3 were randomly assigned to receive either eltrombopag (30, 50, or 75 mg) or placebo daily for 4 weeks. The main efficacy outcome measure was a platelet count of 100,000/mm3 or more at week 4. Eltrombopag or placebo were continued for 12 additional weeks, and peginterferon and ribavirin could be started at week 4.
At week 4, platelet counts were increased to 100,000/mm3 or more in none of the 17 patients receiving placebo. However, in patients with available data, eltrombopag was associated with platelet increases in a dose-dependent manner. Platelet counts of 100,000/mm3 occurred in 9 (75%) of 12 patients receiving a 30-mg dose of eltrombopag daily, in 15 (79%) of 19 receiving a 50-mg dose, and in 20 (95%) of 21 receiving a 75-mg dose (P < .001).
During continued administration of eltrombopag or placebo, antiviral therapy was started in 49 patients, with 4 of 18 patients receiving placebo, 10 of 14 receiving 30 mg eltrombopag, 14 of 19 receiving 50 mg eltrombopag, and 21 of 23 receiving 75 mg eltrombopag. Twelve weeks of antiviral therapy were completed by 36%, 53%, and 65% of patients receiving 30, 50, and 75 mg of eltrombopag, respectively, and by 6% of patients in the placebo group, while administration of eltrombopag or placebo was ongoing.
"We are encouraged by these results and are already working on another multicenter, international, phase 3 trial where we hope these results will be confirmed," Dr. McHutchison said.
Headache was the most frequently reported adverse event during the first 4 weeks of the study. Other adverse effects were dry mouth, abdominal pain, and nausea. During the last 8 weeks of the study, reported adverse events were those typically associated with interferon-based therapy.
Study limitations were small sample size and insufficient power to determine whether adverse events were dose-related.
"Eltrombopag therapy increases platelet counts in patients with thrombocytopenia due to HCV-related cirrhosis, thereby permitting the initiation of antiviral therapy," the authors concluded. "These results require confirmation in phase 3 trials involving standard-duration courses of peginterferon and ribavirin."
GlaxoSmithKline supported this study, employs 4 of its authors, and has various financial arrangements with some other authors. Some of the authors report various financial arrangements with Roche and/or Schering-Plough.
N Engl J Med. 2007;357:2227–2236.
From Smoking Boom, a Major Killer of Women

For Jean Rommes, the crisis came five years ago, on a Monday morning when she had planned to go to work but wound up in the hospital, barely able to breathe. She was 59, the president of a small company in Iowa. Although she had quit smoking a decade earlier, 30 years of cigarettes had taken their toll.
After several days in the hospital, she was sent home tethered to an oxygen tank, with a raft of medicines and a warning: “If I didn’t do something, life was going to continue to be a pretty scary experience.”
Ms. Rommes has chronic obstructive pulmonary disease, or C.O.P.D., a progressive illness that permanently damages the lungs and is usually caused by smoking. Once thought of as an old man’s disease, this disorder has become a major killer in women as well, the consequence of a smoking boom in the 1950s, ’60s and ’70s. The death rate in women nearly tripled from 1980 to 2000, and since 2000, more women than men have died or been hospitalized every year because of the disease.
“Women started smoking in what I call the Virginia Slims era, when they started sponsoring sporting events,” said Dr. Barry J. Make, a lung specialist at National Jewish Medical and Research Center in Denver. “It’s now just catching up to them.”
Chronic obstructive pulmonary disease actually comprises two illnesses: one, emphysema, destroys air sacs deep in the lungs; the other, chronic bronchitis, causes inflammation, congestion and scarring in the airways. The disease kills 120,000 Americans a year, is the fourth leading cause of death and is expected to be third by 2020. About 12 million Americans are known to have it, including many who have long since quit smoking, and studies suggest that 12 million more cases have not been diagnosed. Half the patients are under 65. The disease has left some 900,000 working-age people too sick to work and costs $42 billion a year in medical bills and lost productivity.
“It’s the largest uncontrolled epidemic of disease in the United States today,” said Dr. James Crapo, a professor at the National Jewish Medical and Research Center.
Experts consider the statistics a national disgrace. They say chronic lung disease is misdiagnosed, neglected, improperly treated and stigmatized as self-induced, with patients made to feel they barely deserve help, because they smoked. The disease is mired in a bog of misconception and prejudice, doctors say. It is commonly mistaken for asthma, especially in women, and treated with the wrong drugs.
