Heidi Splete

Thrombolysis with intravenous tissue plasminogen activator for the treatment of acute ischemic stroke does not increase the risk of brain hemorrhage in patients who are also taking warfarin, based on data from an observational study of more than 23,000 patients.

The patients in the study had an international normalized ratio (INR) of 1.7 or lower, which is the same population of warfarin-treated patients for whom intravenous tissue plasminogen activator (TPA) is recommended in the current American Heart Association/American Stroke Association guidelines.

Symptomatic intracranial hemorrhage (sICH) is an adverse event associated with intravenous TPA that may occur more often in patients receiving warfarin, according to Dr. Ying Xian, who was lead investigator on the study, published June 26 in JAMA. But "the true absolute risk of sICH in this population remains a matter of significant debate," and previous studies of bleeding risk associated with warfarin have been small, with inconsistent results, wrote Dr. Xian of the Duke Clinical Research Institute in Durham, N.C. and his colleagues.

The investigators reviewed data from 23,437 adults in the American Heart Association’s Get With the Guidelines - Stroke Registry. The study participants were treated with intravenous TPA at 1,203 registry hospitals between April 2009 and June 2011 (JAMA 2012;307:2600-8).

A total of 1,802 (8%) of the patients were receiving warfarin at the time of treatment with TPA. A total of 1,107 patients (5%) developed sICH after TPA.

Although the unadjusted rate of hemorrhage was significantly higher in warfarin-treated patients, compared with non-warfarin patients (6% vs. 5%, P less than .001), there was no significant difference in hemorrhage rates after risk adjustment (adjusted odds ratio, 1.01). The results were similar regardless of whether or not the patients’ scores on the National Institutes of Health Stroke Scale (NIHSS) were excluded from the risk adjustment, the researchers noted.

Similarly, there was no significant difference in the rates of life-threatening or serious systemic hemorrhage between the warfarin and non-warfarin groups (0.9% for both) and no significant differences between the two groups in TPA complications (11% vs. 8%, respectively) or in-hospital mortality (11% vs. 8%, respectively).

"We found the potential for substantial undertreatment, because up to 50% of warfarin-treated patients who might have been eligible for reperfusion therapy did not receive intravenous TPA," the researchers wrote.

The results also indicated that there was no significant relationship between warfarin use and sICH in a subgroup analysis of patients with INRs between 1.5 and 1.7 or in an exploratory analysis of patients with INRs of 2.0 or lower.

The higher unadjusted incidence of sICH in warfarin patients may be a result of the differences in risk profiles between the warfarin and non-warfarin patients, because those receiving warfarin were significantly older and had higher NIHSS scores, the researchers noted.

The study was limited by several factors, including its retrospective design and a lack of NIHSS information for all patients. More research is needed to explore the effectiveness of intravenous TPA for patients with INRs outside of the range recommended by the guidelines, they added.

The study was supported in part by the American Heart Association – Pharmaceutical Roundtable and from David and Stevie Spina. Dr. Xian had no financial conflicts to disclose. Several coauthors disclosed financial relationships with multiple companies, including Boehringer Ingelheim, Merck, Bristol-Myers Squibb, and Sanofi-aventis, which have supported the Get With the Guidelines – Stroke Program in the past, and Janssen Pharmaceutical Companies of Johnson & Johnson, which currently supports it. Boehringer Ingelheim markets TPA in the United States as Activase.

Thrombolysis with intravenous tissue plasminogen activator for the treatment of acute ischemic stroke does not increase the risk of brain hemorrhage in patients who are also taking warfarin, based on data from an observational study of more than 23,000 patients.

The patients in the study had an international normalized ratio (INR) of 1.7 or lower, which is the same population of warfarin-treated patients for whom intravenous tissue plasminogen activator (TPA) is recommended in the current American Heart Association/American Stroke Association guidelines.

