Damian McNamara

MIAMI — Antifungal prophylaxis for very-low-birth-weight infants could decrease overall incidence of invasive infections and mortality, considerations that may outweigh valid concerns about emerging resistance, according to a poster presentation at a meeting on fungal infections sponsored by Imedex.

“We were seeing a lot of cases of invasive candidiasis in newborns,” Jaime G. Deville, M.D., said in an interview. So he and his associate performed a retrospective cohort study of all neonates at University of California Medical Center in Los Angeles from 1998 to 2002 with proven mycotic disease.

The impetus for the study was a patient with a particularly severe infection. The premature infant had an extremely low birth weight, approximately 650 g and was admitted to the neonatal intensive care unit (NICU). After receiving “all kinds of antibiotics” for sepsis over 2 months, he developed a heart valve infection. Physicians discovered a mass approximately one-fourth the size of his heart, Dr. Deville said. “At the same time, he started to grow Candida albicans.” Surgeons removed the mass, and the patient survived.

Opportunistic infections in the NICU are becoming increasingly common. They are associated with high mortality, prolonged hospital stays, and increased costs, according to Dr. Deville, a pediatrician specializing in infectious disease at the UCLA Medical Center.

The researchers assessed changes in invasive candidiasis incidence, fungal species, risk factors, and possible ways to intervene.

“To be honest, I was very surprised about the very high incidence in very-low-birth-weight infants,” Dr. Deville said in an interview. In this population, incidence of invasive fungal infections was 23% in 1998, 18% in 1999, 57% in 2000, 59% in 2001, and 50% in 2002. The incidence dropped in 2002 because “there was more awareness by the end of the 5-year period.”

Reports in the literature state a lower incidence of invasive fungal infections in newborns, perhaps because these studies are compiled from large pediatric databases, Dr. Deville said. “We think the incidence of invasive fungal infections is much larger than it appears in published papers.”

UCLA is a large tertiary-care center and “our population is selected toward the very sick.” For example, of the 1,686 infants admitted to the NICU during the study, 52% had a primary diagnosis of prematurity, 26% had congenital heart disease, 12% had chromosomal abnormalities, and 10% had noncardiac major malformations.

Overall, mortality from invasive fungal infections in the NICU was 43% in 1998, 50% in 1999, 38% in 2000, 42% in 2001, and 17% in 2002. Again, the researchers attributed the decrease after 2001 to a better index of suspicion for the fungal infections.

High incidence and mortality in very-low-birth-weight infants raise the question of prophylactic treatment in this high-risk population, Dr. Deville said.

That automatically raises concerns about resistance. “It's a very valid concern, but prophylaxis will decrease the overall incidence,” he said. “I don't think it outweighs the decision to 'prophylax'—overall you will see less [invasive candidiasis] and prevent mortality.”

“The take-home message is once you have a sick newborn [who appears] to have an infection, consider candida,” Dr. Deville said. The typical patient is a premature infant in the NICU for a month or 2 with multiple bacterial infections, fevers, and lowered blood pressure.

Early empiric therapy might reduce morbidity and mortality in these neonates. Treatment with amphotericin B is an option, but the drug has a lot of side effects, he said. Also, amphotericin B is delivered by a slow infusion that can take up to 4 hours to administer. Azole therapy is quicker but must be given intravenously in this population.

“We're excited about the echinocandins—they are less toxic than other agents,” he said.

MIAMI — Antifungal prophylaxis for very-low-birth-weight infants could decrease overall incidence of invasive infections and mortality, considerations that may outweigh valid concerns about emerging resistance, according to a poster presentation at a meeting on fungal infections sponsored by Imedex.

“We were seeing a lot of cases of invasive candidiasis in newborns,” Jaime G. Deville, M.D., said in an interview. So he and his associate performed a retrospective cohort study of all neonates at University of California Medical Center in Los Angeles from 1998 to 2002 with proven mycotic disease.

The impetus for the study was a patient with a particularly severe infection. The premature infant had an extremely low birth weight, approximately 650 g and was admitted to the neonatal intensive care unit (NICU). After receiving “all kinds of antibiotics” for sepsis over 2 months, he developed a heart valve infection. Physicians discovered a mass approximately one-fourth the size of his heart, Dr. Deville said. “At the same time, he started to grow Candida albicans.” Surgeons removed the mass, and the patient survived.

Opportunistic infections in the NICU are becoming increasingly common. They are associated with high mortality, prolonged hospital stays, and increased costs, according to Dr. Deville, a pediatrician specializing in infectious disease at the UCLA Medical Center.

The researchers assessed changes in invasive candidiasis incidence, fungal species, risk factors, and possible ways to intervene.

“To be honest, I was very surprised about the very high incidence in very-low-birth-weight infants,” Dr. Deville said in an interview. In this population, incidence of invasive fungal infections was 23% in 1998, 18% in 1999, 57% in 2000, 59% in 2001, and 50% in 2002. The incidence dropped in 2002 because “there was more awareness by the end of the 5-year period.”

Reports in the literature state a lower incidence of invasive fungal infections in newborns, perhaps because these studies are compiled from large pediatric databases, Dr. Deville said. “We think the incidence of invasive fungal infections is much larger than it appears in published papers.”

UCLA is a large tertiary-care center and “our population is selected toward the very sick.” For example, of the 1,686 infants admitted to the NICU during the study, 52% had a primary diagnosis of prematurity, 26% had congenital heart disease, 12% had chromosomal abnormalities, and 10% had noncardiac major malformations.

Overall, mortality from invasive fungal infections in the NICU was 43% in 1998, 50% in 1999, 38% in 2000, 42% in 2001, and 17% in 2002. Again, the researchers attributed the decrease after 2001 to a better index of suspicion for the fungal infections.

High incidence and mortality in very-low-birth-weight infants raise the question of prophylactic treatment in this high-risk population, Dr. Deville said.

That automatically raises concerns about resistance. “It's a very valid concern, but prophylaxis will decrease the overall incidence,” he said. “I don't think it outweighs the decision to 'prophylax'—overall you will see less [invasive candidiasis] and prevent mortality.”

“The take-home message is once you have a sick newborn [who appears] to have an infection, consider candida,” Dr. Deville said. The typical patient is a premature infant in the NICU for a month or 2 with multiple bacterial infections, fevers, and lowered blood pressure.

Early empiric therapy might reduce morbidity and mortality in these neonates. Treatment with amphotericin B is an option, but the drug has a lot of side effects, he said. Also, amphotericin B is delivered by a slow infusion that can take up to 4 hours to administer. Azole therapy is quicker but must be given intravenously in this population.

“We're excited about the echinocandins—they are less toxic than other agents,” he said.

MIAMI — Antifungal prophylaxis for very-low-birth-weight infants could decrease overall incidence of invasive infections and mortality, considerations that may outweigh valid concerns about emerging resistance, according to a poster presentation at a meeting on fungal infections sponsored by Imedex.

“We were seeing a lot of cases of invasive candidiasis in newborns,” Jaime G. Deville, M.D., said in an interview. So he and his associate performed a retrospective cohort study of all neonates at University of California Medical Center in Los Angeles from 1998 to 2002 with proven mycotic disease.

The impetus for the study was a patient with a particularly severe infection. The premature infant had an extremely low birth weight, approximately 650 g and was admitted to the neonatal intensive care unit (NICU). After receiving “all kinds of antibiotics” for sepsis over 2 months, he developed a heart valve infection. Physicians discovered a mass approximately one-fourth the size of his heart, Dr. Deville said. “At the same time, he started to grow Candida albicans.” Surgeons removed the mass, and the patient survived.

Opportunistic infections in the NICU are becoming increasingly common. They are associated with high mortality, prolonged hospital stays, and increased costs, according to Dr. Deville, a pediatrician specializing in infectious disease at the UCLA Medical Center.

The researchers assessed changes in invasive candidiasis incidence, fungal species, risk factors, and possible ways to intervene.

“To be honest, I was very surprised about the very high incidence in very-low-birth-weight infants,” Dr. Deville said in an interview. In this population, incidence of invasive fungal infections was 23% in 1998, 18% in 1999, 57% in 2000, 59% in 2001, and 50% in 2002. The incidence dropped in 2002 because “there was more awareness by the end of the 5-year period.”

Reports in the literature state a lower incidence of invasive fungal infections in newborns, perhaps because these studies are compiled from large pediatric databases, Dr. Deville said. “We think the incidence of invasive fungal infections is much larger than it appears in published papers.”

UCLA is a large tertiary-care center and “our population is selected toward the very sick.” For example, of the 1,686 infants admitted to the NICU during the study, 52% had a primary diagnosis of prematurity, 26% had congenital heart disease, 12% had chromosomal abnormalities, and 10% had noncardiac major malformations.

Overall, mortality from invasive fungal infections in the NICU was 43% in 1998, 50% in 1999, 38% in 2000, 42% in 2001, and 17% in 2002. Again, the researchers attributed the decrease after 2001 to a better index of suspicion for the fungal infections.

High incidence and mortality in very-low-birth-weight infants raise the question of prophylactic treatment in this high-risk population, Dr. Deville said.

That automatically raises concerns about resistance. “It's a very valid concern, but prophylaxis will decrease the overall incidence,” he said. “I don't think it outweighs the decision to 'prophylax'—overall you will see less [invasive candidiasis] and prevent mortality.”

“The take-home message is once you have a sick newborn [who appears] to have an infection, consider candida,” Dr. Deville said. The typical patient is a premature infant in the NICU for a month or 2 with multiple bacterial infections, fevers, and lowered blood pressure.

Early empiric therapy might reduce morbidity and mortality in these neonates. Treatment with amphotericin B is an option, but the drug has a lot of side effects, he said. Also, amphotericin B is delivered by a slow infusion that can take up to 4 hours to administer. Azole therapy is quicker but must be given intravenously in this population.

“We're excited about the echinocandins—they are less toxic than other agents,” he said.

BAL HARBOUR, FLA. – The cognitive impairment seen in some older adults following mild to moderate traumatic brain injury may persist for up to 2 years, according to preliminary results of a longitudinal study.

Previous studies on cognitive impairment following traumatic brain injury (TBI) in older adults have focused on only the first few months of recovery. The current study is one of the few to look at long-term cognitive consequences of TBI in this older population. “Even though the rates of traumatic brain injuries are increasing as our population ages, few studies have examined the cognitive outcomes in this group,” wrote the authors of the poster presented at the annual meeting of the American Neuropsychiatric Association.

The researchers compared 69 older adults hospitalized for TBI with 79 controls matched for age, gender, and education. “Even 2 years after the event, there is evidence of memory, functional, and executive [function] deficits in mild to moderate brain injury patients,” Mark J. Rapoport, M.D., told this newspaper. “We tend to think of these people as better off after a few months.”

“Genetics did not predict outcomes,” said Dr. Rapoport, of Sunnybrook & Women's College Health Sciences Centre, Toronto, Canada.

Previously, researchers found that the presence of the ϵ4 allele in the apolipoprotein E (APOE-ϵ4) gene is associated with increased deposition of amyloid beta-protein after head injury (Nat. Med. 1995;1:135–7). Amyloid beta-protein plays a key role in the pathogenesis of Alzheimer's disease, they noted. Another study supports a negative effect–TBI patients with the APOE-ϵ4 gene had poor cognitive or functional outcome (Neurology 1999;52:244–8).

Both studies suggest a genetic susceptibility to worse outcomes after brain injury. However, a third study found no such effect based on APOE genotype in brain injury patients (Brain 2004;127:2621–8).

“We need to see this over time,” Dr. Rapoport said. The authors noted that APOE genotype might play a more significant role beyond 2 years following an injury, particularly in vulnerable patients (for example, those with mild cognitive impairment).

In the current study, Dr. Rapoport and his colleagues assessed attention, memory, language, and executive function at 1 and 2 years post injury. The investigators controlled for possible confounders, including age, gender, education, APOE genotype, English as a second language, and depression.

