Jeff Evans

HERSHEY, PA. — Patch testing with personal cosmetic products or topical prescriptions may identify allergens that are not found on common series in patients with suspected allergic contact dermatitis to cosmetics, Erin M. Warshaw, M.D., said at a meeting on contact dermatitis sponsored by Pennsylvania State University.

Most of the allergens that are found in cosmetic products function as fragrance, preservative, emulsifier, pigment, antioxidant, or surfactant, said Dr. Warshaw, codirector of the occupational and contact dermatitis clinic at the University of Minnesota, Minneapolis.

At least 6% of the positive reactions to patch tests were thought to be related to cosmetics in a study of 8,093 patients. More than 90% of the patients with reactions related to cosmetics were women and patients aged 20–49 years (J. Am. Acad. Dermatol. 1982;6:909–17). The most common cosmetic products that caused allergic contact dermatitis in that series of patients included skin care products, facial makeup, nail preparations, and fragranced products.

In a separate study of 203 patients with persistent or recurrent eyelid dermatitis, 151 (74%) of the cases were caused by cosmetics. Of the 167 patients with allergic contact dermatitis, 66 (40%) would have been missed by the 24-item thin-layer rapid use epicutaneous (TRUE) test (J. Am. Acad. Dermatol. 2002;47:755–65).

The Chemotechnique Diagnostics cosmetic series contains 48 allergens plus the standard series, but only 6 of these allergens are on the TRUE test. “It's important to patch test to an extended series as well as personal products,” Dr. Warshaw advised.

Preservatives, “probably the most important category” of ingredients in cosmetics, include formaldehyde-releasing chemicals such as quaternium-15, triclosan, benzyl alcohol, Kathon CG, Euxyl K 400, and iodopropynyl butyl carbamate, Dr. Warshaw said. She reviewed some of these preservatives:

▸ Quaternium-15. In more than nine U.S. studies, quaternium-15 has been the most common cause of preservative allergy. The prevalence of allergic contact dermatitis to the preservative has increased in studies conducted by the North American Contact Dermatitis Group, from 2.3% in the 1970s to 9.6% in 1998. Most (58%–66%) of the positive reactions to quaternium-15 during patch testing have been reported to be relevant to a current or past episode of dermatitis.

About half of the patients with an allergy to quaternium-15 will cross-react to other formaldehyde-releasing preservatives such as bronopol, imidazolidinyl urea, diazolidinyl urea, DMDM hydantoin, Grotan BK, ethylene urea melamine formaldehyde (in clothing), and toluene sulfonamide formaldehyde resin (in nail polish), said Dr. Warshaw, also of the department of dermatology at the university.

▸ Triclosan. This antimicrobial agent is found in deodorants, soaps, powders, and “odor eaters.”

▸ Benzyl alcohol (phenylcarbinol). This preservative is a rare allergen that is not on the TRUE test. Patch testing to patients' personal products such as prescription creams and Aveeno lotion will help check for a reaction to this allergen, she said.

▸ Kathon CG. This allergen is on the TRUEtest. It is a mix of methylchloroisothiazolinone and methylisothiazolinone.

Lanolin is another common allergen found in lipstick, lip balm, creams, and waxes, and is found on the TRUE test. Bee glue or wax (propolis), known as the dimethylallyl ester of caffeic acid, is an allergen in lipstick, ointments, and mascara. Propolis is a primary ingredient in Burt's Bees products.

The members-only portion of the American Contact Dermatitis Society Web site, www.contactderm.org

HERSHEY, PA. — Patch testing with personal cosmetic products or topical prescriptions may identify allergens that are not found on common series in patients with suspected allergic contact dermatitis to cosmetics, Erin M. Warshaw, M.D., said at a meeting on contact dermatitis sponsored by Pennsylvania State University.

Most of the allergens that are found in cosmetic products function as fragrance, preservative, emulsifier, pigment, antioxidant, or surfactant, said Dr. Warshaw, codirector of the occupational and contact dermatitis clinic at the University of Minnesota, Minneapolis.

At least 6% of the positive reactions to patch tests were thought to be related to cosmetics in a study of 8,093 patients. More than 90% of the patients with reactions related to cosmetics were women and patients aged 20–49 years (J. Am. Acad. Dermatol. 1982;6:909–17). The most common cosmetic products that caused allergic contact dermatitis in that series of patients included skin care products, facial makeup, nail preparations, and fragranced products.

In a separate study of 203 patients with persistent or recurrent eyelid dermatitis, 151 (74%) of the cases were caused by cosmetics. Of the 167 patients with allergic contact dermatitis, 66 (40%) would have been missed by the 24-item thin-layer rapid use epicutaneous (TRUE) test (J. Am. Acad. Dermatol. 2002;47:755–65).

The Chemotechnique Diagnostics cosmetic series contains 48 allergens plus the standard series, but only 6 of these allergens are on the TRUE test. “It's important to patch test to an extended series as well as personal products,” Dr. Warshaw advised.

Preservatives, “probably the most important category” of ingredients in cosmetics, include formaldehyde-releasing chemicals such as quaternium-15, triclosan, benzyl alcohol, Kathon CG, Euxyl K 400, and iodopropynyl butyl carbamate, Dr. Warshaw said. She reviewed some of these preservatives:

▸ Quaternium-15. In more than nine U.S. studies, quaternium-15 has been the most common cause of preservative allergy. The prevalence of allergic contact dermatitis to the preservative has increased in studies conducted by the North American Contact Dermatitis Group, from 2.3% in the 1970s to 9.6% in 1998. Most (58%–66%) of the positive reactions to quaternium-15 during patch testing have been reported to be relevant to a current or past episode of dermatitis.

About half of the patients with an allergy to quaternium-15 will cross-react to other formaldehyde-releasing preservatives such as bronopol, imidazolidinyl urea, diazolidinyl urea, DMDM hydantoin, Grotan BK, ethylene urea melamine formaldehyde (in clothing), and toluene sulfonamide formaldehyde resin (in nail polish), said Dr. Warshaw, also of the department of dermatology at the university.

▸ Triclosan. This antimicrobial agent is found in deodorants, soaps, powders, and “odor eaters.”

▸ Benzyl alcohol (phenylcarbinol). This preservative is a rare allergen that is not on the TRUE test. Patch testing to patients' personal products such as prescription creams and Aveeno lotion will help check for a reaction to this allergen, she said.

▸ Kathon CG. This allergen is on the TRUEtest. It is a mix of methylchloroisothiazolinone and methylisothiazolinone.

Lanolin is another common allergen found in lipstick, lip balm, creams, and waxes, and is found on the TRUE test. Bee glue or wax (propolis), known as the dimethylallyl ester of caffeic acid, is an allergen in lipstick, ointments, and mascara. Propolis is a primary ingredient in Burt's Bees products.

The members-only portion of the American Contact Dermatitis Society Web site, www.contactderm.org

HERSHEY, PA. — Patch testing with personal cosmetic products or topical prescriptions may identify allergens that are not found on common series in patients with suspected allergic contact dermatitis to cosmetics, Erin M. Warshaw, M.D., said at a meeting on contact dermatitis sponsored by Pennsylvania State University.

Most of the allergens that are found in cosmetic products function as fragrance, preservative, emulsifier, pigment, antioxidant, or surfactant, said Dr. Warshaw, codirector of the occupational and contact dermatitis clinic at the University of Minnesota, Minneapolis.

At least 6% of the positive reactions to patch tests were thought to be related to cosmetics in a study of 8,093 patients. More than 90% of the patients with reactions related to cosmetics were women and patients aged 20–49 years (J. Am. Acad. Dermatol. 1982;6:909–17). The most common cosmetic products that caused allergic contact dermatitis in that series of patients included skin care products, facial makeup, nail preparations, and fragranced products.

In a separate study of 203 patients with persistent or recurrent eyelid dermatitis, 151 (74%) of the cases were caused by cosmetics. Of the 167 patients with allergic contact dermatitis, 66 (40%) would have been missed by the 24-item thin-layer rapid use epicutaneous (TRUE) test (J. Am. Acad. Dermatol. 2002;47:755–65).

The Chemotechnique Diagnostics cosmetic series contains 48 allergens plus the standard series, but only 6 of these allergens are on the TRUE test. “It's important to patch test to an extended series as well as personal products,” Dr. Warshaw advised.

Preservatives, “probably the most important category” of ingredients in cosmetics, include formaldehyde-releasing chemicals such as quaternium-15, triclosan, benzyl alcohol, Kathon CG, Euxyl K 400, and iodopropynyl butyl carbamate, Dr. Warshaw said. She reviewed some of these preservatives:

▸ Quaternium-15. In more than nine U.S. studies, quaternium-15 has been the most common cause of preservative allergy. The prevalence of allergic contact dermatitis to the preservative has increased in studies conducted by the North American Contact Dermatitis Group, from 2.3% in the 1970s to 9.6% in 1998. Most (58%–66%) of the positive reactions to quaternium-15 during patch testing have been reported to be relevant to a current or past episode of dermatitis.

About half of the patients with an allergy to quaternium-15 will cross-react to other formaldehyde-releasing preservatives such as bronopol, imidazolidinyl urea, diazolidinyl urea, DMDM hydantoin, Grotan BK, ethylene urea melamine formaldehyde (in clothing), and toluene sulfonamide formaldehyde resin (in nail polish), said Dr. Warshaw, also of the department of dermatology at the university.

▸ Triclosan. This antimicrobial agent is found in deodorants, soaps, powders, and “odor eaters.”

▸ Benzyl alcohol (phenylcarbinol). This preservative is a rare allergen that is not on the TRUE test. Patch testing to patients' personal products such as prescription creams and Aveeno lotion will help check for a reaction to this allergen, she said.

▸ Kathon CG. This allergen is on the TRUEtest. It is a mix of methylchloroisothiazolinone and methylisothiazolinone.

Lanolin is another common allergen found in lipstick, lip balm, creams, and waxes, and is found on the TRUE test. Bee glue or wax (propolis), known as the dimethylallyl ester of caffeic acid, is an allergen in lipstick, ointments, and mascara. Propolis is a primary ingredient in Burt's Bees products.

The members-only portion of the American Contact Dermatitis Society Web site, www.contactderm.org

Intensity of exposure to tobacco smoke appears to be associated with the rate of metabolic syndrome in a dose-response relationship in adolescents, according to a study in the cross-sectional third National Health and Nutrition Examination Survey.

The study is the first of its kind to associate smoking with metabolic syndrome by using a biologic marker of smoking–serum levels of the nicotine metabolite cotinine–and exposure to environmental tobacco smoke in adolescents, reported Michael Weitzman, M.D., of the University of Rochester (N.Y.) and his colleagues (Circulation 2005;112:862–9).

In the 1988–1994 survey of 2,273 adolescents aged 12–19 years, exposure to environmental tobacco smoke and active smoking were independently tied to nearly fivefold and more than sixfold higher odds of developing metabolic syndrome, respectively, after adjusting for gender, age, race or ethnicity, poverty status, region, and parental history of diabetes or heart attack.

The investigators obtained similar results when they restricted their analysis to individuals with a body mass index at the 85th percentile or higher (those who are overweight and at risk for overweight).

Of 664 adolescents overweight or at risk for overweight, metabolic syndrome occurred at a rate of 5.6% in individuals who were not exposed to tobacco smoke; 19.6% in those exposed to environmental or secondhand smoke; and 23.6% in active smokers. The increase in the rate of metabolic syndrome in adolescents followed a significant trend from those who were not exposed to tobacco smoke, through the lowest to highest level of exposure to environmental tobacco smoke, up to active smokers.

The criteria for metabolic syndrome consisted of a triglyceride level of 110 mg/dL or higher, an HDL cholesterol level of 40 mg/dL or lower, a waist circumference at the 90th percentile or higher, blood pressure in the 90th percentile or higher, and a fasting plasma glucose level of 100 mg/dL or higher.

