Michele G. Sullivan

CHICAGO — Bisexual college women were 60% more likely to report having a sexually transmitted disease during the past year than were their heterosexual counterparts and four times more likely to report an STD than were lesbian college students, according to a study of 30,000 sexually active women.

“It's not clear whether it's the gender of their sex partners, the number of their sex partners, or the combination of these factors that increases their STD risk,” Lisa L. Lindley, Dr.P.H., said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention. “We need more research to understand the elevated sexual risk-taking of bisexual college women.”

Dr. Lindley, of the Arnold School of Public Health at the University of South Carolina in Columbia, drew her data from the spring 2006 National College Health Assessment, a survey of 117 postsecondary institutions, which included data on 95,000 male and female college students.

The majority of sexually active college women in the analysis were white (78%). Blacks and Hispanics constituted 10% of the sample, while students of other races and ethnicities rounded out the group. Most of the women (94%) were heterosexual; 1% described themselves as lesbians, 3% as bisexual, and 1% as unsure of their sexual orientation.

College women who reported having sex only with men during the past year had an average of two sex partners, as did those who reported having sex only with women. Women who reported sex partners of both genders during the past year had an average of five sex partners.

The college students also reported whether they had acquired an STD in the past year (HPV/genital warts, chlamydia, genital herpes, gonorrhea, and/or HIV). No significant differences were reported in the incidence of each STD based on students' sexual orientation, with the exception of HPV/genital warts. Lesbians were least likely to report having HPV/genital warts, while, compared with lesbians, heterosexual women had a fourfold increased risk, bisexual women had a sixfold increased risk, and those unsure of their sexual orientation had a fivefold increased risk.

When all the STDs were taken together, lesbian women had the lowest risk of infection—a 62% decreased risk, compared with heterosexual women. Bisexual women were 60% more likely to have an STD than heterosexual women were. But, compared with lesbian women with their very low rate, bisexual women were four times more likely to have an STD.

However, the study of also found that lesbian students were significantly less likely than either heterosexual or bisexual students to have had a routine gynecologic exam during the past year. While 73% of heterosexual women and 67% of bisexual women had an exam, only 46% of lesbian women did. “Therefore, it's likely that more lesbian women have an STD but don't know it,” Dr. Lindley said.

That finding prompts concern about the future sexual health of this group. “Educational efforts targeting lesbians must address the behavioral risk for STDs, safer sex practices, and the importance of regular gynecological exams and Pap tests,” said Dr. Lindley. “We also need additional research to understand why young lesbians do not seek these exams.”

Dr. Lindley also analyzed the incidence of multiple STDs by gender of sex partners. Women who had sex only with women during the past year had the lowest incidence of multiple infections (4%), while the incidence was 5% among those who had sex only with men. The incidence of multiple STDs was significantly higher in women who had partners of both genders (15%).

The analysis also pointed up an interesting dichotomy between the women's self-proclaimed sexual orientation and their actual sexual behaviors, Dr. Lindley noted. For example, 5% of women who self-identified as lesbians reported having only male sexual contacts in the past year, and 10% of lesbians reported having sex partners of both genders. Among bisexual women, 56% reported sexual contact with only men in the past year, and 10% reported sexual contact with only women; 35% of these women had sex with both men and women in the studied year.

Dr. Lindley reported that she had no financial disclosures.

CHICAGO — Bisexual college women were 60% more likely to report having a sexually transmitted disease during the past year than were their heterosexual counterparts and four times more likely to report an STD than were lesbian college students, according to a study of 30,000 sexually active women.

“It's not clear whether it's the gender of their sex partners, the number of their sex partners, or the combination of these factors that increases their STD risk,” Lisa L. Lindley, Dr.P.H., said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention. “We need more research to understand the elevated sexual risk-taking of bisexual college women.”

Dr. Lindley, of the Arnold School of Public Health at the University of South Carolina in Columbia, drew her data from the spring 2006 National College Health Assessment, a survey of 117 postsecondary institutions, which included data on 95,000 male and female college students.

The majority of sexually active college women in the analysis were white (78%). Blacks and Hispanics constituted 10% of the sample, while students of other races and ethnicities rounded out the group. Most of the women (94%) were heterosexual; 1% described themselves as lesbians, 3% as bisexual, and 1% as unsure of their sexual orientation.

College women who reported having sex only with men during the past year had an average of two sex partners, as did those who reported having sex only with women. Women who reported sex partners of both genders during the past year had an average of five sex partners.

The college students also reported whether they had acquired an STD in the past year (HPV/genital warts, chlamydia, genital herpes, gonorrhea, and/or HIV). No significant differences were reported in the incidence of each STD based on students' sexual orientation, with the exception of HPV/genital warts. Lesbians were least likely to report having HPV/genital warts, while, compared with lesbians, heterosexual women had a fourfold increased risk, bisexual women had a sixfold increased risk, and those unsure of their sexual orientation had a fivefold increased risk.

When all the STDs were taken together, lesbian women had the lowest risk of infection—a 62% decreased risk, compared with heterosexual women. Bisexual women were 60% more likely to have an STD than heterosexual women were. But, compared with lesbian women with their very low rate, bisexual women were four times more likely to have an STD.

However, the study of also found that lesbian students were significantly less likely than either heterosexual or bisexual students to have had a routine gynecologic exam during the past year. While 73% of heterosexual women and 67% of bisexual women had an exam, only 46% of lesbian women did. “Therefore, it's likely that more lesbian women have an STD but don't know it,” Dr. Lindley said.

That finding prompts concern about the future sexual health of this group. “Educational efforts targeting lesbians must address the behavioral risk for STDs, safer sex practices, and the importance of regular gynecological exams and Pap tests,” said Dr. Lindley. “We also need additional research to understand why young lesbians do not seek these exams.”

Dr. Lindley also analyzed the incidence of multiple STDs by gender of sex partners. Women who had sex only with women during the past year had the lowest incidence of multiple infections (4%), while the incidence was 5% among those who had sex only with men. The incidence of multiple STDs was significantly higher in women who had partners of both genders (15%).

The analysis also pointed up an interesting dichotomy between the women's self-proclaimed sexual orientation and their actual sexual behaviors, Dr. Lindley noted. For example, 5% of women who self-identified as lesbians reported having only male sexual contacts in the past year, and 10% of lesbians reported having sex partners of both genders. Among bisexual women, 56% reported sexual contact with only men in the past year, and 10% reported sexual contact with only women; 35% of these women had sex with both men and women in the studied year.

Dr. Lindley reported that she had no financial disclosures.

CHICAGO — Bisexual college women were 60% more likely to report having a sexually transmitted disease during the past year than were their heterosexual counterparts and four times more likely to report an STD than were lesbian college students, according to a study of 30,000 sexually active women.

“It's not clear whether it's the gender of their sex partners, the number of their sex partners, or the combination of these factors that increases their STD risk,” Lisa L. Lindley, Dr.P.H., said at a conference on STD prevention sponsored by the Centers for Disease Control and Prevention. “We need more research to understand the elevated sexual risk-taking of bisexual college women.”

Dr. Lindley, of the Arnold School of Public Health at the University of South Carolina in Columbia, drew her data from the spring 2006 National College Health Assessment, a survey of 117 postsecondary institutions, which included data on 95,000 male and female college students.

The majority of sexually active college women in the analysis were white (78%). Blacks and Hispanics constituted 10% of the sample, while students of other races and ethnicities rounded out the group. Most of the women (94%) were heterosexual; 1% described themselves as lesbians, 3% as bisexual, and 1% as unsure of their sexual orientation.

College women who reported having sex only with men during the past year had an average of two sex partners, as did those who reported having sex only with women. Women who reported sex partners of both genders during the past year had an average of five sex partners.

The college students also reported whether they had acquired an STD in the past year (HPV/genital warts, chlamydia, genital herpes, gonorrhea, and/or HIV). No significant differences were reported in the incidence of each STD based on students' sexual orientation, with the exception of HPV/genital warts. Lesbians were least likely to report having HPV/genital warts, while, compared with lesbians, heterosexual women had a fourfold increased risk, bisexual women had a sixfold increased risk, and those unsure of their sexual orientation had a fivefold increased risk.

When all the STDs were taken together, lesbian women had the lowest risk of infection—a 62% decreased risk, compared with heterosexual women. Bisexual women were 60% more likely to have an STD than heterosexual women were. But, compared with lesbian women with their very low rate, bisexual women were four times more likely to have an STD.

However, the study of also found that lesbian students were significantly less likely than either heterosexual or bisexual students to have had a routine gynecologic exam during the past year. While 73% of heterosexual women and 67% of bisexual women had an exam, only 46% of lesbian women did. “Therefore, it's likely that more lesbian women have an STD but don't know it,” Dr. Lindley said.

That finding prompts concern about the future sexual health of this group. “Educational efforts targeting lesbians must address the behavioral risk for STDs, safer sex practices, and the importance of regular gynecological exams and Pap tests,” said Dr. Lindley. “We also need additional research to understand why young lesbians do not seek these exams.”

Dr. Lindley also analyzed the incidence of multiple STDs by gender of sex partners. Women who had sex only with women during the past year had the lowest incidence of multiple infections (4%), while the incidence was 5% among those who had sex only with men. The incidence of multiple STDs was significantly higher in women who had partners of both genders (15%).

The analysis also pointed up an interesting dichotomy between the women's self-proclaimed sexual orientation and their actual sexual behaviors, Dr. Lindley noted. For example, 5% of women who self-identified as lesbians reported having only male sexual contacts in the past year, and 10% of lesbians reported having sex partners of both genders. Among bisexual women, 56% reported sexual contact with only men in the past year, and 10% reported sexual contact with only women; 35% of these women had sex with both men and women in the studied year.

Dr. Lindley reported that she had no financial disclosures.

SAN FRANCISCO — Adventure tourists, international volunteers, and people visiting their families in the Third World are the travelers most likely to bring home unwanted souvenirs, from malaria to schistosomiasis.

“You're not going to see these things in businessmen who are staying in Hiltons and eating Western food when they go overseas,” Dr. Sukhjit Takhar said at the 12th International Conference on Emergency Medicine. “These are diseases people contract when they are traveling for longer than a couple of weeks, or when they are really getting immersed in the local culture or eating the local food.”

Taking a good travel history is the first step in diagnosing an internationally acquired disease, said Dr. Takhar, an emergency physician at the University of California San Francisco-Fresno.

“Find out where they went, and what they did. Were they staying in a hotel or out in the jungle dissecting monkeys? How long have they been back? This will give you an idea of the incubation period,” Dr. Takhar said.

Also ask them if they took any medicine when they began to feel ill. Many travelers self-medicate with antibiotics, which can quell symptoms but not fully cure the illness.

Managing Malaria

Apart from acute diarrhea, systemic febrile illnesses are the most common syndromes among returning travelers. Most of those will be either malaria or dengue fever.

Among all travelers, 35% will have malaria, which causes about 150 fatalities in returned travelers each year; and 10% will have dengue. More than 60% of travelers with a systemic febrile illness coming from Africa will have malaria, Dr. Takhar added. About 30% of ill travelers returning from Southeast Asia will have dengue fever.

Because of the prevalence, morbidity, and mortality of malaria, especially that caused by the Plasmodium falciparum parasite, patients who appear to have the disease should receive immediate treatment, even if they don't present acutely ill to the ED. “Malaria symptoms are cyclical, so up to 40% of patients will be afebrile when you see them in the ED,” Dr. Takhar said.

Falciparum malaria is the most dangerous form, provoking a flulike illness followed by paroxysmal fevers that last 8–12 hours and culminate in a drenching sweat. After that, the patient may feel well. The less common vivax malaria is also a less serious illness but causes similar symptoms.

The time since onset of symptoms is a clue to the type of malaria, Dr. Takhar said. The incubation period for falciparum malaria is about 10–14 days, while that of vivax malaria may be longer.

A blood smear will diagnose either form, with the parasites appearing in the erythrocytes. If the index of suspicion for malaria is high, however, and the patient reports travel to endemic areas, consider treating presumptively, Dr. Takhar advised. “They can look well and then decompensate very quickly, so don't wait around for a consult from a specialist.”

The treatment of choice in the United States is now quinidine. “Chloroquines don't work very well any more, because the parasites have become resistant,” he said, and the most potent antimalarial, artemether—an extract of the wormwood plant—isn't readily available in the United States.

A negative smear doesn't eliminate the possibility of malaria. “You can have a negative smear and still have it. The patient might have taken some doxycycline or azithromycin when he started feeling bad. Both of these have some antimalarial properties,” he said. “If you don't see the parasites, get another smear in 12–24 hours.”

A negative malaria smear in a febrile patient with a low white blood cell count, thrombocytopenia, and recent travel to the tropics may point to another mosquito-borne illness: dengue fever.

Diagnosing Dengue Fever

The prevalence of dengue has grown dramatically in recent decades. It's now found in more than 100 countries in Africa, Central and South America, the Caribbean, Asia, Southeast Asia, and even around the Mediterranean. “Travelers who don't protect themselves from mosquitoes in these areas will very likely come down with this illness,” he said.

The dengue virus causes a severe flulike illness with high fever, headache, retro-orbital pain, and a myalgia so painful that dengue is nicknamed “breakbone fever,” Dr. Takhar said.

While most cases are self-limiting and require only supportive care, the hemorrhagic form can be deadly. In addition to petechiae, patients may have plasma leakage leading to pleural effusion, dropping platelets, rising hematocrit, and ascites.

Again, treatment is supportive. “You need to give IV fluids, but because these patients leak plasma, you should also put in a central line to measure central venous pressure,” he said. Don't give any aspirin or ibuprofen for the pain, because those agents can exacerbate bleeding.

Tick Bites and Flatworms

Rickettsial diseases are sometimes seen in those who travel to Africa during tick season (April-November). Fever, myalgia, and headache characterize the illnesses; an eschar at the site of the tick bite is another clue. Most rickettsial infections respond quickly to doxycycline.

