Robert Finn

SAN FRANCISCO — Respiratory syncytial virus itself, and not the bronchiolitis associated with the infection, appears to be the cause of the heart damage often seen in young children with the virus, according to a prospective study involving 74 children.

All 74 children were less than 12 months of age and were admitted to the hospital for bronchiolitis, Dr. Susanna Esposito explained in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Aside from their bronchiolitis, the children were healthy.

Investigators excluded children from the study if they had a chronic disease (including a chronic disorder of the pulmonary or cardiovascular system, chronic metabolic diseases, neoplasias, kidney or liver dysfunction, hemoglobinopathies, immunosuppression, and genetic or neurologic disorders) that increased the risk of complications of a respiratory infection.

The investigators from the University of Milan collected the specimens with nasopharyngeal swabs to detect respiratory syncytial virus (RSV) types A and B.

As it turned out, 35 patients (47%) tested positive for RSV infection, and the remaining 39 (53%) did not.

Patients with RSV had significantly more cardiac arrhythmias and a significantly greater degree of abnormal heart rate variability than those without RSV. For example, approximately 25% of the patients with RSV had cardiac arrhythmias, compared with about 5% of those without RSV. Approximately 60% of the patients with RSV exhibited abnormal heart rate variability, compared with approximately 40% of those without RSV.

The investigators found no differences between the two groups in pulse oximetry, chest radiography, respiratory involvement, or cardiac troponin I levels.

The heart involvement appeared to be related to an RSV viral load of 100,000 copies per milliliter or more, and not to drug use or the disease's severity.

“This last finding suggests that RSV can be the direct cause of the heart damage and that arrhythmias can be found also in children with very mild RSV bronchiolitis in whom pulmonary hypertension and lung damage are nonexistent or marginal,” the investigators wrote.

“This means that a careful heart evaluation has to be performed in all the children with RSV bronchiolitis, and that higher viral load is a risk factor for heart damage development,” Dr. Esposito and her associates wrote.

The investigators reported that they had no conflicts of interest.

SAN FRANCISCO — Respiratory syncytial virus itself, and not the bronchiolitis associated with the infection, appears to be the cause of the heart damage often seen in young children with the virus, according to a prospective study involving 74 children.

All 74 children were less than 12 months of age and were admitted to the hospital for bronchiolitis, Dr. Susanna Esposito explained in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Aside from their bronchiolitis, the children were healthy.

Investigators excluded children from the study if they had a chronic disease (including a chronic disorder of the pulmonary or cardiovascular system, chronic metabolic diseases, neoplasias, kidney or liver dysfunction, hemoglobinopathies, immunosuppression, and genetic or neurologic disorders) that increased the risk of complications of a respiratory infection.

The investigators from the University of Milan collected the specimens with nasopharyngeal swabs to detect respiratory syncytial virus (RSV) types A and B.

As it turned out, 35 patients (47%) tested positive for RSV infection, and the remaining 39 (53%) did not.

Patients with RSV had significantly more cardiac arrhythmias and a significantly greater degree of abnormal heart rate variability than those without RSV. For example, approximately 25% of the patients with RSV had cardiac arrhythmias, compared with about 5% of those without RSV. Approximately 60% of the patients with RSV exhibited abnormal heart rate variability, compared with approximately 40% of those without RSV.

The investigators found no differences between the two groups in pulse oximetry, chest radiography, respiratory involvement, or cardiac troponin I levels.

The heart involvement appeared to be related to an RSV viral load of 100,000 copies per milliliter or more, and not to drug use or the disease's severity.

“This last finding suggests that RSV can be the direct cause of the heart damage and that arrhythmias can be found also in children with very mild RSV bronchiolitis in whom pulmonary hypertension and lung damage are nonexistent or marginal,” the investigators wrote.

“This means that a careful heart evaluation has to be performed in all the children with RSV bronchiolitis, and that higher viral load is a risk factor for heart damage development,” Dr. Esposito and her associates wrote.

The investigators reported that they had no conflicts of interest.

SAN FRANCISCO — Respiratory syncytial virus itself, and not the bronchiolitis associated with the infection, appears to be the cause of the heart damage often seen in young children with the virus, according to a prospective study involving 74 children.

All 74 children were less than 12 months of age and were admitted to the hospital for bronchiolitis, Dr. Susanna Esposito explained in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Aside from their bronchiolitis, the children were healthy.

Investigators excluded children from the study if they had a chronic disease (including a chronic disorder of the pulmonary or cardiovascular system, chronic metabolic diseases, neoplasias, kidney or liver dysfunction, hemoglobinopathies, immunosuppression, and genetic or neurologic disorders) that increased the risk of complications of a respiratory infection.

The investigators from the University of Milan collected the specimens with nasopharyngeal swabs to detect respiratory syncytial virus (RSV) types A and B.

As it turned out, 35 patients (47%) tested positive for RSV infection, and the remaining 39 (53%) did not.

Patients with RSV had significantly more cardiac arrhythmias and a significantly greater degree of abnormal heart rate variability than those without RSV. For example, approximately 25% of the patients with RSV had cardiac arrhythmias, compared with about 5% of those without RSV. Approximately 60% of the patients with RSV exhibited abnormal heart rate variability, compared with approximately 40% of those without RSV.

The investigators found no differences between the two groups in pulse oximetry, chest radiography, respiratory involvement, or cardiac troponin I levels.

The heart involvement appeared to be related to an RSV viral load of 100,000 copies per milliliter or more, and not to drug use or the disease's severity.

“This last finding suggests that RSV can be the direct cause of the heart damage and that arrhythmias can be found also in children with very mild RSV bronchiolitis in whom pulmonary hypertension and lung damage are nonexistent or marginal,” the investigators wrote.

“This means that a careful heart evaluation has to be performed in all the children with RSV bronchiolitis, and that higher viral load is a risk factor for heart damage development,” Dr. Esposito and her associates wrote.

The investigators reported that they had no conflicts of interest.

While most exanthems are self-limiting, some are not, making it important to establish a specific diagnosis, according to Dr. Anthony J. Mancini.

Parents want to know how long it's going to take to go away, Dr. Mancini said in an interview. “If you can characterize it … at least they may have some answers. They know that it's going to take a while to resolve, and that saves you from follow-up phone calls and visits to the office when they're frantic because it's still there 4 weeks later.”

Clinicians have learned to keep an eye out for the bad actors, like oral mucosa necrosis that could signal Stevens-Johnson syndrome, or the centripetal spread of exanthem with petechiae from a tick bite that could signal Rocky Mountain spotted fever, he said at a women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF). Dr. Mancini—head of pediatric dermatology at Children's Memorial Hospital in Chicago—reviewed these five newer or atypical exanthems:

Arcanobacterium haemolyticum

Often masquerading as scarlet fever, A. haemolyticum typically appears in adolescents and young adults as a sore throat with a scarlet fever–like rash. It is important for physicians to recognize and diagnose A. haemolyticum because it can be treated, noted Dr. Mancini.

The first clue that it is not scarlet fever or mononucleosis is a negative throat culture for strep and a negative Monospot. Most labs can test for A. haemolyticum, but only if they know to look, because they need to plate it on a different agar.

Although A. haemolyticum will probably resolve on its own with time, children can be treated effectively with a macrolide antibiotic such as an erythromycin, azithromycin, or clarithromycin. Patients do not respond well to penicillin antibiotics, an important distinction from streptococcal infection, he said.

Papular-Purpuric Gloves and Socks Syndrome

Caused most often by parvovirus B19, papular-purpuric gloves and socks syndrome is named for the characteristic rash appearing on a child's palms and soles, with sharp cutoffs at the wrist and ankle, according to Dr. Mancini.

The virus is self-limited and typically requires only symptomatic treatment, but it is important to establish a diagnosis because parvovirus B19 can cause fetal infections in utero and lead to a variety of complications.

Parvovirus B19 also causes Fifth disease, but there is an important difference, he pointed out. The “slapped cheeks” of Fifth disease are thought to appear only after the child is no longer viremic. A child with papular-purpuric glove and socks syndrome may still be viremic when they have a rash, however, and so should be kept away from pregnant women who are early in gestation.

Gianotti-Crosti Syndrome

Most physicians have heard of Gianotti-Crosti syndrome, but many have probably not diagnosed it because they have not looked closely at distribution. “This exanthem likes to involve the outer arms, the outer legs, the buttocks, and the face. It almost always spares the trunk, or at least the trunk will be much less involved than everywhere else,” he said.

Physicians need to remember that, while they may have learned in residency that Gianotti-Crosti syndrome is associated with hepatitis B, that's rarely true in the United States. It is usually caused by the Epstein-Barr virus and requires no treatment. It will resolve, but it may take up to 2 months.

Unilateral Laterothoracic Exanthem

Most physicians “have probably seen unilateral laterothoracic exanthem, but they may have misdiagnosed it as contact dermatitis,” Dr. Mancini said. Beginning on one side of the body, usually at the arm, armpit, or trunk, the exanthem may initially look like a contact dermatitis but then begins to spread. Even after spreading, the exanthem maintains predominance on the initial side of involvement.

The cause is unknown, but it is probably viral, he said. It requires no treatment and typically takes 6-8 weeks to resolve.

Acute Generalized Exanthematous Pustulosis (AGEP)

AGEP is often mistaken for drug-induced pustular psoriasis, and the literature is filled with a wide range of reported drug associations, including amoxicillin, erythromycin, NSAIDs, and even pseudoephedrine, but current thinking is that it is often viral, at least in children.

“It's an important entity to recognize, because AGEP can have a sudden onset, with fevers and numerous widespread nonfollicular pustules, which can look a lot like pustular psoriasis,” Dr. Mancini said. It's self-limited, but children do tend to appear more toxic with AGEP than with some of the other exanthems, especially if they are young. They may have low-grade fevers, and their white counts may be mildly elevated.

Treatment is supportive, with antihistamines, cool compresses, and topical steroids if patients are uncomfortable. AGEP will resolve over 2 weeks or so with desquamation.

Dr. Mancini disclosed being a consultant to SkinMedica and Galderma, and on the speakers bureau of Promius and Galderma. SDEF and this news organization are owned by Elsevier.

An infant with acute generalized exanthematous pustulosis is shown.

Source COURTESY DR. ANTHONY J. MANCINI

While most exanthems are self-limiting, some are not, making it important to establish a specific diagnosis, according to Dr. Anthony J. Mancini.

Parents want to know how long it's going to take to go away, Dr. Mancini said in an interview. “If you can characterize it … at least they may have some answers. They know that it's going to take a while to resolve, and that saves you from follow-up phone calls and visits to the office when they're frantic because it's still there 4 weeks later.”

Clinicians have learned to keep an eye out for the bad actors, like oral mucosa necrosis that could signal Stevens-Johnson syndrome, or the centripetal spread of exanthem with petechiae from a tick bite that could signal Rocky Mountain spotted fever, he said at a women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF). Dr. Mancini—head of pediatric dermatology at Children's Memorial Hospital in Chicago—reviewed these five newer or atypical exanthems:

Arcanobacterium haemolyticum

Often masquerading as scarlet fever, A. haemolyticum typically appears in adolescents and young adults as a sore throat with a scarlet fever–like rash. It is important for physicians to recognize and diagnose A. haemolyticum because it can be treated, noted Dr. Mancini.

