Jeff Evans

Evidence of widespread resistance of influenza against amantadine and rimantadine has prompted calls for restraint in the use of antivirals in order to preserve the therapeutic value of these adamantanes as well as newer generation agents.

Investigators at the Centers for Disease Control and Prevention detected an “alarmingly high” resistance rate of 92% to the adamantane antiviral drugs amantadine and rimantadine in an analysis of 209 influenza A(H3N2) isolates from patients in 26 states from Oct. 1 through Dec. 31, 2005 (JAMA doi:10.1001/jama.295.8.joc60020, published Feb. 2, 2006).

An earlier CDC analysis that found adamantane resistance in 109 of 120 influenza A(H3N2) isolates from patients in 23 states from Oct. 1, 2005, through Jan. 12, 2006, led the CDC to issue a Health Alert on Jan. 14, 2006. The alert recommended that neither amantadine nor rimantadine be used for the treatment or prophylaxis of influenza A infections in the United States for the remainder of the 2005–2006 influenza season.

“If antiviral use is curtailed, susceptible strains could emerge and adamantanes could regain their utility against both epidemic and pandemic influenza,” Dr. David M. Weinstock and Dr. Gianna Zuccotti of Memorial Sloan-Kettering Cancer Center, New York, wrote in an editorial (JAMA doi:10.1001/jama.295.8.jed60009, published Feb. 2, 2006).

In the report, Rick A. Bright, Ph.D., and his colleagues at the CDC noted that adamantane resistance in the United States increased from 1.9% in 2003–2004 to 11% in 2004–2005 to the current 92%. The CDC study also noted that 100% of influenza A(H3N2) isolates obtained from 10 patients in Mexico and 3 patients in Canada were resistant to amantadine and rimantadine. A recent report on influenza A(H3N2) isolates from the 2005–2006 influenza season in Canada found that 43 (91%) of 47 isolates showed resistance to those drugs.

The CDC report “is a clarion call for action from the medical community,” the editorial said. “Physicians and other health care professionals must (1) educate patients and communities; (2) organize an international response through governmental and nongovernmental organizations; (3) advocate against the release of over-the-counter antiviral drugs, either directly by major drug companies or through licensing agreements with generic manufacturers; and (4) recognize the powerful influences that affect prescribing practices before assigning culpability to those who have inappropriately used adamantanes.”

In a related report that appeared just before the CDC report, a systematic review of 52 randomized, controlled trials of the adamantane drugs and the newer generation neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) also raised serious doubts about the wisdom of using the four drugs for routine control of seasonal influenza.

Amantadine and rimantadine neither prevent infection nor affect viral shedding. And even though they shorten the duration of fever, the drugs also have potentially serious adverse effects and promote the rapid emergence of resistant strains. “The evidence does not support” their use for seasonal or pandemic influenza outbreaks, reported Dr. Tom Jefferson of Cochrane Vaccines Field, Alessandria, Italy, and his associates.

Zanamivir and oseltamivir also should not be used routinely for seasonal influenza. They did not prevent infection with influenzalike illness nor interrupt nasal shedding of virus, but they may have a role in limiting symptoms and complications in affected patients, the researchers said (Lancet doi:10.1016/S0140-6736(06)67970-1, published Jan. 19, 2006).

Resistance to oseltamivir therapy among adults infected with influenza A(H1N1) or influenza A(H3N2) virus has been rare, but resistant strains have been reported in up to 18% of Japanese children receiving oseltamivir, Dr. Weinstock and Dr. Zuccotti noted in their editorial.

Zanamivir and oseltamivir should be used only “in a serious epidemic or pandemic alongside other public-health measures such as [the] use of masks, gowns, gloves, quarantine, and handwashing,” Dr. Jefferson said in a statement.

The investigators drew their conclusions from a review of 52 trials of either prevention or treatment of influenzalike illness involving otherwise healthy subjects aged 16–65 years. In addition to the above-mentioned results, “we could find no credible evidence of the effects of neuraminidase inhibitors on avian influenza,” they noted.

The cautions against using these four antivirals are particularly important to note, given that last year the World Health Organization “encouraged member countries to use antivirals” before a pandemic does develop.

Contributing writer Mary Ann Moon contributed to this report.

Evidence of widespread resistance of influenza against amantadine and rimantadine has prompted calls for restraint in the use of antivirals in order to preserve the therapeutic value of these adamantanes as well as newer generation agents.

Investigators at the Centers for Disease Control and Prevention detected an “alarmingly high” resistance rate of 92% to the adamantane antiviral drugs amantadine and rimantadine in an analysis of 209 influenza A(H3N2) isolates from patients in 26 states from Oct. 1 through Dec. 31, 2005 (JAMA doi:10.1001/jama.295.8.joc60020, published Feb. 2, 2006).

An earlier CDC analysis that found adamantane resistance in 109 of 120 influenza A(H3N2) isolates from patients in 23 states from Oct. 1, 2005, through Jan. 12, 2006, led the CDC to issue a Health Alert on Jan. 14, 2006. The alert recommended that neither amantadine nor rimantadine be used for the treatment or prophylaxis of influenza A infections in the United States for the remainder of the 2005–2006 influenza season.

“If antiviral use is curtailed, susceptible strains could emerge and adamantanes could regain their utility against both epidemic and pandemic influenza,” Dr. David M. Weinstock and Dr. Gianna Zuccotti of Memorial Sloan-Kettering Cancer Center, New York, wrote in an editorial (JAMA doi:10.1001/jama.295.8.jed60009, published Feb. 2, 2006).

In the report, Rick A. Bright, Ph.D., and his colleagues at the CDC noted that adamantane resistance in the United States increased from 1.9% in 2003–2004 to 11% in 2004–2005 to the current 92%. The CDC study also noted that 100% of influenza A(H3N2) isolates obtained from 10 patients in Mexico and 3 patients in Canada were resistant to amantadine and rimantadine. A recent report on influenza A(H3N2) isolates from the 2005–2006 influenza season in Canada found that 43 (91%) of 47 isolates showed resistance to those drugs.

The CDC report “is a clarion call for action from the medical community,” the editorial said. “Physicians and other health care professionals must (1) educate patients and communities; (2) organize an international response through governmental and nongovernmental organizations; (3) advocate against the release of over-the-counter antiviral drugs, either directly by major drug companies or through licensing agreements with generic manufacturers; and (4) recognize the powerful influences that affect prescribing practices before assigning culpability to those who have inappropriately used adamantanes.”

In a related report that appeared just before the CDC report, a systematic review of 52 randomized, controlled trials of the adamantane drugs and the newer generation neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) also raised serious doubts about the wisdom of using the four drugs for routine control of seasonal influenza.

Amantadine and rimantadine neither prevent infection nor affect viral shedding. And even though they shorten the duration of fever, the drugs also have potentially serious adverse effects and promote the rapid emergence of resistant strains. “The evidence does not support” their use for seasonal or pandemic influenza outbreaks, reported Dr. Tom Jefferson of Cochrane Vaccines Field, Alessandria, Italy, and his associates.

Zanamivir and oseltamivir also should not be used routinely for seasonal influenza. They did not prevent infection with influenzalike illness nor interrupt nasal shedding of virus, but they may have a role in limiting symptoms and complications in affected patients, the researchers said (Lancet doi:10.1016/S0140-6736(06)67970-1, published Jan. 19, 2006).

Resistance to oseltamivir therapy among adults infected with influenza A(H1N1) or influenza A(H3N2) virus has been rare, but resistant strains have been reported in up to 18% of Japanese children receiving oseltamivir, Dr. Weinstock and Dr. Zuccotti noted in their editorial.

Zanamivir and oseltamivir should be used only “in a serious epidemic or pandemic alongside other public-health measures such as [the] use of masks, gowns, gloves, quarantine, and handwashing,” Dr. Jefferson said in a statement.

The investigators drew their conclusions from a review of 52 trials of either prevention or treatment of influenzalike illness involving otherwise healthy subjects aged 16–65 years. In addition to the above-mentioned results, “we could find no credible evidence of the effects of neuraminidase inhibitors on avian influenza,” they noted.

The cautions against using these four antivirals are particularly important to note, given that last year the World Health Organization “encouraged member countries to use antivirals” before a pandemic does develop.

Contributing writer Mary Ann Moon contributed to this report.

Evidence of widespread resistance of influenza against amantadine and rimantadine has prompted calls for restraint in the use of antivirals in order to preserve the therapeutic value of these adamantanes as well as newer generation agents.

Investigators at the Centers for Disease Control and Prevention detected an “alarmingly high” resistance rate of 92% to the adamantane antiviral drugs amantadine and rimantadine in an analysis of 209 influenza A(H3N2) isolates from patients in 26 states from Oct. 1 through Dec. 31, 2005 (JAMA doi:10.1001/jama.295.8.joc60020, published Feb. 2, 2006).

An earlier CDC analysis that found adamantane resistance in 109 of 120 influenza A(H3N2) isolates from patients in 23 states from Oct. 1, 2005, through Jan. 12, 2006, led the CDC to issue a Health Alert on Jan. 14, 2006. The alert recommended that neither amantadine nor rimantadine be used for the treatment or prophylaxis of influenza A infections in the United States for the remainder of the 2005–2006 influenza season.

“If antiviral use is curtailed, susceptible strains could emerge and adamantanes could regain their utility against both epidemic and pandemic influenza,” Dr. David M. Weinstock and Dr. Gianna Zuccotti of Memorial Sloan-Kettering Cancer Center, New York, wrote in an editorial (JAMA doi:10.1001/jama.295.8.jed60009, published Feb. 2, 2006).

In the report, Rick A. Bright, Ph.D., and his colleagues at the CDC noted that adamantane resistance in the United States increased from 1.9% in 2003–2004 to 11% in 2004–2005 to the current 92%. The CDC study also noted that 100% of influenza A(H3N2) isolates obtained from 10 patients in Mexico and 3 patients in Canada were resistant to amantadine and rimantadine. A recent report on influenza A(H3N2) isolates from the 2005–2006 influenza season in Canada found that 43 (91%) of 47 isolates showed resistance to those drugs.

The CDC report “is a clarion call for action from the medical community,” the editorial said. “Physicians and other health care professionals must (1) educate patients and communities; (2) organize an international response through governmental and nongovernmental organizations; (3) advocate against the release of over-the-counter antiviral drugs, either directly by major drug companies or through licensing agreements with generic manufacturers; and (4) recognize the powerful influences that affect prescribing practices before assigning culpability to those who have inappropriately used adamantanes.”

In a related report that appeared just before the CDC report, a systematic review of 52 randomized, controlled trials of the adamantane drugs and the newer generation neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) also raised serious doubts about the wisdom of using the four drugs for routine control of seasonal influenza.

Amantadine and rimantadine neither prevent infection nor affect viral shedding. And even though they shorten the duration of fever, the drugs also have potentially serious adverse effects and promote the rapid emergence of resistant strains. “The evidence does not support” their use for seasonal or pandemic influenza outbreaks, reported Dr. Tom Jefferson of Cochrane Vaccines Field, Alessandria, Italy, and his associates.

Zanamivir and oseltamivir also should not be used routinely for seasonal influenza. They did not prevent infection with influenzalike illness nor interrupt nasal shedding of virus, but they may have a role in limiting symptoms and complications in affected patients, the researchers said (Lancet doi:10.1016/S0140-6736(06)67970-1, published Jan. 19, 2006).

Resistance to oseltamivir therapy among adults infected with influenza A(H1N1) or influenza A(H3N2) virus has been rare, but resistant strains have been reported in up to 18% of Japanese children receiving oseltamivir, Dr. Weinstock and Dr. Zuccotti noted in their editorial.

Zanamivir and oseltamivir should be used only “in a serious epidemic or pandemic alongside other public-health measures such as [the] use of masks, gowns, gloves, quarantine, and handwashing,” Dr. Jefferson said in a statement.

The investigators drew their conclusions from a review of 52 trials of either prevention or treatment of influenzalike illness involving otherwise healthy subjects aged 16–65 years. In addition to the above-mentioned results, “we could find no credible evidence of the effects of neuraminidase inhibitors on avian influenza,” they noted.

The cautions against using these four antivirals are particularly important to note, given that last year the World Health Organization “encouraged member countries to use antivirals” before a pandemic does develop.

Contributing writer Mary Ann Moon contributed to this report.

Recognition of the early meningococcal disease features of leg pain, cold hands and feet, and abnormal skin color may help get children to the hospital faster than classic symptoms that occur later in the illness, reported Dr. Matthew J. Thompson of the University of Oxford (England), and his associates.

The information about early symptoms came from a retrospective study that provides the first description of the time course of clinical features of meningococcal disease that occur before hospital admission, they said (Lancet 2006 Jan. 11 [Epub doi:10.1016/S0140-6736(06)67932-4]).

Meningococcal disease is typically diagnosed in children at presentation to a hospital after the onset of late-occurring classic symptoms, including hemorrhagic rash, meningism, and impaired consciousness.

“We believe that primary care physicians are overreliant on using these three [classic] symptoms to diagnose meningococcal disease in children, and that parents may be influenced by doctors or public health campaigns to seek medical advice only on the appearance of features such as a rapidly evolving rash,” according to Dr. Thompson and his associates.

But Dr. Keith S. Reisinger, a pediatrician in private practice in Pittsburgh, contended that these early symptoms “are not specific enough to alarm a parent or doctor.”

In the study, parents of 448 children and adolescents with meningococcal disease either completed a questionnaire or an interview regarding the course of their child's disease an average of about 140 days after the illness; in some cases, the questionnaire or interview was supplemented by medical records. Those three early features of meningococcal disease occurred within a median of 7–12 hours after the onset of illness, compared with a median time of onset of 13–22 hours for the three classic symptoms.

The three early features of the disease in children aged 0–16 years varied in frequency and the median hour of onset: cold hands and feet (43% and 12 hours), leg pain (37% and 7 hours), and abnormal color such as pallor or mottling (19% and 10 hours).

Most (72%) of the pediatric patients had one or more of the three early features of meningococcal disease. These were first noticed at a median of 8 hours after the onset of illness, whereas patients were admitted to the hospital a median of 19 hours after the onset of illness.

Few children developed any new symptoms after 24 hours and in all age groups symptoms progressed from fever to sepsis symptoms and then to classic symptoms. Nonspecific symptoms that are common in self-limiting viral illness, such as fever, poor feeding or decreased appetite, nausea, vomiting, and irritability, developed within the first 4–6 hours of disease onset.

Dr. Thompson and his colleagues said that because these earliest symptoms of the disease are so common, it is important for parents to be able to reconsult their doctor on the same day as their initial visit if their child's condition worsens.

But these symptoms are of just as little value as leg pain, cold hands and feet, and abnormal skin color because they are so nonspecific, Dr. Reisinger said in an interview.

The investigators did not have data on the frequency of symptoms or the course of illness of children with other illnesses outside of the hospital, and so they could not make any quantitative estimate of how sensitive or specific the early symptoms could be as diagnostic markers.

“Unfortunately, [the investigators] ignore these limitations and go on to say these findings have 'important implications' for parents and clinicians,” Dr. Reisinger said.

“The greatest limitation of the study is the retrospective nature of recollection by the parents. All these families went through a very traumatic event, and we are left with no idea how accurate their recollections are,” he added.

These early symptoms 'are not specific enough to alarm a parent or doctor.' DR. REISINGER

Recognition of the early meningococcal disease features of leg pain, cold hands and feet, and abnormal skin color may help get children to the hospital faster than classic symptoms that occur later in the illness, reported Dr. Matthew J. Thompson of the University of Oxford (England), and his associates.

The information about early symptoms came from a retrospective study that provides the first description of the time course of clinical features of meningococcal disease that occur before hospital admission, they said (Lancet 2006 Jan. 11 [Epub doi:10.1016/S0140-6736(06)67932-4]).

Meningococcal disease is typically diagnosed in children at presentation to a hospital after the onset of late-occurring classic symptoms, including hemorrhagic rash, meningism, and impaired consciousness.

“We believe that primary care physicians are overreliant on using these three [classic] symptoms to diagnose meningococcal disease in children, and that parents may be influenced by doctors or public health campaigns to seek medical advice only on the appearance of features such as a rapidly evolving rash,” according to Dr. Thompson and his associates.

But Dr. Keith S. Reisinger, a pediatrician in private practice in Pittsburgh, contended that these early symptoms “are not specific enough to alarm a parent or doctor.”