Although incurable, it is treatable, but many patients, and some doctors, mistakenly think little can be done for it. As a result, patients miss out on therapies that could help them feel better and possibly live longer. The therapies vary, but may include drugs, exercise programs, oxygen and lung surgery.
Incorrectly treated, many fall needlessly into a cycle of worsening illness and disability, and wind up in the emergency room over and over again with pneumonia and other exacerbations — breathing crises like the one that put Ms. Rommes in the hospital — that might have been averted.
“Patients often come to me with years of being under treated,” said Dr. Byron Thomashow, the director of the Center for Chest Disease at NewYork-Presbyterian/Columbia hospital.
Still others are overtreated for years with steroids like prednisone, which is meant for short-term use and if used too much can thin the bones, weaken muscles and raise the risk of cataracts.
Adequate treatment means drugs, usually inhaled, that open the airways and quell inflammation — preventive medicines that must be used daily, not just in emergencies. It is essential to quit smoking.
Patients also need antibiotics to fight lung infections, vaccines to prevent flu and pneumonia and lessons on special breathing techniques that can help them make the most of their diminished lungs. Some need oxygen, which can help them be more active and prolong life in severe cases. Many need dietary advice: obesity can worsen symptoms, but some with advanced disease lose so much weight that their muscles begin to waste. Some people with emphysema benefit from surgery to remove diseased parts of their lungs.
Above all, patients need exercise, because shortness of breath drives many to become inactive, and they become increasingly weak, homebound, disabled and depressed. Many could benefit from therapy programs called pulmonary rehabilitation, which combine exercise with education about the disease, drugs and nutrition, but the programs are not available in all parts of the country, and insurance coverage for them varies.
“I have a complicated, severe group of patients, but I will swear to you that very few wind up in hospitals,” Dr. Thomashow said. “I treat aggressively. I use the medicines, I exercise all of them. You can make a difference here. This is an example of how we’re undertreating this entire disease.”
Little-Known Epidemic
Researchers say there is so little public awareness of how common and serious C.O.P.D. is that the O might as well stand for “obscure” or “overlooked.”
The disease may not be well known, but people who have it are a familiar sight. They are the ones who cannot climb half a flight of stairs without getting winded, who have a perpetual smoker’s cough or wheeze, who need oxygen to walk down the block or push a cart through the supermarket. Some grow too weak and short of breath to leave the house. The flu or even a cold can put them in the hospital. In advanced stages, the lung disease can lead to heart failure.
“This is a disease where people eventually fade away because they can no longer cope with life,” said Grace Anne Dorney Koppel, who has chronic lung disease. (Ms. Dorney Koppel, a lawyer, is married to Ted Koppel.) “My God, if you don’t have breath, you don’t have anything.”
Most cases, about 85 percent, are caused by smoking, and symptoms usually start after age 40, in people who have smoked a pack a day for 10 years or more. In the United States, 45 million people smoke, 21 percent of adults. Only about 20 percent of smokers develop chronic lung disease.
The illness is not the same as asthma, but some patients have asthma along with their other lung problems. Most have a combination of emphysema and chronic bronchitis. In about one-sixth of cases, emphysema is the main problem. Women are far more likely than men to develop chronic bronchitis, and are less prone to emphysema. Some studies have suggested that women’s lungs are more sensitive than men’s to the toxins in smoke.
Worldwide, these lung diseases kill 2.5 million people a year. An article in September in The Lancet, a medical journal, said that “if every smoker in the world were to stop smoking today, the rates of C.O.P.D. would probably continue to increase for the next 20 years.” The reason is that although quitting slows the disease, it can develop later.
Cigarettes are the major cause worldwide, but other sources are important in developing countries, especially smoke from indoor fires that burn wood, coal, straw or dung for heating and cooking. Women and children are most likely to be exposed. Outdoor air pollution plays less of a part: it can aggravate existing disease, but is believed to cause only 1 percent of cases in rich countries and 2 percent in poorer ones. Occupational exposures in cotton mills and mines may contribute.
Researchers have differed about whether passive smoking plays a role, but a Lancet article in September predicted that in China, among the 240 million people who are now over 50, 1.9 million who never smoked will die from chronic lung disease — just from exposure to other people’s smoke.