The first clue that it is not scarlet fever or mononucleosis is a negative throat culture for strep and a negative Monospot. Most labs can test for A. haemolyticum, but only if they know to look, because they need to plate it on a different agar.

Although A. haemolyticum will probably resolve on its own with time, children can be treated effectively with a macrolide antibiotic such as an erythromycin, azithromycin, or clarithromycin. Patients do not respond well to penicillin antibiotics, an important distinction from streptococcal infection, he said.

Papular-Purpuric Gloves and Socks Syndrome

Caused most often by parvovirus B19, papular-purpuric gloves and socks syndrome is named for the characteristic rash appearing on a child's palms and soles, with sharp cutoffs at the wrist and ankle, according to Dr. Mancini.

The virus is self-limited and typically requires only symptomatic treatment, but it is important to establish a diagnosis because parvovirus B19 can cause fetal infections in utero and lead to a variety of complications.

Parvovirus B19 also causes Fifth disease, but there is an important difference, he pointed out. The “slapped cheeks” of Fifth disease are thought to appear only after the child is no longer viremic. A child with papular-purpuric glove and socks syndrome may still be viremic when they have a rash, however, and so should be kept away from pregnant women who are early in gestation.

Gianotti-Crosti Syndrome

Most physicians have heard of Gianotti-Crosti syndrome, but many have probably not diagnosed it because they have not looked closely at distribution. “This exanthem likes to involve the outer arms, the outer legs, the buttocks, and the face. It almost always spares the trunk, or at least the trunk will be much less involved than everywhere else,” he said.

Physicians need to remember that, while they may have learned in residency that Gianotti-Crosti syndrome is associated with hepatitis B, that's rarely true in the United States. It is usually caused by the Epstein-Barr virus and requires no treatment. It will resolve, but it may take up to 2 months.

Unilateral Laterothoracic Exanthem

Most physicians “have probably seen unilateral laterothoracic exanthem, but they may have misdiagnosed it as contact dermatitis,” Dr. Mancini said. Beginning on one side of the body, usually at the arm, armpit, or trunk, the exanthem may initially look like a contact dermatitis but then begins to spread. Even after spreading, the exanthem maintains predominance on the initial side of involvement.

The cause is unknown, but it is probably viral, he said. It requires no treatment and typically takes 6-8 weeks to resolve.

Acute Generalized Exanthematous Pustulosis (AGEP)

AGEP is often mistaken for drug-induced pustular psoriasis, and the literature is filled with a wide range of reported drug associations, including amoxicillin, erythromycin, NSAIDs, and even pseudoephedrine, but current thinking is that it is often viral, at least in children.

“It's an important entity to recognize, because AGEP can have a sudden onset, with fevers and numerous widespread nonfollicular pustules, which can look a lot like pustular psoriasis,” Dr. Mancini said. It's self-limited, but children do tend to appear more toxic with AGEP than with some of the other exanthems, especially if they are young. They may have low-grade fevers, and their white counts may be mildly elevated.

Treatment is supportive, with antihistamines, cool compresses, and topical steroids if patients are uncomfortable. AGEP will resolve over 2 weeks or so with desquamation.

Dr. Mancini disclosed being a consultant to SkinMedica and Galderma, and on the speakers bureau of Promius and Galderma. SDEF and this news organization are owned by Elsevier.

An infant with acute generalized exanthematous pustulosis is shown.

Source COURTESY DR. ANTHONY J. MANCINI

While most exanthems are self-limiting, some are not, making it important to establish a specific diagnosis, according to Dr. Anthony J. Mancini.

Parents want to know how long it's going to take to go away, Dr. Mancini said in an interview. “If you can characterize it … at least they may have some answers. They know that it's going to take a while to resolve, and that saves you from follow-up phone calls and visits to the office when they're frantic because it's still there 4 weeks later.”

Clinicians have learned to keep an eye out for the bad actors, like oral mucosa necrosis that could signal Stevens-Johnson syndrome, or the centripetal spread of exanthem with petechiae from a tick bite that could signal Rocky Mountain spotted fever, he said at a women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF). Dr. Mancini—head of pediatric dermatology at Children's Memorial Hospital in Chicago—reviewed these five newer or atypical exanthems:

Arcanobacterium haemolyticum

Often masquerading as scarlet fever, A. haemolyticum typically appears in adolescents and young adults as a sore throat with a scarlet fever–like rash. It is important for physicians to recognize and diagnose A. haemolyticum because it can be treated, noted Dr. Mancini.

The first clue that it is not scarlet fever or mononucleosis is a negative throat culture for strep and a negative Monospot. Most labs can test for A. haemolyticum, but only if they know to look, because they need to plate it on a different agar.

Although A. haemolyticum will probably resolve on its own with time, children can be treated effectively with a macrolide antibiotic such as an erythromycin, azithromycin, or clarithromycin. Patients do not respond well to penicillin antibiotics, an important distinction from streptococcal infection, he said.

Papular-Purpuric Gloves and Socks Syndrome

Caused most often by parvovirus B19, papular-purpuric gloves and socks syndrome is named for the characteristic rash appearing on a child's palms and soles, with sharp cutoffs at the wrist and ankle, according to Dr. Mancini.

The virus is self-limited and typically requires only symptomatic treatment, but it is important to establish a diagnosis because parvovirus B19 can cause fetal infections in utero and lead to a variety of complications.

Parvovirus B19 also causes Fifth disease, but there is an important difference, he pointed out. The “slapped cheeks” of Fifth disease are thought to appear only after the child is no longer viremic. A child with papular-purpuric glove and socks syndrome may still be viremic when they have a rash, however, and so should be kept away from pregnant women who are early in gestation.

Gianotti-Crosti Syndrome

Most physicians have heard of Gianotti-Crosti syndrome, but many have probably not diagnosed it because they have not looked closely at distribution. “This exanthem likes to involve the outer arms, the outer legs, the buttocks, and the face. It almost always spares the trunk, or at least the trunk will be much less involved than everywhere else,” he said.

Physicians need to remember that, while they may have learned in residency that Gianotti-Crosti syndrome is associated with hepatitis B, that's rarely true in the United States. It is usually caused by the Epstein-Barr virus and requires no treatment. It will resolve, but it may take up to 2 months.

Unilateral Laterothoracic Exanthem

Most physicians “have probably seen unilateral laterothoracic exanthem, but they may have misdiagnosed it as contact dermatitis,” Dr. Mancini said. Beginning on one side of the body, usually at the arm, armpit, or trunk, the exanthem may initially look like a contact dermatitis but then begins to spread. Even after spreading, the exanthem maintains predominance on the initial side of involvement.

The cause is unknown, but it is probably viral, he said. It requires no treatment and typically takes 6-8 weeks to resolve.

Acute Generalized Exanthematous Pustulosis (AGEP)

AGEP is often mistaken for drug-induced pustular psoriasis, and the literature is filled with a wide range of reported drug associations, including amoxicillin, erythromycin, NSAIDs, and even pseudoephedrine, but current thinking is that it is often viral, at least in children.

“It's an important entity to recognize, because AGEP can have a sudden onset, with fevers and numerous widespread nonfollicular pustules, which can look a lot like pustular psoriasis,” Dr. Mancini said. It's self-limited, but children do tend to appear more toxic with AGEP than with some of the other exanthems, especially if they are young. They may have low-grade fevers, and their white counts may be mildly elevated.

Treatment is supportive, with antihistamines, cool compresses, and topical steroids if patients are uncomfortable. AGEP will resolve over 2 weeks or so with desquamation.

Dr. Mancini disclosed being a consultant to SkinMedica and Galderma, and on the speakers bureau of Promius and Galderma. SDEF and this news organization are owned by Elsevier.

An infant with acute generalized exanthematous pustulosis is shown.

Source COURTESY DR. ANTHONY J. MANCINI

SAN FRANCISCO — A Web-based survey of 660 patients with lung cancer will lead to four items being added to a widely used quality of life measure, according to a report at the World Conference on Lung Cancer.

Independence, sleep, anxiety, and depression will be included in the Lung Cancer Symptom Survey (LCSS), which has been unchanged for 20 years, said Dr. Richard J. Gralla, who led the study.

The anonymous survey was conducted among patients with lung cancer who registered with NexCura Inc., which provides Web-based tools to assist patients, caregivers, and providers in making evidence-based decisions. It was posted for 1 week in mid-2007 at www.nexcura.com

The respondents' median age was 62 years, 55% were female, and 77% reported having non–small cell lung cancer. In all, 25% of the patients reported having metastatic (stage IV) disease, 35% reported locally advanced (stage III) disease, 34% said they had no current evidence of disease, and 6% said they didn't know the extent of their disease, reported Dr. Gralla, chief of hematology and oncology at North Shore University Hospital in Manhasset, N.Y., and Long Island Jewish Medical Center in New Hyde Park, N.Y. He is a member of NexCura's medical editorial board.

At the time of the survey, 63% had received their diagnosis less than 1 year previously, 24% received it 1-2 years previously, and the remaining 13% had survived more than 2 years since their diagnosis.

Of 20 factors included in the survey, the top five that were rated as very important or most important were quality of life (80% of patients), independence (71%), not being a burden to others (65%), ability to perform normal activities (64%), and ability to sleep (63%). “We were surprised that the top five items were not symptoms of lung cancer,” Dr. Gralla said. “They're more global issues, and the symptoms come in a little bit lower” on the scale.

The next five factors were pain (59%), fatigue (58%), shortness of breath (58%), hemoptysis (58%), and depression (47%). Rated lowest were sexual difficulties (20% of patients ranked this as very important or most important), hoarseness (27%), problems with urination (27%), cough (28%), and meaning of life (32%).

Dr. Gralla acknowledged the limitations of the Web-based survey: Patients had to have access to a computer and some computer literacy. They had to have enough interest in their disease to go online for information and to complete a survey. And, as with all such surveys, patients who were very ill were less able to participate.

Still, the LCSS update is likely to be influential. “This hopefully will have some influence on how the [Food and Drug Administration] looks at evaluation of new drugs,” Dr. Gralla said at the meeting, sponsored by the International Association for the Study of Lung Cancer.

Dr. Gralla stated that he serves as an adviser on lung cancer to NexCura, and two of the four authors of the study are NexCura employees. The study received no specific funding.

SAN FRANCISCO — A Web-based survey of 660 patients with lung cancer will lead to four items being added to a widely used quality of life measure, according to a report at the World Conference on Lung Cancer.

Independence, sleep, anxiety, and depression will be included in the Lung Cancer Symptom Survey (LCSS), which has been unchanged for 20 years, said Dr. Richard J. Gralla, who led the study.

The anonymous survey was conducted among patients with lung cancer who registered with NexCura Inc., which provides Web-based tools to assist patients, caregivers, and providers in making evidence-based decisions. It was posted for 1 week in mid-2007 at www.nexcura.com

The respondents' median age was 62 years, 55% were female, and 77% reported having non–small cell lung cancer. In all, 25% of the patients reported having metastatic (stage IV) disease, 35% reported locally advanced (stage III) disease, 34% said they had no current evidence of disease, and 6% said they didn't know the extent of their disease, reported Dr. Gralla, chief of hematology and oncology at North Shore University Hospital in Manhasset, N.Y., and Long Island Jewish Medical Center in New Hyde Park, N.Y. He is a member of NexCura's medical editorial board.

At the time of the survey, 63% had received their diagnosis less than 1 year previously, 24% received it 1-2 years previously, and the remaining 13% had survived more than 2 years since their diagnosis.