African travelers who swam in lakes may bring home a load of schistosomes. These flatworms live in freshwater snails, which release the larvae into the water. The larvae burrow into a swimmer's skin and take up residence in the liver. After maturing (up to 10 mm long), the worms mate and move into the rectal and mesenteric veins, where they release their eggs. The eggs pass into the intestine, bladder, or rectum, and are excreted.

The worms live up to 4 years, so natives of endemic areas can have huge loads that create chronic disease. However, travelers usually come down with an acute case, called Katayama fever. Symptoms include abdominal pain, cough, diarrhea, eosinophilia, fever, fatigue, and hepatosplenomegaly. Early in the course, the patient may have urticaria and a rash where the larvae penetrated the skin.

Diagnosis is by fecal smear or urinalysis positive for the flatworm's eggs. Schistosomal antibodies can also be positive. Praziquantel is the usual treatment, Dr. Takhar said. It should probably be prescribed by an infectious disease specialist who can provide adequate follow-up.

'You're not going to see these things in businessmen who are staying in Hiltons and eating Western food.' DR. TAKHAR

SAN FRANCISCO — Adventure tourists, international volunteers, and people visiting their families in the Third World are the travelers most likely to bring home unwanted souvenirs, from malaria to schistosomiasis.

“You're not going to see these things in businessmen who are staying in Hiltons and eating Western food when they go overseas,” Dr. Sukhjit Takhar said at the 12th International Conference on Emergency Medicine. “These are diseases people contract when they are traveling for longer than a couple of weeks, or when they are really getting immersed in the local culture or eating the local food.”

Taking a good travel history is the first step in diagnosing an internationally acquired disease, said Dr. Takhar, an emergency physician at the University of California San Francisco-Fresno.

“Find out where they went, and what they did. Were they staying in a hotel or out in the jungle dissecting monkeys? How long have they been back? This will give you an idea of the incubation period,” Dr. Takhar said.

Also ask them if they took any medicine when they began to feel ill. Many travelers self-medicate with antibiotics, which can quell symptoms but not fully cure the illness.

Managing Malaria

Apart from acute diarrhea, systemic febrile illnesses are the most common syndromes among returning travelers. Most of those will be either malaria or dengue fever.

Among all travelers, 35% will have malaria, which causes about 150 fatalities in returned travelers each year; and 10% will have dengue. More than 60% of travelers with a systemic febrile illness coming from Africa will have malaria, Dr. Takhar added. About 30% of ill travelers returning from Southeast Asia will have dengue fever.

Because of the prevalence, morbidity, and mortality of malaria, especially that caused by the Plasmodium falciparum parasite, patients who appear to have the disease should receive immediate treatment, even if they don't present acutely ill to the ED. “Malaria symptoms are cyclical, so up to 40% of patients will be afebrile when you see them in the ED,” Dr. Takhar said.

Falciparum malaria is the most dangerous form, provoking a flulike illness followed by paroxysmal fevers that last 8–12 hours and culminate in a drenching sweat. After that, the patient may feel well. The less common vivax malaria is also a less serious illness but causes similar symptoms.

The time since onset of symptoms is a clue to the type of malaria, Dr. Takhar said. The incubation period for falciparum malaria is about 10–14 days, while that of vivax malaria may be longer.

A blood smear will diagnose either form, with the parasites appearing in the erythrocytes. If the index of suspicion for malaria is high, however, and the patient reports travel to endemic areas, consider treating presumptively, Dr. Takhar advised. “They can look well and then decompensate very quickly, so don't wait around for a consult from a specialist.”

The treatment of choice in the United States is now quinidine. “Chloroquines don't work very well any more, because the parasites have become resistant,” he said, and the most potent antimalarial, artemether—an extract of the wormwood plant—isn't readily available in the United States.

A negative smear doesn't eliminate the possibility of malaria. “You can have a negative smear and still have it. The patient might have taken some doxycycline or azithromycin when he started feeling bad. Both of these have some antimalarial properties,” he said. “If you don't see the parasites, get another smear in 12–24 hours.”

A negative malaria smear in a febrile patient with a low white blood cell count, thrombocytopenia, and recent travel to the tropics may point to another mosquito-borne illness: dengue fever.

Diagnosing Dengue Fever

The prevalence of dengue has grown dramatically in recent decades. It's now found in more than 100 countries in Africa, Central and South America, the Caribbean, Asia, Southeast Asia, and even around the Mediterranean. “Travelers who don't protect themselves from mosquitoes in these areas will very likely come down with this illness,” he said.

The dengue virus causes a severe flulike illness with high fever, headache, retro-orbital pain, and a myalgia so painful that dengue is nicknamed “breakbone fever,” Dr. Takhar said.

While most cases are self-limiting and require only supportive care, the hemorrhagic form can be deadly. In addition to petechiae, patients may have plasma leakage leading to pleural effusion, dropping platelets, rising hematocrit, and ascites.

Again, treatment is supportive. “You need to give IV fluids, but because these patients leak plasma, you should also put in a central line to measure central venous pressure,” he said. Don't give any aspirin or ibuprofen for the pain, because those agents can exacerbate bleeding.

Tick Bites and Flatworms

Rickettsial diseases are sometimes seen in those who travel to Africa during tick season (April-November). Fever, myalgia, and headache characterize the illnesses; an eschar at the site of the tick bite is another clue. Most rickettsial infections respond quickly to doxycycline.

African travelers who swam in lakes may bring home a load of schistosomes. These flatworms live in freshwater snails, which release the larvae into the water. The larvae burrow into a swimmer's skin and take up residence in the liver. After maturing (up to 10 mm long), the worms mate and move into the rectal and mesenteric veins, where they release their eggs. The eggs pass into the intestine, bladder, or rectum, and are excreted.

The worms live up to 4 years, so natives of endemic areas can have huge loads that create chronic disease. However, travelers usually come down with an acute case, called Katayama fever. Symptoms include abdominal pain, cough, diarrhea, eosinophilia, fever, fatigue, and hepatosplenomegaly. Early in the course, the patient may have urticaria and a rash where the larvae penetrated the skin.

Diagnosis is by fecal smear or urinalysis positive for the flatworm's eggs. Schistosomal antibodies can also be positive. Praziquantel is the usual treatment, Dr. Takhar said. It should probably be prescribed by an infectious disease specialist who can provide adequate follow-up.

'You're not going to see these things in businessmen who are staying in Hiltons and eating Western food.' DR. TAKHAR

SAN FRANCISCO — Adventure tourists, international volunteers, and people visiting their families in the Third World are the travelers most likely to bring home unwanted souvenirs, from malaria to schistosomiasis.

“You're not going to see these things in businessmen who are staying in Hiltons and eating Western food when they go overseas,” Dr. Sukhjit Takhar said at the 12th International Conference on Emergency Medicine. “These are diseases people contract when they are traveling for longer than a couple of weeks, or when they are really getting immersed in the local culture or eating the local food.”

Taking a good travel history is the first step in diagnosing an internationally acquired disease, said Dr. Takhar, an emergency physician at the University of California San Francisco-Fresno.

“Find out where they went, and what they did. Were they staying in a hotel or out in the jungle dissecting monkeys? How long have they been back? This will give you an idea of the incubation period,” Dr. Takhar said.

Also ask them if they took any medicine when they began to feel ill. Many travelers self-medicate with antibiotics, which can quell symptoms but not fully cure the illness.

Managing Malaria

Apart from acute diarrhea, systemic febrile illnesses are the most common syndromes among returning travelers. Most of those will be either malaria or dengue fever.

Among all travelers, 35% will have malaria, which causes about 150 fatalities in returned travelers each year; and 10% will have dengue. More than 60% of travelers with a systemic febrile illness coming from Africa will have malaria, Dr. Takhar added. About 30% of ill travelers returning from Southeast Asia will have dengue fever.

Because of the prevalence, morbidity, and mortality of malaria, especially that caused by the Plasmodium falciparum parasite, patients who appear to have the disease should receive immediate treatment, even if they don't present acutely ill to the ED. “Malaria symptoms are cyclical, so up to 40% of patients will be afebrile when you see them in the ED,” Dr. Takhar said.

Falciparum malaria is the most dangerous form, provoking a flulike illness followed by paroxysmal fevers that last 8–12 hours and culminate in a drenching sweat. After that, the patient may feel well. The less common vivax malaria is also a less serious illness but causes similar symptoms.

The time since onset of symptoms is a clue to the type of malaria, Dr. Takhar said. The incubation period for falciparum malaria is about 10–14 days, while that of vivax malaria may be longer.

A blood smear will diagnose either form, with the parasites appearing in the erythrocytes. If the index of suspicion for malaria is high, however, and the patient reports travel to endemic areas, consider treating presumptively, Dr. Takhar advised. “They can look well and then decompensate very quickly, so don't wait around for a consult from a specialist.”

The treatment of choice in the United States is now quinidine. “Chloroquines don't work very well any more, because the parasites have become resistant,” he said, and the most potent antimalarial, artemether—an extract of the wormwood plant—isn't readily available in the United States.

A negative smear doesn't eliminate the possibility of malaria. “You can have a negative smear and still have it. The patient might have taken some doxycycline or azithromycin when he started feeling bad. Both of these have some antimalarial properties,” he said. “If you don't see the parasites, get another smear in 12–24 hours.”

A negative malaria smear in a febrile patient with a low white blood cell count, thrombocytopenia, and recent travel to the tropics may point to another mosquito-borne illness: dengue fever.

Diagnosing Dengue Fever

The prevalence of dengue has grown dramatically in recent decades. It's now found in more than 100 countries in Africa, Central and South America, the Caribbean, Asia, Southeast Asia, and even around the Mediterranean. “Travelers who don't protect themselves from mosquitoes in these areas will very likely come down with this illness,” he said.

The dengue virus causes a severe flulike illness with high fever, headache, retro-orbital pain, and a myalgia so painful that dengue is nicknamed “breakbone fever,” Dr. Takhar said.

While most cases are self-limiting and require only supportive care, the hemorrhagic form can be deadly. In addition to petechiae, patients may have plasma leakage leading to pleural effusion, dropping platelets, rising hematocrit, and ascites.

Again, treatment is supportive. “You need to give IV fluids, but because these patients leak plasma, you should also put in a central line to measure central venous pressure,” he said. Don't give any aspirin or ibuprofen for the pain, because those agents can exacerbate bleeding.

Tick Bites and Flatworms

Rickettsial diseases are sometimes seen in those who travel to Africa during tick season (April-November). Fever, myalgia, and headache characterize the illnesses; an eschar at the site of the tick bite is another clue. Most rickettsial infections respond quickly to doxycycline.

African travelers who swam in lakes may bring home a load of schistosomes. These flatworms live in freshwater snails, which release the larvae into the water. The larvae burrow into a swimmer's skin and take up residence in the liver. After maturing (up to 10 mm long), the worms mate and move into the rectal and mesenteric veins, where they release their eggs. The eggs pass into the intestine, bladder, or rectum, and are excreted.

The worms live up to 4 years, so natives of endemic areas can have huge loads that create chronic disease. However, travelers usually come down with an acute case, called Katayama fever. Symptoms include abdominal pain, cough, diarrhea, eosinophilia, fever, fatigue, and hepatosplenomegaly. Early in the course, the patient may have urticaria and a rash where the larvae penetrated the skin.

Diagnosis is by fecal smear or urinalysis positive for the flatworm's eggs. Schistosomal antibodies can also be positive. Praziquantel is the usual treatment, Dr. Takhar said. It should probably be prescribed by an infectious disease specialist who can provide adequate follow-up.

'You're not going to see these things in businessmen who are staying in Hiltons and eating Western food.' DR. TAKHAR

WASHINGTON — Drug-eluting stents implanted using intravascular ultrasound guidance might be less susceptible to later stent thrombosis, Dr. Probal Roy reported at a symposium sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

His single-center observational study found that IVUS-guided stents were 35% less likely to develop stent thrombosis by 1 year than were stents placed with angiographic guidance alone.

“IVUS guidance should be considered for routine use during drug-eluting stent implantation in patients who are at increased risk for these events,” said Dr. Roy of the Washington (D.C.) Hospital Center.

Dr. Roy and his colleagues examined outcomes in 1,786 patients (mean age 66 years) who received drug-eluting stents during 2003–2006. IVUS guidance was performed in 884 patients; angiographic guidance alone was used in the rest. Groups were matched for age, gender, cardiovascular risk factors, clinical presentation, left ventricular ejection fraction, and angiographic features. IVUS was performed either preintervention, post intervention or both, at the discretion of the operator. There were no significant differences in in-hospital outcomes between the two groups.

However, at 30 days, significantly fewer patients in the IVUS group experienced definite stent thrombosis than did those in the angiography-only group (0.5% vs. 1.4%, respectively). This difference remained significant at 1 year, when rates of definite stent thrombosis were 0.7% in the IVUS group, compared with 2% in the angiographic guidance group. “Freedom from stent thrombosis was largely driven by reductions in subacute stent thrombosis,” Dr. Roy said.

WASHINGTON — Drug-eluting stents implanted using intravascular ultrasound guidance might be less susceptible to later stent thrombosis, Dr. Probal Roy reported at a symposium sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

His single-center observational study found that IVUS-guided stents were 35% less likely to develop stent thrombosis by 1 year than were stents placed with angiographic guidance alone.

“IVUS guidance should be considered for routine use during drug-eluting stent implantation in patients who are at increased risk for these events,” said Dr. Roy of the Washington (D.C.) Hospital Center.

Dr. Roy and his colleagues examined outcomes in 1,786 patients (mean age 66 years) who received drug-eluting stents during 2003–2006. IVUS guidance was performed in 884 patients; angiographic guidance alone was used in the rest. Groups were matched for age, gender, cardiovascular risk factors, clinical presentation, left ventricular ejection fraction, and angiographic features. IVUS was performed either preintervention, post intervention or both, at the discretion of the operator. There were no significant differences in in-hospital outcomes between the two groups.

However, at 30 days, significantly fewer patients in the IVUS group experienced definite stent thrombosis than did those in the angiography-only group (0.5% vs. 1.4%, respectively). This difference remained significant at 1 year, when rates of definite stent thrombosis were 0.7% in the IVUS group, compared with 2% in the angiographic guidance group. “Freedom from stent thrombosis was largely driven by reductions in subacute stent thrombosis,” Dr. Roy said.