In the study, parents of 448 children and adolescents with meningococcal disease either completed a questionnaire or an interview regarding the course of their child's disease an average of about 140 days after the illness; in some cases, the questionnaire or interview was supplemented by medical records. Those three early features of meningococcal disease occurred within a median of 7–12 hours after the onset of illness, compared with a median time of onset of 13–22 hours for the three classic symptoms.

The three early features of the disease in children aged 0–16 years varied in frequency and the median hour of onset: cold hands and feet (43% and 12 hours), leg pain (37% and 7 hours), and abnormal color such as pallor or mottling (19% and 10 hours).

Most (72%) of the pediatric patients had one or more of the three early features of meningococcal disease. These were first noticed at a median of 8 hours after the onset of illness, whereas patients were admitted to the hospital a median of 19 hours after the onset of illness.

Few children developed any new symptoms after 24 hours and in all age groups symptoms progressed from fever to sepsis symptoms and then to classic symptoms. Nonspecific symptoms that are common in self-limiting viral illness, such as fever, poor feeding or decreased appetite, nausea, vomiting, and irritability, developed within the first 4–6 hours of disease onset.

Dr. Thompson and his colleagues said that because these earliest symptoms of the disease are so common, it is important for parents to be able to reconsult their doctor on the same day as their initial visit if their child's condition worsens.

But these symptoms are of just as little value as leg pain, cold hands and feet, and abnormal skin color because they are so nonspecific, Dr. Reisinger said in an interview.

The investigators did not have data on the frequency of symptoms or the course of illness of children with other illnesses outside of the hospital, and so they could not make any quantitative estimate of how sensitive or specific the early symptoms could be as diagnostic markers.

“Unfortunately, [the investigators] ignore these limitations and go on to say these findings have 'important implications' for parents and clinicians,” Dr. Reisinger said.

“The greatest limitation of the study is the retrospective nature of recollection by the parents. All these families went through a very traumatic event, and we are left with no idea how accurate their recollections are,” he added.

These early symptoms 'are not specific enough to alarm a parent or doctor.' DR. REISINGER

Recognition of the early meningococcal disease features of leg pain, cold hands and feet, and abnormal skin color may help get children to the hospital faster than classic symptoms that occur later in the illness, reported Dr. Matthew J. Thompson of the University of Oxford (England), and his associates.

The information about early symptoms came from a retrospective study that provides the first description of the time course of clinical features of meningococcal disease that occur before hospital admission, they said (Lancet 2006 Jan. 11 [Epub doi:10.1016/S0140-6736(06)67932-4]).

Meningococcal disease is typically diagnosed in children at presentation to a hospital after the onset of late-occurring classic symptoms, including hemorrhagic rash, meningism, and impaired consciousness.

“We believe that primary care physicians are overreliant on using these three [classic] symptoms to diagnose meningococcal disease in children, and that parents may be influenced by doctors or public health campaigns to seek medical advice only on the appearance of features such as a rapidly evolving rash,” according to Dr. Thompson and his associates.

But Dr. Keith S. Reisinger, a pediatrician in private practice in Pittsburgh, contended that these early symptoms “are not specific enough to alarm a parent or doctor.”

In the study, parents of 448 children and adolescents with meningococcal disease either completed a questionnaire or an interview regarding the course of their child's disease an average of about 140 days after the illness; in some cases, the questionnaire or interview was supplemented by medical records. Those three early features of meningococcal disease occurred within a median of 7–12 hours after the onset of illness, compared with a median time of onset of 13–22 hours for the three classic symptoms.

The three early features of the disease in children aged 0–16 years varied in frequency and the median hour of onset: cold hands and feet (43% and 12 hours), leg pain (37% and 7 hours), and abnormal color such as pallor or mottling (19% and 10 hours).

Most (72%) of the pediatric patients had one or more of the three early features of meningococcal disease. These were first noticed at a median of 8 hours after the onset of illness, whereas patients were admitted to the hospital a median of 19 hours after the onset of illness.

Few children developed any new symptoms after 24 hours and in all age groups symptoms progressed from fever to sepsis symptoms and then to classic symptoms. Nonspecific symptoms that are common in self-limiting viral illness, such as fever, poor feeding or decreased appetite, nausea, vomiting, and irritability, developed within the first 4–6 hours of disease onset.

Dr. Thompson and his colleagues said that because these earliest symptoms of the disease are so common, it is important for parents to be able to reconsult their doctor on the same day as their initial visit if their child's condition worsens.

But these symptoms are of just as little value as leg pain, cold hands and feet, and abnormal skin color because they are so nonspecific, Dr. Reisinger said in an interview.

The investigators did not have data on the frequency of symptoms or the course of illness of children with other illnesses outside of the hospital, and so they could not make any quantitative estimate of how sensitive or specific the early symptoms could be as diagnostic markers.

“Unfortunately, [the investigators] ignore these limitations and go on to say these findings have 'important implications' for parents and clinicians,” Dr. Reisinger said.

“The greatest limitation of the study is the retrospective nature of recollection by the parents. All these families went through a very traumatic event, and we are left with no idea how accurate their recollections are,” he added.

These early symptoms 'are not specific enough to alarm a parent or doctor.' DR. REISINGER

BETHESDA, MD. – Brief negotiation interviews with emergency department patients who have engaged in harmful and hazardous drinking behaviors may not be much more effective in reducing the frequency and quantity of drinking than providing simple discharge instructions, according to the results of a randomized, controlled trial.

In a trial conducted by Dr. Gail D'Onofrio and her colleagues at Yale-New Haven (Conn.) Hospital, 247 patients who received a brief negotiation interview (BNI) during an ED visit decreased their average number of standard drinks per week from 13.6 to 8.6 after 1 month of follow-up.

These findings were comparable with a drinking decline reported by 247 patients who received only discharge instructions (from 12.6 to 9.2).

Similar reductions in the number of binge episodes per month also occurred in the BNI (from 5.9 to 3.1) and discharge instructions groups (from 5.5 to 3.4), Dr. D'Onofrio reported at the annual conference of the Association for Medical Education and Research in Substance Abuse.

The differences between the groups were sustained at 12 months of follow-up, at a point in which 92% of patients remained in the study, according to Dr. D'Onofrio, who serves as chief of the Yale-New Haven Hospital emergency department.

The study included patients who sustained an injury related to alcohol consumption, men who drank more than 15 drinks per week or 4 or more per day, and women who drank more than 7 drinks per week or more than 3 per day.

No people with alcohol or drug dependence were included in the study, Dr. D'Onofrio said.

The percentage of patients who met low-risk limits for drinking set by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) increased to similar levels in the BNI (0% to 42%) and discharge instructions groups (0% to 39%), according to Dr. Onofrio.

The results did not differ when stratified for sex, severity, or injury.

But at 12 months after the initial ED visit, significantly fewer of the patients who were in the BNI group became injured while drinking (from 18 to 8) than in the discharge instructions group (from 12 to 10).

Significantly fewer women drove under the influence of alcohol during the 12-month period after the intervention (from 24 to 15) than men (from 20 to 19).

The overall effect of the BNI in the trial may have been tempered by the fact that a third of the patients who received discharge instructions were counseled on at least one or more of the components of the BNI, which was not supposed to occur, she said.

The BNI sought to raise the subject of alcohol abuse, alert the patients about NIAAA criteria for at-risk drinking, find out whether the individual thought that there was any connection between his or her drinking and the ED visit, determine how ready the patient was to change his or her drinking behavior, negotiate agreements, offer advice when needed, and offer follow-up visits with primary care.

A total of 58 emergency practitioners (faculty, third- and fourth-year residents, and physician associates) were trained to give a BNI in less than 10 minutes with a manual-guided script.

Discharge instructions given by the practitioners lasted about 1 minute, and patients were given a handout with drinking advice embedded within general information on smoking, exercise, and wearing seat belts.

Prior studies have shown that BNIs are effective in primary care and trauma settings, but none had determined the value of BNIs for harmful and hazardous drinkers in emergency departments, Dr. D'Onofrio said at the conference, which was also sponsored by Brown Medical School.

Upon discharge, ED patients got either a scripted interview or simple instructions. DR. D'ONOFRIO

BETHESDA, MD. – Brief negotiation interviews with emergency department patients who have engaged in harmful and hazardous drinking behaviors may not be much more effective in reducing the frequency and quantity of drinking than providing simple discharge instructions, according to the results of a randomized, controlled trial.

In a trial conducted by Dr. Gail D'Onofrio and her colleagues at Yale-New Haven (Conn.) Hospital, 247 patients who received a brief negotiation interview (BNI) during an ED visit decreased their average number of standard drinks per week from 13.6 to 8.6 after 1 month of follow-up.

These findings were comparable with a drinking decline reported by 247 patients who received only discharge instructions (from 12.6 to 9.2).

Similar reductions in the number of binge episodes per month also occurred in the BNI (from 5.9 to 3.1) and discharge instructions groups (from 5.5 to 3.4), Dr. D'Onofrio reported at the annual conference of the Association for Medical Education and Research in Substance Abuse.

The differences between the groups were sustained at 12 months of follow-up, at a point in which 92% of patients remained in the study, according to Dr. D'Onofrio, who serves as chief of the Yale-New Haven Hospital emergency department.

The study included patients who sustained an injury related to alcohol consumption, men who drank more than 15 drinks per week or 4 or more per day, and women who drank more than 7 drinks per week or more than 3 per day.

No people with alcohol or drug dependence were included in the study, Dr. D'Onofrio said.

The percentage of patients who met low-risk limits for drinking set by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) increased to similar levels in the BNI (0% to 42%) and discharge instructions groups (0% to 39%), according to Dr. Onofrio.

The results did not differ when stratified for sex, severity, or injury.

But at 12 months after the initial ED visit, significantly fewer of the patients who were in the BNI group became injured while drinking (from 18 to 8) than in the discharge instructions group (from 12 to 10).

Significantly fewer women drove under the influence of alcohol during the 12-month period after the intervention (from 24 to 15) than men (from 20 to 19).

The overall effect of the BNI in the trial may have been tempered by the fact that a third of the patients who received discharge instructions were counseled on at least one or more of the components of the BNI, which was not supposed to occur, she said.

The BNI sought to raise the subject of alcohol abuse, alert the patients about NIAAA criteria for at-risk drinking, find out whether the individual thought that there was any connection between his or her drinking and the ED visit, determine how ready the patient was to change his or her drinking behavior, negotiate agreements, offer advice when needed, and offer follow-up visits with primary care.

A total of 58 emergency practitioners (faculty, third- and fourth-year residents, and physician associates) were trained to give a BNI in less than 10 minutes with a manual-guided script.

Discharge instructions given by the practitioners lasted about 1 minute, and patients were given a handout with drinking advice embedded within general information on smoking, exercise, and wearing seat belts.

Prior studies have shown that BNIs are effective in primary care and trauma settings, but none had determined the value of BNIs for harmful and hazardous drinkers in emergency departments, Dr. D'Onofrio said at the conference, which was also sponsored by Brown Medical School.

Upon discharge, ED patients got either a scripted interview or simple instructions. DR. D'ONOFRIO

BETHESDA, MD. – Brief negotiation interviews with emergency department patients who have engaged in harmful and hazardous drinking behaviors may not be much more effective in reducing the frequency and quantity of drinking than providing simple discharge instructions, according to the results of a randomized, controlled trial.

In a trial conducted by Dr. Gail D'Onofrio and her colleagues at Yale-New Haven (Conn.) Hospital, 247 patients who received a brief negotiation interview (BNI) during an ED visit decreased their average number of standard drinks per week from 13.6 to 8.6 after 1 month of follow-up.

These findings were comparable with a drinking decline reported by 247 patients who received only discharge instructions (from 12.6 to 9.2).

Similar reductions in the number of binge episodes per month also occurred in the BNI (from 5.9 to 3.1) and discharge instructions groups (from 5.5 to 3.4), Dr. D'Onofrio reported at the annual conference of the Association for Medical Education and Research in Substance Abuse.

The differences between the groups were sustained at 12 months of follow-up, at a point in which 92% of patients remained in the study, according to Dr. D'Onofrio, who serves as chief of the Yale-New Haven Hospital emergency department.

The study included patients who sustained an injury related to alcohol consumption, men who drank more than 15 drinks per week or 4 or more per day, and women who drank more than 7 drinks per week or more than 3 per day.

No people with alcohol or drug dependence were included in the study, Dr. D'Onofrio said.

The percentage of patients who met low-risk limits for drinking set by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) increased to similar levels in the BNI (0% to 42%) and discharge instructions groups (0% to 39%), according to Dr. Onofrio.

The results did not differ when stratified for sex, severity, or injury.

But at 12 months after the initial ED visit, significantly fewer of the patients who were in the BNI group became injured while drinking (from 18 to 8) than in the discharge instructions group (from 12 to 10).

Significantly fewer women drove under the influence of alcohol during the 12-month period after the intervention (from 24 to 15) than men (from 20 to 19).

The overall effect of the BNI in the trial may have been tempered by the fact that a third of the patients who received discharge instructions were counseled on at least one or more of the components of the BNI, which was not supposed to occur, she said.

The BNI sought to raise the subject of alcohol abuse, alert the patients about NIAAA criteria for at-risk drinking, find out whether the individual thought that there was any connection between his or her drinking and the ED visit, determine how ready the patient was to change his or her drinking behavior, negotiate agreements, offer advice when needed, and offer follow-up visits with primary care.

A total of 58 emergency practitioners (faculty, third- and fourth-year residents, and physician associates) were trained to give a BNI in less than 10 minutes with a manual-guided script.

Discharge instructions given by the practitioners lasted about 1 minute, and patients were given a handout with drinking advice embedded within general information on smoking, exercise, and wearing seat belts.

Prior studies have shown that BNIs are effective in primary care and trauma settings, but none had determined the value of BNIs for harmful and hazardous drinkers in emergency departments, Dr. D'Onofrio said at the conference, which was also sponsored by Brown Medical School.

Upon discharge, ED patients got either a scripted interview or simple instructions. DR. D'ONOFRIO

STOCKHOLM – Integrated individual psychotherapy may be the best method for addressing complex issues that are often unique to geriatric patients, Dr. Joel Sadavoy said at the 12th Congress of the International Psychogeriatric Association.

“The elderly often present to us with a confusing number of problems, and [these problems] originate from many different sources,” said Dr. Sadavoy, president of the IPA.

Older adults are less likely than younger individuals to have support, since they may be no longer married, retired from the work that defined their identity and purpose, and have lower physical health and strength.

Psychopathology in geriatric patients may be more complex than in younger adults because of the interplay between the adaptive challenges of old age, such as illness or loss, and the individual's personality and psychological structure, such as the ability to maintain self-esteem and security in the face of adversity.

The psychological structure of an older adult will strengthen or weaken their coping capacities, according to the so-called diathesis-stress model described by Dr. Aaron T. Beck and Margaret Gatz, Ph.D., Dr. Sadavoy said.

Some clinicians suggest that the use of two or more interventions, such as combining medication and cognitive-behavioral therapy in the course of a single treatment is integrated therapy.

But a more focused definition of integrated psychotherapy is “the concurrent application of more than one psychotherapeutic technique to address symptoms that arise from different levels and sources, both from within a patient and from their environment and interactive surroundings,” he said.

Dr. Sadavoy suggested that integrated psychotherapy works best if it addresses each of three sources of psychopathology in the patient:

▸ Lack of understanding and knowledge about illness and aging.

▸ Maladaptive thoughts and actions that originate from age-related cognitive distortions and perceptions, shifts in interpersonal relationships and identity, and a lack of problem-solving ability.

▸ Psychodynamically determined reactions and emotions that originate from lifelong, unconscious psychological conflicts and perceptions (Can. J. Psychiatry 1994;39:S19–26).

The third source “is of great importance but is probably the most difficult and subtle to deal with,” Dr. Sadavoy said.

A psychotherapist must have broad training and sufficient practice in using the full array of interventions for these sources of psychopathology to implement an integrated approach successfully, he said.

Dr. Sadavoy uses psychoeducation to address misinformation and deficits in knowledge.

Maladaptive cognitive and interpersonal responses and difficulty in problem-solving are dealt with through clarification and modification of cognitive distortions, interpersonal coaching and training, and teaching of problem-solving techniques. “These are three types of therapy that have been shown to be effective in studies of younger and, in some cases, older patients,” said Dr. Sadavoy, who is a professor of psychiatry at the University of Toronto.