Of 20 factors included in the survey, the top five that were rated as very important or most important were quality of life (80% of patients), independence (71%), not being a burden to others (65%), ability to perform normal activities (64%), and ability to sleep (63%). “We were surprised that the top five items were not symptoms of lung cancer,” Dr. Gralla said. “They're more global issues, and the symptoms come in a little bit lower” on the scale.

The next five factors were pain (59%), fatigue (58%), shortness of breath (58%), hemoptysis (58%), and depression (47%). Rated lowest were sexual difficulties (20% of patients ranked this as very important or most important), hoarseness (27%), problems with urination (27%), cough (28%), and meaning of life (32%).

Dr. Gralla acknowledged the limitations of the Web-based survey: Patients had to have access to a computer and some computer literacy. They had to have enough interest in their disease to go online for information and to complete a survey. And, as with all such surveys, patients who were very ill were less able to participate.

Still, the LCSS update is likely to be influential. “This hopefully will have some influence on how the [Food and Drug Administration] looks at evaluation of new drugs,” Dr. Gralla said at the meeting, sponsored by the International Association for the Study of Lung Cancer.

Dr. Gralla stated that he serves as an adviser on lung cancer to NexCura, and two of the four authors of the study are NexCura employees. The study received no specific funding.

SAN FRANCISCO — A Web-based survey of 660 patients with lung cancer will lead to four items being added to a widely used quality of life measure, according to a report at the World Conference on Lung Cancer.

Independence, sleep, anxiety, and depression will be included in the Lung Cancer Symptom Survey (LCSS), which has been unchanged for 20 years, said Dr. Richard J. Gralla, who led the study.

The anonymous survey was conducted among patients with lung cancer who registered with NexCura Inc., which provides Web-based tools to assist patients, caregivers, and providers in making evidence-based decisions. It was posted for 1 week in mid-2007 at www.nexcura.com

The respondents' median age was 62 years, 55% were female, and 77% reported having non–small cell lung cancer. In all, 25% of the patients reported having metastatic (stage IV) disease, 35% reported locally advanced (stage III) disease, 34% said they had no current evidence of disease, and 6% said they didn't know the extent of their disease, reported Dr. Gralla, chief of hematology and oncology at North Shore University Hospital in Manhasset, N.Y., and Long Island Jewish Medical Center in New Hyde Park, N.Y. He is a member of NexCura's medical editorial board.

At the time of the survey, 63% had received their diagnosis less than 1 year previously, 24% received it 1-2 years previously, and the remaining 13% had survived more than 2 years since their diagnosis.

Of 20 factors included in the survey, the top five that were rated as very important or most important were quality of life (80% of patients), independence (71%), not being a burden to others (65%), ability to perform normal activities (64%), and ability to sleep (63%). “We were surprised that the top five items were not symptoms of lung cancer,” Dr. Gralla said. “They're more global issues, and the symptoms come in a little bit lower” on the scale.

The next five factors were pain (59%), fatigue (58%), shortness of breath (58%), hemoptysis (58%), and depression (47%). Rated lowest were sexual difficulties (20% of patients ranked this as very important or most important), hoarseness (27%), problems with urination (27%), cough (28%), and meaning of life (32%).

Dr. Gralla acknowledged the limitations of the Web-based survey: Patients had to have access to a computer and some computer literacy. They had to have enough interest in their disease to go online for information and to complete a survey. And, as with all such surveys, patients who were very ill were less able to participate.

Still, the LCSS update is likely to be influential. “This hopefully will have some influence on how the [Food and Drug Administration] looks at evaluation of new drugs,” Dr. Gralla said at the meeting, sponsored by the International Association for the Study of Lung Cancer.

Dr. Gralla stated that he serves as an adviser on lung cancer to NexCura, and two of the four authors of the study are NexCura employees. The study received no specific funding.

SAN FRANCISCO — An investigational device could make sputum screening a routine part of health examinations in patients at risk for lung cancer, its developers suggested at the World Conference on Lung Cancer.

The Lung Cell Evaluation Device (LuCED) can discriminate normal cells from cancerous cells in sputum with 90% sensitivity and near 100% specificity, according to its manufacturer, VisionGate Inc.

LuCED is available as a research instrument. Dr. Robert Honigberg, VisionGate's consulting chief medical officer, said that the company hopes to receive Food and Drug Administration approval for a noncancer indication—the detection of macrophages in gastroesophageal reflux disease—by 2010, and approval of a lung cancer indication in 2011.

Company officials discussed the device at a press briefing on innovative diagnostics organized by the International Association for the Study of Lung Cancer, which sponsored the conference.

LuCED is based on a patented technology called Cell-CT, which uses light microscopy to assemble highly detailed three-dimensional images of individual cells as they rotate in a capillary tube. The software then quantifies critical morphological features to discriminate normal cells from cancerous ones. The results are entered into a proprietary formula to produce a “LuCED Score” that differentiates cancer cells from normal cells.

“We can get very close to 100% accuracy for normal sputum, and about 90% accuracy on sputum with cancer cells,” said Michael Meyer, VisionGate's vice president for image engineering.

SAN FRANCISCO — An investigational device could make sputum screening a routine part of health examinations in patients at risk for lung cancer, its developers suggested at the World Conference on Lung Cancer.

The Lung Cell Evaluation Device (LuCED) can discriminate normal cells from cancerous cells in sputum with 90% sensitivity and near 100% specificity, according to its manufacturer, VisionGate Inc.

LuCED is available as a research instrument. Dr. Robert Honigberg, VisionGate's consulting chief medical officer, said that the company hopes to receive Food and Drug Administration approval for a noncancer indication—the detection of macrophages in gastroesophageal reflux disease—by 2010, and approval of a lung cancer indication in 2011.

Company officials discussed the device at a press briefing on innovative diagnostics organized by the International Association for the Study of Lung Cancer, which sponsored the conference.

LuCED is based on a patented technology called Cell-CT, which uses light microscopy to assemble highly detailed three-dimensional images of individual cells as they rotate in a capillary tube. The software then quantifies critical morphological features to discriminate normal cells from cancerous ones. The results are entered into a proprietary formula to produce a “LuCED Score” that differentiates cancer cells from normal cells.

“We can get very close to 100% accuracy for normal sputum, and about 90% accuracy on sputum with cancer cells,” said Michael Meyer, VisionGate's vice president for image engineering.

SAN FRANCISCO — An investigational device could make sputum screening a routine part of health examinations in patients at risk for lung cancer, its developers suggested at the World Conference on Lung Cancer.

The Lung Cell Evaluation Device (LuCED) can discriminate normal cells from cancerous cells in sputum with 90% sensitivity and near 100% specificity, according to its manufacturer, VisionGate Inc.

LuCED is available as a research instrument. Dr. Robert Honigberg, VisionGate's consulting chief medical officer, said that the company hopes to receive Food and Drug Administration approval for a noncancer indication—the detection of macrophages in gastroesophageal reflux disease—by 2010, and approval of a lung cancer indication in 2011.

Company officials discussed the device at a press briefing on innovative diagnostics organized by the International Association for the Study of Lung Cancer, which sponsored the conference.

LuCED is based on a patented technology called Cell-CT, which uses light microscopy to assemble highly detailed three-dimensional images of individual cells as they rotate in a capillary tube. The software then quantifies critical morphological features to discriminate normal cells from cancerous ones. The results are entered into a proprietary formula to produce a “LuCED Score” that differentiates cancer cells from normal cells.

“We can get very close to 100% accuracy for normal sputum, and about 90% accuracy on sputum with cancer cells,” said Michael Meyer, VisionGate's vice president for image engineering.

SAN FRANCISCO — Obese adolescents lost significantly more weight on a high-protein, low-carbohydrate diet than on a standard low-fat diet, according to a randomized study involving 46 teens.

At the end of 12 weeks, the teens on the high-protein, low-carbohydrate (HPLC) diet lost an average of 9.0 kg, while those on the low-fat diet lost an average of 5.6 kg, a significant difference, Dr. Nancy F. Krebs of the University of Colorado, Denver, said at a meeting on clinical pediatrics sponsored by the University of California, San Francisco.

Moreover, adolescents in both groups tended to maintain their weight loss over an additional 24 weeks of follow-up. “My hypothesis was that [the HPLC diet] would get them to 12 weeks but they'd rebound,” possibly even ending up heavier than before.

In fact, while adolescents in the HPLC group tended to gain back a little weight within the first 3 months after the end of the diet, they still weighed less than those in the low-fat group. And the HPLC group appeared to maintain that difference for another 3 months, although those differences did not reach statistical significance.

All the adolescents in the study were severely overweight, weighing at least 175% of their ideal body weight. The teens in the HPLC group were placed on a diet limiting them to 20 g/day of carbohydrates. To ensure that they were compliant with this diet, the investigators measured ketone levels twice daily. People on HPLC diets tend to become ketonic quickly, something that can be measured easily with a urine dipstick.

Both groups of adolescents lost equivalent amounts of fat and protein and showed similar improvements in their lipid profiles, but those on the HPLC diet lowered their triglyceride levels significantly more than the low-fat group.

Based on glucose tolerance test results, carbohydrate metabolism improved in both groups. The investigators observed no adverse effects of the HPLC diet.

Dr. Krebs said she has submitted her study for publication and has no relevant conflicts of interest.

Teens on the HPLC diet lost an average of 9.0 kg, while those on the low-fat diet lost an average of 5.6 kg.

Source DR. KREBS

SAN FRANCISCO — Obese adolescents lost significantly more weight on a high-protein, low-carbohydrate diet than on a standard low-fat diet, according to a randomized study involving 46 teens.

At the end of 12 weeks, the teens on the high-protein, low-carbohydrate (HPLC) diet lost an average of 9.0 kg, while those on the low-fat diet lost an average of 5.6 kg, a significant difference, Dr. Nancy F. Krebs of the University of Colorado, Denver, said at a meeting on clinical pediatrics sponsored by the University of California, San Francisco.

Moreover, adolescents in both groups tended to maintain their weight loss over an additional 24 weeks of follow-up. “My hypothesis was that [the HPLC diet] would get them to 12 weeks but they'd rebound,” possibly even ending up heavier than before.

In fact, while adolescents in the HPLC group tended to gain back a little weight within the first 3 months after the end of the diet, they still weighed less than those in the low-fat group. And the HPLC group appeared to maintain that difference for another 3 months, although those differences did not reach statistical significance.

All the adolescents in the study were severely overweight, weighing at least 175% of their ideal body weight. The teens in the HPLC group were placed on a diet limiting them to 20 g/day of carbohydrates. To ensure that they were compliant with this diet, the investigators measured ketone levels twice daily. People on HPLC diets tend to become ketonic quickly, something that can be measured easily with a urine dipstick.

Both groups of adolescents lost equivalent amounts of fat and protein and showed similar improvements in their lipid profiles, but those on the HPLC diet lowered their triglyceride levels significantly more than the low-fat group.

Based on glucose tolerance test results, carbohydrate metabolism improved in both groups. The investigators observed no adverse effects of the HPLC diet.

Dr. Krebs said she has submitted her study for publication and has no relevant conflicts of interest.

Teens on the HPLC diet lost an average of 9.0 kg, while those on the low-fat diet lost an average of 5.6 kg.

Source DR. KREBS

SAN FRANCISCO — Obese adolescents lost significantly more weight on a high-protein, low-carbohydrate diet than on a standard low-fat diet, according to a randomized study involving 46 teens.