The final analysis of data from the first year of the study shows that people with TBI had poorer performance than controls on tests of general cognition, attention/working memory, verbal memory, language, and executive function. There were no differences at 1 year in visual memory test results. A neuropsychiatrist blinded to whether a participant was a case or a control found that no subject met the criteria for Alzheimer's disease or mild cognitive impairment.

The preliminary analysis of the 2-year results suggests there is a greater incidence of impairment in the TBI group versus controls, but the differences between groups are smaller (marginal statistical significance), compared with the first year. Cases had poorer performance than controls on processing speed, verbal memory, language, and word list generation at 2 years. Cases were also rated as having poorer overall functioning than controls.

Possible limitations of the study include recruitment bias and attrition associated with any clinical longitudinal study of TBI. The authors noted that their follow-up rate of more than 70% is higher than rates in similar studies. In addition, investigators did not consider the role of injury severity or psychosocial outcome.

The researchers only enrolled people aged 50 years and older, to be consistent with other studies of TBI in older adults. The average age in the current study was 68 years. Therefore, participants were already at a low baseline risk for mild cognitive impairment or Alzheimer's disease, the authors noted.

“However, subtle changes have developed as early as 2 years post-injury which may be harbingers of more significant and serious cognitive and functional impairment as more time progresses,” they wrote.

BAL HARBOUR, FLA. – The cognitive impairment seen in some older adults following mild to moderate traumatic brain injury may persist for up to 2 years, according to preliminary results of a longitudinal study.

Previous studies on cognitive impairment following traumatic brain injury (TBI) in older adults have focused on only the first few months of recovery. The current study is one of the few to look at long-term cognitive consequences of TBI in this older population. “Even though the rates of traumatic brain injuries are increasing as our population ages, few studies have examined the cognitive outcomes in this group,” wrote the authors of the poster presented at the annual meeting of the American Neuropsychiatric Association.

The researchers compared 69 older adults hospitalized for TBI with 79 controls matched for age, gender, and education. “Even 2 years after the event, there is evidence of memory, functional, and executive [function] deficits in mild to moderate brain injury patients,” Mark J. Rapoport, M.D., told this newspaper. “We tend to think of these people as better off after a few months.”

“Genetics did not predict outcomes,” said Dr. Rapoport, of Sunnybrook & Women's College Health Sciences Centre, Toronto, Canada.

Previously, researchers found that the presence of the ϵ4 allele in the apolipoprotein E (APOE-ϵ4) gene is associated with increased deposition of amyloid beta-protein after head injury (Nat. Med. 1995;1:135–7). Amyloid beta-protein plays a key role in the pathogenesis of Alzheimer's disease, they noted. Another study supports a negative effect–TBI patients with the APOE-ϵ4 gene had poor cognitive or functional outcome (Neurology 1999;52:244–8).

Both studies suggest a genetic susceptibility to worse outcomes after brain injury. However, a third study found no such effect based on APOE genotype in brain injury patients (Brain 2004;127:2621–8).

“We need to see this over time,” Dr. Rapoport said. The authors noted that APOE genotype might play a more significant role beyond 2 years following an injury, particularly in vulnerable patients (for example, those with mild cognitive impairment).

In the current study, Dr. Rapoport and his colleagues assessed attention, memory, language, and executive function at 1 and 2 years post injury. The investigators controlled for possible confounders, including age, gender, education, APOE genotype, English as a second language, and depression.

The final analysis of data from the first year of the study shows that people with TBI had poorer performance than controls on tests of general cognition, attention/working memory, verbal memory, language, and executive function. There were no differences at 1 year in visual memory test results. A neuropsychiatrist blinded to whether a participant was a case or a control found that no subject met the criteria for Alzheimer's disease or mild cognitive impairment.

The preliminary analysis of the 2-year results suggests there is a greater incidence of impairment in the TBI group versus controls, but the differences between groups are smaller (marginal statistical significance), compared with the first year. Cases had poorer performance than controls on processing speed, verbal memory, language, and word list generation at 2 years. Cases were also rated as having poorer overall functioning than controls.

Possible limitations of the study include recruitment bias and attrition associated with any clinical longitudinal study of TBI. The authors noted that their follow-up rate of more than 70% is higher than rates in similar studies. In addition, investigators did not consider the role of injury severity or psychosocial outcome.

The researchers only enrolled people aged 50 years and older, to be consistent with other studies of TBI in older adults. The average age in the current study was 68 years. Therefore, participants were already at a low baseline risk for mild cognitive impairment or Alzheimer's disease, the authors noted.

“However, subtle changes have developed as early as 2 years post-injury which may be harbingers of more significant and serious cognitive and functional impairment as more time progresses,” they wrote.

BAL HARBOUR, FLA. – The cognitive impairment seen in some older adults following mild to moderate traumatic brain injury may persist for up to 2 years, according to preliminary results of a longitudinal study.

Previous studies on cognitive impairment following traumatic brain injury (TBI) in older adults have focused on only the first few months of recovery. The current study is one of the few to look at long-term cognitive consequences of TBI in this older population. “Even though the rates of traumatic brain injuries are increasing as our population ages, few studies have examined the cognitive outcomes in this group,” wrote the authors of the poster presented at the annual meeting of the American Neuropsychiatric Association.

The researchers compared 69 older adults hospitalized for TBI with 79 controls matched for age, gender, and education. “Even 2 years after the event, there is evidence of memory, functional, and executive [function] deficits in mild to moderate brain injury patients,” Mark J. Rapoport, M.D., told this newspaper. “We tend to think of these people as better off after a few months.”

“Genetics did not predict outcomes,” said Dr. Rapoport, of Sunnybrook & Women's College Health Sciences Centre, Toronto, Canada.

Previously, researchers found that the presence of the ϵ4 allele in the apolipoprotein E (APOE-ϵ4) gene is associated with increased deposition of amyloid beta-protein after head injury (Nat. Med. 1995;1:135–7). Amyloid beta-protein plays a key role in the pathogenesis of Alzheimer's disease, they noted. Another study supports a negative effect–TBI patients with the APOE-ϵ4 gene had poor cognitive or functional outcome (Neurology 1999;52:244–8).

Both studies suggest a genetic susceptibility to worse outcomes after brain injury. However, a third study found no such effect based on APOE genotype in brain injury patients (Brain 2004;127:2621–8).

“We need to see this over time,” Dr. Rapoport said. The authors noted that APOE genotype might play a more significant role beyond 2 years following an injury, particularly in vulnerable patients (for example, those with mild cognitive impairment).

In the current study, Dr. Rapoport and his colleagues assessed attention, memory, language, and executive function at 1 and 2 years post injury. The investigators controlled for possible confounders, including age, gender, education, APOE genotype, English as a second language, and depression.

The final analysis of data from the first year of the study shows that people with TBI had poorer performance than controls on tests of general cognition, attention/working memory, verbal memory, language, and executive function. There were no differences at 1 year in visual memory test results. A neuropsychiatrist blinded to whether a participant was a case or a control found that no subject met the criteria for Alzheimer's disease or mild cognitive impairment.

The preliminary analysis of the 2-year results suggests there is a greater incidence of impairment in the TBI group versus controls, but the differences between groups are smaller (marginal statistical significance), compared with the first year. Cases had poorer performance than controls on processing speed, verbal memory, language, and word list generation at 2 years. Cases were also rated as having poorer overall functioning than controls.

Possible limitations of the study include recruitment bias and attrition associated with any clinical longitudinal study of TBI. The authors noted that their follow-up rate of more than 70% is higher than rates in similar studies. In addition, investigators did not consider the role of injury severity or psychosocial outcome.

The researchers only enrolled people aged 50 years and older, to be consistent with other studies of TBI in older adults. The average age in the current study was 68 years. Therefore, participants were already at a low baseline risk for mild cognitive impairment or Alzheimer's disease, the authors noted.

“However, subtle changes have developed as early as 2 years post-injury which may be harbingers of more significant and serious cognitive and functional impairment as more time progresses,” they wrote.

SAN JUAN, P.R. – Patients who are struggling with medication compliance for alcohol dependence may benefit from a clinical intervention that combines medical management and brief counseling sessions, Helen M. Pettinati, Ph.D., said at the annual meeting of the American Academy of Addiction Psychiatry.

The compliance-enhancing intervention for physicians comes from an ongoing combination drug and behavioral treatment study sponsored by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), said Dr. Pettinati, a research director at the Center for Studies of Addiction, University of Pennsylvania, Philadelphia.

During a lengthy initial session, the physician educates the patient about alcohol dependence, explains medication effects and treatment success rates, and emphasizes the importance of adherence.

Follow-up is a series of 15- to 30-minute sessions that include a brief check on medical functioning and whether the patient is drinking and/or medication adherent.

The NIAAA publishes a medical management manual, available for $6 at www.niaaa.nih.gov/publications/combine-text.htm

For example, if a patient is nonadherent with medication and drinking, the “support and advice” dialogue reviews the benefits of alcohol abstinence and pharmacotherapy.

“If the patient has a poor response to treatment, ask first about treatment nonadherence. Many times in a clinical setting someone will tell me their patient does not respond to that agent, but they haven't asked the patient if they were taking the treatment,” Dr. Pettinati explained.

“There are a lot of reasons for nonadherence–only a small percentage actually forget and need help with reminders,” Dr. Pettinati said at a symposium funded by an educational grant from Alkermes Inc. Among her disclosures was receipt of grant research support from the company.

The NIAAA study assessing the medical management approach is a phase III study of Alkermes' injectable, long-acting naltrexone. One aim of the study was to assess if the 30-day form improves compliance. The study included 624 patients with DSM-IV-defined alcohol dependence.

At a higher dose (380 mg), long-acting naltrexone reduced heavy drinking 25% more than did placebo. The 190-mg dose had a 17% advantage over placebo.

“Reductions were seen in the placebo group as well–remember, this is an injectable placebo,” Dr. Pettinati pointed out.

People were compliant–the median number of injections was six. In addition, participants attended a median of 11 out of 12 psychosocial support sessions, she reported.

SAN JUAN, P.R. – Patients who are struggling with medication compliance for alcohol dependence may benefit from a clinical intervention that combines medical management and brief counseling sessions, Helen M. Pettinati, Ph.D., said at the annual meeting of the American Academy of Addiction Psychiatry.

The compliance-enhancing intervention for physicians comes from an ongoing combination drug and behavioral treatment study sponsored by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), said Dr. Pettinati, a research director at the Center for Studies of Addiction, University of Pennsylvania, Philadelphia.

During a lengthy initial session, the physician educates the patient about alcohol dependence, explains medication effects and treatment success rates, and emphasizes the importance of adherence.

Follow-up is a series of 15- to 30-minute sessions that include a brief check on medical functioning and whether the patient is drinking and/or medication adherent.

The NIAAA publishes a medical management manual, available for $6 at www.niaaa.nih.gov/publications/combine-text.htm

For example, if a patient is nonadherent with medication and drinking, the “support and advice” dialogue reviews the benefits of alcohol abstinence and pharmacotherapy.

“If the patient has a poor response to treatment, ask first about treatment nonadherence. Many times in a clinical setting someone will tell me their patient does not respond to that agent, but they haven't asked the patient if they were taking the treatment,” Dr. Pettinati explained.

“There are a lot of reasons for nonadherence–only a small percentage actually forget and need help with reminders,” Dr. Pettinati said at a symposium funded by an educational grant from Alkermes Inc. Among her disclosures was receipt of grant research support from the company.

The NIAAA study assessing the medical management approach is a phase III study of Alkermes' injectable, long-acting naltrexone. One aim of the study was to assess if the 30-day form improves compliance. The study included 624 patients with DSM-IV-defined alcohol dependence.

At a higher dose (380 mg), long-acting naltrexone reduced heavy drinking 25% more than did placebo. The 190-mg dose had a 17% advantage over placebo.

“Reductions were seen in the placebo group as well–remember, this is an injectable placebo,” Dr. Pettinati pointed out.

People were compliant–the median number of injections was six. In addition, participants attended a median of 11 out of 12 psychosocial support sessions, she reported.

