(Embargoed Until: 3 P.M. (CT), Monday, June 16, 2003)
(Embargoed Until: 3 P.M. (CT), Monday, June 16, 2003)
(Embargoed Until: 3 P.M. (CT), Monday, June 16, 2003)
EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, JUNE 16, 2003
To contact Ramon Diaz-Arrastia, M.D., call Rachel Horton at (214) 648-3404.
GENE ASSOCIATED WITH ALZHEIMER DISEASE ALSO LINKED WITH POSTTRAUMATIC BRAIN INJURY SEIZURES
CHICAGO—Presence of a variation of the APOE gene (which has been linked with an increased risk for developing Alzheimer disease), also increases the risk for experiencing seizures after traumatic brain injury, according to an article in the June issue of The Archives of Neurology, one of the JAMA/Archives journals.
Posttraumatic epilepsy (PTE, or seizures) is common after traumatic brain injury (TBI, for example, a head injury sustained during a fall or car crash), occurring in 25 percent to 30 percent of cases of severe head injury, and 5 percent to 10 percent of cases of mild to moderate injury, according to the article. It is estimated that 5,000 to 30,000 new cases of epilepsy each year result from TBI. Previous studies have linked inheritance of a variant of the APOE gene (known as epsilon 4 or e4) with poor outcomes after TBI.
Ramon Diaz-Arrastia, M.D., Ph.D., of The University of Texas Southwestern Medical Center, Dallas, and colleagues investigated whether inheritance of APOE e4 is associated with an increased risk of having posttraumatic seizures.
The researchers obtained information on 106 patients admitted to the neurological service department of an urban, level I trauma center with a diagnosis of moderate or severe traumatic brain injury. Patients were evaluated six months after their injuries using the Glasgow Outcome Scale - Expanded (GOS - E, a measurement of outcomes after TBI, with 1 being the worst outcome). DNA samples were also collected to determine the variation of the APOE gene.
The researchers found that six months after injury, 31 (21 percent) patients had a poor outcome (GOS - E score, 1-4), 47 (44 percent) had an intermediate outcome (GOS - E score, 5-6), and 28 (26 percent) had a favorable outcome (GOS - E score 7-8). Twenty-one patients (20 percent) had at least 1 late posttraumatic seizure.
The researchers found that the risk of late posttraumatic seizures for patients with the e4 variation of the APOE gene was 2.41 times higher than the risk for patients without this genetic variation. However, inheritance of APOE e4 was not associated with an unfavorable GOS - E score.
"Posttraumatic epilepsy is a common and frequently disabling complication of TBI, for which there is no effective prophylactic therapy," write the authors. "Not all patients with TBI develop PTE, and inherited genetic factors may influence the likelihood of developing epilepsy after trauma. Our finding that APOE sigma 4 is associated with increased risk of PTE raises the possibility that therapeutic manipulation of lipid or lipoprotein metabolism in the brain may be useful as an antiepileptogenic therapy."
(Arch Neurol. 2003;60;818-822. Available post-embargo at archneurol.com)
Editor's Note: Dr. Diaz-Arrastia was supported by grants from the National Institutes of Health, Bethesda, Md.
For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail jamaarchmedia{at}ama-assn.org.
Go back to the top.
EMBARGOED UNTIL 3 P.M. (CT), MONDAY, JUNE 16, 2003
To contact Mark Lebwohl, M.D., call Lucia Lee at (212) 241-9200.
NEW DRUG SHOWS PROMISE FOR TREATMENT OF CHRONIC PSORIASIS
CHICAGO—A new drug called alefacept appears to be effective in treating moderate to severe psoriasis and reducing chronic skin lesions associated with the disorder, according to an article in the June issue of The Archives of Dermatology, one of the JAMA/Archives journals.
Psoriasis is a chronic, inflammatory skin disorder estimated to affect up to 2.5 percent of the world's population, according to the article. Although many treatments are available, most patients do not achieve prolonged disease-free periods and most therapeutics have limited long-term tolerability as well as substantial potential toxic effects.