He treats the unconscious conflicts and self-perceptions of older patients with psychodynamic therapies that employ interpretation and working within the transference in therapy.

The degree to which each intervention is used depends on which elements of psychopathology are most evident in a given patient, he said.

During treatment, the psychotherapist should undertake “some major history taking” to gather data on each of the three sources of impairment, organize the data, and develop an integrated intervention plan.

In an example of when an integrated approach works best, Dr. Sadavoy described the case of a 72-year-old woman who showed depressive symptoms, anxiety, and low functioning after a focal cerebrovascular lesion abruptly changed her husband's personality and cognitive function.

The woman's husband had agitation, severe paranoid depression, and executive dysfunction. The man developed new, bizarre behaviors and was unable to run the family business any longer. She felt abandoned. She believed that her husband's symptoms were the recurrence of a depressive episode that was associated with a business failure he had had many years before.

At that time, she was very angry with him because she had to take over the business and rearrange her life in order to do so. Now she felt that she was going through the same thing again, and even though she was concerned for him, she could not shake the feeling of resentment, Dr. Sadavoy explained.

She was at a time in her life when she expected to feel more secure, but she was not sure about whether she could deal with the situation as she had done in the past because of her age, diabetes, and hypertension.

The woman was born into a business-oriented family that had no interest in the arts or intellectual pursuits, unlike her, and she had always thought that her parents were judgmental and rejecting of the things that differed from their perspectives on life.

She married to be rescued from her family, he said.

The woman was not demented and did not have a depressive disorder or any other Axis I disorders, according to Dr. Sadavoy.

He explained her husband's diagnoses and the reasons for his behavior. “She clung to her previous explanatory models but needed to understand in an entirely different fashion that this was not willful behavior but was a brain disturbance,” he said.

They worked through her grief at the loss of the husband she once had, her lost sense of identity as a wife, her anger at his incapacity, and her fear of how she would survive by clarifying her role changes and reformulating her responses to interpersonal conflict. Dr. Sadavoy helped her to create a list of her interpersonal problems and then actively coached her in developing alternate behaviors and problem-solving skills.

At the psychodynamic level, the woman had a deep desire to be recognized as valuable and loved by her mother. They explored this in the context of her lifelong belief that “she was an alien in her own family.”

Her feelings toward her husband's personality change paralleled those toward her family when she described her husband as being coarse, ungiving, unloving, and stupid.

“If she's truly going to be able to deal with what's happening to her husband, stop being angry at him, lose some of her anxiety, and begin to actually focus on problem-solving and dealing with the issues, she has to understand somehow why she is reacting the way she is,” Dr. Sadavoy said.

STOCKHOLM – Integrated individual psychotherapy may be the best method for addressing complex issues that are often unique to geriatric patients, Dr. Joel Sadavoy said at the 12th Congress of the International Psychogeriatric Association.

“The elderly often present to us with a confusing number of problems, and [these problems] originate from many different sources,” said Dr. Sadavoy, president of the IPA.

Older adults are less likely than younger individuals to have support, since they may be no longer married, retired from the work that defined their identity and purpose, and have lower physical health and strength.

Psychopathology in geriatric patients may be more complex than in younger adults because of the interplay between the adaptive challenges of old age, such as illness or loss, and the individual's personality and psychological structure, such as the ability to maintain self-esteem and security in the face of adversity.

The psychological structure of an older adult will strengthen or weaken their coping capacities, according to the so-called diathesis-stress model described by Dr. Aaron T. Beck and Margaret Gatz, Ph.D., Dr. Sadavoy said.

Some clinicians suggest that the use of two or more interventions, such as combining medication and cognitive-behavioral therapy in the course of a single treatment is integrated therapy.

But a more focused definition of integrated psychotherapy is “the concurrent application of more than one psychotherapeutic technique to address symptoms that arise from different levels and sources, both from within a patient and from their environment and interactive surroundings,” he said.

Dr. Sadavoy suggested that integrated psychotherapy works best if it addresses each of three sources of psychopathology in the patient:

▸ Lack of understanding and knowledge about illness and aging.

▸ Maladaptive thoughts and actions that originate from age-related cognitive distortions and perceptions, shifts in interpersonal relationships and identity, and a lack of problem-solving ability.

▸ Psychodynamically determined reactions and emotions that originate from lifelong, unconscious psychological conflicts and perceptions (Can. J. Psychiatry 1994;39:S19–26).

The third source “is of great importance but is probably the most difficult and subtle to deal with,” Dr. Sadavoy said.

A psychotherapist must have broad training and sufficient practice in using the full array of interventions for these sources of psychopathology to implement an integrated approach successfully, he said.

Dr. Sadavoy uses psychoeducation to address misinformation and deficits in knowledge.

Maladaptive cognitive and interpersonal responses and difficulty in problem-solving are dealt with through clarification and modification of cognitive distortions, interpersonal coaching and training, and teaching of problem-solving techniques. “These are three types of therapy that have been shown to be effective in studies of younger and, in some cases, older patients,” said Dr. Sadavoy, who is a professor of psychiatry at the University of Toronto.

He treats the unconscious conflicts and self-perceptions of older patients with psychodynamic therapies that employ interpretation and working within the transference in therapy.

The degree to which each intervention is used depends on which elements of psychopathology are most evident in a given patient, he said.

During treatment, the psychotherapist should undertake “some major history taking” to gather data on each of the three sources of impairment, organize the data, and develop an integrated intervention plan.

In an example of when an integrated approach works best, Dr. Sadavoy described the case of a 72-year-old woman who showed depressive symptoms, anxiety, and low functioning after a focal cerebrovascular lesion abruptly changed her husband's personality and cognitive function.

The woman's husband had agitation, severe paranoid depression, and executive dysfunction. The man developed new, bizarre behaviors and was unable to run the family business any longer. She felt abandoned. She believed that her husband's symptoms were the recurrence of a depressive episode that was associated with a business failure he had had many years before.

At that time, she was very angry with him because she had to take over the business and rearrange her life in order to do so. Now she felt that she was going through the same thing again, and even though she was concerned for him, she could not shake the feeling of resentment, Dr. Sadavoy explained.

She was at a time in her life when she expected to feel more secure, but she was not sure about whether she could deal with the situation as she had done in the past because of her age, diabetes, and hypertension.

The woman was born into a business-oriented family that had no interest in the arts or intellectual pursuits, unlike her, and she had always thought that her parents were judgmental and rejecting of the things that differed from their perspectives on life.

She married to be rescued from her family, he said.

The woman was not demented and did not have a depressive disorder or any other Axis I disorders, according to Dr. Sadavoy.

He explained her husband's diagnoses and the reasons for his behavior. “She clung to her previous explanatory models but needed to understand in an entirely different fashion that this was not willful behavior but was a brain disturbance,” he said.

They worked through her grief at the loss of the husband she once had, her lost sense of identity as a wife, her anger at his incapacity, and her fear of how she would survive by clarifying her role changes and reformulating her responses to interpersonal conflict. Dr. Sadavoy helped her to create a list of her interpersonal problems and then actively coached her in developing alternate behaviors and problem-solving skills.

At the psychodynamic level, the woman had a deep desire to be recognized as valuable and loved by her mother. They explored this in the context of her lifelong belief that “she was an alien in her own family.”

Her feelings toward her husband's personality change paralleled those toward her family when she described her husband as being coarse, ungiving, unloving, and stupid.

“If she's truly going to be able to deal with what's happening to her husband, stop being angry at him, lose some of her anxiety, and begin to actually focus on problem-solving and dealing with the issues, she has to understand somehow why she is reacting the way she is,” Dr. Sadavoy said.

STOCKHOLM – Integrated individual psychotherapy may be the best method for addressing complex issues that are often unique to geriatric patients, Dr. Joel Sadavoy said at the 12th Congress of the International Psychogeriatric Association.

“The elderly often present to us with a confusing number of problems, and [these problems] originate from many different sources,” said Dr. Sadavoy, president of the IPA.

Older adults are less likely than younger individuals to have support, since they may be no longer married, retired from the work that defined their identity and purpose, and have lower physical health and strength.

Psychopathology in geriatric patients may be more complex than in younger adults because of the interplay between the adaptive challenges of old age, such as illness or loss, and the individual's personality and psychological structure, such as the ability to maintain self-esteem and security in the face of adversity.

The psychological structure of an older adult will strengthen or weaken their coping capacities, according to the so-called diathesis-stress model described by Dr. Aaron T. Beck and Margaret Gatz, Ph.D., Dr. Sadavoy said.

Some clinicians suggest that the use of two or more interventions, such as combining medication and cognitive-behavioral therapy in the course of a single treatment is integrated therapy.

But a more focused definition of integrated psychotherapy is “the concurrent application of more than one psychotherapeutic technique to address symptoms that arise from different levels and sources, both from within a patient and from their environment and interactive surroundings,” he said.

Dr. Sadavoy suggested that integrated psychotherapy works best if it addresses each of three sources of psychopathology in the patient:

▸ Lack of understanding and knowledge about illness and aging.

▸ Maladaptive thoughts and actions that originate from age-related cognitive distortions and perceptions, shifts in interpersonal relationships and identity, and a lack of problem-solving ability.

▸ Psychodynamically determined reactions and emotions that originate from lifelong, unconscious psychological conflicts and perceptions (Can. J. Psychiatry 1994;39:S19–26).

The third source “is of great importance but is probably the most difficult and subtle to deal with,” Dr. Sadavoy said.

A psychotherapist must have broad training and sufficient practice in using the full array of interventions for these sources of psychopathology to implement an integrated approach successfully, he said.

Dr. Sadavoy uses psychoeducation to address misinformation and deficits in knowledge.

Maladaptive cognitive and interpersonal responses and difficulty in problem-solving are dealt with through clarification and modification of cognitive distortions, interpersonal coaching and training, and teaching of problem-solving techniques. “These are three types of therapy that have been shown to be effective in studies of younger and, in some cases, older patients,” said Dr. Sadavoy, who is a professor of psychiatry at the University of Toronto.

He treats the unconscious conflicts and self-perceptions of older patients with psychodynamic therapies that employ interpretation and working within the transference in therapy.

The degree to which each intervention is used depends on which elements of psychopathology are most evident in a given patient, he said.

During treatment, the psychotherapist should undertake “some major history taking” to gather data on each of the three sources of impairment, organize the data, and develop an integrated intervention plan.

In an example of when an integrated approach works best, Dr. Sadavoy described the case of a 72-year-old woman who showed depressive symptoms, anxiety, and low functioning after a focal cerebrovascular lesion abruptly changed her husband's personality and cognitive function.

The woman's husband had agitation, severe paranoid depression, and executive dysfunction. The man developed new, bizarre behaviors and was unable to run the family business any longer. She felt abandoned. She believed that her husband's symptoms were the recurrence of a depressive episode that was associated with a business failure he had had many years before.

At that time, she was very angry with him because she had to take over the business and rearrange her life in order to do so. Now she felt that she was going through the same thing again, and even though she was concerned for him, she could not shake the feeling of resentment, Dr. Sadavoy explained.

She was at a time in her life when she expected to feel more secure, but she was not sure about whether she could deal with the situation as she had done in the past because of her age, diabetes, and hypertension.

The woman was born into a business-oriented family that had no interest in the arts or intellectual pursuits, unlike her, and she had always thought that her parents were judgmental and rejecting of the things that differed from their perspectives on life.

She married to be rescued from her family, he said.

The woman was not demented and did not have a depressive disorder or any other Axis I disorders, according to Dr. Sadavoy.

He explained her husband's diagnoses and the reasons for his behavior. “She clung to her previous explanatory models but needed to understand in an entirely different fashion that this was not willful behavior but was a brain disturbance,” he said.

They worked through her grief at the loss of the husband she once had, her lost sense of identity as a wife, her anger at his incapacity, and her fear of how she would survive by clarifying her role changes and reformulating her responses to interpersonal conflict. Dr. Sadavoy helped her to create a list of her interpersonal problems and then actively coached her in developing alternate behaviors and problem-solving skills.

At the psychodynamic level, the woman had a deep desire to be recognized as valuable and loved by her mother. They explored this in the context of her lifelong belief that “she was an alien in her own family.”

Her feelings toward her husband's personality change paralleled those toward her family when she described her husband as being coarse, ungiving, unloving, and stupid.

“If she's truly going to be able to deal with what's happening to her husband, stop being angry at him, lose some of her anxiety, and begin to actually focus on problem-solving and dealing with the issues, she has to understand somehow why she is reacting the way she is,” Dr. Sadavoy said.

STOCKHOLM – Much remains unknown about dysthymia and minor depression in older adults, particularly when it comes to differences in the pathogenesis of early- and late-onset disorders and the interaction of these disorders with comorbidities, Dr. Jeffrey M. Lyness said at the 12th Congress of the International Psychogeriatric Association.

Studying the contributions of early- and late-onset symptomatology to medical comorbidities is a complex proposition. As a result, coming up with specific treatment approaches has proved difficult.

Compared with the number of studies for major depression, relatively few studies have examined the neurobiology of dysthymia, even in younger adults. Studies that have been conducted provide mixed results on whether any real differences or similarities exist between the neurobiology of dysthymia and major depression in either older or younger adults.

Some findings suggest that older male patients with dysthymia may have low serum testosterone levels. Other studies have not clearly indicated whether small-vessel cerebrovascular disease contributes to dysthymia in older patients, said Dr. Lyness, director of the laboratory of depression and medical comorbidity in the geriatrics and neuropsychiatry program at the University of Rochester (N.Y.).

The criteria for dysthymia include symptoms that are less intense but just as chronic as those in major depression, thus creating a “very unusual combination,” he said.

The “most striking feature” about dysthymic disorder in older adults may be that it is less common in community settings in elderly individuals (1%) than in younger people in such settings (3%–4%), he said. “It's not clear why that is;” it is not known whether the lower prevalence is a function of aging or if the higher prevalence in younger people is a characteristic of the current younger generation.

In older adults, the male-to-female ratio is nearly 50:50 for dysthymia. This is in contrast with disorders such as major depression, where women make up the greater proportion of those diagnosed.

Patients with minor depression often fail to meet criteria for dysthymia, Dr. Lyness said, because the waxing and waning nature of minor depression does not meet the 2-year criterion for dysthymia.

The set of nine criteria for minor depression in the appendix of the DSM-IV is the same as that for major depression. But only two to four criteria have to be met for minor depression, instead of five or more for major depression. The symptoms also have to be present for most of the day, nearly every day, for at least 2 weeks for both disorders.

In Dr. Lyness' experience, patients with minor depression often have as many symptoms as do patients with major depression. But they do not meet the criteria for the more severe form of the illness, because they have only two or three miserable days a week but don't feel so bad other days, or they have most of their symptoms for a few hours in the morning or evening.

Minor and “subsyndromal” depressions appear to be on a spectrum between no depression and major depressive disorder based on functional status, neuroimaging scans, and patient outcomes in studies comparing minor and major depression in older adults, he said.

Treatments for minor depression appear to work. But many studies have been plagued by the absence of a difference between active treatments–such as psychotherapy or medications–and placebo, partly because of very high placebo response rates, Dr. Lyness said.

In conducting a series of metaanalyses of trials comparing the efficacy of pharmacotherapy with that of psychosocial therapies in older adults with depression, Dr. Lyness and his colleagues found that psychosocial therapies had “somewhat bigger effect sizes” than did pharmacotherapy in studies that contained less severely depressed patients. The metaanalyses are in press in the American Journal of Psychiatry.

Dr. Lyness suggested that it might be best to educate and observe minor depressive patients who have less severe symptoms and to reserve psychosocial therapies or medications for patients with particularly troublesome symptoms or a history of depression.

Many clinicians suspect that two 75-year-olds who have minor or major depression may be suffering from pathogenetically different disorders when one just had a first episode and the other has had the current episode since 32 years of age. Although such distinctions may be important, they are not easy to study because of the difficulty of determining the actual age of onset in a retrospective manner, Dr. Lyness pointed out.

Investigators must define what they consider to be first onset of depression, especially in older patients who now have major depression but initially met criteria for minor depression when they were younger. The pathogenesis of depression also could change within individuals as they age, even if they have the same symptoms over a long period.

In older adult patients with depression, both early- and late-onset conditions “have strikes against them,” because early-onset patients have longer and greater numbers of episodes, whereas late-onset patients may have several acquired biological factors that affect the brain directly, or there may be psychosocial factors that might “be less amenable to change,” he said.