Their report cannot “conclusively establish an etiologic role for tobacco smoke in the development of metabolic syndrome in youth,” the investigators noted. But a “plausible biologic basis exists for this association” in that “evidence in studies of children suggests that insulin resistance mediates the deleterious effects of excess adiposity on blood pressure and lipids in metabolic syndrome” and “smoking is associated with increased insulin resistance in adults.”

At least two other studies have found increased rates of metabolic syndrome in adult smokers.

Intensity of exposure to tobacco smoke appears to be associated with the rate of metabolic syndrome in a dose-response relationship in adolescents, according to a study in the cross-sectional third National Health and Nutrition Examination Survey.

The study is the first of its kind to associate smoking with metabolic syndrome by using a biologic marker of smoking–serum levels of the nicotine metabolite cotinine–and exposure to environmental tobacco smoke in adolescents, reported Michael Weitzman, M.D., of the University of Rochester (N.Y.) and his colleagues (Circulation 2005;112:862–9).

In the 1988–1994 survey of 2,273 adolescents aged 12–19 years, exposure to environmental tobacco smoke and active smoking were independently tied to nearly fivefold and more than sixfold higher odds of developing metabolic syndrome, respectively, after adjusting for gender, age, race or ethnicity, poverty status, region, and parental history of diabetes or heart attack.

The investigators obtained similar results when they restricted their analysis to individuals with a body mass index at the 85th percentile or higher (those who are overweight and at risk for overweight).

Of 664 adolescents overweight or at risk for overweight, metabolic syndrome occurred at a rate of 5.6% in individuals who were not exposed to tobacco smoke; 19.6% in those exposed to environmental or secondhand smoke; and 23.6% in active smokers. The increase in the rate of metabolic syndrome in adolescents followed a significant trend from those who were not exposed to tobacco smoke, through the lowest to highest level of exposure to environmental tobacco smoke, up to active smokers.

The criteria for metabolic syndrome consisted of a triglyceride level of 110 mg/dL or higher, an HDL cholesterol level of 40 mg/dL or lower, a waist circumference at the 90th percentile or higher, blood pressure in the 90th percentile or higher, and a fasting plasma glucose level of 100 mg/dL or higher.

Their report cannot “conclusively establish an etiologic role for tobacco smoke in the development of metabolic syndrome in youth,” the investigators noted. But a “plausible biologic basis exists for this association” in that “evidence in studies of children suggests that insulin resistance mediates the deleterious effects of excess adiposity on blood pressure and lipids in metabolic syndrome” and “smoking is associated with increased insulin resistance in adults.”

At least two other studies have found increased rates of metabolic syndrome in adult smokers.

Intensity of exposure to tobacco smoke appears to be associated with the rate of metabolic syndrome in a dose-response relationship in adolescents, according to a study in the cross-sectional third National Health and Nutrition Examination Survey.

The study is the first of its kind to associate smoking with metabolic syndrome by using a biologic marker of smoking–serum levels of the nicotine metabolite cotinine–and exposure to environmental tobacco smoke in adolescents, reported Michael Weitzman, M.D., of the University of Rochester (N.Y.) and his colleagues (Circulation 2005;112:862–9).

In the 1988–1994 survey of 2,273 adolescents aged 12–19 years, exposure to environmental tobacco smoke and active smoking were independently tied to nearly fivefold and more than sixfold higher odds of developing metabolic syndrome, respectively, after adjusting for gender, age, race or ethnicity, poverty status, region, and parental history of diabetes or heart attack.

The investigators obtained similar results when they restricted their analysis to individuals with a body mass index at the 85th percentile or higher (those who are overweight and at risk for overweight).

Of 664 adolescents overweight or at risk for overweight, metabolic syndrome occurred at a rate of 5.6% in individuals who were not exposed to tobacco smoke; 19.6% in those exposed to environmental or secondhand smoke; and 23.6% in active smokers. The increase in the rate of metabolic syndrome in adolescents followed a significant trend from those who were not exposed to tobacco smoke, through the lowest to highest level of exposure to environmental tobacco smoke, up to active smokers.

The criteria for metabolic syndrome consisted of a triglyceride level of 110 mg/dL or higher, an HDL cholesterol level of 40 mg/dL or lower, a waist circumference at the 90th percentile or higher, blood pressure in the 90th percentile or higher, and a fasting plasma glucose level of 100 mg/dL or higher.

Their report cannot “conclusively establish an etiologic role for tobacco smoke in the development of metabolic syndrome in youth,” the investigators noted. But a “plausible biologic basis exists for this association” in that “evidence in studies of children suggests that insulin resistance mediates the deleterious effects of excess adiposity on blood pressure and lipids in metabolic syndrome” and “smoking is associated with increased insulin resistance in adults.”

At least two other studies have found increased rates of metabolic syndrome in adult smokers.

Atypical reactions to heroin in users in five states have been attributed to contamination with the β-2 adrenergic receptor agonist clenbuterol, according to a report from the Centers for Disease Control and Prevention.

The 26 cases reported from January through April in Connecticut, New Jersey, New York, North Carolina, and South Carolina are the “first published accounts of poisoning from clenbuterol associated with reported heroin use” (MMWR 2005;54:793–6).

Clenbuterol is approved for limited veterinary use in the United States but is also used illicitly as an alternative to anabolic steroids in humans and livestock because it can increase muscle mass, the report noted. The cases “likely represent a fraction of actual cases of clenbuterol poisoning,” since patients might not undergo medical evaluation for fear of legal repercussions. Patients also might have presumed–as emergency physicians and hospital intensivists might have–that the effects were related to a known coingestant, the report said.

Heroin typically produces euphoria, miosis, and respiratory and central nervous system depression. The cardiovascular effects associated with these cases are not common.

The six most common signs, symptoms, and laboratory findings among the cases included tachycardia (24 of 26 cases), hypokalemia (22 of 24), palpitations (22 of 26), hyperglycemia (19 of 23), chest pain (15 of 26), and hypotension (14 of 26). Other symptoms reported less often have been nausea, shortness of breath, agitation, and tremor.

Only eight of the cases were confirmed because the assay for clenbuterol is not available in the majority of laboratories; other cases were classified as probable (16) and suspected (2).

Heroin-related clenbuterol toxicity may be diagnosed in the laboratory by detecting clenbuterol in urine, blood, or environmental samples (such as heroin).

The report indicated that it is unknown if the cases represent the adulteration of a single source of heroin before widespread distribution or the adulteration of multiple sources, or if the substance used by each patient was heroin contaminated with clenbuterol or pure clenbuterol sold as heroin. In the mid-1990s, heroin adulterated with scopolamine caused widespread poisoning in four states (MMWR 1996;45:457–60).

Atypical reactions to heroin in users in five states have been attributed to contamination with the β-2 adrenergic receptor agonist clenbuterol, according to a report from the Centers for Disease Control and Prevention.

The 26 cases reported from January through April in Connecticut, New Jersey, New York, North Carolina, and South Carolina are the “first published accounts of poisoning from clenbuterol associated with reported heroin use” (MMWR 2005;54:793–6).

Clenbuterol is approved for limited veterinary use in the United States but is also used illicitly as an alternative to anabolic steroids in humans and livestock because it can increase muscle mass, the report noted. The cases “likely represent a fraction of actual cases of clenbuterol poisoning,” since patients might not undergo medical evaluation for fear of legal repercussions. Patients also might have presumed–as emergency physicians and hospital intensivists might have–that the effects were related to a known coingestant, the report said.

Heroin typically produces euphoria, miosis, and respiratory and central nervous system depression. The cardiovascular effects associated with these cases are not common.

The six most common signs, symptoms, and laboratory findings among the cases included tachycardia (24 of 26 cases), hypokalemia (22 of 24), palpitations (22 of 26), hyperglycemia (19 of 23), chest pain (15 of 26), and hypotension (14 of 26). Other symptoms reported less often have been nausea, shortness of breath, agitation, and tremor.

Only eight of the cases were confirmed because the assay for clenbuterol is not available in the majority of laboratories; other cases were classified as probable (16) and suspected (2).

Heroin-related clenbuterol toxicity may be diagnosed in the laboratory by detecting clenbuterol in urine, blood, or environmental samples (such as heroin).

The report indicated that it is unknown if the cases represent the adulteration of a single source of heroin before widespread distribution or the adulteration of multiple sources, or if the substance used by each patient was heroin contaminated with clenbuterol or pure clenbuterol sold as heroin. In the mid-1990s, heroin adulterated with scopolamine caused widespread poisoning in four states (MMWR 1996;45:457–60).

Atypical reactions to heroin in users in five states have been attributed to contamination with the β-2 adrenergic receptor agonist clenbuterol, according to a report from the Centers for Disease Control and Prevention.

The 26 cases reported from January through April in Connecticut, New Jersey, New York, North Carolina, and South Carolina are the “first published accounts of poisoning from clenbuterol associated with reported heroin use” (MMWR 2005;54:793–6).

Clenbuterol is approved for limited veterinary use in the United States but is also used illicitly as an alternative to anabolic steroids in humans and livestock because it can increase muscle mass, the report noted. The cases “likely represent a fraction of actual cases of clenbuterol poisoning,” since patients might not undergo medical evaluation for fear of legal repercussions. Patients also might have presumed–as emergency physicians and hospital intensivists might have–that the effects were related to a known coingestant, the report said.

Heroin typically produces euphoria, miosis, and respiratory and central nervous system depression. The cardiovascular effects associated with these cases are not common.

The six most common signs, symptoms, and laboratory findings among the cases included tachycardia (24 of 26 cases), hypokalemia (22 of 24), palpitations (22 of 26), hyperglycemia (19 of 23), chest pain (15 of 26), and hypotension (14 of 26). Other symptoms reported less often have been nausea, shortness of breath, agitation, and tremor.

Only eight of the cases were confirmed because the assay for clenbuterol is not available in the majority of laboratories; other cases were classified as probable (16) and suspected (2).

Heroin-related clenbuterol toxicity may be diagnosed in the laboratory by detecting clenbuterol in urine, blood, or environmental samples (such as heroin).

The report indicated that it is unknown if the cases represent the adulteration of a single source of heroin before widespread distribution or the adulteration of multiple sources, or if the substance used by each patient was heroin contaminated with clenbuterol or pure clenbuterol sold as heroin. In the mid-1990s, heroin adulterated with scopolamine caused widespread poisoning in four states (MMWR 1996;45:457–60).

STOCKHOLM – Individuals who carry the apolipoprotein E ϵ4 allele that increases the risk of developing Alzheimer's disease may lower their risk to that of a noncarrier through regular exercise, moderate fat intake, and low alcohol consumption, reported Tiia Ngandu at the 12th Congress of the International Psychogeriatric Association.

Ms. Ngandu and her associates studied 1,449 Finnish people who participated in the longitudinal, population-based Cardiovascular Risk Factors, Aging, and Dementia study (CAIDE) in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, the participants were aged 65–79 years when they were re-examined in 1998.

Based on questions answered at midlife, active individuals (exercised at least twice per week) who carried the ϵ4 allele had a significantly lower likelihood of developing Alzheimer's disease (AD) than sedentary carriers, said Ms. Ngandu, a doctoral student at the Aging Research Center at the Karolinska Institute, Stockholm.

Intake of polyunsaturated fatty acids did not alter the odds of developing AD in carriers, but high intake of saturated fatty acids was associated with significantly greater odds of AD in carriers, compared with a low intake.

Carriers who frequently consumed alcohol had a significantly higher likelihood of developing AD than carriers who drank infrequently or never.

None of the lifestyle factors reduced the risk of AD in noncarriers, she noted. “[Apolipoprotein E ϵ4 allele] carriers seem more vulnerable to various environmental effects,” Ms. Ngandu said.

People with a parent with late-onset Alzheimer's disease may undergo genotyping for apolipoprotein E ε4. A positive finding is not diagnostic of Alzheimer's disease, even in a symptomatic patient.