Symptomatic intracranial hemorrhage (sICH) is an adverse event associated with intravenous TPA that may occur more often in patients receiving warfarin, according to Dr. Ying Xian, who was lead investigator on the study, published June 26 in JAMA. But "the true absolute risk of sICH in this population remains a matter of significant debate," and previous studies of bleeding risk associated with warfarin have been small, with inconsistent results, wrote Dr. Xian of the Duke Clinical Research Institute in Durham, N.C. and his colleagues.

The investigators reviewed data from 23,437 adults in the American Heart Association’s Get With the Guidelines - Stroke Registry. The study participants were treated with intravenous TPA at 1,203 registry hospitals between April 2009 and June 2011 (JAMA 2012;307:2600-8).

A total of 1,802 (8%) of the patients were receiving warfarin at the time of treatment with TPA. A total of 1,107 patients (5%) developed sICH after TPA.

Although the unadjusted rate of hemorrhage was significantly higher in warfarin-treated patients, compared with non-warfarin patients (6% vs. 5%, P less than .001), there was no significant difference in hemorrhage rates after risk adjustment (adjusted odds ratio, 1.01). The results were similar regardless of whether or not the patients’ scores on the National Institutes of Health Stroke Scale (NIHSS) were excluded from the risk adjustment, the researchers noted.

Similarly, there was no significant difference in the rates of life-threatening or serious systemic hemorrhage between the warfarin and non-warfarin groups (0.9% for both) and no significant differences between the two groups in TPA complications (11% vs. 8%, respectively) or in-hospital mortality (11% vs. 8%, respectively).

"We found the potential for substantial undertreatment, because up to 50% of warfarin-treated patients who might have been eligible for reperfusion therapy did not receive intravenous TPA," the researchers wrote.

The results also indicated that there was no significant relationship between warfarin use and sICH in a subgroup analysis of patients with INRs between 1.5 and 1.7 or in an exploratory analysis of patients with INRs of 2.0 or lower.

The higher unadjusted incidence of sICH in warfarin patients may be a result of the differences in risk profiles between the warfarin and non-warfarin patients, because those receiving warfarin were significantly older and had higher NIHSS scores, the researchers noted.

The study was limited by several factors, including its retrospective design and a lack of NIHSS information for all patients. More research is needed to explore the effectiveness of intravenous TPA for patients with INRs outside of the range recommended by the guidelines, they added.

The study was supported in part by the American Heart Association – Pharmaceutical Roundtable and from David and Stevie Spina. Dr. Xian had no financial conflicts to disclose. Several coauthors disclosed financial relationships with multiple companies, including Boehringer Ingelheim, Merck, Bristol-Myers Squibb, and Sanofi-aventis, which have supported the Get With the Guidelines – Stroke Program in the past, and Janssen Pharmaceutical Companies of Johnson & Johnson, which currently supports it. Boehringer Ingelheim markets TPA in the United States as Activase.

Thrombolysis with intravenous tissue plasminogen activator for the treatment of acute ischemic stroke does not increase the risk of brain hemorrhage in patients who are also taking warfarin, based on data from an observational study of more than 23,000 patients.

The patients in the study had an international normalized ratio (INR) of 1.7 or lower, which is the same population of warfarin-treated patients for whom intravenous tissue plasminogen activator (TPA) is recommended in the current American Heart Association/American Stroke Association guidelines.

Symptomatic intracranial hemorrhage (sICH) is an adverse event associated with intravenous TPA that may occur more often in patients receiving warfarin, according to Dr. Ying Xian, who was lead investigator on the study, published June 26 in JAMA. But "the true absolute risk of sICH in this population remains a matter of significant debate," and previous studies of bleeding risk associated with warfarin have been small, with inconsistent results, wrote Dr. Xian of the Duke Clinical Research Institute in Durham, N.C. and his colleagues.

The investigators reviewed data from 23,437 adults in the American Heart Association’s Get With the Guidelines - Stroke Registry. The study participants were treated with intravenous TPA at 1,203 registry hospitals between April 2009 and June 2011 (JAMA 2012;307:2600-8).

A total of 1,802 (8%) of the patients were receiving warfarin at the time of treatment with TPA. A total of 1,107 patients (5%) developed sICH after TPA.