Recently, a systematic review of studies of older and middle-aged adults with depressive conditions showed that an earlier age of onset and a larger number of depressive episodes were associated with a worse prognosis. But the presence of medical comorbidities explained most of the differences in prognosis and response to treatment. The review did not distinguish among the subtypes of depression (Am. J. Psychiatry 2005;162:1588–601).

Right now, evidence is too sparse to recommend specific medications or types of psychotherapy based on the older depressed patient's physical comorbidity.

In reviewing studies of about 700 primary care patients at the University of Rochester, Dr. Lyness and his colleagues have found that some physical illnesses–low vision, central nervous system diseases, diabetes, and hypothyroidism–appear to have independent associations with depression.

It may be best to reserve treatments for patients with troublesome depressive symptoms. DR. LYNESS

STOCKHOLM – Much remains unknown about dysthymia and minor depression in older adults, particularly when it comes to differences in the pathogenesis of early- and late-onset disorders and the interaction of these disorders with comorbidities, Dr. Jeffrey M. Lyness said at the 12th Congress of the International Psychogeriatric Association.

Studying the contributions of early- and late-onset symptomatology to medical comorbidities is a complex proposition. As a result, coming up with specific treatment approaches has proved difficult.

Compared with the number of studies for major depression, relatively few studies have examined the neurobiology of dysthymia, even in younger adults. Studies that have been conducted provide mixed results on whether any real differences or similarities exist between the neurobiology of dysthymia and major depression in either older or younger adults.

Some findings suggest that older male patients with dysthymia may have low serum testosterone levels. Other studies have not clearly indicated whether small-vessel cerebrovascular disease contributes to dysthymia in older patients, said Dr. Lyness, director of the laboratory of depression and medical comorbidity in the geriatrics and neuropsychiatry program at the University of Rochester (N.Y.).

The criteria for dysthymia include symptoms that are less intense but just as chronic as those in major depression, thus creating a “very unusual combination,” he said.

The “most striking feature” about dysthymic disorder in older adults may be that it is less common in community settings in elderly individuals (1%) than in younger people in such settings (3%–4%), he said. “It's not clear why that is;” it is not known whether the lower prevalence is a function of aging or if the higher prevalence in younger people is a characteristic of the current younger generation.

In older adults, the male-to-female ratio is nearly 50:50 for dysthymia. This is in contrast with disorders such as major depression, where women make up the greater proportion of those diagnosed.

Patients with minor depression often fail to meet criteria for dysthymia, Dr. Lyness said, because the waxing and waning nature of minor depression does not meet the 2-year criterion for dysthymia.

The set of nine criteria for minor depression in the appendix of the DSM-IV is the same as that for major depression. But only two to four criteria have to be met for minor depression, instead of five or more for major depression. The symptoms also have to be present for most of the day, nearly every day, for at least 2 weeks for both disorders.

In Dr. Lyness' experience, patients with minor depression often have as many symptoms as do patients with major depression. But they do not meet the criteria for the more severe form of the illness, because they have only two or three miserable days a week but don't feel so bad other days, or they have most of their symptoms for a few hours in the morning or evening.

Minor and “subsyndromal” depressions appear to be on a spectrum between no depression and major depressive disorder based on functional status, neuroimaging scans, and patient outcomes in studies comparing minor and major depression in older adults, he said.

Treatments for minor depression appear to work. But many studies have been plagued by the absence of a difference between active treatments–such as psychotherapy or medications–and placebo, partly because of very high placebo response rates, Dr. Lyness said.

In conducting a series of metaanalyses of trials comparing the efficacy of pharmacotherapy with that of psychosocial therapies in older adults with depression, Dr. Lyness and his colleagues found that psychosocial therapies had “somewhat bigger effect sizes” than did pharmacotherapy in studies that contained less severely depressed patients. The metaanalyses are in press in the American Journal of Psychiatry.

Dr. Lyness suggested that it might be best to educate and observe minor depressive patients who have less severe symptoms and to reserve psychosocial therapies or medications for patients with particularly troublesome symptoms or a history of depression.

Many clinicians suspect that two 75-year-olds who have minor or major depression may be suffering from pathogenetically different disorders when one just had a first episode and the other has had the current episode since 32 years of age. Although such distinctions may be important, they are not easy to study because of the difficulty of determining the actual age of onset in a retrospective manner, Dr. Lyness pointed out.

Investigators must define what they consider to be first onset of depression, especially in older patients who now have major depression but initially met criteria for minor depression when they were younger. The pathogenesis of depression also could change within individuals as they age, even if they have the same symptoms over a long period.

In older adult patients with depression, both early- and late-onset conditions “have strikes against them,” because early-onset patients have longer and greater numbers of episodes, whereas late-onset patients may have several acquired biological factors that affect the brain directly, or there may be psychosocial factors that might “be less amenable to change,” he said.

Recently, a systematic review of studies of older and middle-aged adults with depressive conditions showed that an earlier age of onset and a larger number of depressive episodes were associated with a worse prognosis. But the presence of medical comorbidities explained most of the differences in prognosis and response to treatment. The review did not distinguish among the subtypes of depression (Am. J. Psychiatry 2005;162:1588–601).

Right now, evidence is too sparse to recommend specific medications or types of psychotherapy based on the older depressed patient's physical comorbidity.

In reviewing studies of about 700 primary care patients at the University of Rochester, Dr. Lyness and his colleagues have found that some physical illnesses–low vision, central nervous system diseases, diabetes, and hypothyroidism–appear to have independent associations with depression.

It may be best to reserve treatments for patients with troublesome depressive symptoms. DR. LYNESS

STOCKHOLM – Much remains unknown about dysthymia and minor depression in older adults, particularly when it comes to differences in the pathogenesis of early- and late-onset disorders and the interaction of these disorders with comorbidities, Dr. Jeffrey M. Lyness said at the 12th Congress of the International Psychogeriatric Association.

Studying the contributions of early- and late-onset symptomatology to medical comorbidities is a complex proposition. As a result, coming up with specific treatment approaches has proved difficult.

Compared with the number of studies for major depression, relatively few studies have examined the neurobiology of dysthymia, even in younger adults. Studies that have been conducted provide mixed results on whether any real differences or similarities exist between the neurobiology of dysthymia and major depression in either older or younger adults.

Some findings suggest that older male patients with dysthymia may have low serum testosterone levels. Other studies have not clearly indicated whether small-vessel cerebrovascular disease contributes to dysthymia in older patients, said Dr. Lyness, director of the laboratory of depression and medical comorbidity in the geriatrics and neuropsychiatry program at the University of Rochester (N.Y.).

The criteria for dysthymia include symptoms that are less intense but just as chronic as those in major depression, thus creating a “very unusual combination,” he said.

The “most striking feature” about dysthymic disorder in older adults may be that it is less common in community settings in elderly individuals (1%) than in younger people in such settings (3%–4%), he said. “It's not clear why that is;” it is not known whether the lower prevalence is a function of aging or if the higher prevalence in younger people is a characteristic of the current younger generation.

In older adults, the male-to-female ratio is nearly 50:50 for dysthymia. This is in contrast with disorders such as major depression, where women make up the greater proportion of those diagnosed.

Patients with minor depression often fail to meet criteria for dysthymia, Dr. Lyness said, because the waxing and waning nature of minor depression does not meet the 2-year criterion for dysthymia.

The set of nine criteria for minor depression in the appendix of the DSM-IV is the same as that for major depression. But only two to four criteria have to be met for minor depression, instead of five or more for major depression. The symptoms also have to be present for most of the day, nearly every day, for at least 2 weeks for both disorders.

In Dr. Lyness' experience, patients with minor depression often have as many symptoms as do patients with major depression. But they do not meet the criteria for the more severe form of the illness, because they have only two or three miserable days a week but don't feel so bad other days, or they have most of their symptoms for a few hours in the morning or evening.

Minor and “subsyndromal” depressions appear to be on a spectrum between no depression and major depressive disorder based on functional status, neuroimaging scans, and patient outcomes in studies comparing minor and major depression in older adults, he said.

Treatments for minor depression appear to work. But many studies have been plagued by the absence of a difference between active treatments–such as psychotherapy or medications–and placebo, partly because of very high placebo response rates, Dr. Lyness said.

In conducting a series of metaanalyses of trials comparing the efficacy of pharmacotherapy with that of psychosocial therapies in older adults with depression, Dr. Lyness and his colleagues found that psychosocial therapies had “somewhat bigger effect sizes” than did pharmacotherapy in studies that contained less severely depressed patients. The metaanalyses are in press in the American Journal of Psychiatry.

Dr. Lyness suggested that it might be best to educate and observe minor depressive patients who have less severe symptoms and to reserve psychosocial therapies or medications for patients with particularly troublesome symptoms or a history of depression.

Many clinicians suspect that two 75-year-olds who have minor or major depression may be suffering from pathogenetically different disorders when one just had a first episode and the other has had the current episode since 32 years of age. Although such distinctions may be important, they are not easy to study because of the difficulty of determining the actual age of onset in a retrospective manner, Dr. Lyness pointed out.

Investigators must define what they consider to be first onset of depression, especially in older patients who now have major depression but initially met criteria for minor depression when they were younger. The pathogenesis of depression also could change within individuals as they age, even if they have the same symptoms over a long period.

In older adult patients with depression, both early- and late-onset conditions “have strikes against them,” because early-onset patients have longer and greater numbers of episodes, whereas late-onset patients may have several acquired biological factors that affect the brain directly, or there may be psychosocial factors that might “be less amenable to change,” he said.

Recently, a systematic review of studies of older and middle-aged adults with depressive conditions showed that an earlier age of onset and a larger number of depressive episodes were associated with a worse prognosis. But the presence of medical comorbidities explained most of the differences in prognosis and response to treatment. The review did not distinguish among the subtypes of depression (Am. J. Psychiatry 2005;162:1588–601).

Right now, evidence is too sparse to recommend specific medications or types of psychotherapy based on the older depressed patient's physical comorbidity.

In reviewing studies of about 700 primary care patients at the University of Rochester, Dr. Lyness and his colleagues have found that some physical illnesses–low vision, central nervous system diseases, diabetes, and hypothyroidism–appear to have independent associations with depression.

It may be best to reserve treatments for patients with troublesome depressive symptoms. DR. LYNESS

WASHINGTON — Most American travelers to regions endemic for hepatitis B do not receive pretravel health advice and are underimmunized, according to an anonymous survey of 618 adult travelers to such areas.

In the survey of people who traveled to countries with moderate to high rates of hepatitis B from 2000 onward, 31% of respondents visited a health practitioner to get pretravel health advice, 13% saw a travel medicine specialist, and 18% saw other health care providers, Dr. Bradley A. Connor reported during a poster session at the annual meeting of the American Society of Tropical Medicine and Hygiene.

The strongest predictor of not seeking medical advice was travel duration of less than 20 days. Income of less than $100,000 per year also was a strong predictor of not seeking advice from a travel medicine specialist, wrote Dr. Connor, medical director of the New York Center for Travel and Tropical Medicine. The survey respondents were international travelers identified from commercially available mailing lists; they received the survey by mail.

Respondents were significantly more likely to report having a domestic or travel-related risk factor for hepatitis B if they were age 40 years or younger, unmarried and male, or had traveled for more than 20 days. The 150 travelers who were aged 18–40 years reported significantly higher rates of domestic risk factors (sexual, health-related, occupational, and other) for hepatitis B than did the 468 older travelers (43% vs. 17%).

Compared with patients older than 40 years, younger patients also were significantly more likely to participate in activities that were of high risk (12% vs. 7%) or potential risk (48% vs. 27%) for hepatitis B during their most recent trip.

High-risk activities were defined as an accident or illness that required invasive medical attention, a skin-perforating cosmetic procedure, or sexual intercourse with a native who was unknown to the respondent prior to travel. Activities of potential risk for hepatitis B included sharing personal grooming items, participation in certain sporting or adventure activities, cosmetic activities with risk of skin perforation, or an accident or illness that did not require invasive care.

Hepatitis B vaccination rates on departure declined with increasing age from 33% among travelers aged 18–40 years to 19% among those aged 41–59 years and 9% among travelers aged 60 years or older. Of the travelers who had not previously completed hepatitis B vaccination, 40% actually received hepatitis B vaccine during their pretravel visits.

WASHINGTON — Most American travelers to regions endemic for hepatitis B do not receive pretravel health advice and are underimmunized, according to an anonymous survey of 618 adult travelers to such areas.

In the survey of people who traveled to countries with moderate to high rates of hepatitis B from 2000 onward, 31% of respondents visited a health practitioner to get pretravel health advice, 13% saw a travel medicine specialist, and 18% saw other health care providers, Dr. Bradley A. Connor reported during a poster session at the annual meeting of the American Society of Tropical Medicine and Hygiene.

The strongest predictor of not seeking medical advice was travel duration of less than 20 days. Income of less than $100,000 per year also was a strong predictor of not seeking advice from a travel medicine specialist, wrote Dr. Connor, medical director of the New York Center for Travel and Tropical Medicine. The survey respondents were international travelers identified from commercially available mailing lists; they received the survey by mail.

Respondents were significantly more likely to report having a domestic or travel-related risk factor for hepatitis B if they were age 40 years or younger, unmarried and male, or had traveled for more than 20 days. The 150 travelers who were aged 18–40 years reported significantly higher rates of domestic risk factors (sexual, health-related, occupational, and other) for hepatitis B than did the 468 older travelers (43% vs. 17%).

Compared with patients older than 40 years, younger patients also were significantly more likely to participate in activities that were of high risk (12% vs. 7%) or potential risk (48% vs. 27%) for hepatitis B during their most recent trip.

High-risk activities were defined as an accident or illness that required invasive medical attention, a skin-perforating cosmetic procedure, or sexual intercourse with a native who was unknown to the respondent prior to travel. Activities of potential risk for hepatitis B included sharing personal grooming items, participation in certain sporting or adventure activities, cosmetic activities with risk of skin perforation, or an accident or illness that did not require invasive care.

Hepatitis B vaccination rates on departure declined with increasing age from 33% among travelers aged 18–40 years to 19% among those aged 41–59 years and 9% among travelers aged 60 years or older. Of the travelers who had not previously completed hepatitis B vaccination, 40% actually received hepatitis B vaccine during their pretravel visits.

WASHINGTON — Most American travelers to regions endemic for hepatitis B do not receive pretravel health advice and are underimmunized, according to an anonymous survey of 618 adult travelers to such areas.

In the survey of people who traveled to countries with moderate to high rates of hepatitis B from 2000 onward, 31% of respondents visited a health practitioner to get pretravel health advice, 13% saw a travel medicine specialist, and 18% saw other health care providers, Dr. Bradley A. Connor reported during a poster session at the annual meeting of the American Society of Tropical Medicine and Hygiene.

The strongest predictor of not seeking medical advice was travel duration of less than 20 days. Income of less than $100,000 per year also was a strong predictor of not seeking advice from a travel medicine specialist, wrote Dr. Connor, medical director of the New York Center for Travel and Tropical Medicine. The survey respondents were international travelers identified from commercially available mailing lists; they received the survey by mail.

Respondents were significantly more likely to report having a domestic or travel-related risk factor for hepatitis B if they were age 40 years or younger, unmarried and male, or had traveled for more than 20 days. The 150 travelers who were aged 18–40 years reported significantly higher rates of domestic risk factors (sexual, health-related, occupational, and other) for hepatitis B than did the 468 older travelers (43% vs. 17%).

Compared with patients older than 40 years, younger patients also were significantly more likely to participate in activities that were of high risk (12% vs. 7%) or potential risk (48% vs. 27%) for hepatitis B during their most recent trip.

High-risk activities were defined as an accident or illness that required invasive medical attention, a skin-perforating cosmetic procedure, or sexual intercourse with a native who was unknown to the respondent prior to travel. Activities of potential risk for hepatitis B included sharing personal grooming items, participation in certain sporting or adventure activities, cosmetic activities with risk of skin perforation, or an accident or illness that did not require invasive care.

Hepatitis B vaccination rates on departure declined with increasing age from 33% among travelers aged 18–40 years to 19% among those aged 41–59 years and 9% among travelers aged 60 years or older. Of the travelers who had not previously completed hepatitis B vaccination, 40% actually received hepatitis B vaccine during their pretravel visits.