SAN JUAN, P.R. – Patients who are struggling with medication compliance for alcohol dependence may benefit from a clinical intervention that combines medical management and brief counseling sessions, Helen M. Pettinati, Ph.D., said at the annual meeting of the American Academy of Addiction Psychiatry.

The compliance-enhancing intervention for physicians comes from an ongoing combination drug and behavioral treatment study sponsored by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), said Dr. Pettinati, a research director at the Center for Studies of Addiction, University of Pennsylvania, Philadelphia.

During a lengthy initial session, the physician educates the patient about alcohol dependence, explains medication effects and treatment success rates, and emphasizes the importance of adherence.

Follow-up is a series of 15- to 30-minute sessions that include a brief check on medical functioning and whether the patient is drinking and/or medication adherent.

The NIAAA publishes a medical management manual, available for $6 at www.niaaa.nih.gov/publications/combine-text.htm

For example, if a patient is nonadherent with medication and drinking, the “support and advice” dialogue reviews the benefits of alcohol abstinence and pharmacotherapy.

“If the patient has a poor response to treatment, ask first about treatment nonadherence. Many times in a clinical setting someone will tell me their patient does not respond to that agent, but they haven't asked the patient if they were taking the treatment,” Dr. Pettinati explained.

“There are a lot of reasons for nonadherence–only a small percentage actually forget and need help with reminders,” Dr. Pettinati said at a symposium funded by an educational grant from Alkermes Inc. Among her disclosures was receipt of grant research support from the company.

The NIAAA study assessing the medical management approach is a phase III study of Alkermes' injectable, long-acting naltrexone. One aim of the study was to assess if the 30-day form improves compliance. The study included 624 patients with DSM-IV-defined alcohol dependence.

At a higher dose (380 mg), long-acting naltrexone reduced heavy drinking 25% more than did placebo. The 190-mg dose had a 17% advantage over placebo.

“Reductions were seen in the placebo group as well–remember, this is an injectable placebo,” Dr. Pettinati pointed out.

People were compliant–the median number of injections was six. In addition, participants attended a median of 11 out of 12 psychosocial support sessions, she reported.

SAN JUAN, P.R. – Risperidone and ziprasidone increased adherence to inpatient substance abuse treatment for people with schizophrenia or schizoaffective disorder in a comparison that also included olanzapine and typical neuroleptic agents, Elizabeth B. Stuyt, M.D., said at the annual meeting of the American Academy of Addiction Psychiatry.

In the retrospective study, the risperidone (Risperdal) and ziprasidone (Geodon) groups experienced increased length of stay in substance abuse treatment, a higher completion rate, and greater behavioral improvements.

Cigarette smoking may play an important role, said Dr. Stuyt, lead researcher. All 55 participants smoked at baseline, and constituents of cigarette smoke activate the same cytochrome P-450 system enzyme that metabolizes olanzapine (Zyprexa), haloperidol decanoate (Haldol), and fluphenazine decanoate. This enzyme does not metabolize risperidone or ziprasidone, said Dr. Stuyt of the University of Colorado, Denver.

“We thought smoking made the difference,” Dr. Stuyt said in an interview. “The implication is when getting someone to quit smoking, it is good to know which meds they are on.”

All of the patients–31 with schizophrenia and 24 with schizoaffective disorder–had a cooccurring substance abuse disorder.

Most were referrals to the Circle program, a fully integrated, 90-day inpatient dual-diagnosis treatment program for adults who have failed previous attempts to treat substance dependence. The Colorado Mental Health Institute at Pueblo runs the program.

A majority of the participants are referred as a condition of criminal court (75%–80%); others are referred by civil court (5%–10%), and the rest attend voluntarily (10%–20%).

Fifteen of the 55 study patients took olanzapine (mean dose, 18.78 mg/day), 16 took risperidone (mean dose, 3.9 mg/day), 14 took ziprasidone (mean dose, 132.8 mg/day), and 10 took a typical neuroleptic (5 each took haloperidol decanoate and fluphenazine decanoate).

“We knew there were differences [between medications], but we noticed in our program that people on olanzapine were not doing well,” Dr. Stuyt said. “So we looked retrospectively at psychotic diagnoses at admission, what drug they were on, and the outcome.”

The Circle program uses up to 90 days of cognitive-behavioral treatment. Five objectives are assigned at admission based on existing behaviors. Patients are started at a precontemplative stage regarding their substance abuse, even if they say they are committed to quitting. “They have not demonstrated it by their behavior,” she said.

“It's very hard,” Dr. Stuyt said. “I've had medical students say they don't think they could do it.”

As behaviors improve, participants advance up levels in the program. “They are here to 'gift.' They are not snitches, but they write up reports if they break the rules or they see other people doing something wrong,” she said.

The longer the length of stay, the better the outcome, Dr. Stuyt said. The average length of stay was about the same for risperidone (82 days) and ziprasidone (74 days), but stays were shorter for patients taking olanzapine (44 days) or a typical neuroleptic (47 days).

Participants were considered completers if they completed their homework and strategies for self-improvement, Dr. Stuyt said.

There was a 56% success rate overall: 88% of risperidone patients were completers, versus 64% of ziprasidone and 33% of olanzapine patients, she added.

SAN JUAN, P.R. – Risperidone and ziprasidone increased adherence to inpatient substance abuse treatment for people with schizophrenia or schizoaffective disorder in a comparison that also included olanzapine and typical neuroleptic agents, Elizabeth B. Stuyt, M.D., said at the annual meeting of the American Academy of Addiction Psychiatry.

In the retrospective study, the risperidone (Risperdal) and ziprasidone (Geodon) groups experienced increased length of stay in substance abuse treatment, a higher completion rate, and greater behavioral improvements.

Cigarette smoking may play an important role, said Dr. Stuyt, lead researcher. All 55 participants smoked at baseline, and constituents of cigarette smoke activate the same cytochrome P-450 system enzyme that metabolizes olanzapine (Zyprexa), haloperidol decanoate (Haldol), and fluphenazine decanoate. This enzyme does not metabolize risperidone or ziprasidone, said Dr. Stuyt of the University of Colorado, Denver.

“We thought smoking made the difference,” Dr. Stuyt said in an interview. “The implication is when getting someone to quit smoking, it is good to know which meds they are on.”

All of the patients–31 with schizophrenia and 24 with schizoaffective disorder–had a cooccurring substance abuse disorder.

Most were referrals to the Circle program, a fully integrated, 90-day inpatient dual-diagnosis treatment program for adults who have failed previous attempts to treat substance dependence. The Colorado Mental Health Institute at Pueblo runs the program.

A majority of the participants are referred as a condition of criminal court (75%–80%); others are referred by civil court (5%–10%), and the rest attend voluntarily (10%–20%).

Fifteen of the 55 study patients took olanzapine (mean dose, 18.78 mg/day), 16 took risperidone (mean dose, 3.9 mg/day), 14 took ziprasidone (mean dose, 132.8 mg/day), and 10 took a typical neuroleptic (5 each took haloperidol decanoate and fluphenazine decanoate).

“We knew there were differences [between medications], but we noticed in our program that people on olanzapine were not doing well,” Dr. Stuyt said. “So we looked retrospectively at psychotic diagnoses at admission, what drug they were on, and the outcome.”

The Circle program uses up to 90 days of cognitive-behavioral treatment. Five objectives are assigned at admission based on existing behaviors. Patients are started at a precontemplative stage regarding their substance abuse, even if they say they are committed to quitting. “They have not demonstrated it by their behavior,” she said.

“It's very hard,” Dr. Stuyt said. “I've had medical students say they don't think they could do it.”

As behaviors improve, participants advance up levels in the program. “They are here to 'gift.' They are not snitches, but they write up reports if they break the rules or they see other people doing something wrong,” she said.

The longer the length of stay, the better the outcome, Dr. Stuyt said. The average length of stay was about the same for risperidone (82 days) and ziprasidone (74 days), but stays were shorter for patients taking olanzapine (44 days) or a typical neuroleptic (47 days).

Participants were considered completers if they completed their homework and strategies for self-improvement, Dr. Stuyt said.

There was a 56% success rate overall: 88% of risperidone patients were completers, versus 64% of ziprasidone and 33% of olanzapine patients, she added.

SAN JUAN, P.R. – Risperidone and ziprasidone increased adherence to inpatient substance abuse treatment for people with schizophrenia or schizoaffective disorder in a comparison that also included olanzapine and typical neuroleptic agents, Elizabeth B. Stuyt, M.D., said at the annual meeting of the American Academy of Addiction Psychiatry.

In the retrospective study, the risperidone (Risperdal) and ziprasidone (Geodon) groups experienced increased length of stay in substance abuse treatment, a higher completion rate, and greater behavioral improvements.

Cigarette smoking may play an important role, said Dr. Stuyt, lead researcher. All 55 participants smoked at baseline, and constituents of cigarette smoke activate the same cytochrome P-450 system enzyme that metabolizes olanzapine (Zyprexa), haloperidol decanoate (Haldol), and fluphenazine decanoate. This enzyme does not metabolize risperidone or ziprasidone, said Dr. Stuyt of the University of Colorado, Denver.

“We thought smoking made the difference,” Dr. Stuyt said in an interview. “The implication is when getting someone to quit smoking, it is good to know which meds they are on.”

All of the patients–31 with schizophrenia and 24 with schizoaffective disorder–had a cooccurring substance abuse disorder.

Most were referrals to the Circle program, a fully integrated, 90-day inpatient dual-diagnosis treatment program for adults who have failed previous attempts to treat substance dependence. The Colorado Mental Health Institute at Pueblo runs the program.

A majority of the participants are referred as a condition of criminal court (75%–80%); others are referred by civil court (5%–10%), and the rest attend voluntarily (10%–20%).

Fifteen of the 55 study patients took olanzapine (mean dose, 18.78 mg/day), 16 took risperidone (mean dose, 3.9 mg/day), 14 took ziprasidone (mean dose, 132.8 mg/day), and 10 took a typical neuroleptic (5 each took haloperidol decanoate and fluphenazine decanoate).

“We knew there were differences [between medications], but we noticed in our program that people on olanzapine were not doing well,” Dr. Stuyt said. “So we looked retrospectively at psychotic diagnoses at admission, what drug they were on, and the outcome.”

The Circle program uses up to 90 days of cognitive-behavioral treatment. Five objectives are assigned at admission based on existing behaviors. Patients are started at a precontemplative stage regarding their substance abuse, even if they say they are committed to quitting. “They have not demonstrated it by their behavior,” she said.

“It's very hard,” Dr. Stuyt said. “I've had medical students say they don't think they could do it.”

As behaviors improve, participants advance up levels in the program. “They are here to 'gift.' They are not snitches, but they write up reports if they break the rules or they see other people doing something wrong,” she said.

The longer the length of stay, the better the outcome, Dr. Stuyt said. The average length of stay was about the same for risperidone (82 days) and ziprasidone (74 days), but stays were shorter for patients taking olanzapine (44 days) or a typical neuroleptic (47 days).

Participants were considered completers if they completed their homework and strategies for self-improvement, Dr. Stuyt said.

There was a 56% success rate overall: 88% of risperidone patients were completers, versus 64% of ziprasidone and 33% of olanzapine patients, she added.

MIAMI BEACH – Onset time of visual hallucinations can help clinicians distinguish between dementia with Lewy bodies and Alzheimer's disease, according to a study presented at the annual meeting of the American Academy of Neurology.

Patients with dementia with Lewy bodies (DLB) or Alzheimer's disease (AD) can experience visual hallucinations, visual misperceptions, elementary auditory hallucinations, and delusions. However, little is known about how these features differ between groups in incidence or character, said Tanis J. Ferman, Ph.D.

“Is there a way to distinguish between psychoses in these two groups clinically?” asked Dr. Ferman, a psychologist at the Mayo Clinic Jacksonville (Fla.).

To answer that question, Dr. Ferman and her associates compared 108 people with DLB with 154 Alzheimer's patients. They administered the Mayo Fluctuations Questionnaire and the Neuropsychiatric Inventory to informants for each participant. A consensus diagnosis came from a clinical interview, neurologic exam, activities of daily living based on Record of Independent Living results, and a neuropsychiatric evaluation.