The test also is done in some patients with both high cholesterol and elevated triglycerides to determine whether the patient's lipid disorder has a genetic component.

STOCKHOLM – Individuals who carry the apolipoprotein E ϵ4 allele that increases the risk of developing Alzheimer's disease may lower their risk to that of a noncarrier through regular exercise, moderate fat intake, and low alcohol consumption, reported Tiia Ngandu at the 12th Congress of the International Psychogeriatric Association.

Ms. Ngandu and her associates studied 1,449 Finnish people who participated in the longitudinal, population-based Cardiovascular Risk Factors, Aging, and Dementia study (CAIDE) in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, the participants were aged 65–79 years when they were re-examined in 1998.

Based on questions answered at midlife, active individuals (exercised at least twice per week) who carried the ϵ4 allele had a significantly lower likelihood of developing Alzheimer's disease (AD) than sedentary carriers, said Ms. Ngandu, a doctoral student at the Aging Research Center at the Karolinska Institute, Stockholm.

Intake of polyunsaturated fatty acids did not alter the odds of developing AD in carriers, but high intake of saturated fatty acids was associated with significantly greater odds of AD in carriers, compared with a low intake.

Carriers who frequently consumed alcohol had a significantly higher likelihood of developing AD than carriers who drank infrequently or never.

None of the lifestyle factors reduced the risk of AD in noncarriers, she noted. “[Apolipoprotein E ϵ4 allele] carriers seem more vulnerable to various environmental effects,” Ms. Ngandu said.

People with a parent with late-onset Alzheimer's disease may undergo genotyping for apolipoprotein E ε4. A positive finding is not diagnostic of Alzheimer's disease, even in a symptomatic patient.

The test also is done in some patients with both high cholesterol and elevated triglycerides to determine whether the patient's lipid disorder has a genetic component.

STOCKHOLM – Individuals who carry the apolipoprotein E ϵ4 allele that increases the risk of developing Alzheimer's disease may lower their risk to that of a noncarrier through regular exercise, moderate fat intake, and low alcohol consumption, reported Tiia Ngandu at the 12th Congress of the International Psychogeriatric Association.

Ms. Ngandu and her associates studied 1,449 Finnish people who participated in the longitudinal, population-based Cardiovascular Risk Factors, Aging, and Dementia study (CAIDE) in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, the participants were aged 65–79 years when they were re-examined in 1998.

Based on questions answered at midlife, active individuals (exercised at least twice per week) who carried the ϵ4 allele had a significantly lower likelihood of developing Alzheimer's disease (AD) than sedentary carriers, said Ms. Ngandu, a doctoral student at the Aging Research Center at the Karolinska Institute, Stockholm.

Intake of polyunsaturated fatty acids did not alter the odds of developing AD in carriers, but high intake of saturated fatty acids was associated with significantly greater odds of AD in carriers, compared with a low intake.

Carriers who frequently consumed alcohol had a significantly higher likelihood of developing AD than carriers who drank infrequently or never.

None of the lifestyle factors reduced the risk of AD in noncarriers, she noted. “[Apolipoprotein E ϵ4 allele] carriers seem more vulnerable to various environmental effects,” Ms. Ngandu said.

People with a parent with late-onset Alzheimer's disease may undergo genotyping for apolipoprotein E ε4. A positive finding is not diagnostic of Alzheimer's disease, even in a symptomatic patient.

The test also is done in some patients with both high cholesterol and elevated triglycerides to determine whether the patient's lipid disorder has a genetic component.

STOCKHOLM – Clinicians shy away from disclosing a diagnosis of mild cognitive impairment and its potential to convert to Alzheimer's disease.

They also differ in how they word the disclosure when they opt to share the diagnosis and prognosis with the patient and relatives. For their part, families may not want patients to know when they have been diagnosed with Alzheimer's disease, according to reports presented at the 12th Congress of the International Psychogeriatric Association.

“In dementia, disclosure is not common clinical practice”–only about 15% of professionals disclose the diagnosis to patients–“but there seems to be a trend toward more openness about the diagnosis,” said Els Derksen, R.N., a researcher at the Alzheimer's center at St. Radboud University Medical Center, Nijmegen, the Netherlands. But in contrast to several studies of disclosing a diagnosis of dementia, no studies have been published about disclosing a diagnosis of mild cognitive impairment (MCI).

Ms. Derksen discussed the responses of physicians who completed an optional appendix to a questionnaire that was a part of the European DESCRIPA (Development of Screening Guidelines and Diagnostic Criteria for Predementia Alzheimer's Disease) multicenter study. The study included patients with suspected MCI.

In discussions with 101 patients with MCI or possible early dementia, physicians told 28% that they had MCI, 62% that they had abnormal memory or cognitive problems, 4% that they had worrisome symptoms or depression plus memory problems, 3% that they had normal memory problems or forgetfulness, 2% that they had amnestic symptoms, and 1% that they had mixed and vascular dementia.

Among 100 patients who received information about their prognosis, physicians told 4% nothing, 18% that the prognosis was unknown or uncertain, 20% that the condition probably would remain stable, 10% that it probably would progress, and 66% that follow-up would be indicated. (The percentages do not add to 100% because follow-up was included with other information for some patients.)

When physicians were asked to describe their use of the term Alzheimer's disease in their interactions with a total of 80 patients, they reported that they did not use the term at all in 23%. Physicians told 72% that they could possibly convert to Alzheimer's disease. They told 4% of the patients that they had Alzheimer's disease or predementia, and 1% that Alzheimer's was not present or detected.

In nearly all instances, the same information about diagnosis, prognosis, and specific use of the term Alzheimer's disease was given to patients' families.

Alzheimer's disease in its predementia stage was suspected in 77 of 101 patients. A physician's decision to inform a patient of the diagnosis was most often guided by the patient's wish to know, a belief in shared decision making between physician and patient, and initiation of medication.

A qualitative analysis of 41 patients found that there was a difference between some centers in using the terms MCI or more descriptive language such as “memory problems or worrisome symptoms,” which suggests that “some centers are more hesitant than others in disclosure of their suspicions,” Ms. Derksen said.

“I think that further research is needed on how to inform patients about MCI,” she added.

In a separate study, family members of patients with Alzheimer's disease indicated that they did not wish to reveal the diagnosis to the patient primarily because of a concern for causing anxiety and depression in the patient.

Filip Bouckaert, M.D., of the department of old age psychiatry at University Centre St. Jozef, Kortenberg, Belgium, interviewed 50 family members of outpatients with Alzheimer's disease and 50 family members of inpatients with the disease.

Their results, reported during a poster session at the congress, showed that 57% did not want the patient to be told the diagnosis; this included 42% of family members of outpatients and 72% of family members of inpatients.

Half of family members who did not want the patients to know about the diagnosis cited the possibility of causing anxiety or depression as the main reason not to tell. Similarly, half of the family members who thought the patient should be told said that his or her right to know was the primary reason to tell the patient the diagnosis.

More family members approved of the disclosure of diagnosis in patients with mild dementia (86%) than in those with moderate (39%) or severe (31%) dementia.

Despite the wish by most family members not to disclose the diagnosis to their affected relatives, 90% of family members wanted to be told their diagnosis if they developed Alzheimer's disease.

A similar study in Ireland found that 83% of family members said that patients with Alzheimer's disease should not be told the diagnosis (BMJ 1996;313:529–30).

STOCKHOLM – Clinicians shy away from disclosing a diagnosis of mild cognitive impairment and its potential to convert to Alzheimer's disease.

They also differ in how they word the disclosure when they opt to share the diagnosis and prognosis with the patient and relatives. For their part, families may not want patients to know when they have been diagnosed with Alzheimer's disease, according to reports presented at the 12th Congress of the International Psychogeriatric Association.

“In dementia, disclosure is not common clinical practice”–only about 15% of professionals disclose the diagnosis to patients–“but there seems to be a trend toward more openness about the diagnosis,” said Els Derksen, R.N., a researcher at the Alzheimer's center at St. Radboud University Medical Center, Nijmegen, the Netherlands. But in contrast to several studies of disclosing a diagnosis of dementia, no studies have been published about disclosing a diagnosis of mild cognitive impairment (MCI).

Ms. Derksen discussed the responses of physicians who completed an optional appendix to a questionnaire that was a part of the European DESCRIPA (Development of Screening Guidelines and Diagnostic Criteria for Predementia Alzheimer's Disease) multicenter study. The study included patients with suspected MCI.

In discussions with 101 patients with MCI or possible early dementia, physicians told 28% that they had MCI, 62% that they had abnormal memory or cognitive problems, 4% that they had worrisome symptoms or depression plus memory problems, 3% that they had normal memory problems or forgetfulness, 2% that they had amnestic symptoms, and 1% that they had mixed and vascular dementia.

Among 100 patients who received information about their prognosis, physicians told 4% nothing, 18% that the prognosis was unknown or uncertain, 20% that the condition probably would remain stable, 10% that it probably would progress, and 66% that follow-up would be indicated. (The percentages do not add to 100% because follow-up was included with other information for some patients.)

When physicians were asked to describe their use of the term Alzheimer's disease in their interactions with a total of 80 patients, they reported that they did not use the term at all in 23%. Physicians told 72% that they could possibly convert to Alzheimer's disease. They told 4% of the patients that they had Alzheimer's disease or predementia, and 1% that Alzheimer's was not present or detected.

In nearly all instances, the same information about diagnosis, prognosis, and specific use of the term Alzheimer's disease was given to patients' families.

Alzheimer's disease in its predementia stage was suspected in 77 of 101 patients. A physician's decision to inform a patient of the diagnosis was most often guided by the patient's wish to know, a belief in shared decision making between physician and patient, and initiation of medication.

A qualitative analysis of 41 patients found that there was a difference between some centers in using the terms MCI or more descriptive language such as “memory problems or worrisome symptoms,” which suggests that “some centers are more hesitant than others in disclosure of their suspicions,” Ms. Derksen said.

“I think that further research is needed on how to inform patients about MCI,” she added.

In a separate study, family members of patients with Alzheimer's disease indicated that they did not wish to reveal the diagnosis to the patient primarily because of a concern for causing anxiety and depression in the patient.

Filip Bouckaert, M.D., of the department of old age psychiatry at University Centre St. Jozef, Kortenberg, Belgium, interviewed 50 family members of outpatients with Alzheimer's disease and 50 family members of inpatients with the disease.

Their results, reported during a poster session at the congress, showed that 57% did not want the patient to be told the diagnosis; this included 42% of family members of outpatients and 72% of family members of inpatients.

Half of family members who did not want the patients to know about the diagnosis cited the possibility of causing anxiety or depression as the main reason not to tell. Similarly, half of the family members who thought the patient should be told said that his or her right to know was the primary reason to tell the patient the diagnosis.

More family members approved of the disclosure of diagnosis in patients with mild dementia (86%) than in those with moderate (39%) or severe (31%) dementia.

Despite the wish by most family members not to disclose the diagnosis to their affected relatives, 90% of family members wanted to be told their diagnosis if they developed Alzheimer's disease.

A similar study in Ireland found that 83% of family members said that patients with Alzheimer's disease should not be told the diagnosis (BMJ 1996;313:529–30).

STOCKHOLM – Clinicians shy away from disclosing a diagnosis of mild cognitive impairment and its potential to convert to Alzheimer's disease.

They also differ in how they word the disclosure when they opt to share the diagnosis and prognosis with the patient and relatives. For their part, families may not want patients to know when they have been diagnosed with Alzheimer's disease, according to reports presented at the 12th Congress of the International Psychogeriatric Association.

“In dementia, disclosure is not common clinical practice”–only about 15% of professionals disclose the diagnosis to patients–“but there seems to be a trend toward more openness about the diagnosis,” said Els Derksen, R.N., a researcher at the Alzheimer's center at St. Radboud University Medical Center, Nijmegen, the Netherlands. But in contrast to several studies of disclosing a diagnosis of dementia, no studies have been published about disclosing a diagnosis of mild cognitive impairment (MCI).