WASHINGTON — Long-term travelers to countries with high risk for malaria should use personal protective measures and chemoprophylactic regimens based on the risk factors they are likely to encounter, Patricia Schlagenhauf-Lawlor, Ph.D., said at the annual meeting of the American Society of Tropical Medicine and Hygiene.

Long-term travelers—defined by some guidelines as those who travel for more than 6 months—include people visiting friends and relatives, expatriates, occupational travelers such as military personnel, backpackers, and missionaries. These people can use precautions that range widely in their ability to prevent infection, including personal protection measures, standby emergency treatment, rapid tests for malaria, seasonal chemoprophylaxis, and continuous chemoprophylaxis, said Dr. Schlagenhauf-Lawlor of the World Health Organization Collaborating Centre for Travellers' Health at the University of Zürich (Switzerland).

Personal Protection Measures

A review of randomized trials showed that insecticide-treated nets are effective in reducing childhood mortality and morbidity due to malaria (Cochrane Database Syst. Rev. 2005; www.thecochranelibrary.com

Bed nets are “something we should really recommend to our long-term travelers,” Dr. Schlagenhauf-Lawlor said.

Clothing that has been impregnated with insecticides such as permethrin remain effective for several months. Shoes and protective (white or brightly colored) clothing also help to fend off mosquitoes, she added.

Among the mosquito repellents that are available in the United States, DEET (N,N-diethyl-m-toluamide) is still considered the best because it has been widely used and tested and is effective for more than 5 hours at concentrations of 20%. Children older than 2 months of age can use DEET, but it should be at concentrations of 10% or less.

The repellent picaridin (Bayrepel) at 19.2% concentration has been shown to cause less skin irritation while providing a level of protection similar to DEET, especially against the mosquito Anopheles gambiae. Picaridin has been approved by the Environmental Protection Agency and is safe for children older than 2 years, but studies have shown that the level and duration of protection varies between individuals, Dr. Schlagenhauf-Lawlor said.

Clinicians should avoid recommending natural oils such as citronella and eucalyptus because these oils provide only short-term protection, she said.

Mosquitoes generally prefer to bite adults rather than children, men rather than women, and large rather than small people. Some mosquitoes bite more often on the feet and ankles (A. gambiae) or face (A. atroparvus).

Travelers should learn what time of day the malaria-vector mosquitoes bite in the region they are traveling to. Bed nets may be ideal for travelers to Africa where A. gambiae is present, which prefers to feed indoors late at night. In the Amazon, repellents may work best against A. darlingi, which bites mostly in the early evening, she said.

But most long-term travelers have poor compliance with personal protection measures, Dr. Schlagenhauf-Lawlor noted. Experts consider a combination of at least four such measures to be adequate to protect against mosquito bites in high-risk areas for malaria. In a study of business travelers to high-risk areas in Africa, only 4% used four recognized methods of prevention, which include long clothes, air conditioning, repellents, insecticides, mosquito nets, and burn coils (J. Travel Med. 2003;10:219–24). Nearly all other travelers used some personal protection measures: 43% of the travelers used three measures, 25% used two, and 21% used one. Only 2% of tourists to high-risk areas in Africa used four personal protection measures (J. Travel Med. 1998;5:188–92).

Standby Emergency Treatment

The WHO defines standby emergency treatment (SBET) of malaria as the use of antimalarial drugs when malaria is suspected and prompt medical attention is unavailable within 24 hours.

For travelers in some areas, German and Swiss guidelines now recommend wider use of SBET instead of continuous prophylaxis.

“We recommend chemosuppression only when the benefit is 10 times greater than the risk of adverse effects,” Dr. Schlagenhauf-Lawlor said. “That means for most of our travelers, except for those in sub-Saharan Africa, we're recommending standby treatment and antimosquito measures.” This may be at odds with what American physicians would recommend.

Chloroquine and quinine have “very limited use” for SBET, while other drugs such as mefloquine, atovaquone and proguanil (Malarone), and sulfadoxine plus pyrimethamine (Fansidar) are acceptable for SBET. Halofantrine (Halfan) is now contraindicated for SBET because of potential cardiac complications, Dr. Schlagenhauf-Lawlor said.

The German and Swiss guidelines recommend that chloroquine be used for SBET in parts of Central America and the Middle East. The guidelines recommend that travelers to India use mefloquine. Travelers to the Southeast Asian countries of Myanmar, Thailand, Laos, Cambodia, and Vietnam should use Malarone for SBET because of multidrug resistant malarial strains, according to the guidelines.

The guidelines recommend continuous prophylaxis in Papua New Guinea, nearly all of sub-Saharan Africa, and in several provinces of Brazil. Continuous prophylaxis with mefloquine, doxycycline, or Malarone can be more than 90% effective if they are chosen correctly, but they cause “perceived or real” adverse events in more than 80% of patients.

Many patients also fail to adhere to the dosing regimen for continuous prophylaxis and find it difficult to get the drug they need if they are traveling for more than a year, Dr. Schlagenhauf-Lawlor said.

The nonspecific symptoms of malaria make it difficult for patients to self-diagnose the disease, Dr. Schlagenhauf-Lawlor said. In a study of 1,187 Swiss travelers who carried medication for SBET, about 10% became ill with fever while traveling. Even though only nine of the travelers were out of the reach of medical attention, most of those who were ill reacted to their illness contrary to SBET instructions and delayed in seeking medical attention (Bull. World Health Organ. 1995;73:215–21).

A combination of SBET and rapid malaria tests “could be useful for certain selected long-term travelers,” she said. Studies have reported that 68%–91% of travelers were able to use the tests successfully. However, the tests can generate false-positive results and have been difficult for travelers to read at low levels of parasitemia.

Seasonal Prophylaxis

In all but a few countries “it's almost impossible for an adviser to say in advance how the season will be at the destination,” Dr. Schlagenhauf-Lawlor said.

In the sub-Saharan countries of South Africa, Namibia, and Botswana, the transmission seasons are fairly stable, but can shift, she noted.

In South Africa, travelers may want to use continuous prophylaxis during the high-risk season of October through May and revert to SBET during the low-risk season of June through September. But travelers should always use personal protective measures.

Blood-feeding Anopheles gambiae mosquito, a leading malaria vector. CDC

WASHINGTON — Long-term travelers to countries with high risk for malaria should use personal protective measures and chemoprophylactic regimens based on the risk factors they are likely to encounter, Patricia Schlagenhauf-Lawlor, Ph.D., said at the annual meeting of the American Society of Tropical Medicine and Hygiene.

Long-term travelers—defined by some guidelines as those who travel for more than 6 months—include people visiting friends and relatives, expatriates, occupational travelers such as military personnel, backpackers, and missionaries. These people can use precautions that range widely in their ability to prevent infection, including personal protection measures, standby emergency treatment, rapid tests for malaria, seasonal chemoprophylaxis, and continuous chemoprophylaxis, said Dr. Schlagenhauf-Lawlor of the World Health Organization Collaborating Centre for Travellers' Health at the University of Zürich (Switzerland).

Personal Protection Measures

A review of randomized trials showed that insecticide-treated nets are effective in reducing childhood mortality and morbidity due to malaria (Cochrane Database Syst. Rev. 2005; www.thecochranelibrary.com

Bed nets are “something we should really recommend to our long-term travelers,” Dr. Schlagenhauf-Lawlor said.

Clothing that has been impregnated with insecticides such as permethrin remain effective for several months. Shoes and protective (white or brightly colored) clothing also help to fend off mosquitoes, she added.

Among the mosquito repellents that are available in the United States, DEET (N,N-diethyl-m-toluamide) is still considered the best because it has been widely used and tested and is effective for more than 5 hours at concentrations of 20%. Children older than 2 months of age can use DEET, but it should be at concentrations of 10% or less.

The repellent picaridin (Bayrepel) at 19.2% concentration has been shown to cause less skin irritation while providing a level of protection similar to DEET, especially against the mosquito Anopheles gambiae. Picaridin has been approved by the Environmental Protection Agency and is safe for children older than 2 years, but studies have shown that the level and duration of protection varies between individuals, Dr. Schlagenhauf-Lawlor said.

Clinicians should avoid recommending natural oils such as citronella and eucalyptus because these oils provide only short-term protection, she said.

Mosquitoes generally prefer to bite adults rather than children, men rather than women, and large rather than small people. Some mosquitoes bite more often on the feet and ankles (A. gambiae) or face (A. atroparvus).

Travelers should learn what time of day the malaria-vector mosquitoes bite in the region they are traveling to. Bed nets may be ideal for travelers to Africa where A. gambiae is present, which prefers to feed indoors late at night. In the Amazon, repellents may work best against A. darlingi, which bites mostly in the early evening, she said.

But most long-term travelers have poor compliance with personal protection measures, Dr. Schlagenhauf-Lawlor noted. Experts consider a combination of at least four such measures to be adequate to protect against mosquito bites in high-risk areas for malaria. In a study of business travelers to high-risk areas in Africa, only 4% used four recognized methods of prevention, which include long clothes, air conditioning, repellents, insecticides, mosquito nets, and burn coils (J. Travel Med. 2003;10:219–24). Nearly all other travelers used some personal protection measures: 43% of the travelers used three measures, 25% used two, and 21% used one. Only 2% of tourists to high-risk areas in Africa used four personal protection measures (J. Travel Med. 1998;5:188–92).

Standby Emergency Treatment

The WHO defines standby emergency treatment (SBET) of malaria as the use of antimalarial drugs when malaria is suspected and prompt medical attention is unavailable within 24 hours.

For travelers in some areas, German and Swiss guidelines now recommend wider use of SBET instead of continuous prophylaxis.

“We recommend chemosuppression only when the benefit is 10 times greater than the risk of adverse effects,” Dr. Schlagenhauf-Lawlor said. “That means for most of our travelers, except for those in sub-Saharan Africa, we're recommending standby treatment and antimosquito measures.” This may be at odds with what American physicians would recommend.

Chloroquine and quinine have “very limited use” for SBET, while other drugs such as mefloquine, atovaquone and proguanil (Malarone), and sulfadoxine plus pyrimethamine (Fansidar) are acceptable for SBET. Halofantrine (Halfan) is now contraindicated for SBET because of potential cardiac complications, Dr. Schlagenhauf-Lawlor said.

The German and Swiss guidelines recommend that chloroquine be used for SBET in parts of Central America and the Middle East. The guidelines recommend that travelers to India use mefloquine. Travelers to the Southeast Asian countries of Myanmar, Thailand, Laos, Cambodia, and Vietnam should use Malarone for SBET because of multidrug resistant malarial strains, according to the guidelines.

The guidelines recommend continuous prophylaxis in Papua New Guinea, nearly all of sub-Saharan Africa, and in several provinces of Brazil. Continuous prophylaxis with mefloquine, doxycycline, or Malarone can be more than 90% effective if they are chosen correctly, but they cause “perceived or real” adverse events in more than 80% of patients.

Many patients also fail to adhere to the dosing regimen for continuous prophylaxis and find it difficult to get the drug they need if they are traveling for more than a year, Dr. Schlagenhauf-Lawlor said.

The nonspecific symptoms of malaria make it difficult for patients to self-diagnose the disease, Dr. Schlagenhauf-Lawlor said. In a study of 1,187 Swiss travelers who carried medication for SBET, about 10% became ill with fever while traveling. Even though only nine of the travelers were out of the reach of medical attention, most of those who were ill reacted to their illness contrary to SBET instructions and delayed in seeking medical attention (Bull. World Health Organ. 1995;73:215–21).

A combination of SBET and rapid malaria tests “could be useful for certain selected long-term travelers,” she said. Studies have reported that 68%–91% of travelers were able to use the tests successfully. However, the tests can generate false-positive results and have been difficult for travelers to read at low levels of parasitemia.

Seasonal Prophylaxis

In all but a few countries “it's almost impossible for an adviser to say in advance how the season will be at the destination,” Dr. Schlagenhauf-Lawlor said.

In the sub-Saharan countries of South Africa, Namibia, and Botswana, the transmission seasons are fairly stable, but can shift, she noted.

In South Africa, travelers may want to use continuous prophylaxis during the high-risk season of October through May and revert to SBET during the low-risk season of June through September. But travelers should always use personal protective measures.

Blood-feeding Anopheles gambiae mosquito, a leading malaria vector. CDC

WASHINGTON — Long-term travelers to countries with high risk for malaria should use personal protective measures and chemoprophylactic regimens based on the risk factors they are likely to encounter, Patricia Schlagenhauf-Lawlor, Ph.D., said at the annual meeting of the American Society of Tropical Medicine and Hygiene.

Long-term travelers—defined by some guidelines as those who travel for more than 6 months—include people visiting friends and relatives, expatriates, occupational travelers such as military personnel, backpackers, and missionaries. These people can use precautions that range widely in their ability to prevent infection, including personal protection measures, standby emergency treatment, rapid tests for malaria, seasonal chemoprophylaxis, and continuous chemoprophylaxis, said Dr. Schlagenhauf-Lawlor of the World Health Organization Collaborating Centre for Travellers' Health at the University of Zürich (Switzerland).

Personal Protection Measures

A review of randomized trials showed that insecticide-treated nets are effective in reducing childhood mortality and morbidity due to malaria (Cochrane Database Syst. Rev. 2005; www.thecochranelibrary.com

Bed nets are “something we should really recommend to our long-term travelers,” Dr. Schlagenhauf-Lawlor said.

Clothing that has been impregnated with insecticides such as permethrin remain effective for several months. Shoes and protective (white or brightly colored) clothing also help to fend off mosquitoes, she added.

Among the mosquito repellents that are available in the United States, DEET (N,N-diethyl-m-toluamide) is still considered the best because it has been widely used and tested and is effective for more than 5 hours at concentrations of 20%. Children older than 2 months of age can use DEET, but it should be at concentrations of 10% or less.

The repellent picaridin (Bayrepel) at 19.2% concentration has been shown to cause less skin irritation while providing a level of protection similar to DEET, especially against the mosquito Anopheles gambiae. Picaridin has been approved by the Environmental Protection Agency and is safe for children older than 2 years, but studies have shown that the level and duration of protection varies between individuals, Dr. Schlagenhauf-Lawlor said.

Clinicians should avoid recommending natural oils such as citronella and eucalyptus because these oils provide only short-term protection, she said.

Mosquitoes generally prefer to bite adults rather than children, men rather than women, and large rather than small people. Some mosquitoes bite more often on the feet and ankles (A. gambiae) or face (A. atroparvus).

Travelers should learn what time of day the malaria-vector mosquitoes bite in the region they are traveling to. Bed nets may be ideal for travelers to Africa where A. gambiae is present, which prefers to feed indoors late at night. In the Amazon, repellents may work best against A. darlingi, which bites mostly in the early evening, she said.

But most long-term travelers have poor compliance with personal protection measures, Dr. Schlagenhauf-Lawlor noted. Experts consider a combination of at least four such measures to be adequate to protect against mosquito bites in high-risk areas for malaria. In a study of business travelers to high-risk areas in Africa, only 4% used four recognized methods of prevention, which include long clothes, air conditioning, repellents, insecticides, mosquito nets, and burn coils (J. Travel Med. 2003;10:219–24). Nearly all other travelers used some personal protection measures: 43% of the travelers used three measures, 25% used two, and 21% used one. Only 2% of tourists to high-risk areas in Africa used four personal protection measures (J. Travel Med. 1998;5:188–92).

Standby Emergency Treatment

The WHO defines standby emergency treatment (SBET) of malaria as the use of antimalarial drugs when malaria is suspected and prompt medical attention is unavailable within 24 hours.

For travelers in some areas, German and Swiss guidelines now recommend wider use of SBET instead of continuous prophylaxis.

“We recommend chemosuppression only when the benefit is 10 times greater than the risk of adverse effects,” Dr. Schlagenhauf-Lawlor said. “That means for most of our travelers, except for those in sub-Saharan Africa, we're recommending standby treatment and antimosquito measures.” This may be at odds with what American physicians would recommend.

Chloroquine and quinine have “very limited use” for SBET, while other drugs such as mefloquine, atovaquone and proguanil (Malarone), and sulfadoxine plus pyrimethamine (Fansidar) are acceptable for SBET. Halofantrine (Halfan) is now contraindicated for SBET because of potential cardiac complications, Dr. Schlagenhauf-Lawlor said.

The German and Swiss guidelines recommend that chloroquine be used for SBET in parts of Central America and the Middle East. The guidelines recommend that travelers to India use mefloquine. Travelers to the Southeast Asian countries of Myanmar, Thailand, Laos, Cambodia, and Vietnam should use Malarone for SBET because of multidrug resistant malarial strains, according to the guidelines.