“For the most part, patients had mild to mild-to-moderate dementia,” Dr. Ferman said. Mean scores on the Dementia Rating Scale were 114 for the DLB group and 111 for the AD group.

About one-third of each group had ocular disease such as cataracts or macular degeneration: 35.6% in the DLB group and 31.5% in the Alzheimer's group. The groups' mean ages were similar (73 and 74 years), but the DLB group had more males (69% vs. 42%).

Patients with DLB had a higher frequency of psychotic features than patients with AD. “This was not surprising–it's part of the diagnostic criteria,” she said. A total of 63% of the DLB group experienced visual hallucinations, compared with 8% of the AD group.

The onset of visual hallucinations relative to the estimated onset of dementia was 1.7 years in the DLB group and 6 years in the AD group, making it “an absolute discriminator,” Dr. Ferman said in reply to a question from a meeting attendee. “In another study, we found that 4 years was a good cutoff for when they occur in AD vs. DLB, and that was the case in this study.”

Visual hallucination type, patient insight, and degree of distress did not differ significantly between groups. There were no differences in beliefs between groups regarding danger to self, stealing, abandonment, TV figures being real, spouses or others being someone other than who they claimed to be, or the idea that their house was not their home, she noted.

People and animals were the most common hallucination in both groups (91%). Other common hallucinations involved insects (22%) and objects (14%).

Patients with DLB, however, were more likely to see specific recurrent images (70%) than were patients with AD (45%). “One DLB patient, for example, repeatedly saw children sitting on her countertops,” Dr. Ferman said.

In addition, 32% of DLB participants were likely to experience visual hallucinations when drowsy, versus 1% of AD participants. In contrast, 57% of DLB and 90% of AD participants had visual hallucinations when fully awake. “This finding could be secondary to the excessive daytime sleepiness characteristic of DLB patients,” she said.

The researchers observed additional differences. DLB participants were more likely to have visual misperceptions, such as mistaking a lamp for a person, and elementary auditory hallucinations like hearing a car drive up.

In DLB, delusions and auditory hallucinations tended to occur only in those with visual hallucinations. With Alzheimer's patients, delusions, visual hallucinations, and auditory hallucinations occurred independent of each other, Dr. Ferman said.

“DLB patients are more likely to report the images, ignore them, or touch them, which is never reported by AD patients,” she said.

MIAMI BEACH – Onset time of visual hallucinations can help clinicians distinguish between dementia with Lewy bodies and Alzheimer's disease, according to a study presented at the annual meeting of the American Academy of Neurology.

Patients with dementia with Lewy bodies (DLB) or Alzheimer's disease (AD) can experience visual hallucinations, visual misperceptions, elementary auditory hallucinations, and delusions. However, little is known about how these features differ between groups in incidence or character, said Tanis J. Ferman, Ph.D.

“Is there a way to distinguish between psychoses in these two groups clinically?” asked Dr. Ferman, a psychologist at the Mayo Clinic Jacksonville (Fla.).

To answer that question, Dr. Ferman and her associates compared 108 people with DLB with 154 Alzheimer's patients. They administered the Mayo Fluctuations Questionnaire and the Neuropsychiatric Inventory to informants for each participant. A consensus diagnosis came from a clinical interview, neurologic exam, activities of daily living based on Record of Independent Living results, and a neuropsychiatric evaluation.

“For the most part, patients had mild to mild-to-moderate dementia,” Dr. Ferman said. Mean scores on the Dementia Rating Scale were 114 for the DLB group and 111 for the AD group.

About one-third of each group had ocular disease such as cataracts or macular degeneration: 35.6% in the DLB group and 31.5% in the Alzheimer's group. The groups' mean ages were similar (73 and 74 years), but the DLB group had more males (69% vs. 42%).

Patients with DLB had a higher frequency of psychotic features than patients with AD. “This was not surprising–it's part of the diagnostic criteria,” she said. A total of 63% of the DLB group experienced visual hallucinations, compared with 8% of the AD group.

The onset of visual hallucinations relative to the estimated onset of dementia was 1.7 years in the DLB group and 6 years in the AD group, making it “an absolute discriminator,” Dr. Ferman said in reply to a question from a meeting attendee. “In another study, we found that 4 years was a good cutoff for when they occur in AD vs. DLB, and that was the case in this study.”

Visual hallucination type, patient insight, and degree of distress did not differ significantly between groups. There were no differences in beliefs between groups regarding danger to self, stealing, abandonment, TV figures being real, spouses or others being someone other than who they claimed to be, or the idea that their house was not their home, she noted.

People and animals were the most common hallucination in both groups (91%). Other common hallucinations involved insects (22%) and objects (14%).

Patients with DLB, however, were more likely to see specific recurrent images (70%) than were patients with AD (45%). “One DLB patient, for example, repeatedly saw children sitting on her countertops,” Dr. Ferman said.

In addition, 32% of DLB participants were likely to experience visual hallucinations when drowsy, versus 1% of AD participants. In contrast, 57% of DLB and 90% of AD participants had visual hallucinations when fully awake. “This finding could be secondary to the excessive daytime sleepiness characteristic of DLB patients,” she said.

The researchers observed additional differences. DLB participants were more likely to have visual misperceptions, such as mistaking a lamp for a person, and elementary auditory hallucinations like hearing a car drive up.

In DLB, delusions and auditory hallucinations tended to occur only in those with visual hallucinations. With Alzheimer's patients, delusions, visual hallucinations, and auditory hallucinations occurred independent of each other, Dr. Ferman said.

“DLB patients are more likely to report the images, ignore them, or touch them, which is never reported by AD patients,” she said.

MIAMI BEACH – Onset time of visual hallucinations can help clinicians distinguish between dementia with Lewy bodies and Alzheimer's disease, according to a study presented at the annual meeting of the American Academy of Neurology.

Patients with dementia with Lewy bodies (DLB) or Alzheimer's disease (AD) can experience visual hallucinations, visual misperceptions, elementary auditory hallucinations, and delusions. However, little is known about how these features differ between groups in incidence or character, said Tanis J. Ferman, Ph.D.

“Is there a way to distinguish between psychoses in these two groups clinically?” asked Dr. Ferman, a psychologist at the Mayo Clinic Jacksonville (Fla.).

To answer that question, Dr. Ferman and her associates compared 108 people with DLB with 154 Alzheimer's patients. They administered the Mayo Fluctuations Questionnaire and the Neuropsychiatric Inventory to informants for each participant. A consensus diagnosis came from a clinical interview, neurologic exam, activities of daily living based on Record of Independent Living results, and a neuropsychiatric evaluation.

“For the most part, patients had mild to mild-to-moderate dementia,” Dr. Ferman said. Mean scores on the Dementia Rating Scale were 114 for the DLB group and 111 for the AD group.

About one-third of each group had ocular disease such as cataracts or macular degeneration: 35.6% in the DLB group and 31.5% in the Alzheimer's group. The groups' mean ages were similar (73 and 74 years), but the DLB group had more males (69% vs. 42%).

Patients with DLB had a higher frequency of psychotic features than patients with AD. “This was not surprising–it's part of the diagnostic criteria,” she said. A total of 63% of the DLB group experienced visual hallucinations, compared with 8% of the AD group.

The onset of visual hallucinations relative to the estimated onset of dementia was 1.7 years in the DLB group and 6 years in the AD group, making it “an absolute discriminator,” Dr. Ferman said in reply to a question from a meeting attendee. “In another study, we found that 4 years was a good cutoff for when they occur in AD vs. DLB, and that was the case in this study.”

Visual hallucination type, patient insight, and degree of distress did not differ significantly between groups. There were no differences in beliefs between groups regarding danger to self, stealing, abandonment, TV figures being real, spouses or others being someone other than who they claimed to be, or the idea that their house was not their home, she noted.

People and animals were the most common hallucination in both groups (91%). Other common hallucinations involved insects (22%) and objects (14%).

Patients with DLB, however, were more likely to see specific recurrent images (70%) than were patients with AD (45%). “One DLB patient, for example, repeatedly saw children sitting on her countertops,” Dr. Ferman said.

In addition, 32% of DLB participants were likely to experience visual hallucinations when drowsy, versus 1% of AD participants. In contrast, 57% of DLB and 90% of AD participants had visual hallucinations when fully awake. “This finding could be secondary to the excessive daytime sleepiness characteristic of DLB patients,” she said.

The researchers observed additional differences. DLB participants were more likely to have visual misperceptions, such as mistaking a lamp for a person, and elementary auditory hallucinations like hearing a car drive up.

In DLB, delusions and auditory hallucinations tended to occur only in those with visual hallucinations. With Alzheimer's patients, delusions, visual hallucinations, and auditory hallucinations occurred independent of each other, Dr. Ferman said.

“DLB patients are more likely to report the images, ignore them, or touch them, which is never reported by AD patients,” she said.

BAL HARBOUR, FLA. – Impaired graphesthesia, a prevalent finding among patients with mild cognitive impairment, may be an early sign when considered with memory loss that a patient has preclinical Alzheimer's disease, according to a study.

Mild cognitive impairment (MCI) is generally accepted as a precursor to Alzheimer's disease. Some neurologists screen MCI patients with a graphesthesia test, Edward Zamrini, M.D., said in an interview.

Graphesthesia is the sense by which people identify figures or numbers drawn on their hands with a dull-pointed object.

In an assessment for graphesthesia, people hold one hand out in front of them as if reading from it with the hand's long axis perpendicular to the midline axis of the body. While the patient's eyes are closed, the neurologist traces a number “1” on the patient's palm, asking the patient to identify the number out loud. Then the physician traces a second number on the patient's palm before repeating the process on the other hand.

Patients have two chances to identify the number correctly. If they fail to do so, they may be diagnosed with impaired graphesthesia.

Dr. Zamrini and his colleagues assessed more than 200 consecutive new patients at the Memory Disorders Clinic at the University of Alabama, Birmingham. Researchers identified patients by medical records between May 2001 and November 2002.

Investigators took a detailed history, noted medications, and performed a thorough neurologic and cognitive assessment.

Examinations included light touch, pinprick, joint and position sense, vibration sense, and a Mini-Mental State Examination (MMSE). Patients were 58% female and 83% white, and their mean age was 68 years.

Results were presented during a poster session at the annual meeting of the American Neuropsychiatric Association.

A total of 41 of the participants had MCI, 74 had Alzheimer's disease, and 96 were not diagnosed with either condition and were considered the control group. The control group included patients who had vascular dementia, frontal lobe dementia, and other non-Alzheimer's dementias.

The prevalence of impaired graphesthesia was 54% in the MCI group, 79% in the Alzheimer's group, and 33% in controls. The finding of higher impairment in the MCI patients, “even compared with other dementia patients, suggests that what I am catching is an early form of Alzheimer's disease, not only a memory loss,” said Dr. Zamrini, a neurologist at the University of Alabama.

After incorporating such an exam into his practice, “I observed a disproportionately high number of my patients with MCI that have impaired graphesthesia,” he said.

“It's just one more piece of evidence in support of the diagnosis of preclinical Alzheimer's disease, but you have to have the memory loss, too,” Dr. Zamrini said. If additional studies support impaired graphesthesia as a predictive variable, it would be the first physical sign of preclinical Alzheimer's disease.

Although Alzheimer's disease affects memory areas first, the parietal lobes are a “close second,” Dr. Zamrini said. The parietal areas are important to interpretation of senses, including graphesthesia.

Mean MMSE scores were 28 for the MCI group, 21 for the Alzheimer's disease group, and 26 for controls. The researchers grouped patients according to whether their MMSE score was 24 or greater or less than 24 to determine the effect of cognitive impairment on graphesthesia performance. There were significant differences in prevalence of impaired graphesthesia for participants scoring 24 or greater: 51% of the MCI group, 74% of the Alzheimer's group, and 24% of the control group.

The differential diagnosis for impaired graphesthesia should include stroke and severe sensory loss, Dr. Zamrini said.