WASHINGTON — Drug-eluting stents implanted using intravascular ultrasound guidance might be less susceptible to later stent thrombosis, Dr. Probal Roy reported at a symposium sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

His single-center observational study found that IVUS-guided stents were 35% less likely to develop stent thrombosis by 1 year than were stents placed with angiographic guidance alone.

“IVUS guidance should be considered for routine use during drug-eluting stent implantation in patients who are at increased risk for these events,” said Dr. Roy of the Washington (D.C.) Hospital Center.

Dr. Roy and his colleagues examined outcomes in 1,786 patients (mean age 66 years) who received drug-eluting stents during 2003–2006. IVUS guidance was performed in 884 patients; angiographic guidance alone was used in the rest. Groups were matched for age, gender, cardiovascular risk factors, clinical presentation, left ventricular ejection fraction, and angiographic features. IVUS was performed either preintervention, post intervention or both, at the discretion of the operator. There were no significant differences in in-hospital outcomes between the two groups.

However, at 30 days, significantly fewer patients in the IVUS group experienced definite stent thrombosis than did those in the angiography-only group (0.5% vs. 1.4%, respectively). This difference remained significant at 1 year, when rates of definite stent thrombosis were 0.7% in the IVUS group, compared with 2% in the angiographic guidance group. “Freedom from stent thrombosis was largely driven by reductions in subacute stent thrombosis,” Dr. Roy said.

PHOENIX — Children with congenital diaphragmatic hernia are likely to have long-term health problems requiring close, long-term follow-up, Dr. Tim Jancelewicz said at the annual meeting of the American Pediatric Surgical Association.

Dr. Jancelewicz, of the University of California, San Francisco, and his colleagues reviewed 357 clinic visits made over a 10-year period by 90 patients with congenital diaphragmatic hernia (median follow-up 4 years). Of those, 8% required extracorporeal membrane oxygenation (median 15 days). Initial patch repair was done in 57%, and 36% have had recurrence of the hernias.

The children underwent neurodevelopmental assessment, which identified normal neurodevelopmental outcomes in 55% of the cohort. Another 13% had suspect disease, 24% had confirmed abnormal outcomes, findings for 8% were undetermined.

Four factors significantly predicted neurodevelopmental delay: liver herniation at birth, initial patch repair, intubation for at least 15 days, and discharge home on oxygen. Neurodevelopmental delay was seen in 59% of those with liver herniation, 60% of those with initial patch repair, 67% of those with at least 15 days of intubation, and 82% of those who were discharged on oxygen.

All of the children had hearing assessments; only 46% had normal hearing. Two factors, initial patch repair and intubation of at least 15 days, significantly predicted hearing loss. Of those with an initial patch repair, 43% had hearing loss. None of those who had a primary repair had hearing loss. While 44% of those with more than 15 days of intubation developed hearing loss, 95% of those with less than 15 days of intubation had normal hearing.

PHOENIX — Children with congenital diaphragmatic hernia are likely to have long-term health problems requiring close, long-term follow-up, Dr. Tim Jancelewicz said at the annual meeting of the American Pediatric Surgical Association.

Dr. Jancelewicz, of the University of California, San Francisco, and his colleagues reviewed 357 clinic visits made over a 10-year period by 90 patients with congenital diaphragmatic hernia (median follow-up 4 years). Of those, 8% required extracorporeal membrane oxygenation (median 15 days). Initial patch repair was done in 57%, and 36% have had recurrence of the hernias.

The children underwent neurodevelopmental assessment, which identified normal neurodevelopmental outcomes in 55% of the cohort. Another 13% had suspect disease, 24% had confirmed abnormal outcomes, findings for 8% were undetermined.

Four factors significantly predicted neurodevelopmental delay: liver herniation at birth, initial patch repair, intubation for at least 15 days, and discharge home on oxygen. Neurodevelopmental delay was seen in 59% of those with liver herniation, 60% of those with initial patch repair, 67% of those with at least 15 days of intubation, and 82% of those who were discharged on oxygen.

All of the children had hearing assessments; only 46% had normal hearing. Two factors, initial patch repair and intubation of at least 15 days, significantly predicted hearing loss. Of those with an initial patch repair, 43% had hearing loss. None of those who had a primary repair had hearing loss. While 44% of those with more than 15 days of intubation developed hearing loss, 95% of those with less than 15 days of intubation had normal hearing.

PHOENIX — Children with congenital diaphragmatic hernia are likely to have long-term health problems requiring close, long-term follow-up, Dr. Tim Jancelewicz said at the annual meeting of the American Pediatric Surgical Association.

Dr. Jancelewicz, of the University of California, San Francisco, and his colleagues reviewed 357 clinic visits made over a 10-year period by 90 patients with congenital diaphragmatic hernia (median follow-up 4 years). Of those, 8% required extracorporeal membrane oxygenation (median 15 days). Initial patch repair was done in 57%, and 36% have had recurrence of the hernias.

The children underwent neurodevelopmental assessment, which identified normal neurodevelopmental outcomes in 55% of the cohort. Another 13% had suspect disease, 24% had confirmed abnormal outcomes, findings for 8% were undetermined.

Four factors significantly predicted neurodevelopmental delay: liver herniation at birth, initial patch repair, intubation for at least 15 days, and discharge home on oxygen. Neurodevelopmental delay was seen in 59% of those with liver herniation, 60% of those with initial patch repair, 67% of those with at least 15 days of intubation, and 82% of those who were discharged on oxygen.

All of the children had hearing assessments; only 46% had normal hearing. Two factors, initial patch repair and intubation of at least 15 days, significantly predicted hearing loss. Of those with an initial patch repair, 43% had hearing loss. None of those who had a primary repair had hearing loss. While 44% of those with more than 15 days of intubation developed hearing loss, 95% of those with less than 15 days of intubation had normal hearing.

SAN FRANCISCO — While almost unheard of 10 years ago, community-associated methicillin-resistant Staphylococcus aureus has now become the single biggest cause of skin infections in the United States, Dr. Greg Moran said at the 12th International Conference on Emergency Medicine.

“We really don't know what's begun this sudden explosion of resistant staph in the community all over the United States, as well as in Canada and Europe,” said Dr. Moran, an emergency physician at the Olive View-UCLA Medical Center, Sylmar, Calif. “One thing we do know is that this is not a phenomenon of the hospital strains moving into the community. These are genetically distinct strains.”

In his 2006 study, virtually all the skin infections cultured from hospitals in 11 cities across the country were caused by community-associated strains; 78% of those were a single clone of USA300. “There is something about this strain that has given it a very, very strong survival advantage in the community,” Dr. Moran explained. “Almost all of [the skin infections] (98%) carried the Panton-Valentine leukocidin toxin gene and the SCCmec type IV gene.”

The SCCmec gene confers methicillin resistance, while the Panton-Valentine leukocidin toxin gene is associated with spontaneous skin and soft-tissue infections, as well as necrotizing pneumonia. Those mutations make the community-associated MRSA strains much more likely to cause infections than those MRSA strains found in hospitals, Dr. Moran said.

In addition to authoring a seminal paper on the topic (N. Engl. J. Med. 2006;355:666–74), Dr. Moran has kept track of the MRSA skin infections occurring in his own hospital since 1997. There were 25 cases documented that year. “That number rose to almost 450 per year in 2006 and 2007,” he said. “In 2001, 29% of our skin infections were MRSA. That more than doubled by 2003–2004, to 64%. In a very short time, we went from something we virtually never saw in the community, to it being the single largest cause of skin infections.”

Despite their prevalence, most of these infections are not serious and don't grow the “killer flesh-eating super bugs,” Dr. Moran said. “More than 90% of the isolates in our study were susceptible to at least one [antibiotic] agent.”

For most uncomplicated skin infections, he performs an incision and drainage, and he doesn't give antibiotics. “I do give antibiotics if there is a fever, significant associated cellulitis, immune or vascular compromise, if the lesion is in a high-risk area like the hands or face, or if the patient has already failed an incision and drainage,” Dr. Moran explained.

SAN FRANCISCO — While almost unheard of 10 years ago, community-associated methicillin-resistant Staphylococcus aureus has now become the single biggest cause of skin infections in the United States, Dr. Greg Moran said at the 12th International Conference on Emergency Medicine.

“We really don't know what's begun this sudden explosion of resistant staph in the community all over the United States, as well as in Canada and Europe,” said Dr. Moran, an emergency physician at the Olive View-UCLA Medical Center, Sylmar, Calif. “One thing we do know is that this is not a phenomenon of the hospital strains moving into the community. These are genetically distinct strains.”

In his 2006 study, virtually all the skin infections cultured from hospitals in 11 cities across the country were caused by community-associated strains; 78% of those were a single clone of USA300. “There is something about this strain that has given it a very, very strong survival advantage in the community,” Dr. Moran explained. “Almost all of [the skin infections] (98%) carried the Panton-Valentine leukocidin toxin gene and the SCCmec type IV gene.”

The SCCmec gene confers methicillin resistance, while the Panton-Valentine leukocidin toxin gene is associated with spontaneous skin and soft-tissue infections, as well as necrotizing pneumonia. Those mutations make the community-associated MRSA strains much more likely to cause infections than those MRSA strains found in hospitals, Dr. Moran said.

In addition to authoring a seminal paper on the topic (N. Engl. J. Med. 2006;355:666–74), Dr. Moran has kept track of the MRSA skin infections occurring in his own hospital since 1997. There were 25 cases documented that year. “That number rose to almost 450 per year in 2006 and 2007,” he said. “In 2001, 29% of our skin infections were MRSA. That more than doubled by 2003–2004, to 64%. In a very short time, we went from something we virtually never saw in the community, to it being the single largest cause of skin infections.”

Despite their prevalence, most of these infections are not serious and don't grow the “killer flesh-eating super bugs,” Dr. Moran said. “More than 90% of the isolates in our study were susceptible to at least one [antibiotic] agent.”

For most uncomplicated skin infections, he performs an incision and drainage, and he doesn't give antibiotics. “I do give antibiotics if there is a fever, significant associated cellulitis, immune or vascular compromise, if the lesion is in a high-risk area like the hands or face, or if the patient has already failed an incision and drainage,” Dr. Moran explained.

SAN FRANCISCO — While almost unheard of 10 years ago, community-associated methicillin-resistant Staphylococcus aureus has now become the single biggest cause of skin infections in the United States, Dr. Greg Moran said at the 12th International Conference on Emergency Medicine.

“We really don't know what's begun this sudden explosion of resistant staph in the community all over the United States, as well as in Canada and Europe,” said Dr. Moran, an emergency physician at the Olive View-UCLA Medical Center, Sylmar, Calif. “One thing we do know is that this is not a phenomenon of the hospital strains moving into the community. These are genetically distinct strains.”

In his 2006 study, virtually all the skin infections cultured from hospitals in 11 cities across the country were caused by community-associated strains; 78% of those were a single clone of USA300. “There is something about this strain that has given it a very, very strong survival advantage in the community,” Dr. Moran explained. “Almost all of [the skin infections] (98%) carried the Panton-Valentine leukocidin toxin gene and the SCCmec type IV gene.”

The SCCmec gene confers methicillin resistance, while the Panton-Valentine leukocidin toxin gene is associated with spontaneous skin and soft-tissue infections, as well as necrotizing pneumonia. Those mutations make the community-associated MRSA strains much more likely to cause infections than those MRSA strains found in hospitals, Dr. Moran said.

In addition to authoring a seminal paper on the topic (N. Engl. J. Med. 2006;355:666–74), Dr. Moran has kept track of the MRSA skin infections occurring in his own hospital since 1997. There were 25 cases documented that year. “That number rose to almost 450 per year in 2006 and 2007,” he said. “In 2001, 29% of our skin infections were MRSA. That more than doubled by 2003–2004, to 64%. In a very short time, we went from something we virtually never saw in the community, to it being the single largest cause of skin infections.”

Despite their prevalence, most of these infections are not serious and don't grow the “killer flesh-eating super bugs,” Dr. Moran said. “More than 90% of the isolates in our study were susceptible to at least one [antibiotic] agent.”

For most uncomplicated skin infections, he performs an incision and drainage, and he doesn't give antibiotics. “I do give antibiotics if there is a fever, significant associated cellulitis, immune or vascular compromise, if the lesion is in a high-risk area like the hands or face, or if the patient has already failed an incision and drainage,” Dr. Moran explained.

SAN FRANCISCO — Adventure tourists, international volunteers, and people visiting their families in underdeveloped countries are the travelers most likely to bring home unwanted souvenirs, from malaria to schistosomiasis.

“You're not going to see these things in businessmen who are staying in Hiltons and eating Western food when they go overseas,” Dr. Sukhjit Takhar said at the 12th International Conference on Emergency Medicine. “These are diseases that people contract when they are traveling for longer than a couple of weeks, or when they are really getting immersed in the local culture or eating the local food.”

Taking a good travel history is the first step in diagnosing an internationally acquired disease, said Dr. Takhar, an emergency physician at University of California San Francisco-Fresno.

“Find out where they went, and what they did. Were they staying in a hotel or out in the jungle dissecting monkeys? How long have they been back? This will give you an idea of the incubation period,” Dr. Takhar said.

Also ask them if they took any medicine when they began to feel ill. Many travelers self-medicate with antibiotics, which can quell symptoms but not fully cure the illness.

Managing Malaria

Apart from acute diarrhea, systemic febrile illnesses are the most common syndromes among returning travelers. Most of those will be either malaria or dengue fever.

Among all travelers, 35% will have malaria, which causes about 150 fatalities in returned travelers each year; and 10% will have dengue. More than 60% of travelers with a systemic febrile illness coming from Africa will have malaria, Dr. Takhar added. About 30% of ill travelers returning from Southeast Asia will have dengue fever.

Because of the prevalence, morbidity, and mortality of malaria, especially that caused by the Plasmodium falciparum parasite, patients who appear to have the disease should receive immediate treatment, even if they don't present acutely ill to the ED. “Malaria symptoms are cyclical, so up to 40% of patients will be afebrile when you see them in the ED,” Dr. Takhar said.