Mark Lebwohl, M.D., of The Mount Sinai School of Medicine, New York, and colleagues conducted a randomized controlled trial of the drug alefacept in 507 patients with chronic psoriasis. The patients were randomized to three treatment groups: placebo (n=168), 10 milligrams of alefacept per week, injected into the muscle tissue (n=173), and 15 milligrams of alefacept per week (n=166) all given by injection into the thigh muscle. The treatment phase lasted for 12 weeks and was followed by 12 weeks of observation.
Patients were evaluated using the Psoriasis Area Severity Index (PASI) which measures the area of the body affected, and the severity of the psoriasis.
The researchers found that alefacept was associated significant improvements in PASI during the study. A greater percentage of patients in the 15 milligram group than in the placebo group achieved a significant reduction in PASI. Of patients in the 15 milligram group who achieved at least 75 percent PASI reduction 2 weeks after the last dose, 71 percent maintained at least a 50 percent improvement throughout the 12 week follow-up period.
"The clinical data presented herein confirm that IM [delivered via intra muscular injection] alefacept effectively improves psoriasis and produces durable remissions without appearing to compromise normal immune function," write the authors. "Its targeted mechanism of action was associated with a favorable safety profile, with no evidence of opportunistic infections or an increased incidence of malignancy. Patients receiving alefacept may experience prolonged, disease-free intervals with less need for maintenance therapy and potentially fewer retreatment periods."
(Arch Dermatol. 2003;139:719-727 Available post-embargo at archdermatol.com)
Editor's Note: Support for this research, data monitoring and analysis were provided by Biogen, Inc.
Editorial: Clinical Research Delivers New Hope for Patients With Psoriasis
In an accompanying editorial, Alice Gottlieb, M.D., Ph.D., of University of Medicine and Dentistry - Robert Wood Johnson Medical School, New Brunswick, N.J., describes the importance of new therapies for treating the often disfiguring skin disorder psoriasis: "Psoriasis is a life-disabling disorder in which 8 percent to 10 percent of patients aged 18 to 54 years actively contemplate suicide because of their disease."
"The strengths of alefacept are its ability to clear disease, its long-lived remissions, and excellent safety profile," Dr. Gottlieb writes.
"Since treatment with alefacept clears disease in only about one third of patients and its onset of action is slow, it will be important to study the efficacy, time until onset of clearance, and safety of alefacept in combination with cyclosporine, methotrexate, acitretin and phototherapy [other treatments for psoriasis]," writes Dr. Gottlieb.
In addition to further study of the drug, adjusting the dosage, which was fixed at either 10 milligrams or 15 milligrams per week, may provide better results Dr. Gottlieb states: "Fixed doses of alefacept rather than doses adjusted for patient weight were used in the phase 3 intravenous and intramuscular trials. Many patients with psoriasis are overweight, and it may be that higher doses of alefacept are required to achieve clearance in obese patients."
(Arch Dermatol. 2003;139:791-793 Available post-embargo at archdermatol.com)
Editor's Note: This work was funded in part by a grant from the David Ju Foundation, Morris Township, N.J., Johnson & Johnson's Focused Giving Program, New Brunswick, N.J., and general support to the Clinical Research Center from Merck & Co., Inc., Whitehouse Station, N.J. Dr. Gottlieb is an investigator, consultant, and speaker bureau member for Biogen, Amgen, Wyeth, Novartis, and Centocor, Inc. She is also a consultant and investigator for Genentech, Inc., and Xoma Corp.
For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail jamaarchmedia{at}ama-assn.org.
Go back to the top.
EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, JUNE 16, 2003
To contact Christopher E. M. Griffiths, M.D., F.R.C.P., e-mail Christopher.griffiths{at}man.ac.uk
EXCESSIVE WORRYING LINKED WITH LONGER TIME NEEDED TO IMPROVE PSORIASIS
CHICAGO—Psychological distress appears to have a detrimental effect on the outcome of patients treated for psoriasis with ultra violet (UV) light therapy, according to an article in the June issue of The Archives of Dermatology, one of the JAMA/Archives journals.
