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March 17, 2009JAMA news releases are made available to the public after 3 pm US Central time on the first 4 Tuesdays of each month. The Archives of Journals news releases are made available to the public after 3 pm Central time on Mondays. We also provide a list of previous news releases. THIS WEEK'S CONTENTS
JAMA NEWS RELEASES
(Embargoed for Release: 3 p.m. CT Tuesday, March 17, 2009)
JAMA REPORT (VIDEO SCRIPT)
INFORMATION CONTAINED IN THESE NEWS RELEASES IS PROTECTED BY COPYRIGHT. JOURNAL ATTRIBUTION IS REQUIRED. JOURNALISTS CAN NOW ACCESS EMBARGOED JAMA/ARCHIVES STUDIES ON-LINE. Go to www.jamamedia.org for more information and to apply for access. TV Note: This week's JAMA Report video is on religious coping and the use of intensive life-prolonging care near death by patients with advanced cancer. The report will be fed Tuesday, March 17, from 9:00 - 9:30 a.m. ET and 2:00 - 2:30 p.m. ET, on Galaxy 28 (C-Band), Transponder 19, downlink frequency: 4080 vertical, audio 6.2/6.8. For more information, call 312/464-JAMA. Please Note: The FOR THE MEDIA website now has a search feature to enable media to find previous JAMA/Archives news releases on specific medical topics. This search feature link is located on the home page at www.jamamedia.org EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, March 17, 2009
Medication Does Not Appear to Reduce Progression of Atherosclerosis
CHICAGO—Compared to placebo, the drug pactimibe did not effect certain measures of atherosclerosis for patients with familial hypercholesterolemia (high cholesterol levels), but these patients did have an increased incidence of cardiovascular events such as heart attack and stroke, according to a study in the March 18 issue of JAMA. One proposed method to help prevent cardiovascular disease is to block the action of acyl coenzyme A:cholesterol acyltransferase (ACAT), an enzyme involved in cholesterol accumulation. In theory, inhibition of ACAT-1 (an isoform [different form of the same protein] of ACAT) could slow the progression of atherosclerosis (process in which plaque builds up in the inner lining of the arteries) and prevent the development of vulnerable plaque, according to background information in the article. Treatment with ACAT inhibitors, such as the drug pactimibe, have shown promising results for the prevention of atherosclerosis in various animal tests. Marijn C. Meuwese, M.D., of the Academic Medical Center, Amsterdam, and colleagues assessed the efficacy and safety of pactimibe in reducing progression of atherosclerosis in 892 patients with a family history of high cholesterol, which is associated with a higher risk for atherosclerosis. The randomized, placebo-controlled study (Carotid Atherosclerosis Progression Trial Investigating Vascular ACAT Inhibition Treatment Effects [CAPTIVATE]) was conducted at 40 clinics in the United States, Canada, Europe, South Africa and Israel between February 2004 and December 2005. Participants received either 100 mg/d of pactimibe (n = 443) or matching placebo (n = 438), in addition to standard lipid-lowering therapy. Atherosclerosis was assessed by ultrasound measurements of carotid intima-media thickness (CIMT; a measurement of the thickness of the inner wall of a major artery) at the beginning of the study and at 12, 18, and 24 months. Increasing thickness is considered a marker of increasing plaque in the artery. The treatment was discontinued on October 26, 2005, when the parallel ACTIVATE study failed to demonstrate efficacy of pactimibe vs. placebo. After 6 months of treatment with pactimibe, the average percentage change from baseline of low-density-lipoprotein cholesterol (LDL-C) significantly increased by 7.3 percent compared with 1.4 percent in the placebo group. This increase in LDL-C was observed throughout the study and disappeared after discontinuation of the study drug. The annual progression of maximum CIMT showed no difference between groups. However, the annual progression of the average CIMT showed a significant difference between groups as relative average CIMT increase was observed in patients receiving pactimibe (difference, -0.014 mm). Average CIMT progressed significantly in the pactimibe group within 1 year, whereas only minor progression of average CIMT was observed in the placebo group. Serious adverse events were reported more frequently by patients in the pactimibe group than in the placebo group (10.0 percent vs. 7.7 percent). Cardiovascular events (6.3 percent vs. 3.4 percent) as well as the composite of cardiovascular death, heart attack, and stroke (2.3 percent vs. 0.2 percent) occurred more frequently in patients receiving pactimibe vs. placebo. "...in patients with familial hypercholesterolemia, pactimibe had no effect on atherosclerosis as assessed by changes in maximum CIMT compared with placebo but was associated with an increase in mean CIMT as well as increased incidence of major cardiovascular events," the authors write.
They add that the findings from this study and findings from other studies lessen "the promise and further development of this class of drugs for cardiovascular prevention."