The guidelines recommend continuous prophylaxis in Papua New Guinea, nearly all of sub-Saharan Africa, and in several provinces of Brazil. Continuous prophylaxis with mefloquine, doxycycline, or Malarone can be more than 90% effective if they are chosen correctly, but they cause “perceived or real” adverse events in more than 80% of patients.

Many patients also fail to adhere to the dosing regimen for continuous prophylaxis and find it difficult to get the drug they need if they are traveling for more than a year, Dr. Schlagenhauf-Lawlor said.

The nonspecific symptoms of malaria make it difficult for patients to self-diagnose the disease, Dr. Schlagenhauf-Lawlor said. In a study of 1,187 Swiss travelers who carried medication for SBET, about 10% became ill with fever while traveling. Even though only nine of the travelers were out of the reach of medical attention, most of those who were ill reacted to their illness contrary to SBET instructions and delayed in seeking medical attention (Bull. World Health Organ. 1995;73:215–21).

A combination of SBET and rapid malaria tests “could be useful for certain selected long-term travelers,” she said. Studies have reported that 68%–91% of travelers were able to use the tests successfully. However, the tests can generate false-positive results and have been difficult for travelers to read at low levels of parasitemia.

Seasonal Prophylaxis

In all but a few countries “it's almost impossible for an adviser to say in advance how the season will be at the destination,” Dr. Schlagenhauf-Lawlor said.

In the sub-Saharan countries of South Africa, Namibia, and Botswana, the transmission seasons are fairly stable, but can shift, she noted.

In South Africa, travelers may want to use continuous prophylaxis during the high-risk season of October through May and revert to SBET during the low-risk season of June through September. But travelers should always use personal protective measures.

Blood-feeding Anopheles gambiae mosquito, a leading malaria vector. CDC

CHANTILLY, VA. — Thyroid cancer patients who have received radioactive iodine ablation after thyroidectomy and who later have a negative whole body scan for thyroid cancer probably do not need to receive radioactive iodine therapy if their stimulated thyroglobulin levels stay below 10 ng/mL, Dr. R. Michael Tuttle said at the annual meeting of the Mid-Atlantic Chapter of the American Association of Clinical Endocrinologists.

Whether a patient with a very low stimulated thyroglobulin level should be treated again with radioactive iodine (RAI) “is probably one of the most common phone calls I get from around the country,” said Dr. Tuttle of Memorial Sloan-Kettering Cancer Center, New York.

The way thyroid cancer is treated today is “so remarkably different now than it was 10 or 15 years ago,” he said, adding that the detection of persistent thyroid cancer has improved to the point where thyroglobulin (Tg) levels of 1, 0.5, or 0.2 ng/mL can be detected and 3-mm lymph nodes in the tracheal-esophageal groove can be seen with ultrasound in patients who were thought to be cured 20 years ago.

“I can't tell you the number of patients who leave my office mad at me because I've explained to them that I cannot cure their thyroid cancer. Their thyroglobulin level of 0.3 ng/mL is probably going to be there for awhile and taking out that 2-mm lymph node beside their recurrent laryngeal nerve is probably only going to help the surgeon and pathologist because they can bill and code for it, and it is unlikely to help our patient.”

About 80% of full body scans after repeat administration of therapeutic RAI appear to show some uptake by thyroid cells in the neck, but about 40% of these may be lung metastases, based on experience with all forms of thyroid cancer. If physicians give 100–150 mCi of RAI to patients with a high Tg level but a negative body scan, “you're very likely to find real disease,” Dr. Tuttle said, “and I think it's that finding of the lung metastasis that made us all do this.”

Rationale for RAI Changes Over Time

One rationale for using a therapeutic level of RAI when stimulated Tg levels remain high despite a negative diagnostic whole body scan was to localize the disease, not necessarily to treat it, Dr. Tuttle pointed out. Today's imaging modalities of helical CT and PET scans and neck ultrasounds can give the same information that RAI scanning would, without the possibility of side effects.

There is no evidence that repeat RAI treatment for patients who have a high stimulated Tg level after an initially negative whole body scan increases disease-specific or overall survival, Dr. Tuttle said.

Most clinicians would give another course of therapeutic RAI if the stimulated Tg level rose above 10 ng/mL, and most would not use repeat RAI if the stimulated level was below 2 ng/mL. RAI treatment for Tg levels of less than 2 ng/mL offers little potential benefit, while potentially causing complications, including damage to salivary glands, taste buds, and tear ducts. “We don't know what to do between 2 and 10,” Dr. Tuttle said.

Multiple RAI treatments appear to clear small-volume papillary thyroid cancer from pediatric to 30-year-old patients with positive lymph nodes by consistently decreasing stimulated Tg levels and clearing evidence of the tumor on CT scans and x-rays. These patients, who do not have distant metastases, are either cured or go into long-term remissions.

But older patients with thyroid cancer extending beyond the thyroid are more commonly seen than are younger patients with less aggressive, localized disease. Older patients may have a negative whole body scan and the same level of Tg as a younger patient, but the tumor is likely to be visible in the lungs on x-ray, CT, and PET scans. RAI will not help these patients if the lung lesions are poorly differentiated.

In a soon-to-be published study, Dr. Tuttle found that of about 400 thyroid cancer patients who received

Observe or Treat?

Another study involved 70 patients with thyroid cancer who had detectable Tg levels despite having a total thyroidectomy, RAI ablation, a negative whole body scan, and no structural evidence of disease. Of the 28 patients with a median stimulated Tg level of 9.5 ng/mL who were observed instead of being treated with RAI, 19 (68%) had an undetectable stimulated Tg level after 12 years of follow-up. Among the 42 patients with a median Tg level of 55 ng/mL who received RAI, only 12 (29%) had an undetectable stimulated Tg level after 7 years of follow-up (J. Clin. Endocrinol. Metab. 2001;86:4092–7).

Most patients who have undergone thyroidectomy and RAI ablation and have a negative whole body scan and a stimulated Tg level in the range of 2–10 ng/mL will see their Tg level decline to an undetectable level, so they probably should not be treated subsequently with RAI, Dr. Tuttle advised. It is likely that “if you do nothing, you are going to take credit for this thyroglobulin number going down over time all by itself.”

It is not necessary to treat patients with high Tg levels with two to three doses of RAI, he added. In a study of 17 patients with a negative initial whole body scan and an elevated Tg level, 16 patients had a positive scan after RAI therapy. During the course of three subsequent RAI doses, the percentage of patients with a decreasing Tg level increased from 81% to 90% to 100%, but the mean stimulated Tg level only decreased from 74 to 62 to 32 ng/mL, respectively (J. Clin. Endocrinol. Metab. 1995;80:1488–92).

Low Tg: RAI Probably Not Helpful

To determine if follow-up RAI therapy contributes to any changes in the stimulated Tg level of patients with an initial stimulated Tg level below 10 ng/mL, Dr. Tuttle conducted a study of 110 thyroid cancer patients who had Tg levels between 0.6 and 10 ng/mL and a negative whole body scan 1 year after receiving a total thyroidectomy and RAI ablation. At that point, 18 patients received repeat RAI therapy and 92 were observed.

After 1–2 years, stimulated Tg levels subsequently decreased in 71% and became undetectable in 29% of patients who had an initial stimulated Tg level between 0.6 and 2 ng/mL. In patients with an initial stimulated Tg level between 2 and 10 ng/mL, a significantly lower percentage of patients (3%) had an undetectable stimulated Tg level than those who had a decreased level (42%).

But among observed and RAI-treated patients with an initial stimulated Tg level between 2 and 10 ng/mL, there was no significant difference in the percentage of patients who had a reduction (40% vs. 45%, respectively), no change (12% vs. 18%), or an increase (48% vs. 37%) in their stimulated Tg level at follow-up.

There is no evidence that repeat RAI after negative whole body scan increases survival. DR. TUTTLE

CHANTILLY, VA. — Thyroid cancer patients who have received radioactive iodine ablation after thyroidectomy and who later have a negative whole body scan for thyroid cancer probably do not need to receive radioactive iodine therapy if their stimulated thyroglobulin levels stay below 10 ng/mL, Dr. R. Michael Tuttle said at the annual meeting of the Mid-Atlantic Chapter of the American Association of Clinical Endocrinologists.

Whether a patient with a very low stimulated thyroglobulin level should be treated again with radioactive iodine (RAI) “is probably one of the most common phone calls I get from around the country,” said Dr. Tuttle of Memorial Sloan-Kettering Cancer Center, New York.

The way thyroid cancer is treated today is “so remarkably different now than it was 10 or 15 years ago,” he said, adding that the detection of persistent thyroid cancer has improved to the point where thyroglobulin (Tg) levels of 1, 0.5, or 0.2 ng/mL can be detected and 3-mm lymph nodes in the tracheal-esophageal groove can be seen with ultrasound in patients who were thought to be cured 20 years ago.

“I can't tell you the number of patients who leave my office mad at me because I've explained to them that I cannot cure their thyroid cancer. Their thyroglobulin level of 0.3 ng/mL is probably going to be there for awhile and taking out that 2-mm lymph node beside their recurrent laryngeal nerve is probably only going to help the surgeon and pathologist because they can bill and code for it, and it is unlikely to help our patient.”

About 80% of full body scans after repeat administration of therapeutic RAI appear to show some uptake by thyroid cells in the neck, but about 40% of these may be lung metastases, based on experience with all forms of thyroid cancer. If physicians give 100–150 mCi of RAI to patients with a high Tg level but a negative body scan, “you're very likely to find real disease,” Dr. Tuttle said, “and I think it's that finding of the lung metastasis that made us all do this.”

Rationale for RAI Changes Over Time

One rationale for using a therapeutic level of RAI when stimulated Tg levels remain high despite a negative diagnostic whole body scan was to localize the disease, not necessarily to treat it, Dr. Tuttle pointed out. Today's imaging modalities of helical CT and PET scans and neck ultrasounds can give the same information that RAI scanning would, without the possibility of side effects.

There is no evidence that repeat RAI treatment for patients who have a high stimulated Tg level after an initially negative whole body scan increases disease-specific or overall survival, Dr. Tuttle said.

Most clinicians would give another course of therapeutic RAI if the stimulated Tg level rose above 10 ng/mL, and most would not use repeat RAI if the stimulated level was below 2 ng/mL. RAI treatment for Tg levels of less than 2 ng/mL offers little potential benefit, while potentially causing complications, including damage to salivary glands, taste buds, and tear ducts. “We don't know what to do between 2 and 10,” Dr. Tuttle said.

Multiple RAI treatments appear to clear small-volume papillary thyroid cancer from pediatric to 30-year-old patients with positive lymph nodes by consistently decreasing stimulated Tg levels and clearing evidence of the tumor on CT scans and x-rays. These patients, who do not have distant metastases, are either cured or go into long-term remissions.

But older patients with thyroid cancer extending beyond the thyroid are more commonly seen than are younger patients with less aggressive, localized disease. Older patients may have a negative whole body scan and the same level of Tg as a younger patient, but the tumor is likely to be visible in the lungs on x-ray, CT, and PET scans. RAI will not help these patients if the lung lesions are poorly differentiated.

In a soon-to-be published study, Dr. Tuttle found that of about 400 thyroid cancer patients who received

Observe or Treat?

Another study involved 70 patients with thyroid cancer who had detectable Tg levels despite having a total thyroidectomy, RAI ablation, a negative whole body scan, and no structural evidence of disease. Of the 28 patients with a median stimulated Tg level of 9.5 ng/mL who were observed instead of being treated with RAI, 19 (68%) had an undetectable stimulated Tg level after 12 years of follow-up. Among the 42 patients with a median Tg level of 55 ng/mL who received RAI, only 12 (29%) had an undetectable stimulated Tg level after 7 years of follow-up (J. Clin. Endocrinol. Metab. 2001;86:4092–7).

Most patients who have undergone thyroidectomy and RAI ablation and have a negative whole body scan and a stimulated Tg level in the range of 2–10 ng/mL will see their Tg level decline to an undetectable level, so they probably should not be treated subsequently with RAI, Dr. Tuttle advised. It is likely that “if you do nothing, you are going to take credit for this thyroglobulin number going down over time all by itself.”

It is not necessary to treat patients with high Tg levels with two to three doses of RAI, he added. In a study of 17 patients with a negative initial whole body scan and an elevated Tg level, 16 patients had a positive scan after RAI therapy. During the course of three subsequent RAI doses, the percentage of patients with a decreasing Tg level increased from 81% to 90% to 100%, but the mean stimulated Tg level only decreased from 74 to 62 to 32 ng/mL, respectively (J. Clin. Endocrinol. Metab. 1995;80:1488–92).

Low Tg: RAI Probably Not Helpful

To determine if follow-up RAI therapy contributes to any changes in the stimulated Tg level of patients with an initial stimulated Tg level below 10 ng/mL, Dr. Tuttle conducted a study of 110 thyroid cancer patients who had Tg levels between 0.6 and 10 ng/mL and a negative whole body scan 1 year after receiving a total thyroidectomy and RAI ablation. At that point, 18 patients received repeat RAI therapy and 92 were observed.

After 1–2 years, stimulated Tg levels subsequently decreased in 71% and became undetectable in 29% of patients who had an initial stimulated Tg level between 0.6 and 2 ng/mL. In patients with an initial stimulated Tg level between 2 and 10 ng/mL, a significantly lower percentage of patients (3%) had an undetectable stimulated Tg level than those who had a decreased level (42%).

But among observed and RAI-treated patients with an initial stimulated Tg level between 2 and 10 ng/mL, there was no significant difference in the percentage of patients who had a reduction (40% vs. 45%, respectively), no change (12% vs. 18%), or an increase (48% vs. 37%) in their stimulated Tg level at follow-up.

There is no evidence that repeat RAI after negative whole body scan increases survival. DR. TUTTLE

CHANTILLY, VA. — Thyroid cancer patients who have received radioactive iodine ablation after thyroidectomy and who later have a negative whole body scan for thyroid cancer probably do not need to receive radioactive iodine therapy if their stimulated thyroglobulin levels stay below 10 ng/mL, Dr. R. Michael Tuttle said at the annual meeting of the Mid-Atlantic Chapter of the American Association of Clinical Endocrinologists.

Whether a patient with a very low stimulated thyroglobulin level should be treated again with radioactive iodine (RAI) “is probably one of the most common phone calls I get from around the country,” said Dr. Tuttle of Memorial Sloan-Kettering Cancer Center, New York.

The way thyroid cancer is treated today is “so remarkably different now than it was 10 or 15 years ago,” he said, adding that the detection of persistent thyroid cancer has improved to the point where thyroglobulin (Tg) levels of 1, 0.5, or 0.2 ng/mL can be detected and 3-mm lymph nodes in the tracheal-esophageal groove can be seen with ultrasound in patients who were thought to be cured 20 years ago.

“I can't tell you the number of patients who leave my office mad at me because I've explained to them that I cannot cure their thyroid cancer. Their thyroglobulin level of 0.3 ng/mL is probably going to be there for awhile and taking out that 2-mm lymph node beside their recurrent laryngeal nerve is probably only going to help the surgeon and pathologist because they can bill and code for it, and it is unlikely to help our patient.”

About 80% of full body scans after repeat administration of therapeutic RAI appear to show some uptake by thyroid cells in the neck, but about 40% of these may be lung metastases, based on experience with all forms of thyroid cancer. If physicians give 100–150 mCi of RAI to patients with a high Tg level but a negative body scan, “you're very likely to find real disease,” Dr. Tuttle said, “and I think it's that finding of the lung metastasis that made us all do this.”

Rationale for RAI Changes Over Time

One rationale for using a therapeutic level of RAI when stimulated Tg levels remain high despite a negative diagnostic whole body scan was to localize the disease, not necessarily to treat it, Dr. Tuttle pointed out. Today's imaging modalities of helical CT and PET scans and neck ultrasounds can give the same information that RAI scanning would, without the possibility of side effects.

There is no evidence that repeat RAI treatment for patients who have a high stimulated Tg level after an initially negative whole body scan increases disease-specific or overall survival, Dr. Tuttle said.

Most clinicians would give another course of therapeutic RAI if the stimulated Tg level rose above 10 ng/mL, and most would not use repeat RAI if the stimulated level was below 2 ng/mL. RAI treatment for Tg levels of less than 2 ng/mL offers little potential benefit, while potentially causing complications, including damage to salivary glands, taste buds, and tear ducts. “We don't know what to do between 2 and 10,” Dr. Tuttle said.