At the end of 12 weeks, the teens on the high-protein, low-carbohydrate (HPLC) diet lost an average of 9.0 kg, while those on the low-fat diet lost an average of 5.6 kg, a significant difference, Dr. Nancy F. Krebs of the University of Colorado, Denver, said at a meeting on clinical pediatrics sponsored by the University of California, San Francisco.

Moreover, adolescents in both groups tended to maintain their weight loss over an additional 24 weeks of follow-up. “My hypothesis was that [the HPLC diet] would get them to 12 weeks but they'd rebound,” possibly even ending up heavier than before.

In fact, while adolescents in the HPLC group tended to gain back a little weight within the first 3 months after the end of the diet, they still weighed less than those in the low-fat group. And the HPLC group appeared to maintain that difference for another 3 months, although those differences did not reach statistical significance.

All the adolescents in the study were severely overweight, weighing at least 175% of their ideal body weight. The teens in the HPLC group were placed on a diet limiting them to 20 g/day of carbohydrates. To ensure that they were compliant with this diet, the investigators measured ketone levels twice daily. People on HPLC diets tend to become ketonic quickly, something that can be measured easily with a urine dipstick.

Both groups of adolescents lost equivalent amounts of fat and protein and showed similar improvements in their lipid profiles, but those on the HPLC diet lowered their triglyceride levels significantly more than the low-fat group.

Based on glucose tolerance test results, carbohydrate metabolism improved in both groups. The investigators observed no adverse effects of the HPLC diet.

Dr. Krebs said she has submitted her study for publication and has no relevant conflicts of interest.

Teens on the HPLC diet lost an average of 9.0 kg, while those on the low-fat diet lost an average of 5.6 kg.

Source DR. KREBS

The monoclonal antibody belimumab appears to be effective for the treatment of systemic lupus erythematosus, according to the results of a randomized, placebo-controlled trial involving 865 patients.

Human Genome Sciences and Glaxo SmithKline, which codeveloped the biologic, announced the results during a conference call for security analysts. The results have not yet undergone peer review. The trial, BLISS-52, was conducted at 90 clinical sites in 13 countries, primarily in Asia, South America, and Eastern Europe. A second phase III trial, BLISS-76, is in its final stages with 826 patients at 133 clinical sites in 19 countries, primarily in North America and Europe. Patients in BLISS-52 were followed for 52 weeks, while patients in BLISS-76 will be followed for 76 weeks.

H. Thomas Watkins, president and chief executive officer of Human Genome Sciences, said that results from BLISS-76 will be announced in November. If the results are positive, the companies will submit marketing applications in the United States, Europe, and other regions during the first half of 2010, he said.

The two trials have similar designs. Patients were randomized to receive either standard of care plus placebo or standard of care plus 1 mg/kg or 10 mg/kg of belimumab. The drug (or placebo) was delivered intravenously on days 0, 14, 28, and every 28 days thereafter.

The primary end point of BLISS-52 was “patient response,” defined as an improvement in SELENA-SLEDAI instrument scores of 4 or more at week 52 with no clinically significant flare in the BILAG index or worsening of the Physician's Global Assessment score. SELENA SLEDAI refers to the Safety of Estrogen in Lupus Erythematosus National Assessment trial version of the Systemic Lupus Erythematosus Disease Activity Index. BILAG is an index developed by the British Isles Lupus Assessment Group.

Dr. Joan T. Merrill, head of clinical pharmacology at the Oklahoma Medical Research Foundation, Oklahoma City, said in an interview: “The use of these two instruments in the trial design was very clever. The two major weaknesses of the SLEDAI have been overcome in this trial. It is not as sensitive to change as the BILAG, so if you do see a 4-point drop you are impressed. However, the 4-point drop in the overall score could happen while there is significant worsening in some organs, and this was addressed using the BILAG and the Physician's Global Assessment to eliminate such patients from the responder group.”

At week 52, 44% of the patients taking placebo met the primary efficacy end point, compared with 52% of the patients taking 1 mg/kg belimumab, and 58% of the patients taking 10 mg/kg belimumab. Both doses of belimumab proved superior to placebo with a high degree of statistical significance.

There were also significant improvements in several secondary end points. For example, investigators observed improvement in Physician's Global Assessment scores in 4-8 weeks. A significantly higher proportion of patients in both belimumab groups were able to reduce their average prednisone dose by at least 25% from baseline to 7.5 mg/day or less during the final 12 weeks of the study. Health-related quality of life at week 52, as measured by the SF-36 Physical Component Summary score, was significantly better in both belimumab treatment groups.

“This is an outstanding result,” according to Dr. Merrill, who is also the medical director of the Lupus Foundation of America. “By showing an effect on both the efficacy end point and the steroid taper, the treatment impact is more robust than it might seem just looking at the primary outcome.”

Rates of adverse events, serious adverse events, infections, and fatalities were similar in the belimu-mab and placebo groups. The most common adverse events were headache, arthralgia, upper respiratory tract infection, urinary tract infection, and influenza.

Dr. Merrill is a consultant for Genentech Inc., Bristol-Myers Squibb Co., MedImmune Inc., and other companies that develop products for lupus. She was not an investigator in the study being discussed but is involved in the ongoing phase III trial that includes sites in the United States and Western Europe. The companies plan to market belimumab under the trade name Benlysta.

The monoclonal antibody belimumab appears to be effective for the treatment of systemic lupus erythematosus, according to the results of a randomized, placebo-controlled trial involving 865 patients.

Human Genome Sciences and Glaxo SmithKline, which codeveloped the biologic, announced the results during a conference call for security analysts. The results have not yet undergone peer review. The trial, BLISS-52, was conducted at 90 clinical sites in 13 countries, primarily in Asia, South America, and Eastern Europe. A second phase III trial, BLISS-76, is in its final stages with 826 patients at 133 clinical sites in 19 countries, primarily in North America and Europe. Patients in BLISS-52 were followed for 52 weeks, while patients in BLISS-76 will be followed for 76 weeks.

H. Thomas Watkins, president and chief executive officer of Human Genome Sciences, said that results from BLISS-76 will be announced in November. If the results are positive, the companies will submit marketing applications in the United States, Europe, and other regions during the first half of 2010, he said.

The two trials have similar designs. Patients were randomized to receive either standard of care plus placebo or standard of care plus 1 mg/kg or 10 mg/kg of belimumab. The drug (or placebo) was delivered intravenously on days 0, 14, 28, and every 28 days thereafter.

The primary end point of BLISS-52 was “patient response,” defined as an improvement in SELENA-SLEDAI instrument scores of 4 or more at week 52 with no clinically significant flare in the BILAG index or worsening of the Physician's Global Assessment score. SELENA SLEDAI refers to the Safety of Estrogen in Lupus Erythematosus National Assessment trial version of the Systemic Lupus Erythematosus Disease Activity Index. BILAG is an index developed by the British Isles Lupus Assessment Group.

Dr. Joan T. Merrill, head of clinical pharmacology at the Oklahoma Medical Research Foundation, Oklahoma City, said in an interview: “The use of these two instruments in the trial design was very clever. The two major weaknesses of the SLEDAI have been overcome in this trial. It is not as sensitive to change as the BILAG, so if you do see a 4-point drop you are impressed. However, the 4-point drop in the overall score could happen while there is significant worsening in some organs, and this was addressed using the BILAG and the Physician's Global Assessment to eliminate such patients from the responder group.”

At week 52, 44% of the patients taking placebo met the primary efficacy end point, compared with 52% of the patients taking 1 mg/kg belimumab, and 58% of the patients taking 10 mg/kg belimumab. Both doses of belimumab proved superior to placebo with a high degree of statistical significance.

There were also significant improvements in several secondary end points. For example, investigators observed improvement in Physician's Global Assessment scores in 4-8 weeks. A significantly higher proportion of patients in both belimumab groups were able to reduce their average prednisone dose by at least 25% from baseline to 7.5 mg/day or less during the final 12 weeks of the study. Health-related quality of life at week 52, as measured by the SF-36 Physical Component Summary score, was significantly better in both belimumab treatment groups.

“This is an outstanding result,” according to Dr. Merrill, who is also the medical director of the Lupus Foundation of America. “By showing an effect on both the efficacy end point and the steroid taper, the treatment impact is more robust than it might seem just looking at the primary outcome.”

Rates of adverse events, serious adverse events, infections, and fatalities were similar in the belimu-mab and placebo groups. The most common adverse events were headache, arthralgia, upper respiratory tract infection, urinary tract infection, and influenza.

Dr. Merrill is a consultant for Genentech Inc., Bristol-Myers Squibb Co., MedImmune Inc., and other companies that develop products for lupus. She was not an investigator in the study being discussed but is involved in the ongoing phase III trial that includes sites in the United States and Western Europe. The companies plan to market belimumab under the trade name Benlysta.

The monoclonal antibody belimumab appears to be effective for the treatment of systemic lupus erythematosus, according to the results of a randomized, placebo-controlled trial involving 865 patients.

Human Genome Sciences and Glaxo SmithKline, which codeveloped the biologic, announced the results during a conference call for security analysts. The results have not yet undergone peer review. The trial, BLISS-52, was conducted at 90 clinical sites in 13 countries, primarily in Asia, South America, and Eastern Europe. A second phase III trial, BLISS-76, is in its final stages with 826 patients at 133 clinical sites in 19 countries, primarily in North America and Europe. Patients in BLISS-52 were followed for 52 weeks, while patients in BLISS-76 will be followed for 76 weeks.

H. Thomas Watkins, president and chief executive officer of Human Genome Sciences, said that results from BLISS-76 will be announced in November. If the results are positive, the companies will submit marketing applications in the United States, Europe, and other regions during the first half of 2010, he said.

The two trials have similar designs. Patients were randomized to receive either standard of care plus placebo or standard of care plus 1 mg/kg or 10 mg/kg of belimumab. The drug (or placebo) was delivered intravenously on days 0, 14, 28, and every 28 days thereafter.

The primary end point of BLISS-52 was “patient response,” defined as an improvement in SELENA-SLEDAI instrument scores of 4 or more at week 52 with no clinically significant flare in the BILAG index or worsening of the Physician's Global Assessment score. SELENA SLEDAI refers to the Safety of Estrogen in Lupus Erythematosus National Assessment trial version of the Systemic Lupus Erythematosus Disease Activity Index. BILAG is an index developed by the British Isles Lupus Assessment Group.

Dr. Joan T. Merrill, head of clinical pharmacology at the Oklahoma Medical Research Foundation, Oklahoma City, said in an interview: “The use of these two instruments in the trial design was very clever. The two major weaknesses of the SLEDAI have been overcome in this trial. It is not as sensitive to change as the BILAG, so if you do see a 4-point drop you are impressed. However, the 4-point drop in the overall score could happen while there is significant worsening in some organs, and this was addressed using the BILAG and the Physician's Global Assessment to eliminate such patients from the responder group.”

At week 52, 44% of the patients taking placebo met the primary efficacy end point, compared with 52% of the patients taking 1 mg/kg belimumab, and 58% of the patients taking 10 mg/kg belimumab. Both doses of belimumab proved superior to placebo with a high degree of statistical significance.