Falciparum malaria is the most dangerous form, provoking a flulike illness followed by paroxysmal fevers that last 8–12 hours and culminate in a drenching sweat. After that, the patient may feel well. The less common vivax malaria is also a less serious illness but causes similar symptoms.

The time since onset of symptoms is a clue to the type of malaria, Dr. Takhar said. The incubation period for falciparum malaria is about 10–14 days, while that of vivax malaria may be longer.

A blood smear will diagnose either form, with the parasites appearing in the erythrocytes. If the index of suspicion for malaria is high, however, and the patient reports travel to endemic areas, consider treating presumptively, Dr. Takhar advised. “They can look well and then decompensate very quickly, so don't wait around for a consult from a specialist.”

The treatment of choice in the United States is now quinidine. “Chloroquines don't work very well any more, because the parasites have become resistant,” he said, and the most potent antimalarial, artemether—an extract of the wormwood plant—isn't readily available in the United States.

A negative smear doesn't eliminate the possibility of malaria. “You can have a negative smear and still have it. The patient might have taken some doxycycline or azithromycin when he started feeling bad. Both of these have some antimalarial properties,” Dr. Takhar said. “If you don't see the parasites, get another smear in 12–24 hours.”

A negative malaria smear in a febrile patient with a low white blood cell count, thrombocytopenia, and recent travel to the tropics may point to another mosquito-borne illness: dengue fever.

Diagnosing Dengue Fever

The prevalence of dengue has grown dramatically in recent decades. It's now found in more than 100 countries in Africa, Central and South America, the Caribbean, Asia, Southeast Asia, and even around the Mediterranean. The illness affects up to 100 million people annually, with about 25,000 deaths. “Travelers who don't protect themselves from mosquitoes in these areas will very likely come down with this illness,” Dr. Takhar said.

The dengue virus causes a severe flulike illness with high fever, headache, retro-orbital pain, and a myalgia so painful that dengue is nicknamed “breakbone fever,” Dr. Takhar said.

While most cases are self-limiting and require only supportive care, the hemorrhagic form can be deadly. In addition to petechiae, patients may have plasma leakage leading to pleural effusion, dropping platelets, rising hematocrit, and ascites. “These symptoms can be deadly,” Dr. Takhar cautioned.

Again, treatment is supportive. “You need to give IV fluids, but because these patients leak plasma, you should also put in a central line to measure central venous pressure,” he said. Don't give any aspirin or ibuprofen for the pain, because those agents can exacerbate bleeding.

Assessing Tick Bites and Flatworms

Rickettsial diseases are sometimes seen in those who travel to Africa during tick season (April-November). Fever, myalgia, and headache characterize the illnesses; an eschar at the site of the tick bite is another clue. Most rickettsial infections respond very quickly to a course of doxycycline.

African travelers who swam in lakes may bring home a load of schistosomes. The parasitic flatworms live in freshwater snails, which release the larvae into the water. The larvae burrow into a swimmer's skin and take up residence in the liver. After maturing (up to 10 mm long), the worms mate and move into the rectal and mesenteric veins, where they release their eggs. The eggs pass into the intestine, bladder, or rectum, and are excreted.

The worms live up to 4 years, so natives of endemic areas can have huge loads that create chronic disease. However, travelers usually come down with an acute case, called Katayama fever. Symptoms include abdominal pain, cough, diarrhea, eosinophilia, fever, fatigue, and hepatosplenomegaly. Early in the course, the patient may have urticaria and a rash where the larvae penetrated the skin.

Diagnosis is by fecal smear or urinalysis positive for the flatworm's eggs. Schistosomal antibodies can also be positive. Praziquantel is the usual treatment, Dr. Takhar said. It should probably be prescribed by an infectious disease specialist who can provide adequate follow-up.

'You're not going to see these things in businessmen who are staying in Hiltons and eating Western food.' DR. TAKHAR

SAN FRANCISCO — Adventure tourists, international volunteers, and people visiting their families in underdeveloped countries are the travelers most likely to bring home unwanted souvenirs, from malaria to schistosomiasis.

“You're not going to see these things in businessmen who are staying in Hiltons and eating Western food when they go overseas,” Dr. Sukhjit Takhar said at the 12th International Conference on Emergency Medicine. “These are diseases that people contract when they are traveling for longer than a couple of weeks, or when they are really getting immersed in the local culture or eating the local food.”

Taking a good travel history is the first step in diagnosing an internationally acquired disease, said Dr. Takhar, an emergency physician at University of California San Francisco-Fresno.

“Find out where they went, and what they did. Were they staying in a hotel or out in the jungle dissecting monkeys? How long have they been back? This will give you an idea of the incubation period,” Dr. Takhar said.

Also ask them if they took any medicine when they began to feel ill. Many travelers self-medicate with antibiotics, which can quell symptoms but not fully cure the illness.

Managing Malaria

Apart from acute diarrhea, systemic febrile illnesses are the most common syndromes among returning travelers. Most of those will be either malaria or dengue fever.

Among all travelers, 35% will have malaria, which causes about 150 fatalities in returned travelers each year; and 10% will have dengue. More than 60% of travelers with a systemic febrile illness coming from Africa will have malaria, Dr. Takhar added. About 30% of ill travelers returning from Southeast Asia will have dengue fever.

Because of the prevalence, morbidity, and mortality of malaria, especially that caused by the Plasmodium falciparum parasite, patients who appear to have the disease should receive immediate treatment, even if they don't present acutely ill to the ED. “Malaria symptoms are cyclical, so up to 40% of patients will be afebrile when you see them in the ED,” Dr. Takhar said.

Falciparum malaria is the most dangerous form, provoking a flulike illness followed by paroxysmal fevers that last 8–12 hours and culminate in a drenching sweat. After that, the patient may feel well. The less common vivax malaria is also a less serious illness but causes similar symptoms.

The time since onset of symptoms is a clue to the type of malaria, Dr. Takhar said. The incubation period for falciparum malaria is about 10–14 days, while that of vivax malaria may be longer.

A blood smear will diagnose either form, with the parasites appearing in the erythrocytes. If the index of suspicion for malaria is high, however, and the patient reports travel to endemic areas, consider treating presumptively, Dr. Takhar advised. “They can look well and then decompensate very quickly, so don't wait around for a consult from a specialist.”

The treatment of choice in the United States is now quinidine. “Chloroquines don't work very well any more, because the parasites have become resistant,” he said, and the most potent antimalarial, artemether—an extract of the wormwood plant—isn't readily available in the United States.

A negative smear doesn't eliminate the possibility of malaria. “You can have a negative smear and still have it. The patient might have taken some doxycycline or azithromycin when he started feeling bad. Both of these have some antimalarial properties,” Dr. Takhar said. “If you don't see the parasites, get another smear in 12–24 hours.”

A negative malaria smear in a febrile patient with a low white blood cell count, thrombocytopenia, and recent travel to the tropics may point to another mosquito-borne illness: dengue fever.

Diagnosing Dengue Fever

The prevalence of dengue has grown dramatically in recent decades. It's now found in more than 100 countries in Africa, Central and South America, the Caribbean, Asia, Southeast Asia, and even around the Mediterranean. The illness affects up to 100 million people annually, with about 25,000 deaths. “Travelers who don't protect themselves from mosquitoes in these areas will very likely come down with this illness,” Dr. Takhar said.

The dengue virus causes a severe flulike illness with high fever, headache, retro-orbital pain, and a myalgia so painful that dengue is nicknamed “breakbone fever,” Dr. Takhar said.

While most cases are self-limiting and require only supportive care, the hemorrhagic form can be deadly. In addition to petechiae, patients may have plasma leakage leading to pleural effusion, dropping platelets, rising hematocrit, and ascites. “These symptoms can be deadly,” Dr. Takhar cautioned.

Again, treatment is supportive. “You need to give IV fluids, but because these patients leak plasma, you should also put in a central line to measure central venous pressure,” he said. Don't give any aspirin or ibuprofen for the pain, because those agents can exacerbate bleeding.

Assessing Tick Bites and Flatworms

Rickettsial diseases are sometimes seen in those who travel to Africa during tick season (April-November). Fever, myalgia, and headache characterize the illnesses; an eschar at the site of the tick bite is another clue. Most rickettsial infections respond very quickly to a course of doxycycline.

African travelers who swam in lakes may bring home a load of schistosomes. The parasitic flatworms live in freshwater snails, which release the larvae into the water. The larvae burrow into a swimmer's skin and take up residence in the liver. After maturing (up to 10 mm long), the worms mate and move into the rectal and mesenteric veins, where they release their eggs. The eggs pass into the intestine, bladder, or rectum, and are excreted.

The worms live up to 4 years, so natives of endemic areas can have huge loads that create chronic disease. However, travelers usually come down with an acute case, called Katayama fever. Symptoms include abdominal pain, cough, diarrhea, eosinophilia, fever, fatigue, and hepatosplenomegaly. Early in the course, the patient may have urticaria and a rash where the larvae penetrated the skin.

Diagnosis is by fecal smear or urinalysis positive for the flatworm's eggs. Schistosomal antibodies can also be positive. Praziquantel is the usual treatment, Dr. Takhar said. It should probably be prescribed by an infectious disease specialist who can provide adequate follow-up.

'You're not going to see these things in businessmen who are staying in Hiltons and eating Western food.' DR. TAKHAR

SAN FRANCISCO — Adventure tourists, international volunteers, and people visiting their families in underdeveloped countries are the travelers most likely to bring home unwanted souvenirs, from malaria to schistosomiasis.

“You're not going to see these things in businessmen who are staying in Hiltons and eating Western food when they go overseas,” Dr. Sukhjit Takhar said at the 12th International Conference on Emergency Medicine. “These are diseases that people contract when they are traveling for longer than a couple of weeks, or when they are really getting immersed in the local culture or eating the local food.”

Taking a good travel history is the first step in diagnosing an internationally acquired disease, said Dr. Takhar, an emergency physician at University of California San Francisco-Fresno.

“Find out where they went, and what they did. Were they staying in a hotel or out in the jungle dissecting monkeys? How long have they been back? This will give you an idea of the incubation period,” Dr. Takhar said.

Also ask them if they took any medicine when they began to feel ill. Many travelers self-medicate with antibiotics, which can quell symptoms but not fully cure the illness.

Managing Malaria

Apart from acute diarrhea, systemic febrile illnesses are the most common syndromes among returning travelers. Most of those will be either malaria or dengue fever.

Among all travelers, 35% will have malaria, which causes about 150 fatalities in returned travelers each year; and 10% will have dengue. More than 60% of travelers with a systemic febrile illness coming from Africa will have malaria, Dr. Takhar added. About 30% of ill travelers returning from Southeast Asia will have dengue fever.

Because of the prevalence, morbidity, and mortality of malaria, especially that caused by the Plasmodium falciparum parasite, patients who appear to have the disease should receive immediate treatment, even if they don't present acutely ill to the ED. “Malaria symptoms are cyclical, so up to 40% of patients will be afebrile when you see them in the ED,” Dr. Takhar said.

Falciparum malaria is the most dangerous form, provoking a flulike illness followed by paroxysmal fevers that last 8–12 hours and culminate in a drenching sweat. After that, the patient may feel well. The less common vivax malaria is also a less serious illness but causes similar symptoms.

The time since onset of symptoms is a clue to the type of malaria, Dr. Takhar said. The incubation period for falciparum malaria is about 10–14 days, while that of vivax malaria may be longer.

A blood smear will diagnose either form, with the parasites appearing in the erythrocytes. If the index of suspicion for malaria is high, however, and the patient reports travel to endemic areas, consider treating presumptively, Dr. Takhar advised. “They can look well and then decompensate very quickly, so don't wait around for a consult from a specialist.”

The treatment of choice in the United States is now quinidine. “Chloroquines don't work very well any more, because the parasites have become resistant,” he said, and the most potent antimalarial, artemether—an extract of the wormwood plant—isn't readily available in the United States.

A negative smear doesn't eliminate the possibility of malaria. “You can have a negative smear and still have it. The patient might have taken some doxycycline or azithromycin when he started feeling bad. Both of these have some antimalarial properties,” Dr. Takhar said. “If you don't see the parasites, get another smear in 12–24 hours.”

A negative malaria smear in a febrile patient with a low white blood cell count, thrombocytopenia, and recent travel to the tropics may point to another mosquito-borne illness: dengue fever.

Diagnosing Dengue Fever

The prevalence of dengue has grown dramatically in recent decades. It's now found in more than 100 countries in Africa, Central and South America, the Caribbean, Asia, Southeast Asia, and even around the Mediterranean. The illness affects up to 100 million people annually, with about 25,000 deaths. “Travelers who don't protect themselves from mosquitoes in these areas will very likely come down with this illness,” Dr. Takhar said.

The dengue virus causes a severe flulike illness with high fever, headache, retro-orbital pain, and a myalgia so painful that dengue is nicknamed “breakbone fever,” Dr. Takhar said.

While most cases are self-limiting and require only supportive care, the hemorrhagic form can be deadly. In addition to petechiae, patients may have plasma leakage leading to pleural effusion, dropping platelets, rising hematocrit, and ascites. “These symptoms can be deadly,” Dr. Takhar cautioned.

Again, treatment is supportive. “You need to give IV fluids, but because these patients leak plasma, you should also put in a central line to measure central venous pressure,” he said. Don't give any aspirin or ibuprofen for the pain, because those agents can exacerbate bleeding.

Assessing Tick Bites and Flatworms

Rickettsial diseases are sometimes seen in those who travel to Africa during tick season (April-November). Fever, myalgia, and headache characterize the illnesses; an eschar at the site of the tick bite is another clue. Most rickettsial infections respond very quickly to a course of doxycycline.

African travelers who swam in lakes may bring home a load of schistosomes. The parasitic flatworms live in freshwater snails, which release the larvae into the water. The larvae burrow into a swimmer's skin and take up residence in the liver. After maturing (up to 10 mm long), the worms mate and move into the rectal and mesenteric veins, where they release their eggs. The eggs pass into the intestine, bladder, or rectum, and are excreted.