Although the unadjusted rate of hemorrhage was significantly higher in warfarin-treated patients, compared with non-warfarin patients (6% vs. 5%, P less than .001), there was no significant difference in hemorrhage rates after risk adjustment (adjusted odds ratio, 1.01). The results were similar regardless of whether or not the patients’ scores on the National Institutes of Health Stroke Scale (NIHSS) were excluded from the risk adjustment, the researchers noted.

Similarly, there was no significant difference in the rates of life-threatening or serious systemic hemorrhage between the warfarin and non-warfarin groups (0.9% for both) and no significant differences between the two groups in TPA complications (11% vs. 8%, respectively) or in-hospital mortality (11% vs. 8%, respectively).

"We found the potential for substantial undertreatment, because up to 50% of warfarin-treated patients who might have been eligible for reperfusion therapy did not receive intravenous TPA," the researchers wrote.

The results also indicated that there was no significant relationship between warfarin use and sICH in a subgroup analysis of patients with INRs between 1.5 and 1.7 or in an exploratory analysis of patients with INRs of 2.0 or lower.

The higher unadjusted incidence of sICH in warfarin patients may be a result of the differences in risk profiles between the warfarin and non-warfarin patients, because those receiving warfarin were significantly older and had higher NIHSS scores, the researchers noted.

The study was limited by several factors, including its retrospective design and a lack of NIHSS information for all patients. More research is needed to explore the effectiveness of intravenous TPA for patients with INRs outside of the range recommended by the guidelines, they added.

The study was supported in part by the American Heart Association – Pharmaceutical Roundtable and from David and Stevie Spina. Dr. Xian had no financial conflicts to disclose. Several coauthors disclosed financial relationships with multiple companies, including Boehringer Ingelheim, Merck, Bristol-Myers Squibb, and Sanofi-aventis, which have supported the Get With the Guidelines – Stroke Program in the past, and Janssen Pharmaceutical Companies of Johnson & Johnson, which currently supports it. Boehringer Ingelheim markets TPA in the United States as Activase.

A new test for the early detection of dengue fever will be available for distribution on July 2, according to a written statement from the Centers for Disease Control and Prevention.

The new molecular test identifies the dengue virus itself rather than detecting antibodies, and it uses the same equipment and supplies that most public health laboratories already use to diagnose influenza, according to the CDC.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

The test, called the CDC DENV-1-4 Real Time PCR Assay, is designed for use during the first 7 days after dengue symptoms appear, which may be too early for antibody detection.

The ability to diagnose early will give clinicians and public health officials a more complete picture of dengue fever, which is now a reportable disease in the United States, said Jorge L. Muñoz-Jordán, Ph.D., chief of molecular diagnostics and research at the Dengue branch of the CDC, said in the statement.

"The availability of state-of-the-art dengue diagnostics will improve patient management and the public health response to dengue," he said.

Dengue fever is transmitted by Aedes mosquitoes and is a major cause of illness in Puerto Rico and the U.S. Virgin Islands, as well as some parts of the United States in which the mosquitoes are found. U.S. travelers returning home from Latin America, the Caribbean, and Asia are also at risk, the CDC stated.

Symptoms of dengue fever include a high fever; rash or bleeding of the nose and gums; headache, joint, muscle, or bone pain; severe pain behind the eyes; and easy bruising.

The test has been approved by the Food and Drug Administration, and it will be available to labs in the United States and internationally, according to the statement. For more details, visit the CDC website.

A new test for the early detection of dengue fever will be available for distribution on July 2, according to a written statement from the Centers for Disease Control and Prevention.

The new molecular test identifies the dengue virus itself rather than detecting antibodies, and it uses the same equipment and supplies that most public health laboratories already use to diagnose influenza, according to the CDC.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

The test, called the CDC DENV-1-4 Real Time PCR Assay, is designed for use during the first 7 days after dengue symptoms appear, which may be too early for antibody detection.