Many patients with lung disease have other illnesses as well, like heart disease, acid reflux, hypertension, high cholesterol, sinus problems or diabetes. Compared with other smokers, those with C.O.P.D. are more likely to develop lung cancer as well. Researchers suspect that all the ailments stem partly from the same underlying condition, widespread inflammation, a reaction by the immune system that can affect blood vessels, organs and tissues all over the body.
Lung disease can creep up insidiously, because human beings have lung power to spare. Millions of airways, with enough surface area to cover a tennis court, provide so much reserve that most people would not notice it if they lost the use of a third or even half of a lung. But all that extra capacity can hide an impending disaster.
“If it comes on gradually, the body can adjust,” said Dr. Neil Schachter, a lung specialist and professor at Mount Sinai Medical Center in New York. “Some of these patients are at oxygen levels where you and I would be gasping for breath.”
People adjust psychologically as well, cutting back their activities, deciding perhaps that they just do not enjoy sports anymore, that they are getting older, gaining weight or a bit out of shape. But at some point the body can no longer compensate, and denial does not work anymore.
“It’s like trying to breathe through a straw,” Dr. Schachter said. “It’s very uncomfortable.”
By then, half a lung might be ruined. On a CT scan, he said, the lungs may look “moth-eaten,” full of holes where tissue has been destroyed.
Often, the diagnosis is not made until the disease is advanced. Even though breathing tests are easy to perform and recommended for high-risk patients like former and current smokers, many doctors do not bother. People who do get a diagnosis frequently are not taught how to use the inhalers that are the mainstay of treatment. Access to pulmonary rehabilitation is limited because Medicare has left coverage decisions to the states. Some programs have shut down, and there are bills in the House and Senate that would require pulmonary rehabilitation to be covered by Medicare. Medicare may also reduce coverage for home oxygen.
Meanwhile, billions are spent on treating exacerbations, episodes of severe breathing trouble that are often caused by colds, flu or other respiratory infections.
A recent study of 1,600 consecutive hospitalizations for chronic lung disease in five New York hospitals found that once patients were in the hospital, their treatment was generally correct, Dr. Thomashow said. But “most upsetting,” he said, was that the majority had been incorrectly treated before going to the hospital.
For many, trying to control the disease, rather than be controlled by it, is a daily struggle. Diane Williams Hymons, 57, a social service consultant and therapist in Silver Spring, Md., has had lifelong problems with bronchitis, allergies and asthma. In the last five or 10 years, her breathing difficulties have worsened, but she was told only three years ago that she had C.O.P.D. It motivated her to give up cigarettes, after smoking for more than 30 years.
“I have good days, and days that aren’t as great,” she said. “I sometimes have trouble walking up steps. I have to stop and catch my breath.”
She is “usually fine” when sitting, she said.
Her mother, also a former smoker with chronic lung disease, has been in a pulmonary rehabilitation program. Ms. Williams Hymons’s doctor has not recommended such a program for her, but she has no idea why. They have discussed surgery to remove part of her lungs, which helps some people with emphysema, but she said no decision had been made yet because it is not clear whether her main problem is emphysema or asthma. She is not sure what her prognosis is.
A Risky Approach
Ms. Williams Hymons has been taking prednisone pills for years, something both she and her doctor know is risky. But when she tries to cut back, the disease flares up. She has many side effects from the drug.
“My bone density is not looking real good,” she said. “I have cramps in my hands and feet, weight gain and bloating, the moon face, excess facial hair, fat deposits between my shoulder blades. Yes, I have those.”
She has broken two ribs just from coughing, probably because the prednisone has thinned her bones, she said. She went to a hospital for the rib pain last year and was given so much asthma medication to stop the coughing that it caused abnormal heart rhythms. She wound up in the cardiac unit for five days, and now says “never again” to being hospitalized.
Her doctor orders regular bone density tests.
“I know he’s concerned, like I’m concerned,” Ms. Williams Hymons said, “but we can’t seem to kind of get things under control.”
A recent study of 25 primary care practices around the United States treating chronic lung disease found that most did not perform spirometry, a simple breathing test used to diagnose or monitor the disease, even when they had the equipment to do so. The test takes only a few minutes, but doctors said there was not enough time during the usual 15-minute visit. Similarly, the practices did not offer much help with smoking cessation.