There were also significant improvements in several secondary end points. For example, investigators observed improvement in Physician's Global Assessment scores in 4-8 weeks. A significantly higher proportion of patients in both belimumab groups were able to reduce their average prednisone dose by at least 25% from baseline to 7.5 mg/day or less during the final 12 weeks of the study. Health-related quality of life at week 52, as measured by the SF-36 Physical Component Summary score, was significantly better in both belimumab treatment groups.

“This is an outstanding result,” according to Dr. Merrill, who is also the medical director of the Lupus Foundation of America. “By showing an effect on both the efficacy end point and the steroid taper, the treatment impact is more robust than it might seem just looking at the primary outcome.”

Rates of adverse events, serious adverse events, infections, and fatalities were similar in the belimu-mab and placebo groups. The most common adverse events were headache, arthralgia, upper respiratory tract infection, urinary tract infection, and influenza.

Dr. Merrill is a consultant for Genentech Inc., Bristol-Myers Squibb Co., MedImmune Inc., and other companies that develop products for lupus. She was not an investigator in the study being discussed but is involved in the ongoing phase III trial that includes sites in the United States and Western Europe. The companies plan to market belimumab under the trade name Benlysta.

Investigators have made rapid progress on several fronts in understanding the novel influenza A(H1N1) virus responsible for the current pandemic, according to a series of reports.

Investigators tracing the virus's evolutionary history have learned that the novel H1N1 flu virus is a direct, fourth-generation descendant of the virus that caused the disastrous 1918 flu pandemic. They've learned that the most common rapid influenza test is highly specific but not very sensitive for detecting the influenza A(H1N1) virus.

In addition, the virus's worldwide spread closely matched historic patterns of airline travel from Mexico. Furthermore, the unusual age distribution of severe illness and death associated with the virus, affecting mostly children and young adults, may have resulted from relative protection among older individuals who had been exposed to H1N1 during childhood before the 1957 pandemic.

All of the reports are available online at the New England Journal of Medicine's online H1N1 influenza center (http://h1n1.nejm.org

A review article, by Dr. Shanta M. Zimmer and Dr. Donald S. Burke of the University of Pittsburgh, traced the emergence of the influenza A(H1N1) virus to an avian virus that simultaneously appeared in humans and swine in 1918. That virus killed 40 million to 50 million people.

The influenza A(H1N1) virus consists of eight genes that have mutated steadily between 1918 and the present, but the virus has acquired no new gene segments from avian or other sources.

The virus disappeared entirely from humans in 1957 and was replaced by a new strain called H2N2. H1N1 was not detected again until 1976, when the virus was transmitted from a swine to humans, causing an outbreak of respiratory disease among soldiers at Fort Dix, N.J.

Beginning in 1977, the H1N1 virus, accompanied by H3N2, began to co-circulate seasonally in humans. Since then, new H1N1 strains have emerged in swine, with occasional cross-species transmission to humans. In 2008, two distinct H1 swine viruses combined to produce the virus causing the current pandemic.

In an editorial, Dr. David M. Morens, Dr. Jeffrey K. Taubenberger, and Dr. Anthony S. Fauci of the National Institute of Allergy and Infectious Diseases likened the interaction between the various descendants of the 1918 virus and the human community as an “elaborate dance.” They wrote that the “partners have remained linked and in step, even as each strives to take the lead,” and that there's little evidence that this era is about to come to an end.

In a letter to the editor, Dr. Dennis J. Faix of the Naval Health Research Center in San Diego and his colleagues determined that the most commonly used rapid influenza test, called QuickVue Influenza A+B, widely available in doctors' offices in the United States, has a 99% specificity for the novel H1N1 flu virus, compared with definitive polymerase chain reaction-based tests. This means that if the test indicates that the patient's virus is H1N1, it almost certainly is. On the other hand, the sensitivity of the test ranged from 31% to 63% in various populations, meaning that the test may well miss genuine cases of novel H1N1 flu.

In another letter to the editor, Dr. Kamran Khan of St. Michael's Hospital in Toronto and colleagues found that the March through April 2009 worldwide spread of the virus closely matched patterns of global airline transportation originating from Mexico during the same period in 2008. Of 20 countries with the highest volumes of international passengers arriving from Mexico, 16 had confirmed importations of H1N1. (The exceptions were Japan, Chile, Venezuela, and Peru.)

They calculated that countries receiving more than 1,400 passengers from Mexico were at significantly higher risk of importation, and that international air traffic volume alone was 92% sensitive and more than 92% specific in predicting importation.

In an original research study, Dr. Rogelio Pérez-Padilla of the National Institute of Respiratory Diseases of Mexico in Mexico City and colleagues investigated 18 patients who were hospitalized with pneumonia between March 24 and April 24, 2009, and confirmed novel H1N1 flu.

More than half of those patients were between ages 13 and 47 years, and only eight had preexisting medical conditions. Twelve patients required mechanical ventilation, and 7 died. Within 7 days after contact with these initial cases, 22 health care workers developed mild or moderate flulike illness, but none required hospitalization.

In a much larger study involving 2,155 cases of severe pneumonia reported to the Mexican Ministry of Health, Gerardo Chowell, Ph.D., of the National Institutes of Health, Bethesda, Md., and colleagues found that 87% of the deaths and 71% of the cases of severe pneumonia involved patients between ages 5 and 59 years.

This contrasts with 17% of deaths and 32% of cases of severe pneumonia in that age group during the peak of seasonal influenza periods from 2005 to 2008.

Morbidity and mortality among patients aged 60 years and older during the current pandemic has been significantly lower than among younger individuals. The investigators suggested that older individuals were more likely to have acquired some immunity by being exposed to H1N1 strains before those strains disappeared from the human population in 1957.

“If there is good news,” wrote Dr. Morens, Dr. Taubenberger, and Dr. Fauci, “it is that successive pandemics and pandemiclike events generally appear to be decreasing in severity over time. This diminution is surely due in part to advances in medicine and public health, but it may also reflect viral evolutionary 'choices' that favor optimal transmissibility with minimal pathogenicity—a virus that kills its hosts or sends them to bed is not optimally transmissible.”

One of the authors of the report on rapid influenza tests said he had received grant support from Sanofi Pasteur. All the other authors of that article and all the authors of the other articles stated that they had no relevant conflicts of interest.

Investigators have made rapid progress on several fronts in understanding the novel influenza A(H1N1) virus responsible for the current pandemic, according to a series of reports.

Investigators tracing the virus's evolutionary history have learned that the novel H1N1 flu virus is a direct, fourth-generation descendant of the virus that caused the disastrous 1918 flu pandemic. They've learned that the most common rapid influenza test is highly specific but not very sensitive for detecting the influenza A(H1N1) virus.

In addition, the virus's worldwide spread closely matched historic patterns of airline travel from Mexico. Furthermore, the unusual age distribution of severe illness and death associated with the virus, affecting mostly children and young adults, may have resulted from relative protection among older individuals who had been exposed to H1N1 during childhood before the 1957 pandemic.

All of the reports are available online at the New England Journal of Medicine's online H1N1 influenza center (http://h1n1.nejm.org

A review article, by Dr. Shanta M. Zimmer and Dr. Donald S. Burke of the University of Pittsburgh, traced the emergence of the influenza A(H1N1) virus to an avian virus that simultaneously appeared in humans and swine in 1918. That virus killed 40 million to 50 million people.

The influenza A(H1N1) virus consists of eight genes that have mutated steadily between 1918 and the present, but the virus has acquired no new gene segments from avian or other sources.

The virus disappeared entirely from humans in 1957 and was replaced by a new strain called H2N2. H1N1 was not detected again until 1976, when the virus was transmitted from a swine to humans, causing an outbreak of respiratory disease among soldiers at Fort Dix, N.J.

Beginning in 1977, the H1N1 virus, accompanied by H3N2, began to co-circulate seasonally in humans. Since then, new H1N1 strains have emerged in swine, with occasional cross-species transmission to humans. In 2008, two distinct H1 swine viruses combined to produce the virus causing the current pandemic.

In an editorial, Dr. David M. Morens, Dr. Jeffrey K. Taubenberger, and Dr. Anthony S. Fauci of the National Institute of Allergy and Infectious Diseases likened the interaction between the various descendants of the 1918 virus and the human community as an “elaborate dance.” They wrote that the “partners have remained linked and in step, even as each strives to take the lead,” and that there's little evidence that this era is about to come to an end.

In a letter to the editor, Dr. Dennis J. Faix of the Naval Health Research Center in San Diego and his colleagues determined that the most commonly used rapid influenza test, called QuickVue Influenza A+B, widely available in doctors' offices in the United States, has a 99% specificity for the novel H1N1 flu virus, compared with definitive polymerase chain reaction-based tests. This means that if the test indicates that the patient's virus is H1N1, it almost certainly is. On the other hand, the sensitivity of the test ranged from 31% to 63% in various populations, meaning that the test may well miss genuine cases of novel H1N1 flu.

In another letter to the editor, Dr. Kamran Khan of St. Michael's Hospital in Toronto and colleagues found that the March through April 2009 worldwide spread of the virus closely matched patterns of global airline transportation originating from Mexico during the same period in 2008. Of 20 countries with the highest volumes of international passengers arriving from Mexico, 16 had confirmed importations of H1N1. (The exceptions were Japan, Chile, Venezuela, and Peru.)

They calculated that countries receiving more than 1,400 passengers from Mexico were at significantly higher risk of importation, and that international air traffic volume alone was 92% sensitive and more than 92% specific in predicting importation.

In an original research study, Dr. Rogelio Pérez-Padilla of the National Institute of Respiratory Diseases of Mexico in Mexico City and colleagues investigated 18 patients who were hospitalized with pneumonia between March 24 and April 24, 2009, and confirmed novel H1N1 flu.

More than half of those patients were between ages 13 and 47 years, and only eight had preexisting medical conditions. Twelve patients required mechanical ventilation, and 7 died. Within 7 days after contact with these initial cases, 22 health care workers developed mild or moderate flulike illness, but none required hospitalization.

In a much larger study involving 2,155 cases of severe pneumonia reported to the Mexican Ministry of Health, Gerardo Chowell, Ph.D., of the National Institutes of Health, Bethesda, Md., and colleagues found that 87% of the deaths and 71% of the cases of severe pneumonia involved patients between ages 5 and 59 years.

This contrasts with 17% of deaths and 32% of cases of severe pneumonia in that age group during the peak of seasonal influenza periods from 2005 to 2008.

Morbidity and mortality among patients aged 60 years and older during the current pandemic has been significantly lower than among younger individuals. The investigators suggested that older individuals were more likely to have acquired some immunity by being exposed to H1N1 strains before those strains disappeared from the human population in 1957.

“If there is good news,” wrote Dr. Morens, Dr. Taubenberger, and Dr. Fauci, “it is that successive pandemics and pandemiclike events generally appear to be decreasing in severity over time. This diminution is surely due in part to advances in medicine and public health, but it may also reflect viral evolutionary 'choices' that favor optimal transmissibility with minimal pathogenicity—a virus that kills its hosts or sends them to bed is not optimally transmissible.”

One of the authors of the report on rapid influenza tests said he had received grant support from Sanofi Pasteur. All the other authors of that article and all the authors of the other articles stated that they had no relevant conflicts of interest.

Investigators have made rapid progress on several fronts in understanding the novel influenza A(H1N1) virus responsible for the current pandemic, according to a series of reports.