It is easier for specialists to diagnose Alzheimer's disease than mild cognitive impairment because there are many reasons for memory loss.

“Graphesthesia testing may help us in the future with that distinction,” Dr. Zamrini said.

BAL HARBOUR, FLA. – Impaired graphesthesia, a prevalent finding among patients with mild cognitive impairment, may be an early sign when considered with memory loss that a patient has preclinical Alzheimer's disease, according to a study.

Mild cognitive impairment (MCI) is generally accepted as a precursor to Alzheimer's disease. Some neurologists screen MCI patients with a graphesthesia test, Edward Zamrini, M.D., said in an interview.

Graphesthesia is the sense by which people identify figures or numbers drawn on their hands with a dull-pointed object.

In an assessment for graphesthesia, people hold one hand out in front of them as if reading from it with the hand's long axis perpendicular to the midline axis of the body. While the patient's eyes are closed, the neurologist traces a number “1” on the patient's palm, asking the patient to identify the number out loud. Then the physician traces a second number on the patient's palm before repeating the process on the other hand.

Patients have two chances to identify the number correctly. If they fail to do so, they may be diagnosed with impaired graphesthesia.

Dr. Zamrini and his colleagues assessed more than 200 consecutive new patients at the Memory Disorders Clinic at the University of Alabama, Birmingham. Researchers identified patients by medical records between May 2001 and November 2002.

Investigators took a detailed history, noted medications, and performed a thorough neurologic and cognitive assessment.

Examinations included light touch, pinprick, joint and position sense, vibration sense, and a Mini-Mental State Examination (MMSE). Patients were 58% female and 83% white, and their mean age was 68 years.

Results were presented during a poster session at the annual meeting of the American Neuropsychiatric Association.

A total of 41 of the participants had MCI, 74 had Alzheimer's disease, and 96 were not diagnosed with either condition and were considered the control group. The control group included patients who had vascular dementia, frontal lobe dementia, and other non-Alzheimer's dementias.

The prevalence of impaired graphesthesia was 54% in the MCI group, 79% in the Alzheimer's group, and 33% in controls. The finding of higher impairment in the MCI patients, “even compared with other dementia patients, suggests that what I am catching is an early form of Alzheimer's disease, not only a memory loss,” said Dr. Zamrini, a neurologist at the University of Alabama.

After incorporating such an exam into his practice, “I observed a disproportionately high number of my patients with MCI that have impaired graphesthesia,” he said.

“It's just one more piece of evidence in support of the diagnosis of preclinical Alzheimer's disease, but you have to have the memory loss, too,” Dr. Zamrini said. If additional studies support impaired graphesthesia as a predictive variable, it would be the first physical sign of preclinical Alzheimer's disease.

Although Alzheimer's disease affects memory areas first, the parietal lobes are a “close second,” Dr. Zamrini said. The parietal areas are important to interpretation of senses, including graphesthesia.

Mean MMSE scores were 28 for the MCI group, 21 for the Alzheimer's disease group, and 26 for controls. The researchers grouped patients according to whether their MMSE score was 24 or greater or less than 24 to determine the effect of cognitive impairment on graphesthesia performance. There were significant differences in prevalence of impaired graphesthesia for participants scoring 24 or greater: 51% of the MCI group, 74% of the Alzheimer's group, and 24% of the control group.

The differential diagnosis for impaired graphesthesia should include stroke and severe sensory loss, Dr. Zamrini said.

It is easier for specialists to diagnose Alzheimer's disease than mild cognitive impairment because there are many reasons for memory loss.

“Graphesthesia testing may help us in the future with that distinction,” Dr. Zamrini said.

BAL HARBOUR, FLA. – Impaired graphesthesia, a prevalent finding among patients with mild cognitive impairment, may be an early sign when considered with memory loss that a patient has preclinical Alzheimer's disease, according to a study.

Mild cognitive impairment (MCI) is generally accepted as a precursor to Alzheimer's disease. Some neurologists screen MCI patients with a graphesthesia test, Edward Zamrini, M.D., said in an interview.

Graphesthesia is the sense by which people identify figures or numbers drawn on their hands with a dull-pointed object.

In an assessment for graphesthesia, people hold one hand out in front of them as if reading from it with the hand's long axis perpendicular to the midline axis of the body. While the patient's eyes are closed, the neurologist traces a number “1” on the patient's palm, asking the patient to identify the number out loud. Then the physician traces a second number on the patient's palm before repeating the process on the other hand.

Patients have two chances to identify the number correctly. If they fail to do so, they may be diagnosed with impaired graphesthesia.

Dr. Zamrini and his colleagues assessed more than 200 consecutive new patients at the Memory Disorders Clinic at the University of Alabama, Birmingham. Researchers identified patients by medical records between May 2001 and November 2002.

Investigators took a detailed history, noted medications, and performed a thorough neurologic and cognitive assessment.

Examinations included light touch, pinprick, joint and position sense, vibration sense, and a Mini-Mental State Examination (MMSE). Patients were 58% female and 83% white, and their mean age was 68 years.

Results were presented during a poster session at the annual meeting of the American Neuropsychiatric Association.

A total of 41 of the participants had MCI, 74 had Alzheimer's disease, and 96 were not diagnosed with either condition and were considered the control group. The control group included patients who had vascular dementia, frontal lobe dementia, and other non-Alzheimer's dementias.

The prevalence of impaired graphesthesia was 54% in the MCI group, 79% in the Alzheimer's group, and 33% in controls. The finding of higher impairment in the MCI patients, “even compared with other dementia patients, suggests that what I am catching is an early form of Alzheimer's disease, not only a memory loss,” said Dr. Zamrini, a neurologist at the University of Alabama.

After incorporating such an exam into his practice, “I observed a disproportionately high number of my patients with MCI that have impaired graphesthesia,” he said.

“It's just one more piece of evidence in support of the diagnosis of preclinical Alzheimer's disease, but you have to have the memory loss, too,” Dr. Zamrini said. If additional studies support impaired graphesthesia as a predictive variable, it would be the first physical sign of preclinical Alzheimer's disease.

Although Alzheimer's disease affects memory areas first, the parietal lobes are a “close second,” Dr. Zamrini said. The parietal areas are important to interpretation of senses, including graphesthesia.

Mean MMSE scores were 28 for the MCI group, 21 for the Alzheimer's disease group, and 26 for controls. The researchers grouped patients according to whether their MMSE score was 24 or greater or less than 24 to determine the effect of cognitive impairment on graphesthesia performance. There were significant differences in prevalence of impaired graphesthesia for participants scoring 24 or greater: 51% of the MCI group, 74% of the Alzheimer's group, and 24% of the control group.

The differential diagnosis for impaired graphesthesia should include stroke and severe sensory loss, Dr. Zamrini said.

It is easier for specialists to diagnose Alzheimer's disease than mild cognitive impairment because there are many reasons for memory loss.

“Graphesthesia testing may help us in the future with that distinction,” Dr. Zamrini said.

MIAMI BEACH — Calcium hydroxylapatite can effectively fill wrinkles, correct acne and other scars, and augment lips, although there is a learning curve with lips, David J. Goldberg, M.D., said at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Calcium hydroxylapatite (Radiesse, BioForm Medical Inc.) is identical to a natural compound in human bone and teeth. Oncologists, orthopedists, dentists, and other health care professionals have used the material for years in implants and drug delivery systems. The Food and Drug Administration approved the biomaterial for vocal cord injections, as a tissue marker, and for periodontal use for onlay of bone. Nasolabial folds and HIV facial lipoatrophy studies are currently pending.

Soft tissue filler uses are off label, but it is a legal use of the product, according to Dr. Goldberg, who is in private practice in Westwood, N.J.

There is no need for sensitization testing because calcium hydroxylapatite is nonallergic. Other advantages from a patient's perspective include the product's long-term effectiveness, its lack of migration, and minimal downtime (soft tissue swelling for about 24-48 hours and some bruising are possible).

Dr. Goldberg surveyed 155 of his patients 6 months after soft tissue augmentation with the filler, and 90% indicated they would use it again.

Calcium hydroxylapatite is packaged as cellulose-based gel with a glycerin-water base. No reconstitution is required. Its consistent viscosity makes it easy to inject. Other potential advantages for physicians include its stability, a shelf life of 2 years without refrigeration, and its compatibility with other cosmetic procedures, said Dr. Goldberg, who is also director of laser research and Mohs surgery at Mount Sinai School of Medicine, New York.

The filler stays soft in tissue. It is long lasting but not permanent, and eventually resorbs. A disadvantage is predicting exactly how long the correction will last. For example, 12-22 months after injection, 30%-100% of initial results remain, according to Dr. Goldberg. Another potential disadvantage is formation of lip nodules. Use of the filler in lips is best left to experienced operators, he emphasized at the meeting.

A small volume is needed for correction. For example, only 1-2 cc is required for nasolabial folds or the corners of the mouth. A total of about 1 cc is required for upper and lower lip augmentation, unless a very large increase in volume is desired.

Dr. Goldberg recommended a threading technique. Inject a thin thread of the material as the needle is withdrawn. The typical injection is 0.05 cc. A 25- to 27-gauge, 1.25-inch needle is recommended for nasolabial folds. A smaller 0.5-inch, 25- to 27-gauge needle is recommended for injecting the corners of the mouth.

Local anesthesia with epinephrine is recommended. Also consider doing a nerve block prior to lip augmentation. A small amount of local anesthetic in the lips promotes vasoconstriction, Dr. Goldberg said.

The calcium hydroxylapatite implant does not calcify or ossify. The particles act as scaffold for tissue infiltration, he explained. There is a self-limited fibroblastic response. The particles are not osteoinductive: They do not cause fibroblasts to differentiate to become osteoblasts.

MIAMI BEACH — Calcium hydroxylapatite can effectively fill wrinkles, correct acne and other scars, and augment lips, although there is a learning curve with lips, David J. Goldberg, M.D., said at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Calcium hydroxylapatite (Radiesse, BioForm Medical Inc.) is identical to a natural compound in human bone and teeth. Oncologists, orthopedists, dentists, and other health care professionals have used the material for years in implants and drug delivery systems. The Food and Drug Administration approved the biomaterial for vocal cord injections, as a tissue marker, and for periodontal use for onlay of bone. Nasolabial folds and HIV facial lipoatrophy studies are currently pending.

Soft tissue filler uses are off label, but it is a legal use of the product, according to Dr. Goldberg, who is in private practice in Westwood, N.J.

There is no need for sensitization testing because calcium hydroxylapatite is nonallergic. Other advantages from a patient's perspective include the product's long-term effectiveness, its lack of migration, and minimal downtime (soft tissue swelling for about 24-48 hours and some bruising are possible).

Dr. Goldberg surveyed 155 of his patients 6 months after soft tissue augmentation with the filler, and 90% indicated they would use it again.

Calcium hydroxylapatite is packaged as cellulose-based gel with a glycerin-water base. No reconstitution is required. Its consistent viscosity makes it easy to inject. Other potential advantages for physicians include its stability, a shelf life of 2 years without refrigeration, and its compatibility with other cosmetic procedures, said Dr. Goldberg, who is also director of laser research and Mohs surgery at Mount Sinai School of Medicine, New York.

The filler stays soft in tissue. It is long lasting but not permanent, and eventually resorbs. A disadvantage is predicting exactly how long the correction will last. For example, 12-22 months after injection, 30%-100% of initial results remain, according to Dr. Goldberg. Another potential disadvantage is formation of lip nodules. Use of the filler in lips is best left to experienced operators, he emphasized at the meeting.

A small volume is needed for correction. For example, only 1-2 cc is required for nasolabial folds or the corners of the mouth. A total of about 1 cc is required for upper and lower lip augmentation, unless a very large increase in volume is desired.

Dr. Goldberg recommended a threading technique. Inject a thin thread of the material as the needle is withdrawn. The typical injection is 0.05 cc. A 25- to 27-gauge, 1.25-inch needle is recommended for nasolabial folds. A smaller 0.5-inch, 25- to 27-gauge needle is recommended for injecting the corners of the mouth.