The author of the study (published in August in The American Journal of Medicine), Pamela L. Moore, said many of the doctors felt unable to help smokers quit, and believed that as long as patients kept smoking, treatments for lung disease would be for nought. But Dr. Moore said research had found that people are more likely to quit or start cutting back if doctors recommend it.
Labeling the disease self-induced is “an unbelievably painful concept,” Dr. Thomashow said. “Patients blame themselves, their family blames them, we even have evidence that health providers blame them.”
Shame and Blame
Indeed, a patient at a clinic in Manhattan, with nasal oxygen tubing attached to equipment in a backpack, said, “This is one of the evils you must suffer for the things we did in our life.”
Smoking also contributes to heart disease, Dr. Thomashow said, and yet people “don’t waste time blaming the patient.”
“This disease quite frankly has an image problem,” said Dr. James Kiley, the director of lung research at the National Heart, Lung and Blood Institute, which started a campaign last January to educate people about the disease.
In one way or another every patient seems to have encountered what John Walsh, president of the C.O.P.D. Foundation, calls the “shame and blame” attached to this disease.
It is a familiar theme to Ms. Dorney Koppel, who agreed to become a spokeswoman for the institute’s education campaign. She was surprised to be asked to help, she said, because the campaign needed a celebrity, and she is merely married to one. She asked the person who invited her, whether there were no famous people with C.O.P.D.
“I was told, ‘None who will admit it,’” she said.
Ms. Dorney Koppel, who is candid about being a former smoker, calls the illness the Rodney Dangerfield of diseases.
“You don’t get no respect,” she said. “I have to pay publicly for my sins. I have paid.”
Like many patients, Ms. Rommes has both emphysema and chronic bronchitis, along with asthma. She had symptoms for years before receiving the correct diagnosis.
She began smoking in college during the 1960s, when she was 18. People whom she admired smoked, and it seemed cool. She smoked for 30 years.
When she quit in 1992, it was not because she thought she was ill, but because she realized that she was organizing her day around chances to smoke. But she almost certainly was ill. She was only 50, but climbing a flight of stairs left her winded. From what she found in medical dictionaries, she began to suspect she had lung disease.
By 2000 she was so short of breath that she consulted her doctor about it.
He gave her a spirometry test. In one second, healthy adults should be able to blow out 80 percent of the total they can exhale; her score was 34 percent, which, she knows now, indicated moderate to severe lung disease.
“I honestly don’t know whether he knew,” she said of her doctor. “I suspect he did, but he didn’t call it emphysema.”
“He put me on a couple of inhalers and he called it asthma,” Ms. Rommes said. “I sort of ignored the whole thing, because the inhalers did make me feel better. I started to gain some weight, and things got progressively worse.”
She cannot help wondering now if she could have avoided becoming so desperately ill, if she had only known sooner what a dangerous illness she had.
The turning point came in February 2003 when she tried to take a shower and found that she could not breathe. The steam all but suffocated her. She managed to drive from her home in Osceola, Iowa, to her doctor’s office, struggle across the parking lot like someone climbing a mountain and collapse, gasping, onto a couch inside the clinic. Her blood oxygen was perilously low, two-thirds of normal, even when she was given oxygen. The hospital was next door, and her doctor had her admitted immediately.
Fear and Anger
She had Type 2 diabetes as well as lung disease, and her doctor told her that losing weight would help both illnesses. But she said, “He made it pretty clear that he didn’t think I would or could.”
Motivated by fear and anger, she began riding an exercise bike, walking on a treadmill, lifting weights at a gym and eating only 1,200 to 1,500 calories a day, mostly lean meat with plenty of vegetables and fruit.
“I kind of came to the conclusion that if I didn’t, I probably wasn’t going to be around,” Ms. Rommes said. “I wasn’t ready to check out. And my husband was beginning to show the signs of Alzheimer’s disease. I knew that if I couldn’t continue to manage our affairs, it wasn’t going to work out.”
By December 2003, her efforts were starting to pay off. She went from needing oxygen around the clock to using it only for sleeping, and by January 2005 she no longer needed it at all. She was able to lower the doses of her inhalers and diabetes medicines. By February 2005, she had lost 100 pounds.
The daily exercise also helped her deal with the stress of her husband’s illness. He died in June.
“I had no clue that exercise would do as much for ability to breathe as it did,” she said, adding that it helped more than the drugs, which she described as “really pretty minimal.”