Investigators tracing the virus's evolutionary history have learned that the novel H1N1 flu virus is a direct, fourth-generation descendant of the virus that caused the disastrous 1918 flu pandemic. They've learned that the most common rapid influenza test is highly specific but not very sensitive for detecting the influenza A(H1N1) virus.

In addition, the virus's worldwide spread closely matched historic patterns of airline travel from Mexico. Furthermore, the unusual age distribution of severe illness and death associated with the virus, affecting mostly children and young adults, may have resulted from relative protection among older individuals who had been exposed to H1N1 during childhood before the 1957 pandemic.

All of the reports are available online at the New England Journal of Medicine's online H1N1 influenza center (http://h1n1.nejm.org

A review article, by Dr. Shanta M. Zimmer and Dr. Donald S. Burke of the University of Pittsburgh, traced the emergence of the influenza A(H1N1) virus to an avian virus that simultaneously appeared in humans and swine in 1918. That virus killed 40 million to 50 million people.

The influenza A(H1N1) virus consists of eight genes that have mutated steadily between 1918 and the present, but the virus has acquired no new gene segments from avian or other sources.

The virus disappeared entirely from humans in 1957 and was replaced by a new strain called H2N2. H1N1 was not detected again until 1976, when the virus was transmitted from a swine to humans, causing an outbreak of respiratory disease among soldiers at Fort Dix, N.J.

Beginning in 1977, the H1N1 virus, accompanied by H3N2, began to co-circulate seasonally in humans. Since then, new H1N1 strains have emerged in swine, with occasional cross-species transmission to humans. In 2008, two distinct H1 swine viruses combined to produce the virus causing the current pandemic.

In an editorial, Dr. David M. Morens, Dr. Jeffrey K. Taubenberger, and Dr. Anthony S. Fauci of the National Institute of Allergy and Infectious Diseases likened the interaction between the various descendants of the 1918 virus and the human community as an “elaborate dance.” They wrote that the “partners have remained linked and in step, even as each strives to take the lead,” and that there's little evidence that this era is about to come to an end.

In a letter to the editor, Dr. Dennis J. Faix of the Naval Health Research Center in San Diego and his colleagues determined that the most commonly used rapid influenza test, called QuickVue Influenza A+B, widely available in doctors' offices in the United States, has a 99% specificity for the novel H1N1 flu virus, compared with definitive polymerase chain reaction-based tests. This means that if the test indicates that the patient's virus is H1N1, it almost certainly is. On the other hand, the sensitivity of the test ranged from 31% to 63% in various populations, meaning that the test may well miss genuine cases of novel H1N1 flu.

In another letter to the editor, Dr. Kamran Khan of St. Michael's Hospital in Toronto and colleagues found that the March through April 2009 worldwide spread of the virus closely matched patterns of global airline transportation originating from Mexico during the same period in 2008. Of 20 countries with the highest volumes of international passengers arriving from Mexico, 16 had confirmed importations of H1N1. (The exceptions were Japan, Chile, Venezuela, and Peru.)

They calculated that countries receiving more than 1,400 passengers from Mexico were at significantly higher risk of importation, and that international air traffic volume alone was 92% sensitive and more than 92% specific in predicting importation.

In an original research study, Dr. Rogelio Pérez-Padilla of the National Institute of Respiratory Diseases of Mexico in Mexico City and colleagues investigated 18 patients who were hospitalized with pneumonia between March 24 and April 24, 2009, and confirmed novel H1N1 flu.

More than half of those patients were between ages 13 and 47 years, and only eight had preexisting medical conditions. Twelve patients required mechanical ventilation, and 7 died. Within 7 days after contact with these initial cases, 22 health care workers developed mild or moderate flulike illness, but none required hospitalization.

In a much larger study involving 2,155 cases of severe pneumonia reported to the Mexican Ministry of Health, Gerardo Chowell, Ph.D., of the National Institutes of Health, Bethesda, Md., and colleagues found that 87% of the deaths and 71% of the cases of severe pneumonia involved patients between ages 5 and 59 years.

This contrasts with 17% of deaths and 32% of cases of severe pneumonia in that age group during the peak of seasonal influenza periods from 2005 to 2008.

Morbidity and mortality among patients aged 60 years and older during the current pandemic has been significantly lower than among younger individuals. The investigators suggested that older individuals were more likely to have acquired some immunity by being exposed to H1N1 strains before those strains disappeared from the human population in 1957.

“If there is good news,” wrote Dr. Morens, Dr. Taubenberger, and Dr. Fauci, “it is that successive pandemics and pandemiclike events generally appear to be decreasing in severity over time. This diminution is surely due in part to advances in medicine and public health, but it may also reflect viral evolutionary 'choices' that favor optimal transmissibility with minimal pathogenicity—a virus that kills its hosts or sends them to bed is not optimally transmissible.”

One of the authors of the report on rapid influenza tests said he had received grant support from Sanofi Pasteur. All the other authors of that article and all the authors of the other articles stated that they had no relevant conflicts of interest.

LONG BEACH, CALIF. — Identifying patients most at risk for progression to diabetes in 5-10 years may become easier with the development of several scoring systems for quantifying risk.

About 57 million Americans have prediabetes, as judged by impaired fasting glucose level, but only about 10% of them will go on to develop type 2 diabetes within 5 years. Because it's impractical to target all of those 57 million people with intensive interventions, several strategies have emerged to identify those most at risk.

According to speakers at a conference on diabetes sponsored by the Centers for Disease Control and Prevention, some of these strategies appear to get good results. Investigators at the CDC, for example, have developed two simple scoring systems—one of which doesn't even require a blood test—that quantify an individual's chance of developing diabetes within 10 years. And researchers at a private company, Tethys Bioscience of Emeryville, Calif., have developed an algorithm based on seven biomarkers that can categorize individuals as being at high, medium, or low risk for progressing to diabetes within 5 years.

“I think in the U.S. population, our user-friendly scoring systems can really help us to target individuals, at least among blacks and whites, who will benefit most from a prevention program,” said Dr. Henry S. Kahn of the CDC. “Our basic system could be used to identify those maybe who should just be escalated … to a simple blood test. You could use the basic scoring system through elementary examinations to find out which subsets of your community are in the greatest need of prevention resources.”

Dr. Kahn and his colleagues used 10-year follow-up data from the Atherosclerosis Risk in Communities (ARIC) study, which involved 12,729 U.S. adults who did not have diabetes at baseline. The investigators randomly selected 75% of that cohort to derive their scoring systems, reserving the other 25% to demonstrate that the systems work.

The basic scoring system uses only easily obtainable data, and the enhanced scoring system adds information from simple blood tests. Both systems yield a diabetes prediction score (DPS) from 0 to 100 that represents the chance that an individual would develop diabetes within 10 years.

The basic DPS assigns point values to hypertension, family history, black race, age 55-64 years, smoking history, waist circumference, height, resting pulse rate, and weight. Among the validation cohort, basic DPS scores in the lowest quintile corresponded to a 10-year incidence of diabetes of 5%, while scores in the highest quintile corresponded to a 10-year incidence of 32%.

The enhanced DPS eliminates smoking history and weight from the scoring system and adds point values for height and for levels of blood glucose, triglycerides, HDL cholesterol, and uric acid. Among the validation cohort, scores in the lowest quintile corresponded to a 10-year incidence of diabetes of 4%, while scores in the highest quintile corresponded to a 10-year incidence of 46%.

Dr. Kahn said that if incorporated within public health surveys, either scoring system would likely identify some adults with undiagnosed diabetes and some at elevated risk for cardiovascular disease.

The Tethys test employs a different strategy. After analyzing several large European cohorts, investigators identified seven biomarkers that together form a fingerprint identifying individuals likely to develop diabetes within 5 years. Those biomarkers are levels of fasting glucose, hemoglobin A1c, insulin, adiponectin (associated with obesity), ferritin (associated with cell death, especially in the liver), and C-reactive protein and interleukin-2 receptor-alpha (both associated with inflammation and cardiovascular risk).

Michael McKenna, Ph.D, chief scientific officer at Tethys, explained that physicians interested in ordering the test need only request a blood draw and have a standard 3-mL red-cap tube of serum sent to Tethys's CLIA-approved laboratory.

The test, which is called PreDx, yields a score between 0 and 10 that corresponds to the risk of incident diabetes within 5 years. Among the overall test cohort, 5.7% developed diabetes within 5 years. But that was about 2% among the 54% of individuals judged to be at low risk based on their PreDx score, 7% among the 36% judged to be at medium risk, and 20% among the 10% evaluated as high risk. Individuals with high scores were 16.7 times as likely to develop diabetes as those with low scores.

Dr. Eric Book, Tethys's chief medical officer, said that a report describing these results in Northern European populations was to be published in the June 2009 issue of the journal Diabetes Care. But in order to persuade American health plans to cover PreDx, the company will need to demonstrate that the results hold up in multiethnic populations. Those studies will be conducted during summer and fall 2009, with results being published late in 2009 and in spring 2010.

Dr. Kahn reported that he had no conflicts of interest. Dr. McKenna and Dr. Book are both employees of Tethys Bioscience.

LONG BEACH, CALIF. — Identifying patients most at risk for progression to diabetes in 5-10 years may become easier with the development of several scoring systems for quantifying risk.

About 57 million Americans have prediabetes, as judged by impaired fasting glucose level, but only about 10% of them will go on to develop type 2 diabetes within 5 years. Because it's impractical to target all of those 57 million people with intensive interventions, several strategies have emerged to identify those most at risk.

According to speakers at a conference on diabetes sponsored by the Centers for Disease Control and Prevention, some of these strategies appear to get good results. Investigators at the CDC, for example, have developed two simple scoring systems—one of which doesn't even require a blood test—that quantify an individual's chance of developing diabetes within 10 years. And researchers at a private company, Tethys Bioscience of Emeryville, Calif., have developed an algorithm based on seven biomarkers that can categorize individuals as being at high, medium, or low risk for progressing to diabetes within 5 years.

“I think in the U.S. population, our user-friendly scoring systems can really help us to target individuals, at least among blacks and whites, who will benefit most from a prevention program,” said Dr. Henry S. Kahn of the CDC. “Our basic system could be used to identify those maybe who should just be escalated … to a simple blood test. You could use the basic scoring system through elementary examinations to find out which subsets of your community are in the greatest need of prevention resources.”

Dr. Kahn and his colleagues used 10-year follow-up data from the Atherosclerosis Risk in Communities (ARIC) study, which involved 12,729 U.S. adults who did not have diabetes at baseline. The investigators randomly selected 75% of that cohort to derive their scoring systems, reserving the other 25% to demonstrate that the systems work.

The basic scoring system uses only easily obtainable data, and the enhanced scoring system adds information from simple blood tests. Both systems yield a diabetes prediction score (DPS) from 0 to 100 that represents the chance that an individual would develop diabetes within 10 years.

The basic DPS assigns point values to hypertension, family history, black race, age 55-64 years, smoking history, waist circumference, height, resting pulse rate, and weight. Among the validation cohort, basic DPS scores in the lowest quintile corresponded to a 10-year incidence of diabetes of 5%, while scores in the highest quintile corresponded to a 10-year incidence of 32%.

The enhanced DPS eliminates smoking history and weight from the scoring system and adds point values for height and for levels of blood glucose, triglycerides, HDL cholesterol, and uric acid. Among the validation cohort, scores in the lowest quintile corresponded to a 10-year incidence of diabetes of 4%, while scores in the highest quintile corresponded to a 10-year incidence of 46%.