Multiple RAI treatments appear to clear small-volume papillary thyroid cancer from pediatric to 30-year-old patients with positive lymph nodes by consistently decreasing stimulated Tg levels and clearing evidence of the tumor on CT scans and x-rays. These patients, who do not have distant metastases, are either cured or go into long-term remissions.

But older patients with thyroid cancer extending beyond the thyroid are more commonly seen than are younger patients with less aggressive, localized disease. Older patients may have a negative whole body scan and the same level of Tg as a younger patient, but the tumor is likely to be visible in the lungs on x-ray, CT, and PET scans. RAI will not help these patients if the lung lesions are poorly differentiated.

In a soon-to-be published study, Dr. Tuttle found that of about 400 thyroid cancer patients who received

Observe or Treat?

Another study involved 70 patients with thyroid cancer who had detectable Tg levels despite having a total thyroidectomy, RAI ablation, a negative whole body scan, and no structural evidence of disease. Of the 28 patients with a median stimulated Tg level of 9.5 ng/mL who were observed instead of being treated with RAI, 19 (68%) had an undetectable stimulated Tg level after 12 years of follow-up. Among the 42 patients with a median Tg level of 55 ng/mL who received RAI, only 12 (29%) had an undetectable stimulated Tg level after 7 years of follow-up (J. Clin. Endocrinol. Metab. 2001;86:4092–7).

Most patients who have undergone thyroidectomy and RAI ablation and have a negative whole body scan and a stimulated Tg level in the range of 2–10 ng/mL will see their Tg level decline to an undetectable level, so they probably should not be treated subsequently with RAI, Dr. Tuttle advised. It is likely that “if you do nothing, you are going to take credit for this thyroglobulin number going down over time all by itself.”

It is not necessary to treat patients with high Tg levels with two to three doses of RAI, he added. In a study of 17 patients with a negative initial whole body scan and an elevated Tg level, 16 patients had a positive scan after RAI therapy. During the course of three subsequent RAI doses, the percentage of patients with a decreasing Tg level increased from 81% to 90% to 100%, but the mean stimulated Tg level only decreased from 74 to 62 to 32 ng/mL, respectively (J. Clin. Endocrinol. Metab. 1995;80:1488–92).

Low Tg: RAI Probably Not Helpful

To determine if follow-up RAI therapy contributes to any changes in the stimulated Tg level of patients with an initial stimulated Tg level below 10 ng/mL, Dr. Tuttle conducted a study of 110 thyroid cancer patients who had Tg levels between 0.6 and 10 ng/mL and a negative whole body scan 1 year after receiving a total thyroidectomy and RAI ablation. At that point, 18 patients received repeat RAI therapy and 92 were observed.

After 1–2 years, stimulated Tg levels subsequently decreased in 71% and became undetectable in 29% of patients who had an initial stimulated Tg level between 0.6 and 2 ng/mL. In patients with an initial stimulated Tg level between 2 and 10 ng/mL, a significantly lower percentage of patients (3%) had an undetectable stimulated Tg level than those who had a decreased level (42%).

But among observed and RAI-treated patients with an initial stimulated Tg level between 2 and 10 ng/mL, there was no significant difference in the percentage of patients who had a reduction (40% vs. 45%, respectively), no change (12% vs. 18%), or an increase (48% vs. 37%) in their stimulated Tg level at follow-up.

There is no evidence that repeat RAI after negative whole body scan increases survival. DR. TUTTLE

New pediatric circulatory support devices may be ready for clinical trials beginning in 2009, facilitated by grants issued in 2004 by the National Heart, Lung, and Blood Institute. The majority of these devices are based on modifications of currently available heart support systems used in adults.

NHLBI committed $22.4 million during 2004–2009 to the teams to produce devices intended to be ready for clinical trials at the end of the 5-year period.

Each of the five teams that received a contract in the NHLBI's pediatric circulatory support program has reported steady progress in the development of devices, with most already conducting animal studies only 1.5 years into the funding period. The contracts stipulated that pediatric circulatory support devices should be able to support infants and children weighing 2–25 kg for at least 6 months.

Very few options exist for pediatric patients in need of circulatory support, unlike the situation for adults in which ventricular assist devices (VADs) have revolutionized the care of patients with heart failure, said Dr. Brian Duncan, a pediatric heart surgeon who is primary investigator for the Cleveland Clinic's pediatric circulatory device contract.

About 1,800 infants in the United States die from congenital heart defects each year. Another 350 children under 1 year of age develop cardiomyopathy, many of whom require transplantation or die. A total of 1,600 infants have been added to the heart or heart/lung transplant list during the last decade, but fewer than half received a donor organ, which means that fewer than 80 infants on average received a transplant each year, said J. Timothy Baldwin, Ph.D., a biomedical engineer at NHLBI and project officer for the pediatric circulatory support program.

Researchers from the University of Pittsburgh, Carnegie Mellon University, Launchpoint Technologies, and a corporate partner, WorldHeart Corp., are collaborating to develop the PediaFlow, a pediatric VAD for infants.

The device is a miniaturized, fully implantable, turbo-rotary pump that uses suspended magnetic levitation technology. A single wire would penetrate the skin to provide electrical power to the pump, said the principal investigator for the contract, Harvey S. Borovetz, Ph.D., chairman of the department of bioengineering at the University of Pittsburgh.

At the Cleveland Clinic, the “PediPump” team headed by Dr. Duncan is developing several fully implantable VADs for pediatric patients. One pump is about 7 mm in diameter and 70 mm in length, and an even smaller pump is in an earlier stage of design. To test the fit and configuration of designs, the team has been constructing three-dimensional models of the chest cavity based on CT and MRI scans obtained from children who have undergone imaging for clinical purposes. A 3D printer also allows them to create a “biomodel” of the heart that can be held.

Jarvik Heart Inc. is designing the child- and infant-sized Jarvik 2000 booster VADs in which the blood pump is the only implanted part, and the electronics are outside the body, said Dr. Robert Jarvik, president and chief executive officer of Jarvik Heart Inc., in New York.

Both of the new VADs are being designed as permanent implant pumps, with the expectation that they will be durable for at least 5 years. The pump has an output capacity of nearly 5 L/min.

A team at the Pennsylvania State University Medical Center in Hershey has redesigned the mechanical heart valves and flow patterns in a pediatric pulsatile pump it had started developing about 20 years ago based on the Thoratec VAD. The team ran into problems with the earlier pump's valve design and abandoned the project. The researchers are investigating two VADs: a small, extracorporeal device for children under age 1 year that is designed to have a 12-mL stroke volume and a larger device with a 25-mL stroke volume for implantation in older children.

Researchers at Ension Inc. are making a compact extracorporeal membrane oxygenation (ECMO) system that is smaller than available systems so parents can hold their infant. The scaled-down pediatric cardiopulmonary assist system (pCAS) will also be more portable for children who can move around, said Mark J. Gartner, president of Ension and primary investigator for the contract. The team is creating two sizes of the pCAS that can be adjusted as the child grows. It is also is working on a biocompatible coating for the pCAS to help reduce blood clotting.

Pumps for the Jarvik 2000 booster VAD for adults (left) are being developed for children (center) and infants (right). Courtesy Dr. Robert Jarvik

The intravascular PediPump (A) is used as a bi-VAD in patients over 15 kg; the extravascular pump (B) is for patients under 15 kg. Reprinted with permission/The Cleveland Clinic Foundation

New pediatric circulatory support devices may be ready for clinical trials beginning in 2009, facilitated by grants issued in 2004 by the National Heart, Lung, and Blood Institute. The majority of these devices are based on modifications of currently available heart support systems used in adults.

NHLBI committed $22.4 million during 2004–2009 to the teams to produce devices intended to be ready for clinical trials at the end of the 5-year period.

Each of the five teams that received a contract in the NHLBI's pediatric circulatory support program has reported steady progress in the development of devices, with most already conducting animal studies only 1.5 years into the funding period. The contracts stipulated that pediatric circulatory support devices should be able to support infants and children weighing 2–25 kg for at least 6 months.

Very few options exist for pediatric patients in need of circulatory support, unlike the situation for adults in which ventricular assist devices (VADs) have revolutionized the care of patients with heart failure, said Dr. Brian Duncan, a pediatric heart surgeon who is primary investigator for the Cleveland Clinic's pediatric circulatory device contract.

About 1,800 infants in the United States die from congenital heart defects each year. Another 350 children under 1 year of age develop cardiomyopathy, many of whom require transplantation or die. A total of 1,600 infants have been added to the heart or heart/lung transplant list during the last decade, but fewer than half received a donor organ, which means that fewer than 80 infants on average received a transplant each year, said J. Timothy Baldwin, Ph.D., a biomedical engineer at NHLBI and project officer for the pediatric circulatory support program.

Researchers from the University of Pittsburgh, Carnegie Mellon University, Launchpoint Technologies, and a corporate partner, WorldHeart Corp., are collaborating to develop the PediaFlow, a pediatric VAD for infants.

The device is a miniaturized, fully implantable, turbo-rotary pump that uses suspended magnetic levitation technology. A single wire would penetrate the skin to provide electrical power to the pump, said the principal investigator for the contract, Harvey S. Borovetz, Ph.D., chairman of the department of bioengineering at the University of Pittsburgh.

At the Cleveland Clinic, the “PediPump” team headed by Dr. Duncan is developing several fully implantable VADs for pediatric patients. One pump is about 7 mm in diameter and 70 mm in length, and an even smaller pump is in an earlier stage of design. To test the fit and configuration of designs, the team has been constructing three-dimensional models of the chest cavity based on CT and MRI scans obtained from children who have undergone imaging for clinical purposes. A 3D printer also allows them to create a “biomodel” of the heart that can be held.

Jarvik Heart Inc. is designing the child- and infant-sized Jarvik 2000 booster VADs in which the blood pump is the only implanted part, and the electronics are outside the body, said Dr. Robert Jarvik, president and chief executive officer of Jarvik Heart Inc., in New York.

Both of the new VADs are being designed as permanent implant pumps, with the expectation that they will be durable for at least 5 years. The pump has an output capacity of nearly 5 L/min.

A team at the Pennsylvania State University Medical Center in Hershey has redesigned the mechanical heart valves and flow patterns in a pediatric pulsatile pump it had started developing about 20 years ago based on the Thoratec VAD. The team ran into problems with the earlier pump's valve design and abandoned the project. The researchers are investigating two VADs: a small, extracorporeal device for children under age 1 year that is designed to have a 12-mL stroke volume and a larger device with a 25-mL stroke volume for implantation in older children.

Researchers at Ension Inc. are making a compact extracorporeal membrane oxygenation (ECMO) system that is smaller than available systems so parents can hold their infant. The scaled-down pediatric cardiopulmonary assist system (pCAS) will also be more portable for children who can move around, said Mark J. Gartner, president of Ension and primary investigator for the contract. The team is creating two sizes of the pCAS that can be adjusted as the child grows. It is also is working on a biocompatible coating for the pCAS to help reduce blood clotting.

Pumps for the Jarvik 2000 booster VAD for adults (left) are being developed for children (center) and infants (right). Courtesy Dr. Robert Jarvik

The intravascular PediPump (A) is used as a bi-VAD in patients over 15 kg; the extravascular pump (B) is for patients under 15 kg. Reprinted with permission/The Cleveland Clinic Foundation

New pediatric circulatory support devices may be ready for clinical trials beginning in 2009, facilitated by grants issued in 2004 by the National Heart, Lung, and Blood Institute. The majority of these devices are based on modifications of currently available heart support systems used in adults.

NHLBI committed $22.4 million during 2004–2009 to the teams to produce devices intended to be ready for clinical trials at the end of the 5-year period.

Each of the five teams that received a contract in the NHLBI's pediatric circulatory support program has reported steady progress in the development of devices, with most already conducting animal studies only 1.5 years into the funding period. The contracts stipulated that pediatric circulatory support devices should be able to support infants and children weighing 2–25 kg for at least 6 months.

Very few options exist for pediatric patients in need of circulatory support, unlike the situation for adults in which ventricular assist devices (VADs) have revolutionized the care of patients with heart failure, said Dr. Brian Duncan, a pediatric heart surgeon who is primary investigator for the Cleveland Clinic's pediatric circulatory device contract.

About 1,800 infants in the United States die from congenital heart defects each year. Another 350 children under 1 year of age develop cardiomyopathy, many of whom require transplantation or die. A total of 1,600 infants have been added to the heart or heart/lung transplant list during the last decade, but fewer than half received a donor organ, which means that fewer than 80 infants on average received a transplant each year, said J. Timothy Baldwin, Ph.D., a biomedical engineer at NHLBI and project officer for the pediatric circulatory support program.

Researchers from the University of Pittsburgh, Carnegie Mellon University, Launchpoint Technologies, and a corporate partner, WorldHeart Corp., are collaborating to develop the PediaFlow, a pediatric VAD for infants.

The device is a miniaturized, fully implantable, turbo-rotary pump that uses suspended magnetic levitation technology. A single wire would penetrate the skin to provide electrical power to the pump, said the principal investigator for the contract, Harvey S. Borovetz, Ph.D., chairman of the department of bioengineering at the University of Pittsburgh.

At the Cleveland Clinic, the “PediPump” team headed by Dr. Duncan is developing several fully implantable VADs for pediatric patients. One pump is about 7 mm in diameter and 70 mm in length, and an even smaller pump is in an earlier stage of design. To test the fit and configuration of designs, the team has been constructing three-dimensional models of the chest cavity based on CT and MRI scans obtained from children who have undergone imaging for clinical purposes. A 3D printer also allows them to create a “biomodel” of the heart that can be held.

Jarvik Heart Inc. is designing the child- and infant-sized Jarvik 2000 booster VADs in which the blood pump is the only implanted part, and the electronics are outside the body, said Dr. Robert Jarvik, president and chief executive officer of Jarvik Heart Inc., in New York.

Both of the new VADs are being designed as permanent implant pumps, with the expectation that they will be durable for at least 5 years. The pump has an output capacity of nearly 5 L/min.

A team at the Pennsylvania State University Medical Center in Hershey has redesigned the mechanical heart valves and flow patterns in a pediatric pulsatile pump it had started developing about 20 years ago based on the Thoratec VAD. The team ran into problems with the earlier pump's valve design and abandoned the project. The researchers are investigating two VADs: a small, extracorporeal device for children under age 1 year that is designed to have a 12-mL stroke volume and a larger device with a 25-mL stroke volume for implantation in older children.

Researchers at Ension Inc. are making a compact extracorporeal membrane oxygenation (ECMO) system that is smaller than available systems so parents can hold their infant. The scaled-down pediatric cardiopulmonary assist system (pCAS) will also be more portable for children who can move around, said Mark J. Gartner, president of Ension and primary investigator for the contract. The team is creating two sizes of the pCAS that can be adjusted as the child grows. It is also is working on a biocompatible coating for the pCAS to help reduce blood clotting.

Pumps for the Jarvik 2000 booster VAD for adults (left) are being developed for children (center) and infants (right). Courtesy Dr. Robert Jarvik

The intravascular PediPump (A) is used as a bi-VAD in patients over 15 kg; the extravascular pump (B) is for patients under 15 kg. Reprinted with permission/The Cleveland Clinic Foundation

BALTIMORE — Lasers and light therapies have a limited role in the treatment of skin cancers and pigmented lesions, but their judicious use may be appropriate when standard treatments would be time consuming or provide poor cosmetic results, Dr. James Spencer said at a meeting sponsored by the Skin Disease Education Foundation.

Dr. Spencer, director of Mohs micrographic surgery at Mount Sinai Medical Center, New York, presented information to help physicians determine when it may be acceptable or unacceptable to use lasers or photodynamic therapies on skin lesions.

CO₂ Laser

Use of a CO₂ laser in continuous wave mode produces rapid and bloodless thermal destruction of tissue, but this mode has not been shown to be an effective treatment for skin cancer, he said. In a study of 24 basal cell carcinomas (BCCs) treated this way, 50% recurred after 1 year and healing after the procedure produced hypopigmentation and atrophy (J. Dermatol. Surg. Oncol. 1979;5:803–6).