The worms live up to 4 years, so natives of endemic areas can have huge loads that create chronic disease. However, travelers usually come down with an acute case, called Katayama fever. Symptoms include abdominal pain, cough, diarrhea, eosinophilia, fever, fatigue, and hepatosplenomegaly. Early in the course, the patient may have urticaria and a rash where the larvae penetrated the skin.

Diagnosis is by fecal smear or urinalysis positive for the flatworm's eggs. Schistosomal antibodies can also be positive. Praziquantel is the usual treatment, Dr. Takhar said. It should probably be prescribed by an infectious disease specialist who can provide adequate follow-up.

'You're not going to see these things in businessmen who are staying in Hiltons and eating Western food.' DR. TAKHAR

Data from new studies suggest that patients with Parkinson's disease might benefit from deep brain stimulation surgery much earlier in their disease course, offering tantalizing hints that early surgery could actually delay progression by protecting the cells that Parkinson's destroys.

Since its 2002 approval for Parkinson's, bilateral subthalamic nucleus stimulation–a form of deep brain stimulation–has been reserved as a last resort for the most severely affected patients: those whose motor symptoms can no longer be controlled by medications because they experience severe side effects of chronic le-vodopa therapy.

But findings from at least one recent study suggest that early implantation of the electrodes also significantly improves quality of life for patients when some of these issues are just beginning to appear. Experts say this approach might be particularly beneficial for young patients who can be expected to have a long disease course and thus are at greater risk of developing complications of medical treatment.

“The idea behind earlier surgery is not to wait until the last minute, or just consider it a last-ditch effort,” Dr. David Riley, director of the Movement Disorders Center at the Neurological Institute of University Hospitals Case Medical Center, Cleveland, said in an interview. “The studies tell us that people who develop motor fluctuations will do better with surgery than with any combination of medications we can develop. Once a patient is spending more than 25% of the day in the 'off' state, we should be considering him or her for DBS surgery.”

While anecdotal reports and case series have described the results of earlier DBS surgery, researchers are only now beginning to explore the question systematically, said Dr. Michael Schüpbach, a movement disorders researcher at the Groupe Hospitalier Pitié-Salpêtrière, Paris. His 2007 pilot study examined the issue in a small group of patients with earlier disease (Neurology 2007;68:267–71).

“Our patients in general profited from DBS, not only on the motor symptom level, but in their activities of daily living, their disease-specific quality of life, and their overall psychiatric state,” he said in an interview.

The trial, sponsored by Medtronic, included 20 patients with disease duration of 5–10 years, a Hoehn and Yahr stage of 3 or lower, and motor fluctuations during “off” periods for 25% or more of the day. Half of the group received best medical therapy; the other half underwent DBS surgery while continuing on their medication, adjusted as necessary. They were followed for 18 months.

By the end of the follow-up period, Dr. Schüpbach and his colleagues observed several differences between the groups:

▸ Activities of daily living ratings declined significantly in patients who had been medically treated during their “off” periods, while they improved significantly throughout the study in the DBS group.

▸ Motor disability scores during “off” periods declined significantly in the medically treated group, dropping 29% by the study's end. In the DBS group, these scores improved by 69% at the same time point.

▸ By 18 months, medically managed patients experienced a significant 12% increase in their levodopa dosage, whereas their drug-induced motor complications worsened by 15%. Among the DBS patients, however, levodopa dosage decreased by 57% at 18 months, and the severity of drug-induced motor complications lessened by 83%.

▸ Anxiety and overall psychiatric morbidity improved significantly only in the DBS group. These patients also showed a trend toward improved mood, although the change was not significant.

“While this was only a pilot study that needs confirmation, I think it provided a very strong argument not to withhold surgery for the longest possible time, as we now do,” Dr. Schüpbach said.

However, he cautioned, both patients and physicians must carefully weigh the risks and benefits. There were no serious surgical adverse events in his study, but four DBS patients did develop depression, compared with three medically managed patients. “However, with only 20 patients, it's difficult to conclude anything about side effects,” Dr. Schüpbach said. “That would take a bigger study, and in fact, we're recruiting for one now.”

The EARLYSTIM trial, sponsored by the French government, will include 250 patients at 16 centers in France and Germany. Patients must have a Hoehn and Yahr stage of 2.5 or lower while on medication, and disease duration of more than 4 years. Again, the comparator arms are DBS plus medication, or best medical management alone. The patients will be followed for 2 years.

“We want to include patients with extremely early disease with the goal to keep them functional in their work and social context,” Dr. Schüpbach said. “I'm cautiously optimistic that the EARLYSTIM trial will replicate our pilot study.”

A smaller trial is also recruiting in the United States. While this study will provide information about the functional benefit of DBS in early Parkinson's, its main goal is to explore the neuroprotective effect of early surgery.

“To date, no therapy–not medication, surgery, stem cell or gene therapy–has been shown to slow the progression of Parkinson's disease,” Dr. David Charles, director of the Movement Disorders Clinic at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “But recent animal studies have given us some really exciting insight into just how that might be accomplished.”

The Medtronic-sponsored Vanderbilt trial, which is just wrapping up its recruitment phase, will include 30 patients randomized to DBS plus medication or medication alone. These patients must have very early Parkinson's, with a Hoehn and Yahr stage of 2 when off medication; the follow-up is 2 years.

The study's main safety end point is the time to a 20% worsening in motor scores. “One concern with early stimulation is that we could somehow worsen Parkinson's disease, or cause some unforeseen problem, by applying the therapy early,” Dr. Charles said.

But perhaps more intriguing is the efficacy end point–the reduction in symptoms when the patient is off both medication and stimulation. The level to which symptoms decrease might give researchers insight into whether early DBS slows disease progression. Although he called it “a long shot,” Dr. Charles said the two in vivo studies give reason to hope.

In 2006, investigators at Maastricht (the Netherlands) University explored the neuroprotective effect of DBS in rats with a created model of Parkinson's disease–a toxin that killed up to 50% of the dopaminergic cells when injected into the substantia nigra. During the same procedure, some of the rats also underwent implantation of bilateral DBS electrodes. After 1 week, rats who received DBS had 30% more neurons in the substantia nigra than rats who received no treatment–suggesting that the activation of the electrodes had protected the cells from the toxin (Brain Res. 2006;1120:100–5).

“The most exciting study, though, was one performed in monkeys and published last year,” Dr. Charles said. “This study is superior, not only in its primate model, but in its Parkinsonian model, which more closely simulates the disease in humans.”

The French study, cowritten by DBS pioneer Dr. Alim-Louis Benabid, included 28 macaque monkeys (Brain 2007;130:2129–45).

Again, the researchers used a toxin to induce symptoms; in some monkeys, the toxic drug was delivered a week before surgery, allowing time for the dopaminergic cells to die off before brain stimulation began. “We know that by the time a patient presents with the first symptoms of Parkinson's, up to 70% of the substantia nigra neurons have already been lost,” Dr. Charles said. “This model was more similar to the natural history of the disease in humans.”

Monkeys in the experimental group received DBS for about 7 months. At the study's end, they showed up to 24% more nigral cells than did monkeys that had no stimulation.

Dr. Charles explained the theory behind this preservation effect. “Once the substantia nigra begins to degenerate, the subthalamic nucleus becomes hyperactive and increases its output of glutamate, which is toxic to dopamine-manufacturing cells. Although we don't know why the cells begin to die off in the first place, one strategy for protecting them from further depletion could be to reduce the hyperactive output of the subthalamic nucleus; DBS is thought to do that.”

Dr. Schüpbach is less enthusiastic about any potentially disease-modifying effect of DBS. “It's an open question at best,” he said. “We have more than 10 years of experience with DBS in Parkinson's patients, and we know that they do progress in spite of the treatment–especially with axial symptoms, which don't respond to either medication or simulation.”

Neuroprotection will be hard to prove in a small trial, he said. “We considered including it as a secondary outcome in the EARLYSTIM trial. But a power calculation told us that even with 250 patients, we would probably not be able to show a protective effect. If there is one, it would certainly be partial. There is certainly progression in spite of DBS, and it is certainly wrong to recommend it as a neuroprotective treatment without further evidence.”

All the researchers, however, agreed that the benefits of DBS should no longer be thought of as a last resort. In an editorial that accompanied Dr. Schüpbach's 2007 study, Dr. Riley noted that even under currently accepted surgical practice, too few people are getting the procedure. “Only a minor fraction of patents with Parkinson's who would benefit from DBS currently experience this treatment,” he wrote. Dr. Schüpbach's study “indicates that earlier application of DBS represents an improvement over our current approach to managing Parkinson's.”

Dr. Charles said he has received payments from Medtronic lectures and consulting; Dr. Schüpbach said he has no financial ties with the company.

Dr. David Charles checks a patient's deep brain stimulation device. Dr. Charles suspects that DBS reduces the hyperactive output of the subthalamic nucleus. Dana Johnson/Vanderbilt University Medical Center

Data from new studies suggest that patients with Parkinson's disease might benefit from deep brain stimulation surgery much earlier in their disease course, offering tantalizing hints that early surgery could actually delay progression by protecting the cells that Parkinson's destroys.

Since its 2002 approval for Parkinson's, bilateral subthalamic nucleus stimulation–a form of deep brain stimulation–has been reserved as a last resort for the most severely affected patients: those whose motor symptoms can no longer be controlled by medications because they experience severe side effects of chronic le-vodopa therapy.

But findings from at least one recent study suggest that early implantation of the electrodes also significantly improves quality of life for patients when some of these issues are just beginning to appear. Experts say this approach might be particularly beneficial for young patients who can be expected to have a long disease course and thus are at greater risk of developing complications of medical treatment.

“The idea behind earlier surgery is not to wait until the last minute, or just consider it a last-ditch effort,” Dr. David Riley, director of the Movement Disorders Center at the Neurological Institute of University Hospitals Case Medical Center, Cleveland, said in an interview. “The studies tell us that people who develop motor fluctuations will do better with surgery than with any combination of medications we can develop. Once a patient is spending more than 25% of the day in the 'off' state, we should be considering him or her for DBS surgery.”

While anecdotal reports and case series have described the results of earlier DBS surgery, researchers are only now beginning to explore the question systematically, said Dr. Michael Schüpbach, a movement disorders researcher at the Groupe Hospitalier Pitié-Salpêtrière, Paris. His 2007 pilot study examined the issue in a small group of patients with earlier disease (Neurology 2007;68:267–71).

“Our patients in general profited from DBS, not only on the motor symptom level, but in their activities of daily living, their disease-specific quality of life, and their overall psychiatric state,” he said in an interview.

The trial, sponsored by Medtronic, included 20 patients with disease duration of 5–10 years, a Hoehn and Yahr stage of 3 or lower, and motor fluctuations during “off” periods for 25% or more of the day. Half of the group received best medical therapy; the other half underwent DBS surgery while continuing on their medication, adjusted as necessary. They were followed for 18 months.

By the end of the follow-up period, Dr. Schüpbach and his colleagues observed several differences between the groups:

▸ Activities of daily living ratings declined significantly in patients who had been medically treated during their “off” periods, while they improved significantly throughout the study in the DBS group.

▸ Motor disability scores during “off” periods declined significantly in the medically treated group, dropping 29% by the study's end. In the DBS group, these scores improved by 69% at the same time point.

▸ By 18 months, medically managed patients experienced a significant 12% increase in their levodopa dosage, whereas their drug-induced motor complications worsened by 15%. Among the DBS patients, however, levodopa dosage decreased by 57% at 18 months, and the severity of drug-induced motor complications lessened by 83%.

▸ Anxiety and overall psychiatric morbidity improved significantly only in the DBS group. These patients also showed a trend toward improved mood, although the change was not significant.

“While this was only a pilot study that needs confirmation, I think it provided a very strong argument not to withhold surgery for the longest possible time, as we now do,” Dr. Schüpbach said.

However, he cautioned, both patients and physicians must carefully weigh the risks and benefits. There were no serious surgical adverse events in his study, but four DBS patients did develop depression, compared with three medically managed patients. “However, with only 20 patients, it's difficult to conclude anything about side effects,” Dr. Schüpbach said. “That would take a bigger study, and in fact, we're recruiting for one now.”

The EARLYSTIM trial, sponsored by the French government, will include 250 patients at 16 centers in France and Germany. Patients must have a Hoehn and Yahr stage of 2.5 or lower while on medication, and disease duration of more than 4 years. Again, the comparator arms are DBS plus medication, or best medical management alone. The patients will be followed for 2 years.

“We want to include patients with extremely early disease with the goal to keep them functional in their work and social context,” Dr. Schüpbach said. “I'm cautiously optimistic that the EARLYSTIM trial will replicate our pilot study.”

A smaller trial is also recruiting in the United States. While this study will provide information about the functional benefit of DBS in early Parkinson's, its main goal is to explore the neuroprotective effect of early surgery.

“To date, no therapy–not medication, surgery, stem cell or gene therapy–has been shown to slow the progression of Parkinson's disease,” Dr. David Charles, director of the Movement Disorders Clinic at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “But recent animal studies have given us some really exciting insight into just how that might be accomplished.”

The Medtronic-sponsored Vanderbilt trial, which is just wrapping up its recruitment phase, will include 30 patients randomized to DBS plus medication or medication alone. These patients must have very early Parkinson's, with a Hoehn and Yahr stage of 2 when off medication; the follow-up is 2 years.

The study's main safety end point is the time to a 20% worsening in motor scores. “One concern with early stimulation is that we could somehow worsen Parkinson's disease, or cause some unforeseen problem, by applying the therapy early,” Dr. Charles said.

But perhaps more intriguing is the efficacy end point–the reduction in symptoms when the patient is off both medication and stimulation. The level to which symptoms decrease might give researchers insight into whether early DBS slows disease progression. Although he called it “a long shot,” Dr. Charles said the two in vivo studies give reason to hope.