She is hooked on exercise now, getting up every morning at 5 a.m. to walk for 45 minutes on the treadmill. She goes at it hard enough to break a sweat, wearing a blood oxygen monitor to make sure her level does not dip too low (if it does, she slows down or uses special breathing techniques to bring it up). She walks outdoors, as well, and three times a week, she works out with weights at a gym.
“Exercise is absolutely essential, and it’s essential to start it as soon as you know you have C.O.P.D.,” she said.
Exercise does not heal or strengthen the lungs themselves, but it improves overall fitness, which people with lung disease need desperately because their shortness of breath leads to inactivity, muscle wasting and loss of stamina.
“Both my pulmonologist and my regular doctor have made it really, really clear to me that I have not increased my lung capacity at all,” Ms. Rommes said. “But I’ve improved the mechanics. I’ve done everything I know how to do to make the lung capacity as efficient as possible. That’s the key for me; I know there are lots of people with this disease who don’t exercise, who I guess just give up.”
She realizes that she has two serious chronic diseases that could shorten her life. But it does not worry her much, she said, because she figures she is doing everything she can to take care of herself, and would rather spend her time enjoying life — work, reading, opera, traveling, children and grandchildren.
“I will tell pretty much anybody that I have emphysema,” Ms. Rommes said. “They say, ‘Did you smoke?’ I say, ‘Yes I did, for 30 years, and I quit in 1992.’ Maybe it’s why I’ve attacked this the way I did. O.K., I did it to myself, and so I better do everything I can to get out of it. We all do things in our lives that are stupid, and then you do what you can to fix it.”
Alzheimer's, high blood pressure linked in study

By Susan KellyWed Nov 28, 11:37 AM ET
Having high blood pressure reduces blood flow in the brains of Alzheimer's patients, making them more vulnerable to the effects of the disease, researchers reported on Wednesday.
Researchers used a magnetic resonance imaging technique to measure blood flow in the brains of 68 older adults. They found cerebral blood flow was substantially decreased in all patients with high blood pressure and was the lowest in Alzheimer's patients with high blood pressure.
"What we think may be happening is hypertension reflects an extra hit to the brain," said Cyrus Raji of the University of Pittsburgh, who led the study.
The study compared Alzheimer patients to adults with normal cognitive function and a group with mild cognitive impairment, defined as a transitional stage between dementia and normal, age-related deficits in language, attention and reasoning.
Half of the patients in each of the three groups had high blood pressure and half did not.
The researchers used an imaging program called arterial spin-labeled MRI, which calculates blood flow per minute in a section of brain tissue and does not require use of a contrast agent. Contrast agents are compounds the patient receives either orally or intravenously to make the MRI scan easier to see.
"This is a very safe technique, especially for the elderly," Raji said in an interview at the annual meeting of the Radiological Society of North America in Chicago, where he presented his findings.
About 50 million Americans have hypertension, in which the blood circulates through the arteries with too much force, according to the National Heart, Lung and Blood Institute. The condition increases the risk for heart attack, stroke and aneurysm.
"This study demonstrates that good vascular health is also good for the brain," said Oscar Lopez of the University of Pittsburgh, who also worked on the study.
3-D Breast Imaging May Improve Cancer Detection

By Carolyn ColwellHealthDay ReporterWed Nov 28, 5:00 PM ET
WEDNESDAY, Nov. 28 (HealthDay News) -- A 3-D view of breast tissue may give women a more accurate method of detecting breast cancers, according to a trial of a new technology called stereoscopic digital mammography.
False-positive results were almost cut in half with stereo mammography, said the technology's developer David Getty, a division scientist at BBN Technologies in Cambridge, Mass.
"These are women who at the moment are getting a call back from a radiologist saying something suspicious has been found," he explained. However, after subsequent testing, "most of them are finding out there was nothing there," Getty added.
"Being able to cut that number in half would have a dramatic impact" in reducing both patient anxieties and cost, he said.
A second dramatic benefit to the new technology lies in "finding lesions that are being missed on standard mammography. Most of them will turn out to be benign, but some additional cancers will be found," Getty said.
Getty was expected to present the results Wednesday at the Radiological Society of North America's annual meeting in Chicago.