Local anesthesia with epinephrine is recommended. Also consider doing a nerve block prior to lip augmentation. A small amount of local anesthetic in the lips promotes vasoconstriction, Dr. Goldberg said.

The calcium hydroxylapatite implant does not calcify or ossify. The particles act as scaffold for tissue infiltration, he explained. There is a self-limited fibroblastic response. The particles are not osteoinductive: They do not cause fibroblasts to differentiate to become osteoblasts.

MIAMI BEACH — Calcium hydroxylapatite can effectively fill wrinkles, correct acne and other scars, and augment lips, although there is a learning curve with lips, David J. Goldberg, M.D., said at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Calcium hydroxylapatite (Radiesse, BioForm Medical Inc.) is identical to a natural compound in human bone and teeth. Oncologists, orthopedists, dentists, and other health care professionals have used the material for years in implants and drug delivery systems. The Food and Drug Administration approved the biomaterial for vocal cord injections, as a tissue marker, and for periodontal use for onlay of bone. Nasolabial folds and HIV facial lipoatrophy studies are currently pending.

Soft tissue filler uses are off label, but it is a legal use of the product, according to Dr. Goldberg, who is in private practice in Westwood, N.J.

There is no need for sensitization testing because calcium hydroxylapatite is nonallergic. Other advantages from a patient's perspective include the product's long-term effectiveness, its lack of migration, and minimal downtime (soft tissue swelling for about 24-48 hours and some bruising are possible).

Dr. Goldberg surveyed 155 of his patients 6 months after soft tissue augmentation with the filler, and 90% indicated they would use it again.

Calcium hydroxylapatite is packaged as cellulose-based gel with a glycerin-water base. No reconstitution is required. Its consistent viscosity makes it easy to inject. Other potential advantages for physicians include its stability, a shelf life of 2 years without refrigeration, and its compatibility with other cosmetic procedures, said Dr. Goldberg, who is also director of laser research and Mohs surgery at Mount Sinai School of Medicine, New York.

The filler stays soft in tissue. It is long lasting but not permanent, and eventually resorbs. A disadvantage is predicting exactly how long the correction will last. For example, 12-22 months after injection, 30%-100% of initial results remain, according to Dr. Goldberg. Another potential disadvantage is formation of lip nodules. Use of the filler in lips is best left to experienced operators, he emphasized at the meeting.

A small volume is needed for correction. For example, only 1-2 cc is required for nasolabial folds or the corners of the mouth. A total of about 1 cc is required for upper and lower lip augmentation, unless a very large increase in volume is desired.

Dr. Goldberg recommended a threading technique. Inject a thin thread of the material as the needle is withdrawn. The typical injection is 0.05 cc. A 25- to 27-gauge, 1.25-inch needle is recommended for nasolabial folds. A smaller 0.5-inch, 25- to 27-gauge needle is recommended for injecting the corners of the mouth.

Local anesthesia with epinephrine is recommended. Also consider doing a nerve block prior to lip augmentation. A small amount of local anesthetic in the lips promotes vasoconstriction, Dr. Goldberg said.

The calcium hydroxylapatite implant does not calcify or ossify. The particles act as scaffold for tissue infiltration, he explained. There is a self-limited fibroblastic response. The particles are not osteoinductive: They do not cause fibroblasts to differentiate to become osteoblasts.

MIAMI BEACH — Neither donepezil nor vitamin E significantly prevented more patients with mild cognitive impairment from converting to Alzheimer's disease at 3 years than placebo, according to a study presented at the annual meeting of the American Academy of Neurology.

The randomized, controlled trial included 769 people with mild cognitive impairment (MCI). Researchers compared the number of “conversions” to Alzheimer's disease (AD) among 257 people taking 2,000 IU of vitamin E per day, 253 taking 10 mg of donepezil per day, and 259 taking placebo. The mean age was 72 years, and 46% of participants were women.

Rates of progression from MCI to AD were comparable among patients in the three treatment arms at 36 months. When researchers reassessed the data in 6-month increments, they found that people on donepezil were significantly less likely to have progressed to AD at 6 months and 1 year than those taking placebo. At 18 months, the difference was no longer significant, and then results converged with the placebo group. There were no significant differences at any 6-month measurement between vitamin E and placebo.

“Donepezil appears to reduce the risk of progressing from MCI to Alzheimer's disease up to 12 months,” said Leon J. Thal, M.D., professor and chair of the department of neurosciences at the University of California, San Diego, and one of the study authors.

The study is scheduled for publication in the New England Journal of Medicine on June 9. (An online preview was posted at www.nejm.org

A total of 212 patients converted from MCI to AD during the study. About 16% of patients treated with placebo converted each year, or more than 45% by the study's end. One patient progressed to mixed dementia, and another converted to primary progressive aphasia.

Secondary outcomes included cognition and function. There were very few significant differences between vitamin E and placebo, except in scores for executive, language, and overall cognitive scores; these differences were only significant in the first 18 months. However, “donepezil had a [greater] effect on overall function, memory, and language up to 18 months,” Dr. Thal said. Six of seven mental-scoring differences were only significant during the first 18 months of the study.

A genetic factor made a significant difference in conversion of MCI to Alzheimer's disease: ϵ4 allele status for apolipoprotein E (apoE). About 55% of participants tested positive for one or more apoE ϵ4 alleles. “Positives converted at a higher rate and accounted for 76% of conversions,” said Dr. Thal, who is also principal investigator for his university's Alzheimer's disease research center.

Donepezil made a significant difference in participants positive for the allele, compared with placebo, at 12, 24, and 36 months. Most of the treatment effect of donepezil occurred among the apoE ϵ4 carriers.

David S. Knopman, M.D., discussed the study findings in a subsequent presentation at the meeting. “My thinking is that [apoE ϵ4] genotyping should not be done prior to initiating therapy with donepezil in people with MCI, he said.” Dr. Knopman is professor of neurology at the Mayo Clinic, Rochester, Minn., and had no conflict of interest to report.

“Are we there yet? Should MCI be treated with donepezil?” Dr. Knopman asked. “We need to discuss these results with families and give them both views.” On the negative side, treatment with donepezil is not cost effective. On the plus side, the drug provides a 58% 1-year risk reduction “that may be clinically meaningful to some patients and families.”

MIAMI BEACH — Neither donepezil nor vitamin E significantly prevented more patients with mild cognitive impairment from converting to Alzheimer's disease at 3 years than placebo, according to a study presented at the annual meeting of the American Academy of Neurology.

The randomized, controlled trial included 769 people with mild cognitive impairment (MCI). Researchers compared the number of “conversions” to Alzheimer's disease (AD) among 257 people taking 2,000 IU of vitamin E per day, 253 taking 10 mg of donepezil per day, and 259 taking placebo. The mean age was 72 years, and 46% of participants were women.

Rates of progression from MCI to AD were comparable among patients in the three treatment arms at 36 months. When researchers reassessed the data in 6-month increments, they found that people on donepezil were significantly less likely to have progressed to AD at 6 months and 1 year than those taking placebo. At 18 months, the difference was no longer significant, and then results converged with the placebo group. There were no significant differences at any 6-month measurement between vitamin E and placebo.

“Donepezil appears to reduce the risk of progressing from MCI to Alzheimer's disease up to 12 months,” said Leon J. Thal, M.D., professor and chair of the department of neurosciences at the University of California, San Diego, and one of the study authors.

The study is scheduled for publication in the New England Journal of Medicine on June 9. (An online preview was posted at www.nejm.org

A total of 212 patients converted from MCI to AD during the study. About 16% of patients treated with placebo converted each year, or more than 45% by the study's end. One patient progressed to mixed dementia, and another converted to primary progressive aphasia.

Secondary outcomes included cognition and function. There were very few significant differences between vitamin E and placebo, except in scores for executive, language, and overall cognitive scores; these differences were only significant in the first 18 months. However, “donepezil had a [greater] effect on overall function, memory, and language up to 18 months,” Dr. Thal said. Six of seven mental-scoring differences were only significant during the first 18 months of the study.

A genetic factor made a significant difference in conversion of MCI to Alzheimer's disease: ϵ4 allele status for apolipoprotein E (apoE). About 55% of participants tested positive for one or more apoE ϵ4 alleles. “Positives converted at a higher rate and accounted for 76% of conversions,” said Dr. Thal, who is also principal investigator for his university's Alzheimer's disease research center.

Donepezil made a significant difference in participants positive for the allele, compared with placebo, at 12, 24, and 36 months. Most of the treatment effect of donepezil occurred among the apoE ϵ4 carriers.

David S. Knopman, M.D., discussed the study findings in a subsequent presentation at the meeting. “My thinking is that [apoE ϵ4] genotyping should not be done prior to initiating therapy with donepezil in people with MCI, he said.” Dr. Knopman is professor of neurology at the Mayo Clinic, Rochester, Minn., and had no conflict of interest to report.

“Are we there yet? Should MCI be treated with donepezil?” Dr. Knopman asked. “We need to discuss these results with families and give them both views.” On the negative side, treatment with donepezil is not cost effective. On the plus side, the drug provides a 58% 1-year risk reduction “that may be clinically meaningful to some patients and families.”

MIAMI BEACH — Neither donepezil nor vitamin E significantly prevented more patients with mild cognitive impairment from converting to Alzheimer's disease at 3 years than placebo, according to a study presented at the annual meeting of the American Academy of Neurology.

The randomized, controlled trial included 769 people with mild cognitive impairment (MCI). Researchers compared the number of “conversions” to Alzheimer's disease (AD) among 257 people taking 2,000 IU of vitamin E per day, 253 taking 10 mg of donepezil per day, and 259 taking placebo. The mean age was 72 years, and 46% of participants were women.

Rates of progression from MCI to AD were comparable among patients in the three treatment arms at 36 months. When researchers reassessed the data in 6-month increments, they found that people on donepezil were significantly less likely to have progressed to AD at 6 months and 1 year than those taking placebo. At 18 months, the difference was no longer significant, and then results converged with the placebo group. There were no significant differences at any 6-month measurement between vitamin E and placebo.

“Donepezil appears to reduce the risk of progressing from MCI to Alzheimer's disease up to 12 months,” said Leon J. Thal, M.D., professor and chair of the department of neurosciences at the University of California, San Diego, and one of the study authors.

The study is scheduled for publication in the New England Journal of Medicine on June 9. (An online preview was posted at www.nejm.org

A total of 212 patients converted from MCI to AD during the study. About 16% of patients treated with placebo converted each year, or more than 45% by the study's end. One patient progressed to mixed dementia, and another converted to primary progressive aphasia.

Secondary outcomes included cognition and function. There were very few significant differences between vitamin E and placebo, except in scores for executive, language, and overall cognitive scores; these differences were only significant in the first 18 months. However, “donepezil had a [greater] effect on overall function, memory, and language up to 18 months,” Dr. Thal said. Six of seven mental-scoring differences were only significant during the first 18 months of the study.

A genetic factor made a significant difference in conversion of MCI to Alzheimer's disease: ϵ4 allele status for apolipoprotein E (apoE). About 55% of participants tested positive for one or more apoE ϵ4 alleles. “Positives converted at a higher rate and accounted for 76% of conversions,” said Dr. Thal, who is also principal investigator for his university's Alzheimer's disease research center.

Donepezil made a significant difference in participants positive for the allele, compared with placebo, at 12, 24, and 36 months. Most of the treatment effect of donepezil occurred among the apoE ϵ4 carriers.

David S. Knopman, M.D., discussed the study findings in a subsequent presentation at the meeting. “My thinking is that [apoE ϵ4] genotyping should not be done prior to initiating therapy with donepezil in people with MCI, he said.” Dr. Knopman is professor of neurology at the Mayo Clinic, Rochester, Minn., and had no conflict of interest to report.

“Are we there yet? Should MCI be treated with donepezil?” Dr. Knopman asked. “We need to discuss these results with families and give them both views.” On the negative side, treatment with donepezil is not cost effective. On the plus side, the drug provides a 58% 1-year risk reduction “that may be clinically meaningful to some patients and families.”