Ms. Derksen discussed the responses of physicians who completed an optional appendix to a questionnaire that was a part of the European DESCRIPA (Development of Screening Guidelines and Diagnostic Criteria for Predementia Alzheimer's Disease) multicenter study. The study included patients with suspected MCI.

In discussions with 101 patients with MCI or possible early dementia, physicians told 28% that they had MCI, 62% that they had abnormal memory or cognitive problems, 4% that they had worrisome symptoms or depression plus memory problems, 3% that they had normal memory problems or forgetfulness, 2% that they had amnestic symptoms, and 1% that they had mixed and vascular dementia.

Among 100 patients who received information about their prognosis, physicians told 4% nothing, 18% that the prognosis was unknown or uncertain, 20% that the condition probably would remain stable, 10% that it probably would progress, and 66% that follow-up would be indicated. (The percentages do not add to 100% because follow-up was included with other information for some patients.)

When physicians were asked to describe their use of the term Alzheimer's disease in their interactions with a total of 80 patients, they reported that they did not use the term at all in 23%. Physicians told 72% that they could possibly convert to Alzheimer's disease. They told 4% of the patients that they had Alzheimer's disease or predementia, and 1% that Alzheimer's was not present or detected.

In nearly all instances, the same information about diagnosis, prognosis, and specific use of the term Alzheimer's disease was given to patients' families.

Alzheimer's disease in its predementia stage was suspected in 77 of 101 patients. A physician's decision to inform a patient of the diagnosis was most often guided by the patient's wish to know, a belief in shared decision making between physician and patient, and initiation of medication.

A qualitative analysis of 41 patients found that there was a difference between some centers in using the terms MCI or more descriptive language such as “memory problems or worrisome symptoms,” which suggests that “some centers are more hesitant than others in disclosure of their suspicions,” Ms. Derksen said.

“I think that further research is needed on how to inform patients about MCI,” she added.

In a separate study, family members of patients with Alzheimer's disease indicated that they did not wish to reveal the diagnosis to the patient primarily because of a concern for causing anxiety and depression in the patient.

Filip Bouckaert, M.D., of the department of old age psychiatry at University Centre St. Jozef, Kortenberg, Belgium, interviewed 50 family members of outpatients with Alzheimer's disease and 50 family members of inpatients with the disease.

Their results, reported during a poster session at the congress, showed that 57% did not want the patient to be told the diagnosis; this included 42% of family members of outpatients and 72% of family members of inpatients.

Half of family members who did not want the patients to know about the diagnosis cited the possibility of causing anxiety or depression as the main reason not to tell. Similarly, half of the family members who thought the patient should be told said that his or her right to know was the primary reason to tell the patient the diagnosis.

More family members approved of the disclosure of diagnosis in patients with mild dementia (86%) than in those with moderate (39%) or severe (31%) dementia.

Despite the wish by most family members not to disclose the diagnosis to their affected relatives, 90% of family members wanted to be told their diagnosis if they developed Alzheimer's disease.

A similar study in Ireland found that 83% of family members said that patients with Alzheimer's disease should not be told the diagnosis (BMJ 1996;313:529–30).

STOCKHOLM – Off-label use of low-dose risperidone is effective in treating the behavioral and psychological symptoms of patients with dementia, but clinicians must balance the drug's usefulness with its increased risk of cerebrovascular events, Peter P. De Deyn, M.D., said at the 12th Congress of the International Psychogeriatric Association.

Most of the available data on the treatment of the behavioral and psychological symptoms of dementia (BPSD) with atypical antipsychotics relates to risperidone, said Dr. De Deyn of the department of neurology at the University of Antwerp (Belgium).

BPSD include verbal and physical aggression, psychotic symptoms, agitation, anxiety, and depression.

Risperidone is approved to treat schizophrenia and bipolar mania associated with bipolar disorder. In May, the Food and Drug Administration opted not to approve risperidone for psychosis of Alzheimer's disease (AD).

In an analysis of pooled data from 1,150 patients in three double-blind, randomized, placebo-controlled trials, Dr. De Deyn and his associates found that 722 patients who had received risperidone had significantly greater improvement from baseline on the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the Cohen-Mansfield Agitation Inventory (CMAI) at week 4 through the end of treatment at week 12 than did 428 patients who received placebo (Clin. Neurol. Neurosurg. 2005;107:497–508).

Risperidone patients received a mean dose of 1 mg per day in each trial, said Dr. De Deyn, a speaker and consultant for Janssen Pharmaceutica, which markets risperidone as Risperdal.

In the pooled data set, investigators and caregivers similarly judged risperidone patients as having significantly greater improvement on the Clinical Global Impressions scale than did placebo patients.

At a dose of about 1 mg per day, risperidone also has significantly greater efficacy than haloperidol (Haldol) as shown by results of BEHAVE-AD and CMAI–beginning around week 4–6 of treatment–in two trials of treatment for agitation and aggression in patients with dementia (Neurology 1999;53:946–55; Am. J. Geriatr. Psychiatry 2004;12:509–16).

Psychotic symptoms in patients with psychosis at baseline improved significantly more with risperidone than with placebo in an analysis from one of the trials in the pooled data set that used patients' last available scores as the end point.

In all trials, risperidone did not increase extrapyramidal symptomatology more than placebo. But in trials involving doses of 1 mg of haloperidol per day, the conventional antipsychotic significantly increased the rate of such symptoms.

Risperidone has a statistically significant threefold increase in the relative risk of cerebrovascular adverse events in elderly patients with dementia, including transient ischemic attacks and incapacitating strokes.

The risk appears to be a drug-class phenomenon, since other atypical antipsychotics such as olanzapine (Zyprexa) and aripiprazole (Abilify) also have an increased risk of such events, he said. Risperidone has a warning on its label about the risk of cerebrovascular events in elderly patients with dementia.

A Food and Drug Administration analysis of 17 placebo-controlled trials of atypical antipsychotics in patients with dementia-related psychosis concluded that the drugs were associated with a 60%–70% increase in all-cause mortality, most of which was attributable to infections and cardiovascular disease. But in an analysis of all-cause mortality and risperidone in particular, treatment with risperidone did not contribute to a statistically significant increase in mortality within 30 days of ending treatment, Dr. De Deyn said.

All atypical antipsychotics, including risperidone, have a warning about an increased risk of mortality in elderly patients with dementia.

In a separate poster session, Dr. De Deyn presented a metaanalysis of four double-blind, randomized, controlled trials that examined the effects of risperidone in patients with psychosis of AD.

The metaanalysis included patients from the three trials he pooled to analyze the effects of risperidone on BPSD.

These three 12-week trials indicated that treatment with risperidone significantly improved psychosis subscale scores on the BEHAVE-AD from week 8 onward and on the Clinical Global Impressions scales for severity of illness and change beginning at week 2, compared with placebo (Neurology 1999;53:946–55; J. Clin. Psychiatry 1999;60:107–15; J. Clin. Psychiatry 2003;64:134–43).

But a fourth study included in the metaanalysis showed that risperidone did not prove to be better than placebo after 8 weeks of treating psychosis of AD. Patients in this trial–the results of which are slated to be published in the American Journal of Geriatric Psychiatry–had an average Mini-Mental State Examination score of 13, while in other trials the average was between 6 and 8.

The psychotic symptoms of patients in this 8-week trial were also less pronounced than those of patients in the three other trials, Dr. De Deyn said.

STOCKHOLM – Off-label use of low-dose risperidone is effective in treating the behavioral and psychological symptoms of patients with dementia, but clinicians must balance the drug's usefulness with its increased risk of cerebrovascular events, Peter P. De Deyn, M.D., said at the 12th Congress of the International Psychogeriatric Association.

Most of the available data on the treatment of the behavioral and psychological symptoms of dementia (BPSD) with atypical antipsychotics relates to risperidone, said Dr. De Deyn of the department of neurology at the University of Antwerp (Belgium).

BPSD include verbal and physical aggression, psychotic symptoms, agitation, anxiety, and depression.

Risperidone is approved to treat schizophrenia and bipolar mania associated with bipolar disorder. In May, the Food and Drug Administration opted not to approve risperidone for psychosis of Alzheimer's disease (AD).

In an analysis of pooled data from 1,150 patients in three double-blind, randomized, placebo-controlled trials, Dr. De Deyn and his associates found that 722 patients who had received risperidone had significantly greater improvement from baseline on the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the Cohen-Mansfield Agitation Inventory (CMAI) at week 4 through the end of treatment at week 12 than did 428 patients who received placebo (Clin. Neurol. Neurosurg. 2005;107:497–508).

Risperidone patients received a mean dose of 1 mg per day in each trial, said Dr. De Deyn, a speaker and consultant for Janssen Pharmaceutica, which markets risperidone as Risperdal.

In the pooled data set, investigators and caregivers similarly judged risperidone patients as having significantly greater improvement on the Clinical Global Impressions scale than did placebo patients.

At a dose of about 1 mg per day, risperidone also has significantly greater efficacy than haloperidol (Haldol) as shown by results of BEHAVE-AD and CMAI–beginning around week 4–6 of treatment–in two trials of treatment for agitation and aggression in patients with dementia (Neurology 1999;53:946–55; Am. J. Geriatr. Psychiatry 2004;12:509–16).

Psychotic symptoms in patients with psychosis at baseline improved significantly more with risperidone than with placebo in an analysis from one of the trials in the pooled data set that used patients' last available scores as the end point.

In all trials, risperidone did not increase extrapyramidal symptomatology more than placebo. But in trials involving doses of 1 mg of haloperidol per day, the conventional antipsychotic significantly increased the rate of such symptoms.

Risperidone has a statistically significant threefold increase in the relative risk of cerebrovascular adverse events in elderly patients with dementia, including transient ischemic attacks and incapacitating strokes.

The risk appears to be a drug-class phenomenon, since other atypical antipsychotics such as olanzapine (Zyprexa) and aripiprazole (Abilify) also have an increased risk of such events, he said. Risperidone has a warning on its label about the risk of cerebrovascular events in elderly patients with dementia.

A Food and Drug Administration analysis of 17 placebo-controlled trials of atypical antipsychotics in patients with dementia-related psychosis concluded that the drugs were associated with a 60%–70% increase in all-cause mortality, most of which was attributable to infections and cardiovascular disease. But in an analysis of all-cause mortality and risperidone in particular, treatment with risperidone did not contribute to a statistically significant increase in mortality within 30 days of ending treatment, Dr. De Deyn said.

All atypical antipsychotics, including risperidone, have a warning about an increased risk of mortality in elderly patients with dementia.

In a separate poster session, Dr. De Deyn presented a metaanalysis of four double-blind, randomized, controlled trials that examined the effects of risperidone in patients with psychosis of AD.

The metaanalysis included patients from the three trials he pooled to analyze the effects of risperidone on BPSD.

These three 12-week trials indicated that treatment with risperidone significantly improved psychosis subscale scores on the BEHAVE-AD from week 8 onward and on the Clinical Global Impressions scales for severity of illness and change beginning at week 2, compared with placebo (Neurology 1999;53:946–55; J. Clin. Psychiatry 1999;60:107–15; J. Clin. Psychiatry 2003;64:134–43).

But a fourth study included in the metaanalysis showed that risperidone did not prove to be better than placebo after 8 weeks of treating psychosis of AD. Patients in this trial–the results of which are slated to be published in the American Journal of Geriatric Psychiatry–had an average Mini-Mental State Examination score of 13, while in other trials the average was between 6 and 8.

The psychotic symptoms of patients in this 8-week trial were also less pronounced than those of patients in the three other trials, Dr. De Deyn said.

STOCKHOLM – Off-label use of low-dose risperidone is effective in treating the behavioral and psychological symptoms of patients with dementia, but clinicians must balance the drug's usefulness with its increased risk of cerebrovascular events, Peter P. De Deyn, M.D., said at the 12th Congress of the International Psychogeriatric Association.