The five-year trial, conducted at Emory University in Atlanta and scheduled to end in December, focused on almost 1,100 women at elevated risk for breast cancer. According to Getty, the trial was a collaboration with Dr. Carl D'Orsi, the director of Emory's breast imaging center.
Results so far show that that stereo mammography reduced false-positives by 49 percent. The stereoscopic equipment failed to detect 24 out of 109 cancerous lesions, compared to 40 out of 109 lesions not found through standard digital mammography, Getty said.
Another advantage of the stereoscopic digital mammography is that it "is much better at picking up cluster calcifications [that] can be associated with malignancy," Getty added.
This technology also allows radiologists to get a picture of the entire breast volume in a slice-by-slice view. "It certainly helps, because you're seeing all of the tissue in depth," Getty explained. The capacity of mammography to detect problems in dense breasts is not an issue with the stereoscopic digital equipment because it "doesn't look as dense, because tissue is being spread out in depth," he said.
A stereoscopic mammogram image works on principles similar to the old Viewmaster slide viewers used by children, Getty explained. Each of two images inserted in the Viewmaster were channeled to a different eye, and the brain's "visual cortex -- the magician in all this -- then combines the two images, artificially recreating what your two eyes normally create when you walk around in a three-dimensional world," Getty said. Similarly, the viewing monitor for stereo mammography merges two distinct images to create a 3-D look at tissue.
Experts say stereo mammography does show promise, but more work is needed.
"Stereo mammography is a step in the right direction, but it is not a breakthrough," said Dr. David Bluemke, a professor of radiology and medicine at Johns Hopkins Medical Institutions in Baltimore. "True 3-D tomographic imaging of the breast is ultimately needed." By giving radiologist a view of slices through the breast, 3-D tomography would allow radiologist to see lesions that are otherwise obscured by being superimposed on normal breast tissue, he explained.
Stereoscopic digital mammography "seems very promising," added Dr. Kristin Byrne, the chief of breast imaging at Lenox Hill Hospital in New York City. "It would make mammography that much better."
With current technology, the problem of calling back a woman whose breasts show a suspicious area is that radiologists often can't find that same suspicious tissue in a second view, so the woman has to follow-up with further monitoring in another six months or have a biopsy, she noted.
More information
There's more on breast cancer at the U.S. National Cancer Institute.
Progesterone Won't Shield Women Against Alzheimer's

2 hours, 3 minutes ago
THURSDAY, Nov. 29 (HealthDay News) -- There's no evidence that progesterone -- which is often given with estrogen in hormone replacement therapy -- offers women any protection against Alzheimer's disease, U.S. researchers say.
They conducted tests on female mice genetically engineered to develop an Alzheimer's-like disease to come to this conclusion.
Treatment with estrogen blocked the Alzheimer's-like symptoms in the mice, while treatment with progesterone did not. In fact, when the mice were given both hormones, progesterone appeared to block estrogen's main benefit -- preventing the buildup of beta amyloid protein in the brain, a key factor in Alzheimer's.
The researchers, led by gerontologist Christian Pike of the University of Southern California, did find that progesterone seemed to inhibit tau hyperphosphorylation, another chemical process implicated in Alzheimer's.
The study appears in this week's issue of the Journal of Neuroscience.
Previous research suggested that estrogen offers women some protection against Alzheimer's disease. The authors of this new study wanted to determine if the same might be true of progesterone.
The findings may provide guidance for the design of human trials examining hormone therapy and Alzheimer's, Pike said. Future studies may need to focus on both the dosage and formulations of progestins (synthetic versions of progesterone given to humans), as well as the starting age for hormone therapy, he noted.
More information
The U.S. National Institute on Aging discusses whether Alzheimer's can be prevented.

Wednesday, November 28, 2007

Depression Treatment for Older Diabetics Prolongs Life

PHILADELPHIA, Nov. 27 -- The five-year death rate in older depressed diabetic patients was cut in half when they received treatment for the depression, researchers here reported.
Action Points
Explain that the study found that a dedicated depression treatment program reduced death rates over five years in older diabetic patients.
Point out that the reasons for the lower death rate were unclear and may not have been entirely related to the treatment program.
After adjusting for demographic variables and other medical conditions, the hazard ratio for death was 0.49 for those in the aggressive treatment program, compared with the death rate in those receiving usual care (95% CI: 0.24 to 0.98), reported Hillary Bogner, M.D., of the University of Pennsylvania, and colleagues in the December issue of Diabetes Care.