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org. EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, March 17, 2009
Use of Religious Faith to Cope With Advanced Cancer Associated With Receiving Intensive Medical Care Near Death
CHICAGO—Patients with advanced cancer who used their religious faith to help cope were more likely to receive intensive life-prolonging medical care such as mechanical ventilation or cardiopulmonary resuscitation during their last week of life, according to a study in the March 18 issue of JAMA. For patients facing a life-threatening illness, religious coping, such as through prayer, meditation and religious study can offer patients a sense of meaning, comfort, control and personal growth, according to background information in the article. "Positive religious coping has been widely associated with improved psychological adjustment to stressors including serious illness," the authors write. They add that religion may influence patients' medical decisions, but little is known about the associations between religious coping and the use of intensive life-prolonging care at the end of life. Andrea C. Phelps, M.D., of Beth Israel Deaconess Medical Center, Boston, and colleagues examined the relationship between 345 patients with advanced cancer and their use of religious coping at the start of the study and their receipt of intensive medical care during their last week of life. Positive religious coping was assessed by a questionnaire. Interviews at the beginning of the study also assessed psychosocial and religious/spiritual measures, advance care planning and end-of-life treatment preferences. Patients were followed up until death, a median (midpoint) of 122 days after the assessment at the beginning of the study. Patients were asked about how much they rely on religion to cope with illness. A total of 272 patients (78.8 percent) reported that religion helps them cope "to a moderate extent" or more and 109 (31.6 percent) endorsed the statement that "it is the most important thing that keeps you going." Most patients (55.9 percent) endorsed engaging in times of prayer, meditation, or religious study at least daily. The researchers found that patients with a high level of positive religious coping at the start of the study had nearly three times the odds of receiving mechanical ventilation and intensive life-prolonging care in the last week of life compared with patients with a low level of religious coping. A high level of positive religious coping was also significantly associated with preferring heroic measures (wanting physicians to do everything possible to keep the patient alive) compared with patients with a low level and was associated with less advance care planning in all forms: do-not-resuscitate order, living will and health care proxy/durable power of attorney. "These results suggest that relying upon religion to cope with terminal cancer may contribute to receiving aggressive medical care near death," the authors write.
"Taken together, these results highlight the need for clinicians to recognize and be sensitive to the influence of religious coping on medical decisions and goals of care at the end of life. When appropriate, clinicians might include chaplains or other trained professionals (e.g., liaison psychiatrists) to inquire about religious coping during family meetings while the patient is in an intensive care unit and end-of-life discussions occurring earlier in the disease course. Because aggressive end-of-life cancer care has been associated with poor quality of death and caregiver bereavement adjustment, intensive end-of-life care might represent a negative outcome for religious copers. These findings merit further discussion within religious communities, and consideration from those providing pastoral counsel to terminally ill patients with cancer."
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org. EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, March 17, 2009
Narcolepsy Drug Being Used to Improve Cognitive Performance Affects Brain Dopamine Activity, Suggesting Potential For Abuse and Dependence
CHICAGO—Preliminary research in healthy men suggests that the narcolepsy drug modafinil, increasingly being used to enhance cognitive abilities, affects the activity of dopamine in the brain in a way that may create the potential for abuse and dependence, according to a study in the March 18 issue of JAMA. Modafinil, a wake-promoting drug used in the treatment of sleep disorders, may enhance cognition and is used off-label for the treatment of cognitive dysfunction in some psychiatric disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder [ADHD]). The Physicians' Desk Reference cautions that it can produce psychoactive and euphoric effects typical of central nervous system stimulant drugs, and there is debate surrounding its potential for abuse, according to background information in the article. The mechanisms of action of modafinil are not well understood but are believed to differ from those of stimulant medications (such as methylphenidate and amphetamine), which increase dopamine (a neurotransmitter in the brain essential for the normal functioning of the central nervous system) in the brain by targeting the dopamine transporters, a mechanism that underlies the abuse potential of these drugs. However, there is growing evidence that dopamine may also play a role in the mode of action of modafinil. Nora D. Volkow, M.D., of the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md., and colleagues at Brookhaven National Laboratory conducted a study to test whether modafinil, at therapeutic doses, would elevate extracellular (located or occurring outside of cells) dopamine in the brain by blocking the dopamine transporter. The study included 10 healthy men, between the ages of 23-46 years, who received either placebo or modafinil: 200 mg, the dose recommended for narcolepsy; or 400 mg, a dose shown to be beneficial for the treatment of ADHD. The effects of modafinil on extracellular dopamine and on dopamine transporters were measured by positron emission tomography (a radiographic technique used to examine biochemical activity in tissue). The researchers found: "In this pilot study, modafinil acutely increased dopamine levels and blocked dopamine transporters in the human brain. Because drugs that increase dopamine have the potential for abuse, and considering the increasing use of modafinil for multiple purposes, these results suggest that risk for addiction in vulnerable persons merits heightened awareness." Modafinil also increased dopamine in the nucleus accumbens, a brain region critical for the rewarding effects of drugs of abuse.
"Modafinil was developed with an expectation that a medication could have a non-dopaminergic target for its wake-promoting effects. However, the current findings in humans, along with preclinical studies, documenting the indispensable role of dopamine in the wake-promoting effects of modafinil, support modafinil's dopamine-enhancing effects as a mechanism for its therapeutic actions."
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org.
JAMA REPORTS
VIDEO: Windows Media | Quicktime
STUDY FINDS PATIENTS WHO USE RELIGION TO COPE WITH ADVANCED CANCER ARE MORE LIKELY TO RECEIVE INTENSIVE, LIFE-PROLONGING CARE NEAR DEATH
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