Most of the available data on the treatment of the behavioral and psychological symptoms of dementia (BPSD) with atypical antipsychotics relates to risperidone, said Dr. De Deyn of the department of neurology at the University of Antwerp (Belgium).

BPSD include verbal and physical aggression, psychotic symptoms, agitation, anxiety, and depression.

Risperidone is approved to treat schizophrenia and bipolar mania associated with bipolar disorder. In May, the Food and Drug Administration opted not to approve risperidone for psychosis of Alzheimer's disease (AD).

In an analysis of pooled data from 1,150 patients in three double-blind, randomized, placebo-controlled trials, Dr. De Deyn and his associates found that 722 patients who had received risperidone had significantly greater improvement from baseline on the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the Cohen-Mansfield Agitation Inventory (CMAI) at week 4 through the end of treatment at week 12 than did 428 patients who received placebo (Clin. Neurol. Neurosurg. 2005;107:497–508).

Risperidone patients received a mean dose of 1 mg per day in each trial, said Dr. De Deyn, a speaker and consultant for Janssen Pharmaceutica, which markets risperidone as Risperdal.

In the pooled data set, investigators and caregivers similarly judged risperidone patients as having significantly greater improvement on the Clinical Global Impressions scale than did placebo patients.

At a dose of about 1 mg per day, risperidone also has significantly greater efficacy than haloperidol (Haldol) as shown by results of BEHAVE-AD and CMAI–beginning around week 4–6 of treatment–in two trials of treatment for agitation and aggression in patients with dementia (Neurology 1999;53:946–55; Am. J. Geriatr. Psychiatry 2004;12:509–16).

Psychotic symptoms in patients with psychosis at baseline improved significantly more with risperidone than with placebo in an analysis from one of the trials in the pooled data set that used patients' last available scores as the end point.

In all trials, risperidone did not increase extrapyramidal symptomatology more than placebo. But in trials involving doses of 1 mg of haloperidol per day, the conventional antipsychotic significantly increased the rate of such symptoms.

Risperidone has a statistically significant threefold increase in the relative risk of cerebrovascular adverse events in elderly patients with dementia, including transient ischemic attacks and incapacitating strokes.

The risk appears to be a drug-class phenomenon, since other atypical antipsychotics such as olanzapine (Zyprexa) and aripiprazole (Abilify) also have an increased risk of such events, he said. Risperidone has a warning on its label about the risk of cerebrovascular events in elderly patients with dementia.

A Food and Drug Administration analysis of 17 placebo-controlled trials of atypical antipsychotics in patients with dementia-related psychosis concluded that the drugs were associated with a 60%–70% increase in all-cause mortality, most of which was attributable to infections and cardiovascular disease. But in an analysis of all-cause mortality and risperidone in particular, treatment with risperidone did not contribute to a statistically significant increase in mortality within 30 days of ending treatment, Dr. De Deyn said.

All atypical antipsychotics, including risperidone, have a warning about an increased risk of mortality in elderly patients with dementia.

In a separate poster session, Dr. De Deyn presented a metaanalysis of four double-blind, randomized, controlled trials that examined the effects of risperidone in patients with psychosis of AD.

The metaanalysis included patients from the three trials he pooled to analyze the effects of risperidone on BPSD.

These three 12-week trials indicated that treatment with risperidone significantly improved psychosis subscale scores on the BEHAVE-AD from week 8 onward and on the Clinical Global Impressions scales for severity of illness and change beginning at week 2, compared with placebo (Neurology 1999;53:946–55; J. Clin. Psychiatry 1999;60:107–15; J. Clin. Psychiatry 2003;64:134–43).

But a fourth study included in the metaanalysis showed that risperidone did not prove to be better than placebo after 8 weeks of treating psychosis of AD. Patients in this trial–the results of which are slated to be published in the American Journal of Geriatric Psychiatry–had an average Mini-Mental State Examination score of 13, while in other trials the average was between 6 and 8.

The psychotic symptoms of patients in this 8-week trial were also less pronounced than those of patients in the three other trials, Dr. De Deyn said.

STOCKHOLM – Preliminary results of the ongoing European Alzheimer's Disease Consortium's DESCRIPA study are pointing the way toward clinical criteria that may help single out which types of mild cognitive impairment lead to Alzheimer's disease, speakers reported at the 12th Congress of the International Psychogeriatric Association.

Twenty-five centers conducted DESCRIPA (Development of Screening Guidelines and Diagnostic Criteria for Predementia Alzheimer's Disease), a prospective cohort study that included 850 patients with suspected mild cognitive impairment (MCI). Presentations at the congress involved data on various subsets of the 850 patients.

The study investigators had no predefined criteria for MCI but included patients who were aged 55 years or older and had received consecutive referrals for cognitive impairment. They excluded patients who had a diagnosis of dementia at baseline and obvious causes of cognitive impairment such as stroke and depression. Based on neuropsychologic testing, patients were divided into four MCI subtypes: subjective complaints (no impairments on cognitive testing), nonamnestic (impairments on fluency, trail making, or single-institution tests), amnestic single domain (impairment on a word recall test), and amnestic multiple domain (impairment on word recall and at least one other memory test).

Impact of Apo E Genotype

The frequency of the ϵ4 allele of the apolipoprotein E gene (apo E) varies significantly with specific MCI subtypes and between regions of Europe but does not have strong enough predictive value alone to distinguish among MCI subtypes, according to Caroline Graff, M.D., Ph.D., of the Karolinska University Hospital, Huddinge, Sweden.

The distribution of ϵ4 allele frequency and the average age of patients differed significantly among the four MCI subtypes in a group of 386 patients at 11 centers who were genotyped for apo E allele status. The frequency of the ϵ4 allele increased from 17% of nonamnestic patients to 21% of those with subjective MCI, 30% of amnestic multiple domain, and 32% of amnestic single domain. Age varied from 66 years in subjective MCI to 72 years in amnestic single-domain patients. The differences were still significant when the four subtypes were collapsed into a nonamnestic group composed of the subjective and nonamnestic MCI patients (19%, 68 years) and an amnestic group composed of the amnestic single- and multiple-domain groups (31%, 72 years).

The distribution of MCI subtypes and age was significantly different among the centers. Frequency of the ϵ4 allele also varied according to the centers' location in Europe. The average frequency was lowest (8%) in Thessaloniki, Greece, and highest (33%) in Bath, England.

The variables of center, age, and apo E genotype were significantly associated with MCI subtype in a multivariate logistic regression analysis. The effect of center was the strongest predictor of MCI subtype, and it could not be explained by the effect of age or apo E status alone. “There is something else inherent in center,” Dr. Graff said.

If one hypothesizes that the different MCI subtypes predict the type of dementia that a person will develop, this could mean that the prevalence of the different types of dementia differ among these countries, she pointed out.

EEG Abnormalities in Amnestic Subtype

Decline in the function of posterior cortical regions of the brain such as the temporal, occipital, and parietal lobes characterize the resting EEG of patients with amnestic MCI, Flavio Nobili, M.D., reported at the congress.

In a preliminary analysis, the temporal, occipital and parietal cortical regions of the brain in 96 patients who had digital EEG performed at five centers had significant reductions in α-1 frequency, compared with the same regions in 55 control patients matched for age, sex, and education. This result is “consistent with the hypothesis of a transition stage between amnestic MCI and Alzheimer's disease,” said Dr. Nobili of the department of clinical neurophysiology at the University of Genoa (Italy).

Other studies of resting EEG in MCI patients have shown decreases in α frequency. It's known that deafferentation of thalamo-cortical and cortico-cortical brain connections and deficits in neurotransmission underlie the slowing down of EEG readings in Alzheimer's disease (AD) patients. Even in early stages of AD, EEG readings typically show decreases in α frequency and a shift to a lower α peak frequency.

A follow-up study will be necessary to determine the influence that the heterogeneity of the amnestic MCI population has on these results since the distribution of EEG power in defined, early-stage AD also is very heterogeneic, he noted.

Importance of Noncognitive Symptoms

Noncognitive symptoms are common in MCI patients but do not appear to occur at significantly different rates in MCI subtypes, according to a preliminary study of 324 patients with full Neuropsychiatric Inventory (NPI) scores.

Noncognitive symptoms are common in AD patients but have been poorly studied in MCI. The subgroup of patients with amnestic MCI as well as the symptoms of depression have been the focus of most studies on the subject, said Inez Ramakers, a doctoral student at Maastricht University (the Netherlands).

In the study, 79% of the patients had at least one noncognitive symptom as defined by domain scores on the NPI. Noncognitive symptoms were clinically significant in 39% of patients, consisting mainly of apathy, depression, anxiety, and irritability.

The NPI scores did not differ significantly among the MCI subtypes. But the subjective MCI group had a significantly better NPI score and significantly less apathy than did the other three MCI subtypes combined. After 1 year of follow-up in 88 patients, NPI score has not been a significant predictor of dementia.

Atrophy on MRI Related to Subtype

Medial temporal lobe atrophy is associated with MCI subtypes and measures of cognition but not vascular risk factors, Laura van de Pol reported during the DESCRIPA session. “It has been suggested that the different types of MCI may reflect differences in underlying neuropathologies and may therefore potentially progress to different sorts of dementia,” said Ms. van de Pol of the Vrije University Medical Center, Amsterdam.

In 214 patients who underwent MRI scans at five centers, the severity of medial temporal lobe atrophy followed a significant trend from mild to more severe in subjective, nonamnestic, amnestic single-domain, and amnestic multiple-domain MCI patients. But the severity of white matter hyperintensity did not differ between the subtypes, Ms. van de Pol said.

Medial temporal lobe atrophy, but not white matter hyperintensity, was significantly and negatively correlated with cognitive testing with the Mini Mental State Examination (MMSE) word list learning, delayed word list recall, and fluency.

But vascular risk factors such as blood pressure, atherosclerosis, hypercholesterolemia, and diabetes mellitus were significantly and positively correlated with white matter hyperintensity while medial temporal lobe atrophy was not.

In a 1-year follow-up with 73 patients, medial temporal lobe atrophy was significantly correlated with a decline in delayed recall; white matter hyperintensity was not correlated with any cognitive measure.

Ms. van de Pol noted that medial temporal lobe atrophy and white matter hyperintensity did not interact with each other on cognition. Their association with patients with MCI subtypes seems to reflect different etiologies in which medial temporal lobe atrophy may be a marker of AD neuropathology, and white matter hyperintensity reflects vascular disease that does not contribute to cognitive impairment in these MCI subtypes.

Total Tau Protein Signals Decline

The total level of tau protein in an MCI subtype increases as the level of cognitive impairment rises and is correlated with worsening neuropsychology, according to a preliminary study of proteins in the cerebrospinal fluid (CSF) of 84 patients.

The percentage of patients with an abnormal total tau protein level produced a significant trend from 20% of MCI patients with subjective complaints up to about 80% of amnestic multiple-domain patients, said Peter Jelle Visser, M.D., also of Maastricht University. Levels of amyloid β 1–42 and phosphorylated tau did not follow a significant trend.

CSF levels of total and phosphorylated tau correlated significantly with declining performance on the MMSE and tests of delayed recall, fluency, and trail making. Follow-up at 1 year in 33 patients (27 nondemented, 6 AD) showed that the increase in levels of total and phosphorylated tau was significantly higher in patients with AD than in those without dementia.

To further investigate the possibility that even the 20% of subjective MCI patients with abnormal CSF protein levels could develop dementia in follow-up, Dr. Visser suggested that “other studies should not only focus on amnestic MCI but also on the other forms of MCI.”

STOCKHOLM – Preliminary results of the ongoing European Alzheimer's Disease Consortium's DESCRIPA study are pointing the way toward clinical criteria that may help single out which types of mild cognitive impairment lead to Alzheimer's disease, speakers reported at the 12th Congress of the International Psychogeriatric Association.