In 2006, investigators at Maastricht (the Netherlands) University explored the neuroprotective effect of DBS in rats with a created model of Parkinson's disease–a toxin that killed up to 50% of the dopaminergic cells when injected into the substantia nigra. During the same procedure, some of the rats also underwent implantation of bilateral DBS electrodes. After 1 week, rats who received DBS had 30% more neurons in the substantia nigra than rats who received no treatment–suggesting that the activation of the electrodes had protected the cells from the toxin (Brain Res. 2006;1120:100–5).

“The most exciting study, though, was one performed in monkeys and published last year,” Dr. Charles said. “This study is superior, not only in its primate model, but in its Parkinsonian model, which more closely simulates the disease in humans.”

The French study, cowritten by DBS pioneer Dr. Alim-Louis Benabid, included 28 macaque monkeys (Brain 2007;130:2129–45).

Again, the researchers used a toxin to induce symptoms; in some monkeys, the toxic drug was delivered a week before surgery, allowing time for the dopaminergic cells to die off before brain stimulation began. “We know that by the time a patient presents with the first symptoms of Parkinson's, up to 70% of the substantia nigra neurons have already been lost,” Dr. Charles said. “This model was more similar to the natural history of the disease in humans.”

Monkeys in the experimental group received DBS for about 7 months. At the study's end, they showed up to 24% more nigral cells than did monkeys that had no stimulation.

Dr. Charles explained the theory behind this preservation effect. “Once the substantia nigra begins to degenerate, the subthalamic nucleus becomes hyperactive and increases its output of glutamate, which is toxic to dopamine-manufacturing cells. Although we don't know why the cells begin to die off in the first place, one strategy for protecting them from further depletion could be to reduce the hyperactive output of the subthalamic nucleus; DBS is thought to do that.”

Dr. Schüpbach is less enthusiastic about any potentially disease-modifying effect of DBS. “It's an open question at best,” he said. “We have more than 10 years of experience with DBS in Parkinson's patients, and we know that they do progress in spite of the treatment–especially with axial symptoms, which don't respond to either medication or simulation.”

Neuroprotection will be hard to prove in a small trial, he said. “We considered including it as a secondary outcome in the EARLYSTIM trial. But a power calculation told us that even with 250 patients, we would probably not be able to show a protective effect. If there is one, it would certainly be partial. There is certainly progression in spite of DBS, and it is certainly wrong to recommend it as a neuroprotective treatment without further evidence.”

All the researchers, however, agreed that the benefits of DBS should no longer be thought of as a last resort. In an editorial that accompanied Dr. Schüpbach's 2007 study, Dr. Riley noted that even under currently accepted surgical practice, too few people are getting the procedure. “Only a minor fraction of patents with Parkinson's who would benefit from DBS currently experience this treatment,” he wrote. Dr. Schüpbach's study “indicates that earlier application of DBS represents an improvement over our current approach to managing Parkinson's.”

Dr. Charles said he has received payments from Medtronic lectures and consulting; Dr. Schüpbach said he has no financial ties with the company.

Dr. David Charles checks a patient's deep brain stimulation device. Dr. Charles suspects that DBS reduces the hyperactive output of the subthalamic nucleus. Dana Johnson/Vanderbilt University Medical Center

Data from new studies suggest that patients with Parkinson's disease might benefit from deep brain stimulation surgery much earlier in their disease course, offering tantalizing hints that early surgery could actually delay progression by protecting the cells that Parkinson's destroys.

Since its 2002 approval for Parkinson's, bilateral subthalamic nucleus stimulation–a form of deep brain stimulation–has been reserved as a last resort for the most severely affected patients: those whose motor symptoms can no longer be controlled by medications because they experience severe side effects of chronic le-vodopa therapy.

But findings from at least one recent study suggest that early implantation of the electrodes also significantly improves quality of life for patients when some of these issues are just beginning to appear. Experts say this approach might be particularly beneficial for young patients who can be expected to have a long disease course and thus are at greater risk of developing complications of medical treatment.

“The idea behind earlier surgery is not to wait until the last minute, or just consider it a last-ditch effort,” Dr. David Riley, director of the Movement Disorders Center at the Neurological Institute of University Hospitals Case Medical Center, Cleveland, said in an interview. “The studies tell us that people who develop motor fluctuations will do better with surgery than with any combination of medications we can develop. Once a patient is spending more than 25% of the day in the 'off' state, we should be considering him or her for DBS surgery.”

While anecdotal reports and case series have described the results of earlier DBS surgery, researchers are only now beginning to explore the question systematically, said Dr. Michael Schüpbach, a movement disorders researcher at the Groupe Hospitalier Pitié-Salpêtrière, Paris. His 2007 pilot study examined the issue in a small group of patients with earlier disease (Neurology 2007;68:267–71).

“Our patients in general profited from DBS, not only on the motor symptom level, but in their activities of daily living, their disease-specific quality of life, and their overall psychiatric state,” he said in an interview.

The trial, sponsored by Medtronic, included 20 patients with disease duration of 5–10 years, a Hoehn and Yahr stage of 3 or lower, and motor fluctuations during “off” periods for 25% or more of the day. Half of the group received best medical therapy; the other half underwent DBS surgery while continuing on their medication, adjusted as necessary. They were followed for 18 months.

By the end of the follow-up period, Dr. Schüpbach and his colleagues observed several differences between the groups:

▸ Activities of daily living ratings declined significantly in patients who had been medically treated during their “off” periods, while they improved significantly throughout the study in the DBS group.

▸ Motor disability scores during “off” periods declined significantly in the medically treated group, dropping 29% by the study's end. In the DBS group, these scores improved by 69% at the same time point.

▸ By 18 months, medically managed patients experienced a significant 12% increase in their levodopa dosage, whereas their drug-induced motor complications worsened by 15%. Among the DBS patients, however, levodopa dosage decreased by 57% at 18 months, and the severity of drug-induced motor complications lessened by 83%.

▸ Anxiety and overall psychiatric morbidity improved significantly only in the DBS group. These patients also showed a trend toward improved mood, although the change was not significant.

“While this was only a pilot study that needs confirmation, I think it provided a very strong argument not to withhold surgery for the longest possible time, as we now do,” Dr. Schüpbach said.

However, he cautioned, both patients and physicians must carefully weigh the risks and benefits. There were no serious surgical adverse events in his study, but four DBS patients did develop depression, compared with three medically managed patients. “However, with only 20 patients, it's difficult to conclude anything about side effects,” Dr. Schüpbach said. “That would take a bigger study, and in fact, we're recruiting for one now.”

The EARLYSTIM trial, sponsored by the French government, will include 250 patients at 16 centers in France and Germany. Patients must have a Hoehn and Yahr stage of 2.5 or lower while on medication, and disease duration of more than 4 years. Again, the comparator arms are DBS plus medication, or best medical management alone. The patients will be followed for 2 years.

“We want to include patients with extremely early disease with the goal to keep them functional in their work and social context,” Dr. Schüpbach said. “I'm cautiously optimistic that the EARLYSTIM trial will replicate our pilot study.”

A smaller trial is also recruiting in the United States. While this study will provide information about the functional benefit of DBS in early Parkinson's, its main goal is to explore the neuroprotective effect of early surgery.

“To date, no therapy–not medication, surgery, stem cell or gene therapy–has been shown to slow the progression of Parkinson's disease,” Dr. David Charles, director of the Movement Disorders Clinic at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “But recent animal studies have given us some really exciting insight into just how that might be accomplished.”

The Medtronic-sponsored Vanderbilt trial, which is just wrapping up its recruitment phase, will include 30 patients randomized to DBS plus medication or medication alone. These patients must have very early Parkinson's, with a Hoehn and Yahr stage of 2 when off medication; the follow-up is 2 years.

The study's main safety end point is the time to a 20% worsening in motor scores. “One concern with early stimulation is that we could somehow worsen Parkinson's disease, or cause some unforeseen problem, by applying the therapy early,” Dr. Charles said.

But perhaps more intriguing is the efficacy end point–the reduction in symptoms when the patient is off both medication and stimulation. The level to which symptoms decrease might give researchers insight into whether early DBS slows disease progression. Although he called it “a long shot,” Dr. Charles said the two in vivo studies give reason to hope.

In 2006, investigators at Maastricht (the Netherlands) University explored the neuroprotective effect of DBS in rats with a created model of Parkinson's disease–a toxin that killed up to 50% of the dopaminergic cells when injected into the substantia nigra. During the same procedure, some of the rats also underwent implantation of bilateral DBS electrodes. After 1 week, rats who received DBS had 30% more neurons in the substantia nigra than rats who received no treatment–suggesting that the activation of the electrodes had protected the cells from the toxin (Brain Res. 2006;1120:100–5).

“The most exciting study, though, was one performed in monkeys and published last year,” Dr. Charles said. “This study is superior, not only in its primate model, but in its Parkinsonian model, which more closely simulates the disease in humans.”

The French study, cowritten by DBS pioneer Dr. Alim-Louis Benabid, included 28 macaque monkeys (Brain 2007;130:2129–45).

Again, the researchers used a toxin to induce symptoms; in some monkeys, the toxic drug was delivered a week before surgery, allowing time for the dopaminergic cells to die off before brain stimulation began. “We know that by the time a patient presents with the first symptoms of Parkinson's, up to 70% of the substantia nigra neurons have already been lost,” Dr. Charles said. “This model was more similar to the natural history of the disease in humans.”

Monkeys in the experimental group received DBS for about 7 months. At the study's end, they showed up to 24% more nigral cells than did monkeys that had no stimulation.

Dr. Charles explained the theory behind this preservation effect. “Once the substantia nigra begins to degenerate, the subthalamic nucleus becomes hyperactive and increases its output of glutamate, which is toxic to dopamine-manufacturing cells. Although we don't know why the cells begin to die off in the first place, one strategy for protecting them from further depletion could be to reduce the hyperactive output of the subthalamic nucleus; DBS is thought to do that.”

Dr. Schüpbach is less enthusiastic about any potentially disease-modifying effect of DBS. “It's an open question at best,” he said. “We have more than 10 years of experience with DBS in Parkinson's patients, and we know that they do progress in spite of the treatment–especially with axial symptoms, which don't respond to either medication or simulation.”

Neuroprotection will be hard to prove in a small trial, he said. “We considered including it as a secondary outcome in the EARLYSTIM trial. But a power calculation told us that even with 250 patients, we would probably not be able to show a protective effect. If there is one, it would certainly be partial. There is certainly progression in spite of DBS, and it is certainly wrong to recommend it as a neuroprotective treatment without further evidence.”

All the researchers, however, agreed that the benefits of DBS should no longer be thought of as a last resort. In an editorial that accompanied Dr. Schüpbach's 2007 study, Dr. Riley noted that even under currently accepted surgical practice, too few people are getting the procedure. “Only a minor fraction of patents with Parkinson's who would benefit from DBS currently experience this treatment,” he wrote. Dr. Schüpbach's study “indicates that earlier application of DBS represents an improvement over our current approach to managing Parkinson's.”

Dr. Charles said he has received payments from Medtronic lectures and consulting; Dr. Schüpbach said he has no financial ties with the company.

Dr. David Charles checks a patient's deep brain stimulation device. Dr. Charles suspects that DBS reduces the hyperactive output of the subthalamic nucleus. Dana Johnson/Vanderbilt University Medical Center

SAN FRANCISCO – Two brief mental state exams can reliably differentiate delirium from dementia in the elderly emergency department patient.

Because delirium usually is caused by an organic illness, confusional symptoms may disappear once the underlying problem is treated, said Dr. Allen Yuen, director of emergency medicine at Epworth Hospital, Melbourne. Dementia, the product of a progressive disease, is largely untreatable.

“Poor differentiation between the confusional states is associated with poor outcomes in the patients, with increased morbidity and mortality, longer hospital stays, and functional decline,” he said at the 12th International Conference on Emergency Medicine.

There are three types of confusion in the elderly patient, Dr. Yuen said at the meeting, which was hosted by the American College of Emergency Physicians. Delirium is characterized by the sudden onset of symptoms. Patients may appear either drowsy or agitated. They can exhibit variable short-term memory, poor attention, disorganized thoughts, and even hallucinations.

The underlying causes can range from serious cardiovascular disorders–such as cerebral ischemia, myocardial infarction, and pulmonary embolism–to such seemingly innocuous problems as a urinary tract infection, pain, cold, urinary retention, and constipation.

Dementia is a state of chronic confusion induced by a long-term neurologic illness such as Alzheimer's disease. This is progressive and irreversible. Short-term memory is impaired, and the patient may not be able to perform simple tasks when asked. Language may be impaired. Family members may report aggression or personality changes.

Acute or chronic confusion occurs when a treatable illness, such as infection, brings on acute delirium in a patient with dementia.

A combination of the Confusion Assessment Method (CAM) and the Mini-Mental State Exam (MMSE) is highly effective in differentiating the types of confusion, Dr. Yuen said. “A positive CAM and an MMSE score of more than 25 are strongly predictive of delirium,” he said.

CAM has sensitivity of 95%–100% and a specificity of up to 95% for diagnosing delirium in the elderly. It relies on observations both by family members or caretakers and clinicians to assess four symptoms: acute confusional onset, inattention, disorganized thinking, and altered level of consciousness. The diagnosis of delirium by CAM requires the presence of both the first and second feature and at least one of the other two.

The MMSE, while not considered a diagnostic tool, does identify patients with cognitive impairment suggestive of dementia. The screen measures orientation, short-term memory, calculation ability, and language. A score of 18–26 indicates mild dementia, although, highly educated patients with early dementia may still achieve a score of up to 30, Dr. Yuen noted.

The usual battery of tests (complete blood count, electrolytes, blood urea nitrogen and glucose, liver function, C-reactive protein, and urinalysis) often will reveal the physical problem underlying delirium. A chest x-ray, electrocardiogram, and brain CT may be helpful as well.

In addition to the indicated therapy, patients will benefit from supportive care. A quiet room with a clock, family photos, and personal items can help them regain their orientation. Any assistive devices the patient regularly uses, such as hearing aids or glasses, should be available. “Patients and their family members will need reassurance and encouragement,” Dr. Yuen said. “Patients usually do much better if the family is present–24 hours a day if possible. This is especially true if the patient doesn't speak English.”