Dr. Kahn said that if incorporated within public health surveys, either scoring system would likely identify some adults with undiagnosed diabetes and some at elevated risk for cardiovascular disease.

The Tethys test employs a different strategy. After analyzing several large European cohorts, investigators identified seven biomarkers that together form a fingerprint identifying individuals likely to develop diabetes within 5 years. Those biomarkers are levels of fasting glucose, hemoglobin A1c, insulin, adiponectin (associated with obesity), ferritin (associated with cell death, especially in the liver), and C-reactive protein and interleukin-2 receptor-alpha (both associated with inflammation and cardiovascular risk).

Michael McKenna, Ph.D, chief scientific officer at Tethys, explained that physicians interested in ordering the test need only request a blood draw and have a standard 3-mL red-cap tube of serum sent to Tethys's CLIA-approved laboratory.

The test, which is called PreDx, yields a score between 0 and 10 that corresponds to the risk of incident diabetes within 5 years. Among the overall test cohort, 5.7% developed diabetes within 5 years. But that was about 2% among the 54% of individuals judged to be at low risk based on their PreDx score, 7% among the 36% judged to be at medium risk, and 20% among the 10% evaluated as high risk. Individuals with high scores were 16.7 times as likely to develop diabetes as those with low scores.

Dr. Eric Book, Tethys's chief medical officer, said that a report describing these results in Northern European populations was to be published in the June 2009 issue of the journal Diabetes Care. But in order to persuade American health plans to cover PreDx, the company will need to demonstrate that the results hold up in multiethnic populations. Those studies will be conducted during summer and fall 2009, with results being published late in 2009 and in spring 2010.

Dr. Kahn reported that he had no conflicts of interest. Dr. McKenna and Dr. Book are both employees of Tethys Bioscience.

LONG BEACH, CALIF. — Identifying patients most at risk for progression to diabetes in 5-10 years may become easier with the development of several scoring systems for quantifying risk.

About 57 million Americans have prediabetes, as judged by impaired fasting glucose level, but only about 10% of them will go on to develop type 2 diabetes within 5 years. Because it's impractical to target all of those 57 million people with intensive interventions, several strategies have emerged to identify those most at risk.

According to speakers at a conference on diabetes sponsored by the Centers for Disease Control and Prevention, some of these strategies appear to get good results. Investigators at the CDC, for example, have developed two simple scoring systems—one of which doesn't even require a blood test—that quantify an individual's chance of developing diabetes within 10 years. And researchers at a private company, Tethys Bioscience of Emeryville, Calif., have developed an algorithm based on seven biomarkers that can categorize individuals as being at high, medium, or low risk for progressing to diabetes within 5 years.

“I think in the U.S. population, our user-friendly scoring systems can really help us to target individuals, at least among blacks and whites, who will benefit most from a prevention program,” said Dr. Henry S. Kahn of the CDC. “Our basic system could be used to identify those maybe who should just be escalated … to a simple blood test. You could use the basic scoring system through elementary examinations to find out which subsets of your community are in the greatest need of prevention resources.”

Dr. Kahn and his colleagues used 10-year follow-up data from the Atherosclerosis Risk in Communities (ARIC) study, which involved 12,729 U.S. adults who did not have diabetes at baseline. The investigators randomly selected 75% of that cohort to derive their scoring systems, reserving the other 25% to demonstrate that the systems work.

The basic scoring system uses only easily obtainable data, and the enhanced scoring system adds information from simple blood tests. Both systems yield a diabetes prediction score (DPS) from 0 to 100 that represents the chance that an individual would develop diabetes within 10 years.

The basic DPS assigns point values to hypertension, family history, black race, age 55-64 years, smoking history, waist circumference, height, resting pulse rate, and weight. Among the validation cohort, basic DPS scores in the lowest quintile corresponded to a 10-year incidence of diabetes of 5%, while scores in the highest quintile corresponded to a 10-year incidence of 32%.

The enhanced DPS eliminates smoking history and weight from the scoring system and adds point values for height and for levels of blood glucose, triglycerides, HDL cholesterol, and uric acid. Among the validation cohort, scores in the lowest quintile corresponded to a 10-year incidence of diabetes of 4%, while scores in the highest quintile corresponded to a 10-year incidence of 46%.

Dr. Kahn said that if incorporated within public health surveys, either scoring system would likely identify some adults with undiagnosed diabetes and some at elevated risk for cardiovascular disease.

The Tethys test employs a different strategy. After analyzing several large European cohorts, investigators identified seven biomarkers that together form a fingerprint identifying individuals likely to develop diabetes within 5 years. Those biomarkers are levels of fasting glucose, hemoglobin A1c, insulin, adiponectin (associated with obesity), ferritin (associated with cell death, especially in the liver), and C-reactive protein and interleukin-2 receptor-alpha (both associated with inflammation and cardiovascular risk).

Michael McKenna, Ph.D, chief scientific officer at Tethys, explained that physicians interested in ordering the test need only request a blood draw and have a standard 3-mL red-cap tube of serum sent to Tethys's CLIA-approved laboratory.

The test, which is called PreDx, yields a score between 0 and 10 that corresponds to the risk of incident diabetes within 5 years. Among the overall test cohort, 5.7% developed diabetes within 5 years. But that was about 2% among the 54% of individuals judged to be at low risk based on their PreDx score, 7% among the 36% judged to be at medium risk, and 20% among the 10% evaluated as high risk. Individuals with high scores were 16.7 times as likely to develop diabetes as those with low scores.

Dr. Eric Book, Tethys's chief medical officer, said that a report describing these results in Northern European populations was to be published in the June 2009 issue of the journal Diabetes Care. But in order to persuade American health plans to cover PreDx, the company will need to demonstrate that the results hold up in multiethnic populations. Those studies will be conducted during summer and fall 2009, with results being published late in 2009 and in spring 2010.

Dr. Kahn reported that he had no conflicts of interest. Dr. McKenna and Dr. Book are both employees of Tethys Bioscience.

SAN FRANCISCO — A placebo-controlled trial of omega-3 fatty acid food supplements in patients with acute lung injury or acute respiratory distress syndrome was terminated early when an interim analysis showed that mortality was worse in patients taking the supplements.

Within 60 days, 27% of patients taking omega-3 fatty acids had died, versus 16% of controls, a significant difference, Dr. Michael A. Matthay said at a meeting on critical care medicine sponsored by the University of California, San Francisco. Patients taking the supplements also had fewer ventilator-free days within 28 days (14.6 days versus 17.4 days for controls) and fewer ICU-free days within 28 days (13.9 days versus 16.8 days for controls).

“There were some phase II data indicating that maybe omega-3s would be beneficial in these patients,” said Dr. Matthay of UCSF. “It's a sobering result, for sure.”

The study was part of a trial called EDEN-Omega (Early vs. Delayed Enteral Feeding and Omega-3 Fatty Acid/Antioxidant Supplementation for Treating People With Acute Lung Injury or Acute Respiratory Distress Syndrome), which was intended to test both omega-3 supplementation and early versus delayed enteral feeding. Although the data safety and monitoring board terminated the omega-3 arm of the study after 272 patients had been recruited, the enteral feeding arm is ongoing.

Patients had a P/F (arterial oxygen pressure to fraction of inspired oxygen ratio, or PaO2 to FiO2 ratio) below 300 mm Hg, bilateral infiltrates, a requirement for positive pressure ventilation via endotracheal tube, and no clinical evidence of left-sided cardiac failure. Patients were excluded for severe liver disease, severe chronic respiratory disease, and other reasons. Patients were randomized to receive either full-calorie enteral feeding or full-calorie enteral feeding plus twice-daily supplementation with omega-3 fatty acids, gamma linolenic acid, and antioxidants. The supplements were continued for 21 days or until mechanical ventilation was no longer required.

At study termination, the increase in 60-day mortality in the supplement group just reached significance (P = .05). The differences in ventilator-free days and ICU-free days were somewhat more certain (P values of .03 and .02). “One can argue about whether there was enough power here to conclude for sure that [omega-3 fatty acid] was deleterious, but it's certainly strongly in that direction,” Dr. Matthay said.

Dr. Matthay stated that he had no conflicts of interest to declare. The study was supported by the National Heart, Lung, and Blood Institute.

At 60 days, 27% of patients taking omega-3 fatty acids had died, versus 16% of controls. © CLAYTON HANSEN/ISTOCKPHOTO

SAN FRANCISCO — A placebo-controlled trial of omega-3 fatty acid food supplements in patients with acute lung injury or acute respiratory distress syndrome was terminated early when an interim analysis showed that mortality was worse in patients taking the supplements.

Within 60 days, 27% of patients taking omega-3 fatty acids had died, versus 16% of controls, a significant difference, Dr. Michael A. Matthay said at a meeting on critical care medicine sponsored by the University of California, San Francisco. Patients taking the supplements also had fewer ventilator-free days within 28 days (14.6 days versus 17.4 days for controls) and fewer ICU-free days within 28 days (13.9 days versus 16.8 days for controls).

“There were some phase II data indicating that maybe omega-3s would be beneficial in these patients,” said Dr. Matthay of UCSF. “It's a sobering result, for sure.”

The study was part of a trial called EDEN-Omega (Early vs. Delayed Enteral Feeding and Omega-3 Fatty Acid/Antioxidant Supplementation for Treating People With Acute Lung Injury or Acute Respiratory Distress Syndrome), which was intended to test both omega-3 supplementation and early versus delayed enteral feeding. Although the data safety and monitoring board terminated the omega-3 arm of the study after 272 patients had been recruited, the enteral feeding arm is ongoing.

Patients had a P/F (arterial oxygen pressure to fraction of inspired oxygen ratio, or PaO2 to FiO2 ratio) below 300 mm Hg, bilateral infiltrates, a requirement for positive pressure ventilation via endotracheal tube, and no clinical evidence of left-sided cardiac failure. Patients were excluded for severe liver disease, severe chronic respiratory disease, and other reasons. Patients were randomized to receive either full-calorie enteral feeding or full-calorie enteral feeding plus twice-daily supplementation with omega-3 fatty acids, gamma linolenic acid, and antioxidants. The supplements were continued for 21 days or until mechanical ventilation was no longer required.

At study termination, the increase in 60-day mortality in the supplement group just reached significance (P = .05). The differences in ventilator-free days and ICU-free days were somewhat more certain (P values of .03 and .02). “One can argue about whether there was enough power here to conclude for sure that [omega-3 fatty acid] was deleterious, but it's certainly strongly in that direction,” Dr. Matthay said.

Dr. Matthay stated that he had no conflicts of interest to declare. The study was supported by the National Heart, Lung, and Blood Institute.

At 60 days, 27% of patients taking omega-3 fatty acids had died, versus 16% of controls. © CLAYTON HANSEN/ISTOCKPHOTO

SAN FRANCISCO — A placebo-controlled trial of omega-3 fatty acid food supplements in patients with acute lung injury or acute respiratory distress syndrome was terminated early when an interim analysis showed that mortality was worse in patients taking the supplements.

Within 60 days, 27% of patients taking omega-3 fatty acids had died, versus 16% of controls, a significant difference, Dr. Michael A. Matthay said at a meeting on critical care medicine sponsored by the University of California, San Francisco. Patients taking the supplements also had fewer ventilator-free days within 28 days (14.6 days versus 17.4 days for controls) and fewer ICU-free days within 28 days (13.9 days versus 16.8 days for controls).