Twenty-five centers conducted DESCRIPA (Development of Screening Guidelines and Diagnostic Criteria for Predementia Alzheimer's Disease), a prospective cohort study that included 850 patients with suspected mild cognitive impairment (MCI). Presentations at the congress involved data on various subsets of the 850 patients.

The study investigators had no predefined criteria for MCI but included patients who were aged 55 years or older and had received consecutive referrals for cognitive impairment. They excluded patients who had a diagnosis of dementia at baseline and obvious causes of cognitive impairment such as stroke and depression. Based on neuropsychologic testing, patients were divided into four MCI subtypes: subjective complaints (no impairments on cognitive testing), nonamnestic (impairments on fluency, trail making, or single-institution tests), amnestic single domain (impairment on a word recall test), and amnestic multiple domain (impairment on word recall and at least one other memory test).

Impact of Apo E Genotype

The frequency of the ϵ4 allele of the apolipoprotein E gene (apo E) varies significantly with specific MCI subtypes and between regions of Europe but does not have strong enough predictive value alone to distinguish among MCI subtypes, according to Caroline Graff, M.D., Ph.D., of the Karolinska University Hospital, Huddinge, Sweden.

The distribution of ϵ4 allele frequency and the average age of patients differed significantly among the four MCI subtypes in a group of 386 patients at 11 centers who were genotyped for apo E allele status. The frequency of the ϵ4 allele increased from 17% of nonamnestic patients to 21% of those with subjective MCI, 30% of amnestic multiple domain, and 32% of amnestic single domain. Age varied from 66 years in subjective MCI to 72 years in amnestic single-domain patients. The differences were still significant when the four subtypes were collapsed into a nonamnestic group composed of the subjective and nonamnestic MCI patients (19%, 68 years) and an amnestic group composed of the amnestic single- and multiple-domain groups (31%, 72 years).

The distribution of MCI subtypes and age was significantly different among the centers. Frequency of the ϵ4 allele also varied according to the centers' location in Europe. The average frequency was lowest (8%) in Thessaloniki, Greece, and highest (33%) in Bath, England.

The variables of center, age, and apo E genotype were significantly associated with MCI subtype in a multivariate logistic regression analysis. The effect of center was the strongest predictor of MCI subtype, and it could not be explained by the effect of age or apo E status alone. “There is something else inherent in center,” Dr. Graff said.

If one hypothesizes that the different MCI subtypes predict the type of dementia that a person will develop, this could mean that the prevalence of the different types of dementia differ among these countries, she pointed out.

EEG Abnormalities in Amnestic Subtype

Decline in the function of posterior cortical regions of the brain such as the temporal, occipital, and parietal lobes characterize the resting EEG of patients with amnestic MCI, Flavio Nobili, M.D., reported at the congress.

In a preliminary analysis, the temporal, occipital and parietal cortical regions of the brain in 96 patients who had digital EEG performed at five centers had significant reductions in α-1 frequency, compared with the same regions in 55 control patients matched for age, sex, and education. This result is “consistent with the hypothesis of a transition stage between amnestic MCI and Alzheimer's disease,” said Dr. Nobili of the department of clinical neurophysiology at the University of Genoa (Italy).

Other studies of resting EEG in MCI patients have shown decreases in α frequency. It's known that deafferentation of thalamo-cortical and cortico-cortical brain connections and deficits in neurotransmission underlie the slowing down of EEG readings in Alzheimer's disease (AD) patients. Even in early stages of AD, EEG readings typically show decreases in α frequency and a shift to a lower α peak frequency.

A follow-up study will be necessary to determine the influence that the heterogeneity of the amnestic MCI population has on these results since the distribution of EEG power in defined, early-stage AD also is very heterogeneic, he noted.

Importance of Noncognitive Symptoms

Noncognitive symptoms are common in MCI patients but do not appear to occur at significantly different rates in MCI subtypes, according to a preliminary study of 324 patients with full Neuropsychiatric Inventory (NPI) scores.

Noncognitive symptoms are common in AD patients but have been poorly studied in MCI. The subgroup of patients with amnestic MCI as well as the symptoms of depression have been the focus of most studies on the subject, said Inez Ramakers, a doctoral student at Maastricht University (the Netherlands).

In the study, 79% of the patients had at least one noncognitive symptom as defined by domain scores on the NPI. Noncognitive symptoms were clinically significant in 39% of patients, consisting mainly of apathy, depression, anxiety, and irritability.

The NPI scores did not differ significantly among the MCI subtypes. But the subjective MCI group had a significantly better NPI score and significantly less apathy than did the other three MCI subtypes combined. After 1 year of follow-up in 88 patients, NPI score has not been a significant predictor of dementia.

Atrophy on MRI Related to Subtype

Medial temporal lobe atrophy is associated with MCI subtypes and measures of cognition but not vascular risk factors, Laura van de Pol reported during the DESCRIPA session. “It has been suggested that the different types of MCI may reflect differences in underlying neuropathologies and may therefore potentially progress to different sorts of dementia,” said Ms. van de Pol of the Vrije University Medical Center, Amsterdam.

In 214 patients who underwent MRI scans at five centers, the severity of medial temporal lobe atrophy followed a significant trend from mild to more severe in subjective, nonamnestic, amnestic single-domain, and amnestic multiple-domain MCI patients. But the severity of white matter hyperintensity did not differ between the subtypes, Ms. van de Pol said.

Medial temporal lobe atrophy, but not white matter hyperintensity, was significantly and negatively correlated with cognitive testing with the Mini Mental State Examination (MMSE) word list learning, delayed word list recall, and fluency.

But vascular risk factors such as blood pressure, atherosclerosis, hypercholesterolemia, and diabetes mellitus were significantly and positively correlated with white matter hyperintensity while medial temporal lobe atrophy was not.

In a 1-year follow-up with 73 patients, medial temporal lobe atrophy was significantly correlated with a decline in delayed recall; white matter hyperintensity was not correlated with any cognitive measure.

Ms. van de Pol noted that medial temporal lobe atrophy and white matter hyperintensity did not interact with each other on cognition. Their association with patients with MCI subtypes seems to reflect different etiologies in which medial temporal lobe atrophy may be a marker of AD neuropathology, and white matter hyperintensity reflects vascular disease that does not contribute to cognitive impairment in these MCI subtypes.

Total Tau Protein Signals Decline

The total level of tau protein in an MCI subtype increases as the level of cognitive impairment rises and is correlated with worsening neuropsychology, according to a preliminary study of proteins in the cerebrospinal fluid (CSF) of 84 patients.

The percentage of patients with an abnormal total tau protein level produced a significant trend from 20% of MCI patients with subjective complaints up to about 80% of amnestic multiple-domain patients, said Peter Jelle Visser, M.D., also of Maastricht University. Levels of amyloid β 1–42 and phosphorylated tau did not follow a significant trend.

CSF levels of total and phosphorylated tau correlated significantly with declining performance on the MMSE and tests of delayed recall, fluency, and trail making. Follow-up at 1 year in 33 patients (27 nondemented, 6 AD) showed that the increase in levels of total and phosphorylated tau was significantly higher in patients with AD than in those without dementia.

To further investigate the possibility that even the 20% of subjective MCI patients with abnormal CSF protein levels could develop dementia in follow-up, Dr. Visser suggested that “other studies should not only focus on amnestic MCI but also on the other forms of MCI.”

STOCKHOLM – Preliminary results of the ongoing European Alzheimer's Disease Consortium's DESCRIPA study are pointing the way toward clinical criteria that may help single out which types of mild cognitive impairment lead to Alzheimer's disease, speakers reported at the 12th Congress of the International Psychogeriatric Association.

Twenty-five centers conducted DESCRIPA (Development of Screening Guidelines and Diagnostic Criteria for Predementia Alzheimer's Disease), a prospective cohort study that included 850 patients with suspected mild cognitive impairment (MCI). Presentations at the congress involved data on various subsets of the 850 patients.

The study investigators had no predefined criteria for MCI but included patients who were aged 55 years or older and had received consecutive referrals for cognitive impairment. They excluded patients who had a diagnosis of dementia at baseline and obvious causes of cognitive impairment such as stroke and depression. Based on neuropsychologic testing, patients were divided into four MCI subtypes: subjective complaints (no impairments on cognitive testing), nonamnestic (impairments on fluency, trail making, or single-institution tests), amnestic single domain (impairment on a word recall test), and amnestic multiple domain (impairment on word recall and at least one other memory test).

Impact of Apo E Genotype

The frequency of the ϵ4 allele of the apolipoprotein E gene (apo E) varies significantly with specific MCI subtypes and between regions of Europe but does not have strong enough predictive value alone to distinguish among MCI subtypes, according to Caroline Graff, M.D., Ph.D., of the Karolinska University Hospital, Huddinge, Sweden.

The distribution of ϵ4 allele frequency and the average age of patients differed significantly among the four MCI subtypes in a group of 386 patients at 11 centers who were genotyped for apo E allele status. The frequency of the ϵ4 allele increased from 17% of nonamnestic patients to 21% of those with subjective MCI, 30% of amnestic multiple domain, and 32% of amnestic single domain. Age varied from 66 years in subjective MCI to 72 years in amnestic single-domain patients. The differences were still significant when the four subtypes were collapsed into a nonamnestic group composed of the subjective and nonamnestic MCI patients (19%, 68 years) and an amnestic group composed of the amnestic single- and multiple-domain groups (31%, 72 years).

The distribution of MCI subtypes and age was significantly different among the centers. Frequency of the ϵ4 allele also varied according to the centers' location in Europe. The average frequency was lowest (8%) in Thessaloniki, Greece, and highest (33%) in Bath, England.

The variables of center, age, and apo E genotype were significantly associated with MCI subtype in a multivariate logistic regression analysis. The effect of center was the strongest predictor of MCI subtype, and it could not be explained by the effect of age or apo E status alone. “There is something else inherent in center,” Dr. Graff said.

If one hypothesizes that the different MCI subtypes predict the type of dementia that a person will develop, this could mean that the prevalence of the different types of dementia differ among these countries, she pointed out.

EEG Abnormalities in Amnestic Subtype

Decline in the function of posterior cortical regions of the brain such as the temporal, occipital, and parietal lobes characterize the resting EEG of patients with amnestic MCI, Flavio Nobili, M.D., reported at the congress.

In a preliminary analysis, the temporal, occipital and parietal cortical regions of the brain in 96 patients who had digital EEG performed at five centers had significant reductions in α-1 frequency, compared with the same regions in 55 control patients matched for age, sex, and education. This result is “consistent with the hypothesis of a transition stage between amnestic MCI and Alzheimer's disease,” said Dr. Nobili of the department of clinical neurophysiology at the University of Genoa (Italy).

Other studies of resting EEG in MCI patients have shown decreases in α frequency. It's known that deafferentation of thalamo-cortical and cortico-cortical brain connections and deficits in neurotransmission underlie the slowing down of EEG readings in Alzheimer's disease (AD) patients. Even in early stages of AD, EEG readings typically show decreases in α frequency and a shift to a lower α peak frequency.

A follow-up study will be necessary to determine the influence that the heterogeneity of the amnestic MCI population has on these results since the distribution of EEG power in defined, early-stage AD also is very heterogeneic, he noted.

Importance of Noncognitive Symptoms

Noncognitive symptoms are common in MCI patients but do not appear to occur at significantly different rates in MCI subtypes, according to a preliminary study of 324 patients with full Neuropsychiatric Inventory (NPI) scores.

Noncognitive symptoms are common in AD patients but have been poorly studied in MCI. The subgroup of patients with amnestic MCI as well as the symptoms of depression have been the focus of most studies on the subject, said Inez Ramakers, a doctoral student at Maastricht University (the Netherlands).

In the study, 79% of the patients had at least one noncognitive symptom as defined by domain scores on the NPI. Noncognitive symptoms were clinically significant in 39% of patients, consisting mainly of apathy, depression, anxiety, and irritability.