Drugs and restraints should be avoided or kept to the absolute minimum needed to ensure the patient's safety, he said. Use restraints only for extreme agitation, aggressiveness, or risk of self-harm, not to prevent injury or falls. “They're not effective for this and may even contribute to falls if used inappropriately,” Dr. Yuen added.

Drugs should be considered only for hallucinations or delusions that may increase the risk of harm to self or others, Dr. Yuen said. “Don't use them routinely, and use them only until the cause of the delirium is reversed.”

SAN FRANCISCO – Two brief mental state exams can reliably differentiate delirium from dementia in the elderly emergency department patient.

Because delirium usually is caused by an organic illness, confusional symptoms may disappear once the underlying problem is treated, said Dr. Allen Yuen, director of emergency medicine at Epworth Hospital, Melbourne. Dementia, the product of a progressive disease, is largely untreatable.

“Poor differentiation between the confusional states is associated with poor outcomes in the patients, with increased morbidity and mortality, longer hospital stays, and functional decline,” he said at the 12th International Conference on Emergency Medicine.

There are three types of confusion in the elderly patient, Dr. Yuen said at the meeting, which was hosted by the American College of Emergency Physicians. Delirium is characterized by the sudden onset of symptoms. Patients may appear either drowsy or agitated. They can exhibit variable short-term memory, poor attention, disorganized thoughts, and even hallucinations.

The underlying causes can range from serious cardiovascular disorders–such as cerebral ischemia, myocardial infarction, and pulmonary embolism–to such seemingly innocuous problems as a urinary tract infection, pain, cold, urinary retention, and constipation.

Dementia is a state of chronic confusion induced by a long-term neurologic illness such as Alzheimer's disease. This is progressive and irreversible. Short-term memory is impaired, and the patient may not be able to perform simple tasks when asked. Language may be impaired. Family members may report aggression or personality changes.

Acute or chronic confusion occurs when a treatable illness, such as infection, brings on acute delirium in a patient with dementia.

A combination of the Confusion Assessment Method (CAM) and the Mini-Mental State Exam (MMSE) is highly effective in differentiating the types of confusion, Dr. Yuen said. “A positive CAM and an MMSE score of more than 25 are strongly predictive of delirium,” he said.

CAM has sensitivity of 95%–100% and a specificity of up to 95% for diagnosing delirium in the elderly. It relies on observations both by family members or caretakers and clinicians to assess four symptoms: acute confusional onset, inattention, disorganized thinking, and altered level of consciousness. The diagnosis of delirium by CAM requires the presence of both the first and second feature and at least one of the other two.

The MMSE, while not considered a diagnostic tool, does identify patients with cognitive impairment suggestive of dementia. The screen measures orientation, short-term memory, calculation ability, and language. A score of 18–26 indicates mild dementia, although, highly educated patients with early dementia may still achieve a score of up to 30, Dr. Yuen noted.

The usual battery of tests (complete blood count, electrolytes, blood urea nitrogen and glucose, liver function, C-reactive protein, and urinalysis) often will reveal the physical problem underlying delirium. A chest x-ray, electrocardiogram, and brain CT may be helpful as well.

In addition to the indicated therapy, patients will benefit from supportive care. A quiet room with a clock, family photos, and personal items can help them regain their orientation. Any assistive devices the patient regularly uses, such as hearing aids or glasses, should be available. “Patients and their family members will need reassurance and encouragement,” Dr. Yuen said. “Patients usually do much better if the family is present–24 hours a day if possible. This is especially true if the patient doesn't speak English.”

Drugs and restraints should be avoided or kept to the absolute minimum needed to ensure the patient's safety, he said. Use restraints only for extreme agitation, aggressiveness, or risk of self-harm, not to prevent injury or falls. “They're not effective for this and may even contribute to falls if used inappropriately,” Dr. Yuen added.

Drugs should be considered only for hallucinations or delusions that may increase the risk of harm to self or others, Dr. Yuen said. “Don't use them routinely, and use them only until the cause of the delirium is reversed.”

SAN FRANCISCO – Two brief mental state exams can reliably differentiate delirium from dementia in the elderly emergency department patient.

Because delirium usually is caused by an organic illness, confusional symptoms may disappear once the underlying problem is treated, said Dr. Allen Yuen, director of emergency medicine at Epworth Hospital, Melbourne. Dementia, the product of a progressive disease, is largely untreatable.

“Poor differentiation between the confusional states is associated with poor outcomes in the patients, with increased morbidity and mortality, longer hospital stays, and functional decline,” he said at the 12th International Conference on Emergency Medicine.

There are three types of confusion in the elderly patient, Dr. Yuen said at the meeting, which was hosted by the American College of Emergency Physicians. Delirium is characterized by the sudden onset of symptoms. Patients may appear either drowsy or agitated. They can exhibit variable short-term memory, poor attention, disorganized thoughts, and even hallucinations.

The underlying causes can range from serious cardiovascular disorders–such as cerebral ischemia, myocardial infarction, and pulmonary embolism–to such seemingly innocuous problems as a urinary tract infection, pain, cold, urinary retention, and constipation.

Dementia is a state of chronic confusion induced by a long-term neurologic illness such as Alzheimer's disease. This is progressive and irreversible. Short-term memory is impaired, and the patient may not be able to perform simple tasks when asked. Language may be impaired. Family members may report aggression or personality changes.

Acute or chronic confusion occurs when a treatable illness, such as infection, brings on acute delirium in a patient with dementia.

A combination of the Confusion Assessment Method (CAM) and the Mini-Mental State Exam (MMSE) is highly effective in differentiating the types of confusion, Dr. Yuen said. “A positive CAM and an MMSE score of more than 25 are strongly predictive of delirium,” he said.

CAM has sensitivity of 95%–100% and a specificity of up to 95% for diagnosing delirium in the elderly. It relies on observations both by family members or caretakers and clinicians to assess four symptoms: acute confusional onset, inattention, disorganized thinking, and altered level of consciousness. The diagnosis of delirium by CAM requires the presence of both the first and second feature and at least one of the other two.

The MMSE, while not considered a diagnostic tool, does identify patients with cognitive impairment suggestive of dementia. The screen measures orientation, short-term memory, calculation ability, and language. A score of 18–26 indicates mild dementia, although, highly educated patients with early dementia may still achieve a score of up to 30, Dr. Yuen noted.

The usual battery of tests (complete blood count, electrolytes, blood urea nitrogen and glucose, liver function, C-reactive protein, and urinalysis) often will reveal the physical problem underlying delirium. A chest x-ray, electrocardiogram, and brain CT may be helpful as well.

In addition to the indicated therapy, patients will benefit from supportive care. A quiet room with a clock, family photos, and personal items can help them regain their orientation. Any assistive devices the patient regularly uses, such as hearing aids or glasses, should be available. “Patients and their family members will need reassurance and encouragement,” Dr. Yuen said. “Patients usually do much better if the family is present–24 hours a day if possible. This is especially true if the patient doesn't speak English.”

Drugs and restraints should be avoided or kept to the absolute minimum needed to ensure the patient's safety, he said. Use restraints only for extreme agitation, aggressiveness, or risk of self-harm, not to prevent injury or falls. “They're not effective for this and may even contribute to falls if used inappropriately,” Dr. Yuen added.

Drugs should be considered only for hallucinations or delusions that may increase the risk of harm to self or others, Dr. Yuen said. “Don't use them routinely, and use them only until the cause of the delirium is reversed.”

A drug that inhibits the formation of neurotoxic amyloid-β₄₂ peptides slowed functional decline in patients with mild Alzheimer's disease by 46%, Dr. Gordon K. Wilcock and his colleagues have reported.

Patients who took the drug for 24 months fared significantly better than did those who switched to it after a year on placebo, prompting the investigators to conclude that tarenflurbil is truly a disease-modifying agent. “The randomized-start analysis suggests that, in patients with mild [Alzheimer's disease], treatment for 24 months resulted in greater benefit than did delayed treatment for 12 months,” they wrote. “This smaller benefit in a delayed-start group is consistent with modification of the underlying disease process rather than a purely symptomatic effect” (Lancet Neurol. 2008;7:483–93).

Although tarenflurbil showed no significant functional or cognitive benefit for those with moderate disease, its benefit for early Alzheimer's disease (AD) patients raises hopes that an effective disease-modifying agent might be in the offing. A phase III trial of the drug was set to wrap up this spring, and the results are eagerly awaited, Dr. Paul Aisen of the University of California, San Diego wrote in an accompanying commentary (Lancet Neurol. 2008;7:468–9). “In a few months, we will learn whether tarenflurbil will be the first anti-amyloid strategy to be efficacious in a pivotal trial,” wrote Dr. Aisen.

The study took place in 31 sites in Canada and the United Kingdom from November 2003 to April 2006. Dr. Wilcock of the University of Oxford, England, and his colleagues randomized 210 patients with mild to moderate Alzheimer's disease to one of three treatment regimens: tarenflurbil 400 mg twice daily, tarenflurbil 800 mg twice daily, or placebo.

After 12 months, 86 patients were included in a 12-month extension trial. In this study, patients taking the study drug continued on their respective regimens, while those taking placebo were randomized into the two active treatment arms.

Both trials included patients who had been stable on anticholinesterase drugs for at least 3 months prior to the study. All participants were assessed using the Alzheimer's Disease Assessment Scale, cognitive section (ADAS-cog), the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL), and the Clinical Dementia Rating (CDR) sum of box score. The patients' mean age was 74 years; the mean Mini-Mental State Examination score was 21. About 95% were taking anticholinesterase drugs. Mild Alzheimer's was present in 130 patients at baseline, while the rest had moderate-stage disease.

Neither dosage of the study drug had any beneficial effect on patients with moderate AD, Dr. Wilcock and his coinvestigators said. In fact, after 12 months, those taking placebo actually fared better than those taking the higher dosage of tarenflurbil did. “In this group, treatment with placebo was associated with a significantly lower rate of decline in global function than was 800 mg tarenflurbil,” the authors wrote.

Patients with mild disease responded much better to the drug. Compared with patients on placebo, those taking the 1,600- mg/day dosage experienced a 46% lower rate of decline on the ADCS-ADL and a 36% lower rate of decline on the CDR–both significant differences. While there was a trend toward a slower rate of cognitive decline (34% lower, compared with placebo), the difference did not reach statistical significance.

Global function was also assessed as an exploratory outcome measure with the clinician interview-based impression of change plus caregiver input. In this analysis, 31% of the patients taking the 1,600-mg/day dosage showed improved or unchanged function at 12 months, compared with only 19% of patients taking placebo.

After the initial 12-month study, 86 Canadian patients were enrolled in the 12-month extension study. Again, there were no significant beneficial effects in patients with moderate disease. However, compared with those on placebo, those taking 1,600 mg/day had significant slowing of decline in all three outcome measures: 44% less decline on the ADCS-ADL, 38% less decline on the CDR, and 61% less decline on the ADAS-cog.

There were five deaths in the first study; none was associated with the study drug.

Tarenflurbil is a selective amyloid-lowering agent (SALA). It works by changing the point at which the enzyme γ-secretase cleaves the amyloid-β protein. This prevents the formation of the toxic longer-chain amyloid-β₄₂. SALAs such as tarenflurbil are designed to reduce soluble amyloid-β levels, with the aim of preventing plaque formation.

The drug was previously named R-flurbiprofen. Results of the phase II trial were initially reported at the July 2006 International Conference on Alzheimer's Disease. Dr. Wilcock is a paid investigator for Myriad Pharmaceuticals, the Salt Lake City company that funded the study.

A drug that inhibits the formation of neurotoxic amyloid-β₄₂ peptides slowed functional decline in patients with mild Alzheimer's disease by 46%, Dr. Gordon K. Wilcock and his colleagues have reported.

Patients who took the drug for 24 months fared significantly better than did those who switched to it after a year on placebo, prompting the investigators to conclude that tarenflurbil is truly a disease-modifying agent. “The randomized-start analysis suggests that, in patients with mild [Alzheimer's disease], treatment for 24 months resulted in greater benefit than did delayed treatment for 12 months,” they wrote. “This smaller benefit in a delayed-start group is consistent with modification of the underlying disease process rather than a purely symptomatic effect” (Lancet Neurol. 2008;7:483–93).

Although tarenflurbil showed no significant functional or cognitive benefit for those with moderate disease, its benefit for early Alzheimer's disease (AD) patients raises hopes that an effective disease-modifying agent might be in the offing. A phase III trial of the drug was set to wrap up this spring, and the results are eagerly awaited, Dr. Paul Aisen of the University of California, San Diego wrote in an accompanying commentary (Lancet Neurol. 2008;7:468–9). “In a few months, we will learn whether tarenflurbil will be the first anti-amyloid strategy to be efficacious in a pivotal trial,” wrote Dr. Aisen.

The study took place in 31 sites in Canada and the United Kingdom from November 2003 to April 2006. Dr. Wilcock of the University of Oxford, England, and his colleagues randomized 210 patients with mild to moderate Alzheimer's disease to one of three treatment regimens: tarenflurbil 400 mg twice daily, tarenflurbil 800 mg twice daily, or placebo.

After 12 months, 86 patients were included in a 12-month extension trial. In this study, patients taking the study drug continued on their respective regimens, while those taking placebo were randomized into the two active treatment arms.

Both trials included patients who had been stable on anticholinesterase drugs for at least 3 months prior to the study. All participants were assessed using the Alzheimer's Disease Assessment Scale, cognitive section (ADAS-cog), the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL), and the Clinical Dementia Rating (CDR) sum of box score. The patients' mean age was 74 years; the mean Mini-Mental State Examination score was 21. About 95% were taking anticholinesterase drugs. Mild Alzheimer's was present in 130 patients at baseline, while the rest had moderate-stage disease.

Neither dosage of the study drug had any beneficial effect on patients with moderate AD, Dr. Wilcock and his coinvestigators said. In fact, after 12 months, those taking placebo actually fared better than those taking the higher dosage of tarenflurbil did. “In this group, treatment with placebo was associated with a significantly lower rate of decline in global function than was 800 mg tarenflurbil,” the authors wrote.