KEY BISCAYNE, FLA. — With the growing number of organ transplant recipients living longer, it has become increasingly important to treat and counsel these patients about their significantly higher risk of skin cancers, according to a presentation at the annual meeting of the Noah Worcester Dermatological Society.

Mucocutaneous lesions are the most common cancer type among organ transplant patients. The risk may be highest for squamous cell carcinoma, but it is also elevated for rare cancer types. In addition, skin cancers tend to be more aggressive and carry a worse prognosis for organ recipients.

Greater patient education is warranted. The International Transplant Skin Cancer Collaborative (www.itscc.org

There are more than 150,000 living organ transplant recipients. It is likely that 70% of these patients will eventually develop skin cancer, according to Marc D. Brown, M.D., professor of dermatology, University of Rochester (N.Y.).

An estimated 37% of tumors are mucocutaneous. Patients also develop lymphoma (17%), lung cancer (6%), and Kaposi's sarcoma, uterine, and colorectal cancers (4% each). Skin cancer can include squamous cell carcinoma, basal cell carcinoma, melanoma, sarcoma, Merkel cell carcinoma, angiosarcoma, verrucous carcinoma, atypical fibroxanthoma, and leiomyosarcoma.

There is a 65-fold increased incidence of cutaneous squamous cell carcinoma in organ transplant recipients, compared with the general population in Norway (J. Am. Acad. Dermatol. 1999;40:177–86). Researchers are less certain about melanoma incidence. The Norwegian study of 2,561 kidney and heart recipients found three times increased risk of melanoma, but another study of 5,356 patients in Sweden found no increased risk (Br. J. Dermatol. 2000;143:513–9).

Not only are skin cancers more common in organ transplant recipients, they also tend to progress more rapidly. Multiple lesions are more likely. Recurrence and metastasis rates are higher as well.

Incidence of skin cancer increases with the duration of long-term immunosuppression. Other contributing factors are exposure to UV radiation, genetic risk, and infection with human papilloma virus.

The risk of skin cancer might vary by the type of organ transplanted, according to some researchers. For example, squamous cell carcinoma may be two to three times more likely in cardiac vs. renal transplant recipients. In addition, there may be a lower risk of skin cancer after a liver is transplanted, compared with other organs, but additional research is needed, Dr. Brown pointed out.

The International Transplant Skin Cancer Collaborative suggests a full body exam at least annually, with particular attention to previous sites of nonmetastatic skin cancer. In addition, treat actinic keratoses aggressively and lower the threshold for considering a skin biopsy in these patients, the group suggests.

“You can never be faulted for following these high-risk patients too closely,” Dr. Brown said.

The collaborative promotes increased patient education on sun exposure and skin and lymph node self-examination. A telephone survey of 200 organ transplant recipients found 88% were unaware of their increased risk for skin cancer (Dermatol. Surg. 2004;30:610–15). A total of 35% reported regular sunscreen usage in the survey, but 35% also reported getting a sunburn the previous summer.

A separate survey of 122 renal transplant recipients found 41% could not recall skin cancer education (J. Am. Acad. Dermatol. 1999;40:697–701). Although 27% reported seeing a dermatologist after transplantation, only 14% had regular follow-up.

These skin lesions emerged on the back of a patient's head next to a scar left after surgery to remove a previous cancer. Courtesy Dr. Marc D. Brown

A Typical, Challenging Case

A 68-year-old white male with Fitzpatrick type III skin had a bilateral lung transplant in 1993. Four years later, he developed squamous cell carcinoma, primarily in situ. The lesions progressed, and he was diagnosed with squamous cell carcinoma on his vertex and parietal scalp areas in 1998. The lesions were present against a background of multiple actinic keratoses, and were removed by electrodesiccation and curettage.

In mid-2000, the patient had two-stage Mohs' surgery for the vertex squamous cell carcinoma.

Two months later, he presented with “poorly differentiated squamous cell carcinoma without a connection to the epidermis,” said Dr. Brown.

The patient had radiation therapy after developing eight metastases within 1 month. In September of 2000, he developed additional metastases within the radiation site. Clinicians reduced his immunosuppressive drugs by 50%, and the patient developed more than 30 metastatic nodules. The patient then had multiple excisions and radiation therapy with capecitabine (Xeloda) for sensitization. The patient never developed adenopathy. CT scans of his chest were negative. In March 2002, he began a trial of intralesional methotrexate every 2 weeks with excellent resolution, Dr. Brown reported. The patient died in July 2002.

KEY BISCAYNE, FLA. — With the growing number of organ transplant recipients living longer, it has become increasingly important to treat and counsel these patients about their significantly higher risk of skin cancers, according to a presentation at the annual meeting of the Noah Worcester Dermatological Society.

Mucocutaneous lesions are the most common cancer type among organ transplant patients. The risk may be highest for squamous cell carcinoma, but it is also elevated for rare cancer types. In addition, skin cancers tend to be more aggressive and carry a worse prognosis for organ recipients.

Greater patient education is warranted. The International Transplant Skin Cancer Collaborative (www.itscc.org

There are more than 150,000 living organ transplant recipients. It is likely that 70% of these patients will eventually develop skin cancer, according to Marc D. Brown, M.D., professor of dermatology, University of Rochester (N.Y.).

An estimated 37% of tumors are mucocutaneous. Patients also develop lymphoma (17%), lung cancer (6%), and Kaposi's sarcoma, uterine, and colorectal cancers (4% each). Skin cancer can include squamous cell carcinoma, basal cell carcinoma, melanoma, sarcoma, Merkel cell carcinoma, angiosarcoma, verrucous carcinoma, atypical fibroxanthoma, and leiomyosarcoma.

There is a 65-fold increased incidence of cutaneous squamous cell carcinoma in organ transplant recipients, compared with the general population in Norway (J. Am. Acad. Dermatol. 1999;40:177–86). Researchers are less certain about melanoma incidence. The Norwegian study of 2,561 kidney and heart recipients found three times increased risk of melanoma, but another study of 5,356 patients in Sweden found no increased risk (Br. J. Dermatol. 2000;143:513–9).

Not only are skin cancers more common in organ transplant recipients, they also tend to progress more rapidly. Multiple lesions are more likely. Recurrence and metastasis rates are higher as well.

Incidence of skin cancer increases with the duration of long-term immunosuppression. Other contributing factors are exposure to UV radiation, genetic risk, and infection with human papilloma virus.

The risk of skin cancer might vary by the type of organ transplanted, according to some researchers. For example, squamous cell carcinoma may be two to three times more likely in cardiac vs. renal transplant recipients. In addition, there may be a lower risk of skin cancer after a liver is transplanted, compared with other organs, but additional research is needed, Dr. Brown pointed out.

The International Transplant Skin Cancer Collaborative suggests a full body exam at least annually, with particular attention to previous sites of nonmetastatic skin cancer. In addition, treat actinic keratoses aggressively and lower the threshold for considering a skin biopsy in these patients, the group suggests.

“You can never be faulted for following these high-risk patients too closely,” Dr. Brown said.

The collaborative promotes increased patient education on sun exposure and skin and lymph node self-examination. A telephone survey of 200 organ transplant recipients found 88% were unaware of their increased risk for skin cancer (Dermatol. Surg. 2004;30:610–15). A total of 35% reported regular sunscreen usage in the survey, but 35% also reported getting a sunburn the previous summer.

A separate survey of 122 renal transplant recipients found 41% could not recall skin cancer education (J. Am. Acad. Dermatol. 1999;40:697–701). Although 27% reported seeing a dermatologist after transplantation, only 14% had regular follow-up.

These skin lesions emerged on the back of a patient's head next to a scar left after surgery to remove a previous cancer. Courtesy Dr. Marc D. Brown

A Typical, Challenging Case

A 68-year-old white male with Fitzpatrick type III skin had a bilateral lung transplant in 1993. Four years later, he developed squamous cell carcinoma, primarily in situ. The lesions progressed, and he was diagnosed with squamous cell carcinoma on his vertex and parietal scalp areas in 1998. The lesions were present against a background of multiple actinic keratoses, and were removed by electrodesiccation and curettage.

In mid-2000, the patient had two-stage Mohs' surgery for the vertex squamous cell carcinoma.

Two months later, he presented with “poorly differentiated squamous cell carcinoma without a connection to the epidermis,” said Dr. Brown.

The patient had radiation therapy after developing eight metastases within 1 month. In September of 2000, he developed additional metastases within the radiation site. Clinicians reduced his immunosuppressive drugs by 50%, and the patient developed more than 30 metastatic nodules. The patient then had multiple excisions and radiation therapy with capecitabine (Xeloda) for sensitization. The patient never developed adenopathy. CT scans of his chest were negative. In March 2002, he began a trial of intralesional methotrexate every 2 weeks with excellent resolution, Dr. Brown reported. The patient died in July 2002.

KEY BISCAYNE, FLA. — With the growing number of organ transplant recipients living longer, it has become increasingly important to treat and counsel these patients about their significantly higher risk of skin cancers, according to a presentation at the annual meeting of the Noah Worcester Dermatological Society.

Mucocutaneous lesions are the most common cancer type among organ transplant patients. The risk may be highest for squamous cell carcinoma, but it is also elevated for rare cancer types. In addition, skin cancers tend to be more aggressive and carry a worse prognosis for organ recipients.

Greater patient education is warranted. The International Transplant Skin Cancer Collaborative (www.itscc.org

There are more than 150,000 living organ transplant recipients. It is likely that 70% of these patients will eventually develop skin cancer, according to Marc D. Brown, M.D., professor of dermatology, University of Rochester (N.Y.).

An estimated 37% of tumors are mucocutaneous. Patients also develop lymphoma (17%), lung cancer (6%), and Kaposi's sarcoma, uterine, and colorectal cancers (4% each). Skin cancer can include squamous cell carcinoma, basal cell carcinoma, melanoma, sarcoma, Merkel cell carcinoma, angiosarcoma, verrucous carcinoma, atypical fibroxanthoma, and leiomyosarcoma.

There is a 65-fold increased incidence of cutaneous squamous cell carcinoma in organ transplant recipients, compared with the general population in Norway (J. Am. Acad. Dermatol. 1999;40:177–86). Researchers are less certain about melanoma incidence. The Norwegian study of 2,561 kidney and heart recipients found three times increased risk of melanoma, but another study of 5,356 patients in Sweden found no increased risk (Br. J. Dermatol. 2000;143:513–9).

Not only are skin cancers more common in organ transplant recipients, they also tend to progress more rapidly. Multiple lesions are more likely. Recurrence and metastasis rates are higher as well.

Incidence of skin cancer increases with the duration of long-term immunosuppression. Other contributing factors are exposure to UV radiation, genetic risk, and infection with human papilloma virus.

The risk of skin cancer might vary by the type of organ transplanted, according to some researchers. For example, squamous cell carcinoma may be two to three times more likely in cardiac vs. renal transplant recipients. In addition, there may be a lower risk of skin cancer after a liver is transplanted, compared with other organs, but additional research is needed, Dr. Brown pointed out.

The International Transplant Skin Cancer Collaborative suggests a full body exam at least annually, with particular attention to previous sites of nonmetastatic skin cancer. In addition, treat actinic keratoses aggressively and lower the threshold for considering a skin biopsy in these patients, the group suggests.

“You can never be faulted for following these high-risk patients too closely,” Dr. Brown said.

The collaborative promotes increased patient education on sun exposure and skin and lymph node self-examination. A telephone survey of 200 organ transplant recipients found 88% were unaware of their increased risk for skin cancer (Dermatol. Surg. 2004;30:610–15). A total of 35% reported regular sunscreen usage in the survey, but 35% also reported getting a sunburn the previous summer.

A separate survey of 122 renal transplant recipients found 41% could not recall skin cancer education (J. Am. Acad. Dermatol. 1999;40:697–701). Although 27% reported seeing a dermatologist after transplantation, only 14% had regular follow-up.