The NPI scores did not differ significantly among the MCI subtypes. But the subjective MCI group had a significantly better NPI score and significantly less apathy than did the other three MCI subtypes combined. After 1 year of follow-up in 88 patients, NPI score has not been a significant predictor of dementia.

Atrophy on MRI Related to Subtype

Medial temporal lobe atrophy is associated with MCI subtypes and measures of cognition but not vascular risk factors, Laura van de Pol reported during the DESCRIPA session. “It has been suggested that the different types of MCI may reflect differences in underlying neuropathologies and may therefore potentially progress to different sorts of dementia,” said Ms. van de Pol of the Vrije University Medical Center, Amsterdam.

In 214 patients who underwent MRI scans at five centers, the severity of medial temporal lobe atrophy followed a significant trend from mild to more severe in subjective, nonamnestic, amnestic single-domain, and amnestic multiple-domain MCI patients. But the severity of white matter hyperintensity did not differ between the subtypes, Ms. van de Pol said.

Medial temporal lobe atrophy, but not white matter hyperintensity, was significantly and negatively correlated with cognitive testing with the Mini Mental State Examination (MMSE) word list learning, delayed word list recall, and fluency.

But vascular risk factors such as blood pressure, atherosclerosis, hypercholesterolemia, and diabetes mellitus were significantly and positively correlated with white matter hyperintensity while medial temporal lobe atrophy was not.

In a 1-year follow-up with 73 patients, medial temporal lobe atrophy was significantly correlated with a decline in delayed recall; white matter hyperintensity was not correlated with any cognitive measure.

Ms. van de Pol noted that medial temporal lobe atrophy and white matter hyperintensity did not interact with each other on cognition. Their association with patients with MCI subtypes seems to reflect different etiologies in which medial temporal lobe atrophy may be a marker of AD neuropathology, and white matter hyperintensity reflects vascular disease that does not contribute to cognitive impairment in these MCI subtypes.

Total Tau Protein Signals Decline

The total level of tau protein in an MCI subtype increases as the level of cognitive impairment rises and is correlated with worsening neuropsychology, according to a preliminary study of proteins in the cerebrospinal fluid (CSF) of 84 patients.

The percentage of patients with an abnormal total tau protein level produced a significant trend from 20% of MCI patients with subjective complaints up to about 80% of amnestic multiple-domain patients, said Peter Jelle Visser, M.D., also of Maastricht University. Levels of amyloid β 1–42 and phosphorylated tau did not follow a significant trend.

CSF levels of total and phosphorylated tau correlated significantly with declining performance on the MMSE and tests of delayed recall, fluency, and trail making. Follow-up at 1 year in 33 patients (27 nondemented, 6 AD) showed that the increase in levels of total and phosphorylated tau was significantly higher in patients with AD than in those without dementia.

To further investigate the possibility that even the 20% of subjective MCI patients with abnormal CSF protein levels could develop dementia in follow-up, Dr. Visser suggested that “other studies should not only focus on amnestic MCI but also on the other forms of MCI.”

A single course of betamethasone before an elective cesarean section at term may decrease the risk of developing neonatal respiratory distress or transient tachypnea, according to the results of a randomized, controlled trial.

The 10-center trial is the first of its kind to test the use of prenatal corticosteroids in women who were delivered by elective cesarean section at term (BMJ, doi:10.1136/bmj.38547.416493.06 [2005]).

Infants whose mothers received betamethasone had a significantly lower rate of admission to the special care baby unit (11 of 467) than control infants (24 of 475). Betamethasone treatment reduced the incidence of admission to a special care baby unit by 54%, reported Peter Stutchfield, M.D., of Glan Clwyd Hospital (Wales) and his colleagues.

Still, Alex Vidaeff, M.D., of the University of Texas, Houston, questioned the significance of the study. “I don't see any clinical utility for U.S. practitioners because of a lack of external validity,” he said in an interview.

Dr. Vidaeff, who has particular interest in research on corticosteroids and fetal maturation, as well as expertise working with H-441 adenocarcinoma lung cells, said interpretation of the study results is difficult without more information on the selection of patients for the study. He also noted that the risk-benefit ratio at more than 34 weeks' gestation is not favorable because the risk level already is low in this group.

In the study, during the 48 hours before elective cesarean section, the women received either two intramuscular doses of 12 mg of betamethasone separated by 24 hours or treatment as usual without corticosteroids.

The severity and type of respiratory distress (transient tachypnea in 10 treated and 19 control babies or respiratory distress syndrome in 1 treated and 5 control babies) were similar among all babies who were admitted to a special care baby unit.

Among mothers who had a baby admitted to a special care baby unit, significantly more mothers of infants exposed to betamethasone received general anesthesia than did mothers of control infants (45% vs. 0%). Admitted babies exposed to betamethasone needed neonatal resuscitation (73% vs. 12%) or ventilation through a mask (36% vs. 0%) significantly more often than control babies.

But 2.9% of control babies received intensive care, compared with only 0.4% of babies treated with betamethasone.

The probability of admission to the special care baby unit with respiratory distress declined as the gestational age of the baby increased in the betamethasone and control groups from 37 weeks (5% vs. 11%, respectively) to 38 weeks (3% vs. 6%) to 39 weeks (0.6% vs. 1.5%), according to a logistic regression model.

There were no reports of wound infection or neonatal sepsis. Among seven women who received betamethasone, five reported generalized flushing, one had nausea, one had tenderness at the injection site, and one noted increased energy with difficulty sleeping.

“The reduced incidence of transient tachypnea in the steroid group is consistent with the hypothesis that corticosteroids, increased in mother and fetus through the stress of labor, encourage the expression of the epithelial channel gene and allow the lung to switch from fluid secretion to fluid absorption,” Dr. Stutchfield and his colleagues wrote. “Without another source of corticosteroid, elective cesarean section will disrupt this process.”

A single course of betamethasone before an elective cesarean section at term may decrease the risk of developing neonatal respiratory distress or transient tachypnea, according to the results of a randomized, controlled trial.

The 10-center trial is the first of its kind to test the use of prenatal corticosteroids in women who were delivered by elective cesarean section at term (BMJ, doi:10.1136/bmj.38547.416493.06 [2005]).

Infants whose mothers received betamethasone had a significantly lower rate of admission to the special care baby unit (11 of 467) than control infants (24 of 475). Betamethasone treatment reduced the incidence of admission to a special care baby unit by 54%, reported Peter Stutchfield, M.D., of Glan Clwyd Hospital (Wales) and his colleagues.

Still, Alex Vidaeff, M.D., of the University of Texas, Houston, questioned the significance of the study. “I don't see any clinical utility for U.S. practitioners because of a lack of external validity,” he said in an interview.

Dr. Vidaeff, who has particular interest in research on corticosteroids and fetal maturation, as well as expertise working with H-441 adenocarcinoma lung cells, said interpretation of the study results is difficult without more information on the selection of patients for the study. He also noted that the risk-benefit ratio at more than 34 weeks' gestation is not favorable because the risk level already is low in this group.

In the study, during the 48 hours before elective cesarean section, the women received either two intramuscular doses of 12 mg of betamethasone separated by 24 hours or treatment as usual without corticosteroids.

The severity and type of respiratory distress (transient tachypnea in 10 treated and 19 control babies or respiratory distress syndrome in 1 treated and 5 control babies) were similar among all babies who were admitted to a special care baby unit.

Among mothers who had a baby admitted to a special care baby unit, significantly more mothers of infants exposed to betamethasone received general anesthesia than did mothers of control infants (45% vs. 0%). Admitted babies exposed to betamethasone needed neonatal resuscitation (73% vs. 12%) or ventilation through a mask (36% vs. 0%) significantly more often than control babies.

But 2.9% of control babies received intensive care, compared with only 0.4% of babies treated with betamethasone.

The probability of admission to the special care baby unit with respiratory distress declined as the gestational age of the baby increased in the betamethasone and control groups from 37 weeks (5% vs. 11%, respectively) to 38 weeks (3% vs. 6%) to 39 weeks (0.6% vs. 1.5%), according to a logistic regression model.

There were no reports of wound infection or neonatal sepsis. Among seven women who received betamethasone, five reported generalized flushing, one had nausea, one had tenderness at the injection site, and one noted increased energy with difficulty sleeping.

“The reduced incidence of transient tachypnea in the steroid group is consistent with the hypothesis that corticosteroids, increased in mother and fetus through the stress of labor, encourage the expression of the epithelial channel gene and allow the lung to switch from fluid secretion to fluid absorption,” Dr. Stutchfield and his colleagues wrote. “Without another source of corticosteroid, elective cesarean section will disrupt this process.”

A single course of betamethasone before an elective cesarean section at term may decrease the risk of developing neonatal respiratory distress or transient tachypnea, according to the results of a randomized, controlled trial.

The 10-center trial is the first of its kind to test the use of prenatal corticosteroids in women who were delivered by elective cesarean section at term (BMJ, doi:10.1136/bmj.38547.416493.06 [2005]).

Infants whose mothers received betamethasone had a significantly lower rate of admission to the special care baby unit (11 of 467) than control infants (24 of 475). Betamethasone treatment reduced the incidence of admission to a special care baby unit by 54%, reported Peter Stutchfield, M.D., of Glan Clwyd Hospital (Wales) and his colleagues.

Still, Alex Vidaeff, M.D., of the University of Texas, Houston, questioned the significance of the study. “I don't see any clinical utility for U.S. practitioners because of a lack of external validity,” he said in an interview.

Dr. Vidaeff, who has particular interest in research on corticosteroids and fetal maturation, as well as expertise working with H-441 adenocarcinoma lung cells, said interpretation of the study results is difficult without more information on the selection of patients for the study. He also noted that the risk-benefit ratio at more than 34 weeks' gestation is not favorable because the risk level already is low in this group.

In the study, during the 48 hours before elective cesarean section, the women received either two intramuscular doses of 12 mg of betamethasone separated by 24 hours or treatment as usual without corticosteroids.

The severity and type of respiratory distress (transient tachypnea in 10 treated and 19 control babies or respiratory distress syndrome in 1 treated and 5 control babies) were similar among all babies who were admitted to a special care baby unit.

Among mothers who had a baby admitted to a special care baby unit, significantly more mothers of infants exposed to betamethasone received general anesthesia than did mothers of control infants (45% vs. 0%). Admitted babies exposed to betamethasone needed neonatal resuscitation (73% vs. 12%) or ventilation through a mask (36% vs. 0%) significantly more often than control babies.

But 2.9% of control babies received intensive care, compared with only 0.4% of babies treated with betamethasone.

The probability of admission to the special care baby unit with respiratory distress declined as the gestational age of the baby increased in the betamethasone and control groups from 37 weeks (5% vs. 11%, respectively) to 38 weeks (3% vs. 6%) to 39 weeks (0.6% vs. 1.5%), according to a logistic regression model.

There were no reports of wound infection or neonatal sepsis. Among seven women who received betamethasone, five reported generalized flushing, one had nausea, one had tenderness at the injection site, and one noted increased energy with difficulty sleeping.

“The reduced incidence of transient tachypnea in the steroid group is consistent with the hypothesis that corticosteroids, increased in mother and fetus through the stress of labor, encourage the expression of the epithelial channel gene and allow the lung to switch from fluid secretion to fluid absorption,” Dr. Stutchfield and his colleagues wrote. “Without another source of corticosteroid, elective cesarean section will disrupt this process.”

QUEBEC CITY — The woman's origin from Singapore and her extensive history of living in nine countries from age 26 to 39 years until she immigrated to Canada was crucial in leading to her diagnosis of borderline lepromatous leprosy, Michael Kalisiak, M.D., reported at the annual conference of the Canadian Dermatology Association.