Patients with mild disease responded much better to the drug. Compared with patients on placebo, those taking the 1,600- mg/day dosage experienced a 46% lower rate of decline on the ADCS-ADL and a 36% lower rate of decline on the CDR–both significant differences. While there was a trend toward a slower rate of cognitive decline (34% lower, compared with placebo), the difference did not reach statistical significance.

Global function was also assessed as an exploratory outcome measure with the clinician interview-based impression of change plus caregiver input. In this analysis, 31% of the patients taking the 1,600-mg/day dosage showed improved or unchanged function at 12 months, compared with only 19% of patients taking placebo.

After the initial 12-month study, 86 Canadian patients were enrolled in the 12-month extension study. Again, there were no significant beneficial effects in patients with moderate disease. However, compared with those on placebo, those taking 1,600 mg/day had significant slowing of decline in all three outcome measures: 44% less decline on the ADCS-ADL, 38% less decline on the CDR, and 61% less decline on the ADAS-cog.

There were five deaths in the first study; none was associated with the study drug.

Tarenflurbil is a selective amyloid-lowering agent (SALA). It works by changing the point at which the enzyme γ-secretase cleaves the amyloid-β protein. This prevents the formation of the toxic longer-chain amyloid-β₄₂. SALAs such as tarenflurbil are designed to reduce soluble amyloid-β levels, with the aim of preventing plaque formation.

The drug was previously named R-flurbiprofen. Results of the phase II trial were initially reported at the July 2006 International Conference on Alzheimer's Disease. Dr. Wilcock is a paid investigator for Myriad Pharmaceuticals, the Salt Lake City company that funded the study.

A drug that inhibits the formation of neurotoxic amyloid-β₄₂ peptides slowed functional decline in patients with mild Alzheimer's disease by 46%, Dr. Gordon K. Wilcock and his colleagues have reported.

Patients who took the drug for 24 months fared significantly better than did those who switched to it after a year on placebo, prompting the investigators to conclude that tarenflurbil is truly a disease-modifying agent. “The randomized-start analysis suggests that, in patients with mild [Alzheimer's disease], treatment for 24 months resulted in greater benefit than did delayed treatment for 12 months,” they wrote. “This smaller benefit in a delayed-start group is consistent with modification of the underlying disease process rather than a purely symptomatic effect” (Lancet Neurol. 2008;7:483–93).

Although tarenflurbil showed no significant functional or cognitive benefit for those with moderate disease, its benefit for early Alzheimer's disease (AD) patients raises hopes that an effective disease-modifying agent might be in the offing. A phase III trial of the drug was set to wrap up this spring, and the results are eagerly awaited, Dr. Paul Aisen of the University of California, San Diego wrote in an accompanying commentary (Lancet Neurol. 2008;7:468–9). “In a few months, we will learn whether tarenflurbil will be the first anti-amyloid strategy to be efficacious in a pivotal trial,” wrote Dr. Aisen.

The study took place in 31 sites in Canada and the United Kingdom from November 2003 to April 2006. Dr. Wilcock of the University of Oxford, England, and his colleagues randomized 210 patients with mild to moderate Alzheimer's disease to one of three treatment regimens: tarenflurbil 400 mg twice daily, tarenflurbil 800 mg twice daily, or placebo.

After 12 months, 86 patients were included in a 12-month extension trial. In this study, patients taking the study drug continued on their respective regimens, while those taking placebo were randomized into the two active treatment arms.

Both trials included patients who had been stable on anticholinesterase drugs for at least 3 months prior to the study. All participants were assessed using the Alzheimer's Disease Assessment Scale, cognitive section (ADAS-cog), the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL), and the Clinical Dementia Rating (CDR) sum of box score. The patients' mean age was 74 years; the mean Mini-Mental State Examination score was 21. About 95% were taking anticholinesterase drugs. Mild Alzheimer's was present in 130 patients at baseline, while the rest had moderate-stage disease.

Neither dosage of the study drug had any beneficial effect on patients with moderate AD, Dr. Wilcock and his coinvestigators said. In fact, after 12 months, those taking placebo actually fared better than those taking the higher dosage of tarenflurbil did. “In this group, treatment with placebo was associated with a significantly lower rate of decline in global function than was 800 mg tarenflurbil,” the authors wrote.

Patients with mild disease responded much better to the drug. Compared with patients on placebo, those taking the 1,600- mg/day dosage experienced a 46% lower rate of decline on the ADCS-ADL and a 36% lower rate of decline on the CDR–both significant differences. While there was a trend toward a slower rate of cognitive decline (34% lower, compared with placebo), the difference did not reach statistical significance.

Global function was also assessed as an exploratory outcome measure with the clinician interview-based impression of change plus caregiver input. In this analysis, 31% of the patients taking the 1,600-mg/day dosage showed improved or unchanged function at 12 months, compared with only 19% of patients taking placebo.

After the initial 12-month study, 86 Canadian patients were enrolled in the 12-month extension study. Again, there were no significant beneficial effects in patients with moderate disease. However, compared with those on placebo, those taking 1,600 mg/day had significant slowing of decline in all three outcome measures: 44% less decline on the ADCS-ADL, 38% less decline on the CDR, and 61% less decline on the ADAS-cog.

There were five deaths in the first study; none was associated with the study drug.

Tarenflurbil is a selective amyloid-lowering agent (SALA). It works by changing the point at which the enzyme γ-secretase cleaves the amyloid-β protein. This prevents the formation of the toxic longer-chain amyloid-β₄₂. SALAs such as tarenflurbil are designed to reduce soluble amyloid-β levels, with the aim of preventing plaque formation.

The drug was previously named R-flurbiprofen. Results of the phase II trial were initially reported at the July 2006 International Conference on Alzheimer's Disease. Dr. Wilcock is a paid investigator for Myriad Pharmaceuticals, the Salt Lake City company that funded the study.

SAN FRANCISCO — Children who present to the emergency department with cellulitis may be better served by admittance to the hospital than by receiving short-term intravenous antibiotics in the ED.

In a retrospective review, children who received antibiotics in the ED were 50 times more likely to fail therapy within 7 days than were those who were admitted and then treated, Dr. April J. Kam reported at the 12th International Conference on Emergency Medicine.

In addition to the treatment failure rate, Dr. Kam said in an interview, tying up an ED room with hours and hours of intravenous antibiotic therapy doesn't make financial or logistic sense.

"Children who receive three doses of IV antibiotics in this setting can be in the ED for 21 hours," said Dr. Kam, a pediatric emergency medicine fellow at the Hospital for Sick Children, Toronto. Dr. Kam examined outcomes in 321 children (average age 7 years) who presented to the ED with cellulitis over a 1-year period. The portals of entry for the infection were insect bite (21%), trauma (19%), skin abnormality (12%), and dental condition (6%). For 42% of the children, the portal was some other method, or there was no known portal.

Among the group, 154 were discharged on oral antibiotics, 82 were admitted to the hospital for intravenous antibiotic therapy, and 85 received intravenous antibiotic therapy in the ED. Children who were admitted tended to be sicker, with significantly higher temperatures and more clinical signs of infection. In addition, significantly more of them had already visited a physician for the infection, and had already taken antibiotics for it.

Dr. Kam defined treatment failure in three ways: a repeat ED visit within 7 days with a change of treatment; three or more doses of intravenous antibiotics administered in the ED before the disposition determination; or more than 10 hours of treatment before the disposition determination.

By those criteria, significantly more children receiving short-course ED antibiotics failed treatment (57% vs. 2% of those admitted and 5% of those discharged on oral therapy). Children taking the short-course antibiotics were 50 times more likely to have a treatment failure than were admitted children; children discharged on oral therapy were twice as likely to fail treatment as were admitted children.

Dr. Kam also looked at the amount of blood work drawn in the entire cohort. Only 10% who were discharged on oral therapy had a complete blood count done, and 6% had a blood culture. However, a CBC was performed in 94% of short-course and 98% of admitted patients, while a culture was performed in 89% of short-course and 90% of admitted patients.

Unfortunately, she said, the cultures were noncontributory in almost every case. Only one culture grew a pathogen, and that child was clinically septic. Three other cultures grew contaminants. "It seems like the mindset is, 'Well, we're already putting an IV in, so we might as well get blood.' But these tests don't really add much to the diagnostic picture," Dr. Kam explained.

Treatment choices are clearer for children on either end of the spectrum, she said. Those who seem largely well usually get oral antibiotics and discharge, while those who are clinically sick are admitted.

"After performing this review, I'm rethinking my own decision making. I don't even consider the short-course therapy any more. If the child is well enough to go home, I discharge, and if the child is not well enough to go home, I admit."

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Children who present to the emergency department with cellulitis may be better served by admittance to the hospital than by receiving short-term intravenous antibiotics in the ED.

In a retrospective review, children who received antibiotics in the ED were 50 times more likely to fail therapy within 7 days than were those who were admitted and then treated, Dr. April J. Kam reported at the 12th International Conference on Emergency Medicine.

In addition to the treatment failure rate, Dr. Kam said in an interview, tying up an ED room with hours and hours of intravenous antibiotic therapy doesn't make financial or logistic sense.

"Children who receive three doses of IV antibiotics in this setting can be in the ED for 21 hours," said Dr. Kam, a pediatric emergency medicine fellow at the Hospital for Sick Children, Toronto. Dr. Kam examined outcomes in 321 children (average age 7 years) who presented to the ED with cellulitis over a 1-year period. The portals of entry for the infection were insect bite (21%), trauma (19%), skin abnormality (12%), and dental condition (6%). For 42% of the children, the portal was some other method, or there was no known portal.

Among the group, 154 were discharged on oral antibiotics, 82 were admitted to the hospital for intravenous antibiotic therapy, and 85 received intravenous antibiotic therapy in the ED. Children who were admitted tended to be sicker, with significantly higher temperatures and more clinical signs of infection. In addition, significantly more of them had already visited a physician for the infection, and had already taken antibiotics for it.

Dr. Kam defined treatment failure in three ways: a repeat ED visit within 7 days with a change of treatment; three or more doses of intravenous antibiotics administered in the ED before the disposition determination; or more than 10 hours of treatment before the disposition determination.

By those criteria, significantly more children receiving short-course ED antibiotics failed treatment (57% vs. 2% of those admitted and 5% of those discharged on oral therapy). Children taking the short-course antibiotics were 50 times more likely to have a treatment failure than were admitted children; children discharged on oral therapy were twice as likely to fail treatment as were admitted children.

Dr. Kam also looked at the amount of blood work drawn in the entire cohort. Only 10% who were discharged on oral therapy had a complete blood count done, and 6% had a blood culture. However, a CBC was performed in 94% of short-course and 98% of admitted patients, while a culture was performed in 89% of short-course and 90% of admitted patients.

Unfortunately, she said, the cultures were noncontributory in almost every case. Only one culture grew a pathogen, and that child was clinically septic. Three other cultures grew contaminants. "It seems like the mindset is, 'Well, we're already putting an IV in, so we might as well get blood.' But these tests don't really add much to the diagnostic picture," Dr. Kam explained.

Treatment choices are clearer for children on either end of the spectrum, she said. Those who seem largely well usually get oral antibiotics and discharge, while those who are clinically sick are admitted.

"After performing this review, I'm rethinking my own decision making. I don't even consider the short-course therapy any more. If the child is well enough to go home, I discharge, and if the child is not well enough to go home, I admit."

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Children who present to the emergency department with cellulitis may be better served by admittance to the hospital than by receiving short-term intravenous antibiotics in the ED.

In a retrospective review, children who received antibiotics in the ED were 50 times more likely to fail therapy within 7 days than were those who were admitted and then treated, Dr. April J. Kam reported at the 12th International Conference on Emergency Medicine.

In addition to the treatment failure rate, Dr. Kam said in an interview, tying up an ED room with hours and hours of intravenous antibiotic therapy doesn't make financial or logistic sense.

"Children who receive three doses of IV antibiotics in this setting can be in the ED for 21 hours," said Dr. Kam, a pediatric emergency medicine fellow at the Hospital for Sick Children, Toronto. Dr. Kam examined outcomes in 321 children (average age 7 years) who presented to the ED with cellulitis over a 1-year period. The portals of entry for the infection were insect bite (21%), trauma (19%), skin abnormality (12%), and dental condition (6%). For 42% of the children, the portal was some other method, or there was no known portal.

Among the group, 154 were discharged on oral antibiotics, 82 were admitted to the hospital for intravenous antibiotic therapy, and 85 received intravenous antibiotic therapy in the ED. Children who were admitted tended to be sicker, with significantly higher temperatures and more clinical signs of infection. In addition, significantly more of them had already visited a physician for the infection, and had already taken antibiotics for it.

Dr. Kam defined treatment failure in three ways: a repeat ED visit within 7 days with a change of treatment; three or more doses of intravenous antibiotics administered in the ED before the disposition determination; or more than 10 hours of treatment before the disposition determination.

By those criteria, significantly more children receiving short-course ED antibiotics failed treatment (57% vs. 2% of those admitted and 5% of those discharged on oral therapy). Children taking the short-course antibiotics were 50 times more likely to have a treatment failure than were admitted children; children discharged on oral therapy were twice as likely to fail treatment as were admitted children.

Dr. Kam also looked at the amount of blood work drawn in the entire cohort. Only 10% who were discharged on oral therapy had a complete blood count done, and 6% had a blood culture. However, a CBC was performed in 94% of short-course and 98% of admitted patients, while a culture was performed in 89% of short-course and 90% of admitted patients.

Unfortunately, she said, the cultures were noncontributory in almost every case. Only one culture grew a pathogen, and that child was clinically septic. Three other cultures grew contaminants. "It seems like the mindset is, 'Well, we're already putting an IV in, so we might as well get blood.' But these tests don't really add much to the diagnostic picture," Dr. Kam explained.

Treatment choices are clearer for children on either end of the spectrum, she said. Those who seem largely well usually get oral antibiotics and discharge, while those who are clinically sick are admitted.

"After performing this review, I'm rethinking my own decision making. I don't even consider the short-course therapy any more. If the child is well enough to go home, I discharge, and if the child is not well enough to go home, I admit."

ELSEVIER GLOBAL MEDICAL NEWS