Some studies have tested the theory that treatment of superficial skin cancers with the CO₂ laser in ultrapulsed mode could destroy the tumor and avoid scarring. In a series of 51 BCCs that were treated with the CO₂ laser in ultrapulsed mode, dermatologic surgeons were able to ablate 21 superficial BCCs reliably if the level of ablation penetrated to the midreticular dermis or deeper. Attempts to use this method with 28 nodular and 2 infiltrating BCCs were not successful (Br. J. Plast. Surg. 2000;53:286–93).

In another study, two or three passes of an ultrapulsed CO₂ laser on 17 superficial BCCs and 13 squamous cell carcinomas (SCCs) in situ with 3-mm margins onto normal skin left an unacceptably high rate of lesions positive for cancer when they were excised and examined in serial sections. For superficial BCCs, two passes left five of eight lesions positive and three passes left zero of nine lesions positive. Treatment of in situ SCC with two passes yielded two of six lesions positive while three passes resulted in three of seven lesions being positive (Arch. Dermatol. 1998;134:1247–52).

Dr. Spencer said that he did not think CO₂ lasers should realistically be a part of a dermatologist's armamentarium against skin cancer, but he suggested that the CO₂ laser may be considered to treat actinic cheilitis and basal cell nevus syndrome, "where your role is not cure, but control, and you're trying to avoid too much mutilating surgery."

Intravenous and Topical PDT

Intravenously administered photodynamic therapy (PDT) with agents such as porfimer sodium (Photofrin) is being studied for a variety of cancers, but its side effect of photosensitivity for 4–6 weeks through the skin and eyes creates a problem in using it for skin cancers. "If you're dying of a stomach cancer, you will hide in a dark room for a month, but if you've got some basal cell skin cancers, I don't think you will," Dr. Spencer said.

In a prospective study, PDT with intravenous Photofrin and red light yielded a complete response rate of 88% after an average follow-up of 29 months in 37 patients who had a total of 151 BCCs (most patients had basal cell nevus syndrome). Tumors recurred, however, in 36% of lesions on the nose and in 89% of morpheaform tumors (Arch. Dermatol. 1992;128:1597–601).

PDT researchers are studying shorter-acting light-sensitizing compounds that preferentially accumulate in malignant cells to avoid the problem of persistent photosensitivity with Photofrin. Verteporfin, an intravenously administered agent approved for ophthalmologic use that photosensitizes patients for only a few days, is undergoing clinical trials to test its efficacy in skin cancer, he said.

Topical PDT agents such as delta-aminolevulinic acid (ALA), which avoid the photosensitizing problem altogether, have had reported recurrence rates of 44% in 95 superficial BCCs and 69% in 35 superficial SCCs after 19 months of follow-up (Arch. Dermatol. 1998;134:821–6). "You should not be doing this in your practice," said Dr. Spencer, who also has a private practice in St. Petersburg, Fla.

Eyelid tumors may represent the best opportunity to try topical ALA because it is usually desirable to avoid surgery in that area and ALA may be able to more fully penetrate the thin skin of the eyelid, he suggested. In one study, topical PDT ALA treatment clinically resolved 8 of 19 nodular BCCs on the eyelids and periocular skin, while the other lesions had partial or no response (Acta Ophthalmol. Scand. 1999;77:182–8).

In a study of topical PDT with methyl-5 ALA, 79% of 350 nodular BCCs that were curetted before treatment with PDT were clinically clear. After 2–4 years' follow-up, 11% of the clinically clear lesions recurred (Br. J. Dermatol. 2001;145:467–71).

Lasers That Target Melanin

Lasers should not be used as a substitute for surgical removal of lentigo maligna, Dr. Spencer said.

In 11 patients with lentigo maligna who were treated with the Q-switched ruby laser on four occasions in a 6-month period, 6 of 13 biopsies taken after treatment were still positive for the lesion. Studies of lentigo maligna treatments with 532-nm and 1,064-nm Q-switched Nd:YAG lasers have shown similar results.

Some people may want to undergo laser removal of common acquired nevi for cosmetic reasons. There is a variable response to such treatment, in which nevi partially or completely lighten in color. This "debulks" and superficially removes the nevus from the epidermis but leaves residual nevus cells in the dermis, he said.

It is unclear if laser treatment of dysplastic or congenital, especially giant, nevi reduces the risk of melanoma. Treatment of atypical-appearing melanocytic lesions with lasers can provide an excellent cosmetic result, but it may run the risk of promoting malignant transformation. Lasers strip a lesion of its outer layer of UV-protecting melanin and create a scar in the papillary dermis that may clinically mask a deeper component, Dr. Spencer said.

"These concerns are very real," he said, but "people have been cautiously trying lasers on nevi for 20 years, and we haven't seen any malignant transformation."

Dr. Spencer said that laser removal of nevi "should be studied in a more formal way, but people have been very afraid to do this."

Clinicians have widely accepted the removal of nevi of Ota with lasers for only cosmetic improvement, so laser removal of large congenital and common acquired nevi should be considered, he said.

The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.

BALTIMORE — Lasers and light therapies have a limited role in the treatment of skin cancers and pigmented lesions, but their judicious use may be appropriate when standard treatments would be time consuming or provide poor cosmetic results, Dr. James Spencer said at a meeting sponsored by the Skin Disease Education Foundation.

Dr. Spencer, director of Mohs micrographic surgery at Mount Sinai Medical Center, New York, presented information to help physicians determine when it may be acceptable or unacceptable to use lasers or photodynamic therapies on skin lesions.

CO₂ Laser

Use of a CO₂ laser in continuous wave mode produces rapid and bloodless thermal destruction of tissue, but this mode has not been shown to be an effective treatment for skin cancer, he said. In a study of 24 basal cell carcinomas (BCCs) treated this way, 50% recurred after 1 year and healing after the procedure produced hypopigmentation and atrophy (J. Dermatol. Surg. Oncol. 1979;5:803–6).

Some studies have tested the theory that treatment of superficial skin cancers with the CO₂ laser in ultrapulsed mode could destroy the tumor and avoid scarring. In a series of 51 BCCs that were treated with the CO₂ laser in ultrapulsed mode, dermatologic surgeons were able to ablate 21 superficial BCCs reliably if the level of ablation penetrated to the midreticular dermis or deeper. Attempts to use this method with 28 nodular and 2 infiltrating BCCs were not successful (Br. J. Plast. Surg. 2000;53:286–93).

In another study, two or three passes of an ultrapulsed CO₂ laser on 17 superficial BCCs and 13 squamous cell carcinomas (SCCs) in situ with 3-mm margins onto normal skin left an unacceptably high rate of lesions positive for cancer when they were excised and examined in serial sections. For superficial BCCs, two passes left five of eight lesions positive and three passes left zero of nine lesions positive. Treatment of in situ SCC with two passes yielded two of six lesions positive while three passes resulted in three of seven lesions being positive (Arch. Dermatol. 1998;134:1247–52).

Dr. Spencer said that he did not think CO₂ lasers should realistically be a part of a dermatologist's armamentarium against skin cancer, but he suggested that the CO₂ laser may be considered to treat actinic cheilitis and basal cell nevus syndrome, "where your role is not cure, but control, and you're trying to avoid too much mutilating surgery."

Intravenous and Topical PDT

Intravenously administered photodynamic therapy (PDT) with agents such as porfimer sodium (Photofrin) is being studied for a variety of cancers, but its side effect of photosensitivity for 4–6 weeks through the skin and eyes creates a problem in using it for skin cancers. "If you're dying of a stomach cancer, you will hide in a dark room for a month, but if you've got some basal cell skin cancers, I don't think you will," Dr. Spencer said.

In a prospective study, PDT with intravenous Photofrin and red light yielded a complete response rate of 88% after an average follow-up of 29 months in 37 patients who had a total of 151 BCCs (most patients had basal cell nevus syndrome). Tumors recurred, however, in 36% of lesions on the nose and in 89% of morpheaform tumors (Arch. Dermatol. 1992;128:1597–601).

PDT researchers are studying shorter-acting light-sensitizing compounds that preferentially accumulate in malignant cells to avoid the problem of persistent photosensitivity with Photofrin. Verteporfin, an intravenously administered agent approved for ophthalmologic use that photosensitizes patients for only a few days, is undergoing clinical trials to test its efficacy in skin cancer, he said.

Topical PDT agents such as delta-aminolevulinic acid (ALA), which avoid the photosensitizing problem altogether, have had reported recurrence rates of 44% in 95 superficial BCCs and 69% in 35 superficial SCCs after 19 months of follow-up (Arch. Dermatol. 1998;134:821–6). "You should not be doing this in your practice," said Dr. Spencer, who also has a private practice in St. Petersburg, Fla.

Eyelid tumors may represent the best opportunity to try topical ALA because it is usually desirable to avoid surgery in that area and ALA may be able to more fully penetrate the thin skin of the eyelid, he suggested. In one study, topical PDT ALA treatment clinically resolved 8 of 19 nodular BCCs on the eyelids and periocular skin, while the other lesions had partial or no response (Acta Ophthalmol. Scand. 1999;77:182–8).

In a study of topical PDT with methyl-5 ALA, 79% of 350 nodular BCCs that were curetted before treatment with PDT were clinically clear. After 2–4 years' follow-up, 11% of the clinically clear lesions recurred (Br. J. Dermatol. 2001;145:467–71).

Lasers That Target Melanin

Lasers should not be used as a substitute for surgical removal of lentigo maligna, Dr. Spencer said.

In 11 patients with lentigo maligna who were treated with the Q-switched ruby laser on four occasions in a 6-month period, 6 of 13 biopsies taken after treatment were still positive for the lesion. Studies of lentigo maligna treatments with 532-nm and 1,064-nm Q-switched Nd:YAG lasers have shown similar results.

Some people may want to undergo laser removal of common acquired nevi for cosmetic reasons. There is a variable response to such treatment, in which nevi partially or completely lighten in color. This "debulks" and superficially removes the nevus from the epidermis but leaves residual nevus cells in the dermis, he said.

It is unclear if laser treatment of dysplastic or congenital, especially giant, nevi reduces the risk of melanoma. Treatment of atypical-appearing melanocytic lesions with lasers can provide an excellent cosmetic result, but it may run the risk of promoting malignant transformation. Lasers strip a lesion of its outer layer of UV-protecting melanin and create a scar in the papillary dermis that may clinically mask a deeper component, Dr. Spencer said.

"These concerns are very real," he said, but "people have been cautiously trying lasers on nevi for 20 years, and we haven't seen any malignant transformation."

Dr. Spencer said that laser removal of nevi "should be studied in a more formal way, but people have been very afraid to do this."

Clinicians have widely accepted the removal of nevi of Ota with lasers for only cosmetic improvement, so laser removal of large congenital and common acquired nevi should be considered, he said.

The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.

BALTIMORE — Lasers and light therapies have a limited role in the treatment of skin cancers and pigmented lesions, but their judicious use may be appropriate when standard treatments would be time consuming or provide poor cosmetic results, Dr. James Spencer said at a meeting sponsored by the Skin Disease Education Foundation.

Dr. Spencer, director of Mohs micrographic surgery at Mount Sinai Medical Center, New York, presented information to help physicians determine when it may be acceptable or unacceptable to use lasers or photodynamic therapies on skin lesions.

CO₂ Laser

Use of a CO₂ laser in continuous wave mode produces rapid and bloodless thermal destruction of tissue, but this mode has not been shown to be an effective treatment for skin cancer, he said. In a study of 24 basal cell carcinomas (BCCs) treated this way, 50% recurred after 1 year and healing after the procedure produced hypopigmentation and atrophy (J. Dermatol. Surg. Oncol. 1979;5:803–6).

Some studies have tested the theory that treatment of superficial skin cancers with the CO₂ laser in ultrapulsed mode could destroy the tumor and avoid scarring. In a series of 51 BCCs that were treated with the CO₂ laser in ultrapulsed mode, dermatologic surgeons were able to ablate 21 superficial BCCs reliably if the level of ablation penetrated to the midreticular dermis or deeper. Attempts to use this method with 28 nodular and 2 infiltrating BCCs were not successful (Br. J. Plast. Surg. 2000;53:286–93).

In another study, two or three passes of an ultrapulsed CO₂ laser on 17 superficial BCCs and 13 squamous cell carcinomas (SCCs) in situ with 3-mm margins onto normal skin left an unacceptably high rate of lesions positive for cancer when they were excised and examined in serial sections. For superficial BCCs, two passes left five of eight lesions positive and three passes left zero of nine lesions positive. Treatment of in situ SCC with two passes yielded two of six lesions positive while three passes resulted in three of seven lesions being positive (Arch. Dermatol. 1998;134:1247–52).

Dr. Spencer said that he did not think CO₂ lasers should realistically be a part of a dermatologist's armamentarium against skin cancer, but he suggested that the CO₂ laser may be considered to treat actinic cheilitis and basal cell nevus syndrome, "where your role is not cure, but control, and you're trying to avoid too much mutilating surgery."

Intravenous and Topical PDT

Intravenously administered photodynamic therapy (PDT) with agents such as porfimer sodium (Photofrin) is being studied for a variety of cancers, but its side effect of photosensitivity for 4–6 weeks through the skin and eyes creates a problem in using it for skin cancers. "If you're dying of a stomach cancer, you will hide in a dark room for a month, but if you've got some basal cell skin cancers, I don't think you will," Dr. Spencer said.

In a prospective study, PDT with intravenous Photofrin and red light yielded a complete response rate of 88% after an average follow-up of 29 months in 37 patients who had a total of 151 BCCs (most patients had basal cell nevus syndrome). Tumors recurred, however, in 36% of lesions on the nose and in 89% of morpheaform tumors (Arch. Dermatol. 1992;128:1597–601).

PDT researchers are studying shorter-acting light-sensitizing compounds that preferentially accumulate in malignant cells to avoid the problem of persistent photosensitivity with Photofrin. Verteporfin, an intravenously administered agent approved for ophthalmologic use that photosensitizes patients for only a few days, is undergoing clinical trials to test its efficacy in skin cancer, he said.

Topical PDT agents such as delta-aminolevulinic acid (ALA), which avoid the photosensitizing problem altogether, have had reported recurrence rates of 44% in 95 superficial BCCs and 69% in 35 superficial SCCs after 19 months of follow-up (Arch. Dermatol. 1998;134:821–6). "You should not be doing this in your practice," said Dr. Spencer, who also has a private practice in St. Petersburg, Fla.

Eyelid tumors may represent the best opportunity to try topical ALA because it is usually desirable to avoid surgery in that area and ALA may be able to more fully penetrate the thin skin of the eyelid, he suggested. In one study, topical PDT ALA treatment clinically resolved 8 of 19 nodular BCCs on the eyelids and periocular skin, while the other lesions had partial or no response (Acta Ophthalmol. Scand. 1999;77:182–8).

In a study of topical PDT with methyl-5 ALA, 79% of 350 nodular BCCs that were curetted before treatment with PDT were clinically clear. After 2–4 years' follow-up, 11% of the clinically clear lesions recurred (Br. J. Dermatol. 2001;145:467–71).

Lasers That Target Melanin

Lasers should not be used as a substitute for surgical removal of lentigo maligna, Dr. Spencer said.

In 11 patients with lentigo maligna who were treated with the Q-switched ruby laser on four occasions in a 6-month period, 6 of 13 biopsies taken after treatment were still positive for the lesion. Studies of lentigo maligna treatments with 532-nm and 1,064-nm Q-switched Nd:YAG lasers have shown similar results.

Some people may want to undergo laser removal of common acquired nevi for cosmetic reasons. There is a variable response to such treatment, in which nevi partially or completely lighten in color. This "debulks" and superficially removes the nevus from the epidermis but leaves residual nevus cells in the dermis, he said.

It is unclear if laser treatment of dysplastic or congenital, especially giant, nevi reduces the risk of melanoma. Treatment of atypical-appearing melanocytic lesions with lasers can provide an excellent cosmetic result, but it may run the risk of promoting malignant transformation. Lasers strip a lesion of its outer layer of UV-protecting melanin and create a scar in the papillary dermis that may clinically mask a deeper component, Dr. Spencer said.

"These concerns are very real," he said, but "people have been cautiously trying lasers on nevi for 20 years, and we haven't seen any malignant transformation."

Dr. Spencer said that laser removal of nevi "should be studied in a more formal way, but people have been very afraid to do this."

Clinicians have widely accepted the removal of nevi of Ota with lasers for only cosmetic improvement, so laser removal of large congenital and common acquired nevi should be considered, he said.

The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.