Inflammatory skin diseases, including psoriasis, are often believed by patients to be exacerbated by stressful life events, according to the article. Previous studies have shown that cognitive behavioral therapy in addition to medical treatment of the disorder significantly improves the severity of psoriasis during and after treatment. Other studies have shown that patients listening to stress reduction tapes while undergoing psoralen-UV-A (PUVA) photochemotherapy (a type of treatment for psoriasis that uses ultraviolet light) or UV-B phototherapy had a faster time to improvement of their psoriasis compared to patients that did not listen to the tapes.
Christopher E. M. Griffiths, M.D., F.R.C.P., of Hope Hospital, Manchester, England, and colleagues investigated whether psychological distress was related to treatment outcome in patients with psoriasis.
The researchers assessed severity of psoriasis, psychological distress, skin type, family history of psoriasis and alcohol consumption in 112 patients with psoriasis before starting PUVA therapy.
The researchers found that pathological or high-level worrying was the only significant predictor of the time needed for PUVA to clear psoriasis. The time it took for the therapy to clear psoriasis differed markedly between high-level (n=38) and low-level (n=74) worriers. Patients in the high-level worry group took 1.8 times longer for their psoriasis to respond and clear with PUVA therapy compared to the low-level worry group (the 50th percentile time to clearance was approximately 100 days vs. approximately 80 days in the high and low worry groups, respectively).
"This study shows that psychological distress, in the form of excessive worrying, significantly slows the rate of clearance of psoriasis in patients undergoing standard therapy with PUVA," write the authors. "These findings provide further evidence of the existence of a brain-skin axis. Focus on this fascinating area is needed to identify potential mechanisms and to encompass a holistic approach to the treatment of chronic inflammatory skin disease."
(Arch Dermatol. 2003;139:752-756 Available post-embargo at archdermatol.com)
Editor's Note: This study was supported by a grant from the Psoriasis Association of Great Britain and Ireland, Northampton, England.
For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail jamaarchmedia{at}ama-assn.org.
Go back to the top.
EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, JUNE 16, 2003
To contact Henry A. Milczuk, M.D., call Tamara Hargens at (503) 494-8653.
INTRAVENOUS SEDATION SAFE FOR SOME PEDIATRIC EAR, NOSE AND THROAT PROCEDURES
CHICAGO—Various minor procedures in otolaryngology (surgeries involving the ear, nose and throat) can be performed safely and effectively in children using intravenous sedation (IVS) versus general anesthesia, according to an article in The Archives of Otolaryngology — Head & Neck Surgery, one of the JAMA/Archives journals.
Many procedures in the otolaryngology practice have required general anesthesia because of they are painful and cause anxiety in children, according to the article.
Henry A. Milczuk, M.D., of Oregon Health & Science University, Portland, Ore., received records of patients younger than 18 years old who underwent tympastomy tube removal (ear tube removal) or patch myringoplasty (surgery of the eardrum), nasal ciliary biopsy (a biopsy of the lining of the nose), fine needle aspiration (taking a tissue sample using a thin needle) or other minor procedures between September 1, 1998 and August 31, 2001. The patients' procedures were performed either in an outpatient clinic using IVS, or in an operating room using general anesthesia (GA).
In all, 103 procedures were performed (54 with IVS and 49 with GA). The most common procedure was ear tube removal with patch myringoplasty (IVS, 52 ears; GA, 42 ears). Outcomes were similar in both groups, including incidence of hypoxia (low oxygen level in the blood), airway obstruction, and bradycardia (a slowing of the heart rate) all of which resolved spontaneously or resolved with non-invasive interventions such as giving oxygen.
The researchers also found that average hospital charges were significantly higher for the GA group (IVS, $356.22, GA, $1,515.55, on average).
"This review demonstrates that pediatric otolaryngology procedures can be performed effectively and safely in a hospital-based outpatient clinic when IVS and monitoring are provided by a pediatric sedation team," write the authors. "Although our economic analysis has limitations, it appears that a significant decrease in hospital chargers occurs with this approach."
(Arch Oto. 2003;129:637-641 Available post-embargo at archoto.com)
For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail jamaarchmedia{at}ama-assn.org.
Go back to the top.