These skin lesions emerged on the back of a patient's head next to a scar left after surgery to remove a previous cancer. Courtesy Dr. Marc D. Brown

A Typical, Challenging Case

A 68-year-old white male with Fitzpatrick type III skin had a bilateral lung transplant in 1993. Four years later, he developed squamous cell carcinoma, primarily in situ. The lesions progressed, and he was diagnosed with squamous cell carcinoma on his vertex and parietal scalp areas in 1998. The lesions were present against a background of multiple actinic keratoses, and were removed by electrodesiccation and curettage.

In mid-2000, the patient had two-stage Mohs' surgery for the vertex squamous cell carcinoma.

Two months later, he presented with “poorly differentiated squamous cell carcinoma without a connection to the epidermis,” said Dr. Brown.

The patient had radiation therapy after developing eight metastases within 1 month. In September of 2000, he developed additional metastases within the radiation site. Clinicians reduced his immunosuppressive drugs by 50%, and the patient developed more than 30 metastatic nodules. The patient then had multiple excisions and radiation therapy with capecitabine (Xeloda) for sensitization. The patient never developed adenopathy. CT scans of his chest were negative. In March 2002, he began a trial of intralesional methotrexate every 2 weeks with excellent resolution, Dr. Brown reported. The patient died in July 2002.

MIAMI — The echinocandin antifungal agents appear to have little significant toxicity and may prove safer than the azoles or amphotericin B in terms of potential interactions, said Paul O. Gubbins, Pharm.D.

“Echinocandins are an exciting new class. To date, there are few significant drug-drug interactions,” he said at a meeting on fungal infections sponsored by Imedex.

The echinocandin caspofungin (Cancidas) has “no significant interaction” with cytochrome P-450 (CYP450) metabolism or P-glycoprotein, according to product labeling. The most abundant enzyme in the CYP450 system, CYP3A4, metabolizes about 50%-60% of all medicines.

The recently approved echinocandin micafungin (Mycamine) is not a substrate or inhibitor for P-glycoprotein, a transmembrane efflux pump in the liver, intestine, kidneys, and blood-brain barrier.

With a lower potential for interactions, the echinocandins may be ideal for combination therapy, said Dr. Gubbins, chair of the department of pharmacy practice, University of Arkansas, Little Rock.

Traditional formulations of amphotericin B have renal toxicity that can produce additive drug interactions. “We're all familiar with the toxicities of amphotericin B. They are subtle and, in most cases, unavoidable. Consider renal-sparing alternatives” such as lipid amphotericin B or caspofungin, he suggested.

When prescribing traditional amphotericin B, monitor serum levels of drugs that have a narrow therapeutic index and are eliminated by the kidneys. Examples include aminoglycosides and 5-flucytosine.

Some patients, such as organ transplant recipients, require closer monitoring. They often must use drugs—such as immunosuppressants—that increase the risk of fungal infections, he noted.

The azoles can interact through multiple mechanisms, including CYP450 metabolism, gastric pH-dependent effects, and P-glycoprotein activity.

“Interactions can be managed with alternative drugs in the affected class or by switching agents,” Dr. Gubbins said.

Itraconazole leads the azole class in terms of potential interactions. The antifungal interacts through the CYP450 system with statins, especially lovastatin, simvastatin, and atorvastatin (Lipitor), and this can lead to skeletal muscle toxicity. Other affected agents include benzodiazepines, anxiolytics, immunosuppressants, and corticosteroids. With corticosteroids, he said, “The key is, it doesn't matter if you give these orally or IV, or if they're inhaled, you can get interactions.”

Itraconazole can also have significant pH interactions. Dr. Gubbins suggested that patients take the tablets with a high-fat meal in order to slow gastric emptying or with a meal that contains enough protein to buffer the stomach contents. Other techniques for reducing pH interactions include spacing the administration of tablets, considering itraconazole oral solution, or switching to another agent.

P-glycoprotein interactions are significant only for itraconazole, not for voriconazole (Vfend), or fluconazole, he said.

Several agents lower serum levels of itraconazole, including phenytoin, phenobarbital, rifampin, and rifabutin (Mycobutin), but “remember that itraconazole affects other medications more than other medications affect itraconazole,” he said. “The ones we're worried about are the ones with a narrow therapeutic index, such as digoxin.”

Fluconazole affects more CYP450 enzymes than does itraconazole. Interactions depend largely on fluconazole concentration and are typically seen with doses above 200 mg. Of particular concern are interactions between fluconazole and phenytoin or warfarin. “With phenytoin, if you do not see a response, it could be that [phenytoin] is inhibiting fluconazole,” he said.

“We also worry about the anticoagulant warfarin. … This interaction is almost guaranteed.” Decreasing the warfarin dose might help, but “you almost always need to move to another antifungal.”

Drugs that affect voriconazole include phenytoin, rifampin, and rifabutin. Other potential interactions include carbamazepine, protease inhibitors, nonnucleoside reverse transcriptase inhibitors, benzodiazepines, and statins.

MIAMI — The echinocandin antifungal agents appear to have little significant toxicity and may prove safer than the azoles or amphotericin B in terms of potential interactions, said Paul O. Gubbins, Pharm.D.

“Echinocandins are an exciting new class. To date, there are few significant drug-drug interactions,” he said at a meeting on fungal infections sponsored by Imedex.

The echinocandin caspofungin (Cancidas) has “no significant interaction” with cytochrome P-450 (CYP450) metabolism or P-glycoprotein, according to product labeling. The most abundant enzyme in the CYP450 system, CYP3A4, metabolizes about 50%-60% of all medicines.

The recently approved echinocandin micafungin (Mycamine) is not a substrate or inhibitor for P-glycoprotein, a transmembrane efflux pump in the liver, intestine, kidneys, and blood-brain barrier.

With a lower potential for interactions, the echinocandins may be ideal for combination therapy, said Dr. Gubbins, chair of the department of pharmacy practice, University of Arkansas, Little Rock.

Traditional formulations of amphotericin B have renal toxicity that can produce additive drug interactions. “We're all familiar with the toxicities of amphotericin B. They are subtle and, in most cases, unavoidable. Consider renal-sparing alternatives” such as lipid amphotericin B or caspofungin, he suggested.

When prescribing traditional amphotericin B, monitor serum levels of drugs that have a narrow therapeutic index and are eliminated by the kidneys. Examples include aminoglycosides and 5-flucytosine.

Some patients, such as organ transplant recipients, require closer monitoring. They often must use drugs—such as immunosuppressants—that increase the risk of fungal infections, he noted.

The azoles can interact through multiple mechanisms, including CYP450 metabolism, gastric pH-dependent effects, and P-glycoprotein activity.

“Interactions can be managed with alternative drugs in the affected class or by switching agents,” Dr. Gubbins said.

Itraconazole leads the azole class in terms of potential interactions. The antifungal interacts through the CYP450 system with statins, especially lovastatin, simvastatin, and atorvastatin (Lipitor), and this can lead to skeletal muscle toxicity. Other affected agents include benzodiazepines, anxiolytics, immunosuppressants, and corticosteroids. With corticosteroids, he said, “The key is, it doesn't matter if you give these orally or IV, or if they're inhaled, you can get interactions.”

Itraconazole can also have significant pH interactions. Dr. Gubbins suggested that patients take the tablets with a high-fat meal in order to slow gastric emptying or with a meal that contains enough protein to buffer the stomach contents. Other techniques for reducing pH interactions include spacing the administration of tablets, considering itraconazole oral solution, or switching to another agent.

P-glycoprotein interactions are significant only for itraconazole, not for voriconazole (Vfend), or fluconazole, he said.

Several agents lower serum levels of itraconazole, including phenytoin, phenobarbital, rifampin, and rifabutin (Mycobutin), but “remember that itraconazole affects other medications more than other medications affect itraconazole,” he said. “The ones we're worried about are the ones with a narrow therapeutic index, such as digoxin.”

Fluconazole affects more CYP450 enzymes than does itraconazole. Interactions depend largely on fluconazole concentration and are typically seen with doses above 200 mg. Of particular concern are interactions between fluconazole and phenytoin or warfarin. “With phenytoin, if you do not see a response, it could be that [phenytoin] is inhibiting fluconazole,” he said.

“We also worry about the anticoagulant warfarin. … This interaction is almost guaranteed.” Decreasing the warfarin dose might help, but “you almost always need to move to another antifungal.”

Drugs that affect voriconazole include phenytoin, rifampin, and rifabutin. Other potential interactions include carbamazepine, protease inhibitors, nonnucleoside reverse transcriptase inhibitors, benzodiazepines, and statins.

MIAMI — The echinocandin antifungal agents appear to have little significant toxicity and may prove safer than the azoles or amphotericin B in terms of potential interactions, said Paul O. Gubbins, Pharm.D.

“Echinocandins are an exciting new class. To date, there are few significant drug-drug interactions,” he said at a meeting on fungal infections sponsored by Imedex.

The echinocandin caspofungin (Cancidas) has “no significant interaction” with cytochrome P-450 (CYP450) metabolism or P-glycoprotein, according to product labeling. The most abundant enzyme in the CYP450 system, CYP3A4, metabolizes about 50%-60% of all medicines.

The recently approved echinocandin micafungin (Mycamine) is not a substrate or inhibitor for P-glycoprotein, a transmembrane efflux pump in the liver, intestine, kidneys, and blood-brain barrier.

With a lower potential for interactions, the echinocandins may be ideal for combination therapy, said Dr. Gubbins, chair of the department of pharmacy practice, University of Arkansas, Little Rock.

Traditional formulations of amphotericin B have renal toxicity that can produce additive drug interactions. “We're all familiar with the toxicities of amphotericin B. They are subtle and, in most cases, unavoidable. Consider renal-sparing alternatives” such as lipid amphotericin B or caspofungin, he suggested.

When prescribing traditional amphotericin B, monitor serum levels of drugs that have a narrow therapeutic index and are eliminated by the kidneys. Examples include aminoglycosides and 5-flucytosine.

Some patients, such as organ transplant recipients, require closer monitoring. They often must use drugs—such as immunosuppressants—that increase the risk of fungal infections, he noted.

The azoles can interact through multiple mechanisms, including CYP450 metabolism, gastric pH-dependent effects, and P-glycoprotein activity.

“Interactions can be managed with alternative drugs in the affected class or by switching agents,” Dr. Gubbins said.

Itraconazole leads the azole class in terms of potential interactions. The antifungal interacts through the CYP450 system with statins, especially lovastatin, simvastatin, and atorvastatin (Lipitor), and this can lead to skeletal muscle toxicity. Other affected agents include benzodiazepines, anxiolytics, immunosuppressants, and corticosteroids. With corticosteroids, he said, “The key is, it doesn't matter if you give these orally or IV, or if they're inhaled, you can get interactions.”

Itraconazole can also have significant pH interactions. Dr. Gubbins suggested that patients take the tablets with a high-fat meal in order to slow gastric emptying or with a meal that contains enough protein to buffer the stomach contents. Other techniques for reducing pH interactions include spacing the administration of tablets, considering itraconazole oral solution, or switching to another agent.

P-glycoprotein interactions are significant only for itraconazole, not for voriconazole (Vfend), or fluconazole, he said.

Several agents lower serum levels of itraconazole, including phenytoin, phenobarbital, rifampin, and rifabutin (Mycobutin), but “remember that itraconazole affects other medications more than other medications affect itraconazole,” he said. “The ones we're worried about are the ones with a narrow therapeutic index, such as digoxin.”

Fluconazole affects more CYP450 enzymes than does itraconazole. Interactions depend largely on fluconazole concentration and are typically seen with doses above 200 mg. Of particular concern are interactions between fluconazole and phenytoin or warfarin. “With phenytoin, if you do not see a response, it could be that [phenytoin] is inhibiting fluconazole,” he said.

“We also worry about the anticoagulant warfarin. … This interaction is almost guaranteed.” Decreasing the warfarin dose might help, but “you almost always need to move to another antifungal.”

Drugs that affect voriconazole include phenytoin, rifampin, and rifabutin. Other potential interactions include carbamazepine, protease inhibitors, nonnucleoside reverse transcriptase inhibitors, benzodiazepines, and statins.