"Depression is not only common in persons with diabetes, but contributes to not taking medicines, not following prescribed diets, and overall reduced quality of life," said Dr. Bogner.
The study used data from the Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT), which was intended to test the effectiveness of depression treatment programs in preventing suicide among the elderly. Dr. Bogner's team also used death records from a national registry to supplement the PROSPECT data.
In PROSPECT, patients with depression were assigned to usual care or to the aggressive treatment program. In the former, subjects' regular physicians were informed of the depression diagnosis and given information on depression treatment in the elderly, with actual treatment left to their discretion.
The treatment program was directed by trained care managers and followed a predetermined plan, beginning with citalopram (Celexa) and interpersonal psychotherapy. Those refusing medication were treated solely with psychotherapy. Care managers checked on patient compliance, responses, and side effects, and gave additional care at regular intervals or as needed.
Patients were followed for five years. For the diabetes study, data on a subset of 584 patients, ages 60 to 94 (mean of 70), were analyzed. Of these, 123 had diabetes, as reported by patients during a baseline interview.
During the course of the study, about 17% of nondiabetic subjects died, with little difference between the study arms. About 27% of diabetics in the treatment group died, as did 38% of diabetics assigned to usual care.
Dr. Bogner's group said it was unclear why the treatment program seemed more effective in diabetic patients. Their data did not allow analysis of the exact mechanisms underlying the treatment program's apparent effectiveness in the diabetic patients.
They suggested that "both physiologic factors, such as increased inflammation and poor glucose regulation, and behavioral processes, such as poor adherence, may link depression with increased mortality in patients with diabetes." "The potential mediators between treatment assignments and outcomes for patients with diabetes deserve further study," they said.
The group cautioned that their data had other limitations as well. For example, they relied on subjects' self-report of diabetes, although it is estimated that up to one-third of people with diabetes are unaware of it.
Also, diabetic patients in the treatment program may have had a reduced death rate for reasons not related to the treatment, the report said. Patients in that group could have been seen by their physicians more frequently and therefore received better care for other conditions.
"Statisticians are wary of subgroup analyses," the report acknowledged as well. "At the same time, large-scale intervention studies carried out in primary care practice are limited, so we need to make the most of the data we have."
Both PROSPECT and the diabetes subgroup study were funded by the National Institute of Mental Health.
No disclosure was made about financial relationships with for-profit companies.Primary source: Diabetes CareSource reference: Bogner H, et al "Diabetes, depression and death: A randomized controlled trial of a depression treatment program for older adults based in primary care (PROSPECT)" Diabetes Care 2007; 30: 3005-10.
Focus on Big Picture to Promote Statin Adherence

MONTREAL, Nov. 27 -- A conversation about a patient's overall cardiovascular risk provided better motivation to adhere to statin treatment, particularly among those at high risk, than reporting cholesterol levels alone, researchers found.
Action Points
Consider calculating and sharing overall cardiovascular risk profiles with patients to improve adherence to hyperlipidemia treatment.
Note that the National Cholesterol Education Program's Adult Treatment Panel III recommends calculating the future risk of cardiovascular events to identify high-risk patients.
Consistent feedback using a risk-profile tool helped patients achieve a greater decline in LDL cholesterol (−3.3 mg/dL) and in total-to-HDL cholesterol ratio (−0.1) than patients receiving standard care, according to results of a yearlong study published in the Nov. 26 issue of the journal Archives of Internal Medicine.
Controlling for baseline between-group differences in cholesterol levels, patients shown their risk profile were 26% more likely to reach lipid targets (95% CI: 7% to 48%), reported Steven A. Grover, M.D., M.P.A., F.R.C.P.C., of McGill University here, and colleagues.
And, the higher a patient's risk, the greater the effect of the risk profile, the researchers said.
Guidelines of the National Cholesterol Education Program's Adult Treatment Panel III already recommend calculating the future risk of cardiovascular events to identify high-risk patients, they said.
The findings provide proof of principle that simply sharing this information with patients may improve the effectiveness of statin therapy, they said.
However, the impact "was disappointingly small, and there was no clear impact in the highest-risk group (those with previous cardiovascular disease)," commented Rod Jackson, M.B.Ch.B., Ph.D., and Sue Wells, M.B.Ch.B., M.P.H., of the University of Auckland in Auckland, New Zealand, in an accompanying editorial.