Her countries of residence included Iran, Trinidad, Scotland, United States, Indonesia, the Netherlands, and Norway, with brief periods in Kenya and Ecuador; some of these countries have an intermediate incidence of leprosy.

For 3 years prior to her skin manifestations, the patient visited neurologists for her neuropathic symptoms, which initially occurred as numbness and occasional pain in her left anterior thigh and later spread to her left hand and left and right lower legs. She also reported decreased grip strength in her left hand, according to Dr. Kalisiak, a second-year dermatology resident at the University of Alberta, Edmonton.

The neurologists discovered numerous motor and sensory deficits in those areas but excluded any common causes of neuropathy after extensive testing. They diagnosed her with idiopathic polyneuropathy.

On staining with hematoxylin and eosin, skin biopsies of the faint erythematous patches showed mild, nonspecific perivascular and periappendigeal infiltrate whereas biopsies from the nodules showed a heavy infiltrate in the deep dermis and beyond. Fite's stain revealed numerous lepra bacilli in the biopsy specimens (in red on biopsy of a nodule). Nasal scrapings were positive for acid-fast bacilli and polymerase chain reaction confirmed the presence of Mycobacterium leprae.

Dr. Kalisiak and his colleagues began daily treatment with 600 mg of rifampin, 100 mg of dapsone, 50 mg of clofazimine. The regimen also included gabapentin for neuropathic pain that will be continued for at least 1 year.

QUEBEC CITY — The woman's origin from Singapore and her extensive history of living in nine countries from age 26 to 39 years until she immigrated to Canada was crucial in leading to her diagnosis of borderline lepromatous leprosy, Michael Kalisiak, M.D., reported at the annual conference of the Canadian Dermatology Association.

Her countries of residence included Iran, Trinidad, Scotland, United States, Indonesia, the Netherlands, and Norway, with brief periods in Kenya and Ecuador; some of these countries have an intermediate incidence of leprosy.

For 3 years prior to her skin manifestations, the patient visited neurologists for her neuropathic symptoms, which initially occurred as numbness and occasional pain in her left anterior thigh and later spread to her left hand and left and right lower legs. She also reported decreased grip strength in her left hand, according to Dr. Kalisiak, a second-year dermatology resident at the University of Alberta, Edmonton.

The neurologists discovered numerous motor and sensory deficits in those areas but excluded any common causes of neuropathy after extensive testing. They diagnosed her with idiopathic polyneuropathy.

On staining with hematoxylin and eosin, skin biopsies of the faint erythematous patches showed mild, nonspecific perivascular and periappendigeal infiltrate whereas biopsies from the nodules showed a heavy infiltrate in the deep dermis and beyond. Fite's stain revealed numerous lepra bacilli in the biopsy specimens (in red on biopsy of a nodule). Nasal scrapings were positive for acid-fast bacilli and polymerase chain reaction confirmed the presence of Mycobacterium leprae.

Dr. Kalisiak and his colleagues began daily treatment with 600 mg of rifampin, 100 mg of dapsone, 50 mg of clofazimine. The regimen also included gabapentin for neuropathic pain that will be continued for at least 1 year.

QUEBEC CITY — The woman's origin from Singapore and her extensive history of living in nine countries from age 26 to 39 years until she immigrated to Canada was crucial in leading to her diagnosis of borderline lepromatous leprosy, Michael Kalisiak, M.D., reported at the annual conference of the Canadian Dermatology Association.

Her countries of residence included Iran, Trinidad, Scotland, United States, Indonesia, the Netherlands, and Norway, with brief periods in Kenya and Ecuador; some of these countries have an intermediate incidence of leprosy.

For 3 years prior to her skin manifestations, the patient visited neurologists for her neuropathic symptoms, which initially occurred as numbness and occasional pain in her left anterior thigh and later spread to her left hand and left and right lower legs. She also reported decreased grip strength in her left hand, according to Dr. Kalisiak, a second-year dermatology resident at the University of Alberta, Edmonton.

The neurologists discovered numerous motor and sensory deficits in those areas but excluded any common causes of neuropathy after extensive testing. They diagnosed her with idiopathic polyneuropathy.

On staining with hematoxylin and eosin, skin biopsies of the faint erythematous patches showed mild, nonspecific perivascular and periappendigeal infiltrate whereas biopsies from the nodules showed a heavy infiltrate in the deep dermis and beyond. Fite's stain revealed numerous lepra bacilli in the biopsy specimens (in red on biopsy of a nodule). Nasal scrapings were positive for acid-fast bacilli and polymerase chain reaction confirmed the presence of Mycobacterium leprae.

Dr. Kalisiak and his colleagues began daily treatment with 600 mg of rifampin, 100 mg of dapsone, 50 mg of clofazimine. The regimen also included gabapentin for neuropathic pain that will be continued for at least 1 year.

NEW YORK — The notion that people who come to the emergency department with a less-than-acute health problem are an important cause of overcrowding there is probably not true, Michael J. Schull, M.D., reported at the annual meeting of the Society for Academic Emergency Medicine.

Administrators, politicians, researchers, and physicians often blame low-acuity patients for worsened emergency department (ED) crowding. Plans to reduce ED overcrowding include diverting ED patients with health problems that are not acute to places such as fast-track emergent care centers or primary care clinics.

But it is unknown if non-acutely ill or injured patients are actually responsible for extended lengths of stay for patients with more acute conditions, said Dr. Schull, an emergency physician at the Institute for Clinical Evaluative Sciences at Sunnybrook and Women's College Health Sciences Centre, Toronto.

With his colleagues, Dr. Schull analyzed the assumption that patients with less urgent health problems contribute to ED overcrowding by reviewing consecutive 8-hour intervals in an administrative data set that included all visits to all high-volume EDs in Ontario during 2002–2003.

Overall, the investigators analyzed 4.1 million visits to 110 EDs (16 teaching and 94 community) that had patient volumes ranging from 13,000 to 81,000 per year.

He classified ED patients as in need of acute care if they were admitted to the hospital; at the other end of the spectrum were patients who, arriving at the ED under their own power, were considered not in need of acute care; they received a score of 4 or 5 on the Canadian Triage & Acuity Scale, and were later discharged. All other ED patients were deemed to have health problems in medium need of urgent care.

A patient's entire length of stay in the ED was credited to the 8-hour interval in which he or she arrived, even if the stay extended into the next interval.

Dr. Schull did not find that the EDs were able to reduce the collective length of stay of patients with medium or highly acute problems when fewer patients with non-urgent problems were present.

For every new patient with a non-acute problem, the combined length of stay for patients with medium and highly acute problems increased by only 0.6 minutes.

Each new patient with a highly acute medical problem increased the total length of stay for others with urgent or moderately acute problems by 7 minutes.

“Those [times] are really meaningful when you think of it in terms of what the actual arrival rates of these patients are,” he added.

During a typical 8-hour interval, a median of 16 new low-acuity patients arrived at an ED, resulting in an average increase in the length of stay of medium- and high-acuity patients of 9.7 minutes (4% increase), which is not clinically significant, Dr. Schull said.

A median of three new high-acuity patient arrived at an ED during the 8-hour interval, increasing the mean length of stay of medium- and high-acuity patients by 21 minutes (9%).

NEW YORK — The notion that people who come to the emergency department with a less-than-acute health problem are an important cause of overcrowding there is probably not true, Michael J. Schull, M.D., reported at the annual meeting of the Society for Academic Emergency Medicine.

Administrators, politicians, researchers, and physicians often blame low-acuity patients for worsened emergency department (ED) crowding. Plans to reduce ED overcrowding include diverting ED patients with health problems that are not acute to places such as fast-track emergent care centers or primary care clinics.

But it is unknown if non-acutely ill or injured patients are actually responsible for extended lengths of stay for patients with more acute conditions, said Dr. Schull, an emergency physician at the Institute for Clinical Evaluative Sciences at Sunnybrook and Women's College Health Sciences Centre, Toronto.

With his colleagues, Dr. Schull analyzed the assumption that patients with less urgent health problems contribute to ED overcrowding by reviewing consecutive 8-hour intervals in an administrative data set that included all visits to all high-volume EDs in Ontario during 2002–2003.

Overall, the investigators analyzed 4.1 million visits to 110 EDs (16 teaching and 94 community) that had patient volumes ranging from 13,000 to 81,000 per year.

He classified ED patients as in need of acute care if they were admitted to the hospital; at the other end of the spectrum were patients who, arriving at the ED under their own power, were considered not in need of acute care; they received a score of 4 or 5 on the Canadian Triage & Acuity Scale, and were later discharged. All other ED patients were deemed to have health problems in medium need of urgent care.

A patient's entire length of stay in the ED was credited to the 8-hour interval in which he or she arrived, even if the stay extended into the next interval.

Dr. Schull did not find that the EDs were able to reduce the collective length of stay of patients with medium or highly acute problems when fewer patients with non-urgent problems were present.

For every new patient with a non-acute problem, the combined length of stay for patients with medium and highly acute problems increased by only 0.6 minutes.

Each new patient with a highly acute medical problem increased the total length of stay for others with urgent or moderately acute problems by 7 minutes.

“Those [times] are really meaningful when you think of it in terms of what the actual arrival rates of these patients are,” he added.

During a typical 8-hour interval, a median of 16 new low-acuity patients arrived at an ED, resulting in an average increase in the length of stay of medium- and high-acuity patients of 9.7 minutes (4% increase), which is not clinically significant, Dr. Schull said.

A median of three new high-acuity patient arrived at an ED during the 8-hour interval, increasing the mean length of stay of medium- and high-acuity patients by 21 minutes (9%).

NEW YORK — The notion that people who come to the emergency department with a less-than-acute health problem are an important cause of overcrowding there is probably not true, Michael J. Schull, M.D., reported at the annual meeting of the Society for Academic Emergency Medicine.

Administrators, politicians, researchers, and physicians often blame low-acuity patients for worsened emergency department (ED) crowding. Plans to reduce ED overcrowding include diverting ED patients with health problems that are not acute to places such as fast-track emergent care centers or primary care clinics.

But it is unknown if non-acutely ill or injured patients are actually responsible for extended lengths of stay for patients with more acute conditions, said Dr. Schull, an emergency physician at the Institute for Clinical Evaluative Sciences at Sunnybrook and Women's College Health Sciences Centre, Toronto.

With his colleagues, Dr. Schull analyzed the assumption that patients with less urgent health problems contribute to ED overcrowding by reviewing consecutive 8-hour intervals in an administrative data set that included all visits to all high-volume EDs in Ontario during 2002–2003.

Overall, the investigators analyzed 4.1 million visits to 110 EDs (16 teaching and 94 community) that had patient volumes ranging from 13,000 to 81,000 per year.

He classified ED patients as in need of acute care if they were admitted to the hospital; at the other end of the spectrum were patients who, arriving at the ED under their own power, were considered not in need of acute care; they received a score of 4 or 5 on the Canadian Triage & Acuity Scale, and were later discharged. All other ED patients were deemed to have health problems in medium need of urgent care.

A patient's entire length of stay in the ED was credited to the 8-hour interval in which he or she arrived, even if the stay extended into the next interval.

Dr. Schull did not find that the EDs were able to reduce the collective length of stay of patients with medium or highly acute problems when fewer patients with non-urgent problems were present.

For every new patient with a non-acute problem, the combined length of stay for patients with medium and highly acute problems increased by only 0.6 minutes.

Each new patient with a highly acute medical problem increased the total length of stay for others with urgent or moderately acute problems by 7 minutes.

“Those [times] are really meaningful when you think of it in terms of what the actual arrival rates of these patients are,” he added.

During a typical 8-hour interval, a median of 16 new low-acuity patients arrived at an ED, resulting in an average increase in the length of stay of medium- and high-acuity patients of 9.7 minutes (4% increase), which is not clinically significant, Dr. Schull said.

A median of three new high-acuity patient arrived at an ED during the 8-hour interval, increasing the mean length of stay of medium- and high-acuity patients by 21 minutes (9%).