“There were some phase II data indicating that maybe omega-3s would be beneficial in these patients,” said Dr. Matthay of UCSF. “It's a sobering result, for sure.”

The study was part of a trial called EDEN-Omega (Early vs. Delayed Enteral Feeding and Omega-3 Fatty Acid/Antioxidant Supplementation for Treating People With Acute Lung Injury or Acute Respiratory Distress Syndrome), which was intended to test both omega-3 supplementation and early versus delayed enteral feeding. Although the data safety and monitoring board terminated the omega-3 arm of the study after 272 patients had been recruited, the enteral feeding arm is ongoing.

Patients had a P/F (arterial oxygen pressure to fraction of inspired oxygen ratio, or PaO2 to FiO2 ratio) below 300 mm Hg, bilateral infiltrates, a requirement for positive pressure ventilation via endotracheal tube, and no clinical evidence of left-sided cardiac failure. Patients were excluded for severe liver disease, severe chronic respiratory disease, and other reasons. Patients were randomized to receive either full-calorie enteral feeding or full-calorie enteral feeding plus twice-daily supplementation with omega-3 fatty acids, gamma linolenic acid, and antioxidants. The supplements were continued for 21 days or until mechanical ventilation was no longer required.

At study termination, the increase in 60-day mortality in the supplement group just reached significance (P = .05). The differences in ventilator-free days and ICU-free days were somewhat more certain (P values of .03 and .02). “One can argue about whether there was enough power here to conclude for sure that [omega-3 fatty acid] was deleterious, but it's certainly strongly in that direction,” Dr. Matthay said.

Dr. Matthay stated that he had no conflicts of interest to declare. The study was supported by the National Heart, Lung, and Blood Institute.

At 60 days, 27% of patients taking omega-3 fatty acids had died, versus 16% of controls. © CLAYTON HANSEN/ISTOCKPHOTO

SAN FRANCISCO — A placebo-controlled clinical trial of albuterol in acute lung injury was terminated after the first interim analysis showed that the beta-2 agonist was no better than placebo.

The data and safety monitoring board (DSMB) found that patients given aerosolized albuterol had no improvement in ventilator-free days or 60-day mortality, Dr. Michael A. Matthay reported at a meeting on critical care medicine sponsored by the University of California, San Francisco.

Dr. Matthay of UCSF said there were good reasons to suspect that beta-2 agonist therapy would be beneficial in acute lung injury (ALI). In preclinical studies, the therapy increased the resolution of alveolar edema by promoting sodium and chloride transport, and reduced lung vascular permeability. In a clinical trial, ALI patients treated intravenously with salbutamol had lower lung water levels.

The ALTA (Albuterol for the Treatment of ALI) trial used aerosolized albuterol because observational studies suggested that therapeutic levels of albuterol could be achieved in the pulmonary edema fluid of ALI patients. The drug does not simply deposit in the airways.

All patients had a P/F (arterial oxygen pressure to fraction of inspired oxygen ratio, or PaO2 to FiO2 ratio) below 300 mm Hg, bilateral infiltrates, and no clinical evidence of left atrial hypertension. The patients were receiving positive pressure ventilation via endotracheal tube. Patients were excluded if they had moderate to severe liver disease, moderate to severe chronic obstructive pulmonary disease, chronic or acute need for beta agonists, or acute myocardial infarction within 30 days. Patients were given aerosolized albuterol at 5 mg/2.5 mL, or 2.5 mL of normal saline, every 4 hours until day 10 or until 24 hours after extubation. The albuterol dose was reduced to 2.5 mg/2.5 mL if the patient developed tachycardia or arrhythmia.

At the time the DSMB terminated the trial, 282 patients had been enrolled. There were no significant differences between albuterol and placebo groups on any baseline demographic or laboratory measurement, including Acute Physiology and Chronic Health Evaluation (APACHE) III score, number of organ failures, tidal volume, type of primary lung injury, electrolytes, blood pressure, and central venous pressure.

The investigators found that plasma albuterol levels were in the expected range in virtually all patients who were assessed.

The study's primary outcome was the number of ventilator-free days within 28 days after admission. Patients receiving albuterol had a mean of 14.5 ventilator-free days versus 16.5 days for control patients. A secondary outcome was 60-day mortality, which was 23% among patients taking albuterol and 17.7% among control patients. Neither of those differences was statistically significant.

The investigators found no evidence of albuterol's effectiveness in any subgroup analysis, including analyses limited by gender, in patients with P/F below 200 mm Hg, and in patients with or without shock.

Dr. Matthay, who was the principal investigator of the ALTA trial, suggested three possible reasons that albuterol did not perform as expected.

It could be that the alveolar epithelium may have been too injured to respond to beta agonist therapy. The aerosol route could have delivered inadequate levels of albuterol to the injured alveoli. Or conservative fluid management and lower tidal volume ventilation might have reduced lung injury and lung water to the extent that any additional fluid clearance with albuterol therapy had no beneficial effect.

Dr. Matthay said that he had no conflicts of interest to disclose. The ALTA study was supported by the National Heart, Lung, and Blood Institute.

SAN FRANCISCO — A placebo-controlled clinical trial of albuterol in acute lung injury was terminated after the first interim analysis showed that the beta-2 agonist was no better than placebo.

The data and safety monitoring board (DSMB) found that patients given aerosolized albuterol had no improvement in ventilator-free days or 60-day mortality, Dr. Michael A. Matthay reported at a meeting on critical care medicine sponsored by the University of California, San Francisco.

Dr. Matthay of UCSF said there were good reasons to suspect that beta-2 agonist therapy would be beneficial in acute lung injury (ALI). In preclinical studies, the therapy increased the resolution of alveolar edema by promoting sodium and chloride transport, and reduced lung vascular permeability. In a clinical trial, ALI patients treated intravenously with salbutamol had lower lung water levels.

The ALTA (Albuterol for the Treatment of ALI) trial used aerosolized albuterol because observational studies suggested that therapeutic levels of albuterol could be achieved in the pulmonary edema fluid of ALI patients. The drug does not simply deposit in the airways.

All patients had a P/F (arterial oxygen pressure to fraction of inspired oxygen ratio, or PaO2 to FiO2 ratio) below 300 mm Hg, bilateral infiltrates, and no clinical evidence of left atrial hypertension. The patients were receiving positive pressure ventilation via endotracheal tube. Patients were excluded if they had moderate to severe liver disease, moderate to severe chronic obstructive pulmonary disease, chronic or acute need for beta agonists, or acute myocardial infarction within 30 days. Patients were given aerosolized albuterol at 5 mg/2.5 mL, or 2.5 mL of normal saline, every 4 hours until day 10 or until 24 hours after extubation. The albuterol dose was reduced to 2.5 mg/2.5 mL if the patient developed tachycardia or arrhythmia.

At the time the DSMB terminated the trial, 282 patients had been enrolled. There were no significant differences between albuterol and placebo groups on any baseline demographic or laboratory measurement, including Acute Physiology and Chronic Health Evaluation (APACHE) III score, number of organ failures, tidal volume, type of primary lung injury, electrolytes, blood pressure, and central venous pressure.

The investigators found that plasma albuterol levels were in the expected range in virtually all patients who were assessed.

The study's primary outcome was the number of ventilator-free days within 28 days after admission. Patients receiving albuterol had a mean of 14.5 ventilator-free days versus 16.5 days for control patients. A secondary outcome was 60-day mortality, which was 23% among patients taking albuterol and 17.7% among control patients. Neither of those differences was statistically significant.

The investigators found no evidence of albuterol's effectiveness in any subgroup analysis, including analyses limited by gender, in patients with P/F below 200 mm Hg, and in patients with or without shock.

Dr. Matthay, who was the principal investigator of the ALTA trial, suggested three possible reasons that albuterol did not perform as expected.

It could be that the alveolar epithelium may have been too injured to respond to beta agonist therapy. The aerosol route could have delivered inadequate levels of albuterol to the injured alveoli. Or conservative fluid management and lower tidal volume ventilation might have reduced lung injury and lung water to the extent that any additional fluid clearance with albuterol therapy had no beneficial effect.

Dr. Matthay said that he had no conflicts of interest to disclose. The ALTA study was supported by the National Heart, Lung, and Blood Institute.

SAN FRANCISCO — A placebo-controlled clinical trial of albuterol in acute lung injury was terminated after the first interim analysis showed that the beta-2 agonist was no better than placebo.

The data and safety monitoring board (DSMB) found that patients given aerosolized albuterol had no improvement in ventilator-free days or 60-day mortality, Dr. Michael A. Matthay reported at a meeting on critical care medicine sponsored by the University of California, San Francisco.

Dr. Matthay of UCSF said there were good reasons to suspect that beta-2 agonist therapy would be beneficial in acute lung injury (ALI). In preclinical studies, the therapy increased the resolution of alveolar edema by promoting sodium and chloride transport, and reduced lung vascular permeability. In a clinical trial, ALI patients treated intravenously with salbutamol had lower lung water levels.

The ALTA (Albuterol for the Treatment of ALI) trial used aerosolized albuterol because observational studies suggested that therapeutic levels of albuterol could be achieved in the pulmonary edema fluid of ALI patients. The drug does not simply deposit in the airways.

All patients had a P/F (arterial oxygen pressure to fraction of inspired oxygen ratio, or PaO2 to FiO2 ratio) below 300 mm Hg, bilateral infiltrates, and no clinical evidence of left atrial hypertension. The patients were receiving positive pressure ventilation via endotracheal tube. Patients were excluded if they had moderate to severe liver disease, moderate to severe chronic obstructive pulmonary disease, chronic or acute need for beta agonists, or acute myocardial infarction within 30 days. Patients were given aerosolized albuterol at 5 mg/2.5 mL, or 2.5 mL of normal saline, every 4 hours until day 10 or until 24 hours after extubation. The albuterol dose was reduced to 2.5 mg/2.5 mL if the patient developed tachycardia or arrhythmia.

At the time the DSMB terminated the trial, 282 patients had been enrolled. There were no significant differences between albuterol and placebo groups on any baseline demographic or laboratory measurement, including Acute Physiology and Chronic Health Evaluation (APACHE) III score, number of organ failures, tidal volume, type of primary lung injury, electrolytes, blood pressure, and central venous pressure.

The investigators found that plasma albuterol levels were in the expected range in virtually all patients who were assessed.

The study's primary outcome was the number of ventilator-free days within 28 days after admission. Patients receiving albuterol had a mean of 14.5 ventilator-free days versus 16.5 days for control patients. A secondary outcome was 60-day mortality, which was 23% among patients taking albuterol and 17.7% among control patients. Neither of those differences was statistically significant.

The investigators found no evidence of albuterol's effectiveness in any subgroup analysis, including analyses limited by gender, in patients with P/F below 200 mm Hg, and in patients with or without shock.

Dr. Matthay, who was the principal investigator of the ALTA trial, suggested three possible reasons that albuterol did not perform as expected.

It could be that the alveolar epithelium may have been too injured to respond to beta agonist therapy. The aerosol route could have delivered inadequate levels of albuterol to the injured alveoli. Or conservative fluid management and lower tidal volume ventilation might have reduced lung injury and lung water to the extent that any additional fluid clearance with albuterol therapy had no beneficial effect.

Dr. Matthay said that he had no conflicts of interest to disclose. The ALTA study was supported by the National Heart, Lung, and Blood Institute.