The study, called Cardiovascular Health Evaluation to Improve Compliance and Knowledge Among Uninformed Patients (CHECK-UP), included 233 primary care physicians and 3,053 patients.
The patients were all likely to have untreated hyperlipidemia at baseline with diabetes, established cardiovascular disease, or multiple risk factors adding up to at least a 10% calculated 10-year Framingham coronary risk.
One group was randomized to discuss their individual coronary risk profile at quarterly office visits whereas the others received standard care, which did not systematically include risk profile assessment.
The profile was a one-page computer printout showing the probability of developing heart disease. It was calculated with the Cardiovascular Life Expectancy Model for heart disease patients. For primary prevention patients, it was calculated with Framingham equations and also showed the "cardiovascular age," the patient's age minus the years of life expectancy they would lose with their current heart risk.
Participants purchased medications from their normal pharmacy out-of-pocket or using private insurance or public drug plans.
Although statin doses were similar between groups, LDL cholesterol levels dropped more in the risk profile group than in the control group (mean change: −51.2 versus −48.0 mg/dL, P=0.02). The same was true for total cholesterol (mean difference: −3.9 mg/dL, 95% confidence interval: −6.4 to −1.4 mg/dL) and the ratio of total cholesterol to HDL cholesterol (−0.1, 95% CI: −0.2 to −0.1).
Among patients with pre-existing cardiovascular disease, the risk profile had a similar magnitude of impact but the difference between groups was not significant (OR: 1.25, 95% CI: 0.89 to 1.75).
"In the presence of symptomatic disease, it seems that a risk profile did not substantially improve the effectiveness of treatment," the researchers said.
One explanation may be that these patients were "already well aware of their high-risk status, which could have neutralized the study intervention," Drs. Jackson and Wells said.
However, the benefit remained for primary prevention patients (OR: 1.26, 95% CI: 1.04 to 1.53) driven primarily by those with diabetes (OR: 1.42, 95% CI: 1.11 to 1.81).
Notably, primary prevention patients with a large gap between their cardiovascular age and their actual age were more likely to reach treatment targets.
Participants with the smallest age gap, ranging from −6.10 to 0.43 years, showed no benefit (OR: 0.92 versus usual care), whereas those in the highest age gap quintile were 69% more likely to hit their cholesterol targets with the profile than with usual care (P=0.04).
"Informing patients of their coronary risk may also increase the effectiveness of primary prevention by identifying individuals most likely to benefit from treatment while reassuring those at low risk," Dr. Grover and colleagues wrote.
The information may also help physicians select treatment, they wrote.
But, cardiovascular risk profiles require more work to calculate and to manage than the simple yes-no definitions for hypertension or high cholesterol, Drs. Jackson and Wells said.
"Risk prediction is not rocket science, but, similar to a tax return, most of us cannot do it in our heads," they said. "Then comes the hard part: discussing the predicted risk and the predicted treatment benefit with the patient."
Furthermore, only 45% to 66% of high-risk cardiovascular patients had reached lipid targets within a year, "and thus, a large treatment gap still persisted," noted Charles B. Eaton, M.D., M.S., of Brown University and Memorial Hospital of Rhode Island in Providence, R.I., in a second accompanying editorial.
The study was funded by Pfizer Canada.
Dr. Grover and two co-authors reported receiving research grants from Pfizer, sanofi-aventis, and AstraZeneca. Dr. Grover also reported receiving speaker honoraria from Pfizer, sanofi-aventis, and Orynx, and has either been a consultant to or participated on an advisory board for AstraZeneca, sanofi-aventis, and Pfizer.
The editorialists reported no conflicts of interest.Additional source: Archives of Internal MedicineSource reference: Grover S, et al "Patient knowledge of coronary risk profile improves the effectiveness of dyslipidemia therapy. The CHECK-UP study: a randomized controlled trial"Arch Intern Med 2007; 167: 2296-2303. Additional source: Archives of Internal MedicineSource reference: Eaton CB, "Using cardiovascular age equivalent to close the treatment gap for dyslipidemia"Arch Intern Med 2007; 167: 2288.
Jackson R, Wells S, "Prediction is difficult, particularly about the future"Arch Intern Med 2007; 167: 2286-2287.