The ability to diagnose early will give clinicians and public health officials a more complete picture of dengue fever, which is now a reportable disease in the United States, said Jorge L. Muñoz-Jordán, Ph.D., chief of molecular diagnostics and research at the Dengue branch of the CDC, said in the statement.

"The availability of state-of-the-art dengue diagnostics will improve patient management and the public health response to dengue," he said.

Dengue fever is transmitted by Aedes mosquitoes and is a major cause of illness in Puerto Rico and the U.S. Virgin Islands, as well as some parts of the United States in which the mosquitoes are found. U.S. travelers returning home from Latin America, the Caribbean, and Asia are also at risk, the CDC stated.

Symptoms of dengue fever include a high fever; rash or bleeding of the nose and gums; headache, joint, muscle, or bone pain; severe pain behind the eyes; and easy bruising.

The test has been approved by the Food and Drug Administration, and it will be available to labs in the United States and internationally, according to the statement. For more details, visit the CDC website.

A new test for the early detection of dengue fever will be available for distribution on July 2, according to a written statement from the Centers for Disease Control and Prevention.

The new molecular test identifies the dengue virus itself rather than detecting antibodies, and it uses the same equipment and supplies that most public health laboratories already use to diagnose influenza, according to the CDC.

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

The test, called the CDC DENV-1-4 Real Time PCR Assay, is designed for use during the first 7 days after dengue symptoms appear, which may be too early for antibody detection.

The ability to diagnose early will give clinicians and public health officials a more complete picture of dengue fever, which is now a reportable disease in the United States, said Jorge L. Muñoz-Jordán, Ph.D., chief of molecular diagnostics and research at the Dengue branch of the CDC, said in the statement.

"The availability of state-of-the-art dengue diagnostics will improve patient management and the public health response to dengue," he said.

Dengue fever is transmitted by Aedes mosquitoes and is a major cause of illness in Puerto Rico and the U.S. Virgin Islands, as well as some parts of the United States in which the mosquitoes are found. U.S. travelers returning home from Latin America, the Caribbean, and Asia are also at risk, the CDC stated.

Symptoms of dengue fever include a high fever; rash or bleeding of the nose and gums; headache, joint, muscle, or bone pain; severe pain behind the eyes; and easy bruising.

The test has been approved by the Food and Drug Administration, and it will be available to labs in the United States and internationally, according to the statement. For more details, visit the CDC website.

A noninvasive DNA screening test effectively detected chromosome abnormalities in fetuses of women with singleton pregnancies, based on data from approximately 3,000 women published online in June in the American Journal of Obstetrics and Gynecology.

Data from previous case-control studies have shown that the Digital Analysis of Selected Regions (DANSR) assay can identify chromosome abnormalities by evaluating specific fragments of maternal cell-free DNA (cfDNA), said Dr. Mary E. Norton of Stanford (Calif.) University and her colleagues.

In this multicenter, prospective cohort study, the researchers included pregnant women aged 18-50 years with singleton pregnancies who were planning to undergo invasive prenatal diagnostic testing for any reason. Women with multiples, those with known chromosome abnormalities, or those who had already undergone an invasive prenatal test in the current pregnancy were excluded. The final analysis included samples from 3,228 women with a mean maternal age of 34 years and a mean gestational age of 17 weeks (Am. J. Obstet. Gynecol. 2012 [doi:10.1016/j.ajog.2012.05.021]).

The sensitivity of the test was 100% for trisomy 21 malformations. A total of 81 cases of trisomy 21 were identified and all were classified as high risk, with one false positive out of 2,888 normal cases, for a false positive rate of 0.3% (specificity 99.97%). Similarly, the sensitivity was 97% for trisomy 18. A total of 38 cases of trisomy 18 were identified, and 37 were classified as high-risk, with 2 false positives for a false positive rate of 0.07% (specificity 99.93%).

The positive predictive values for trisomy 21 and trisomy 18 were 98.8% and 94.9%, respectively. The negative predictive values for trisomy 21 and trisomy 18 were 100% and 99.96%, respectively.

Another 73 cases of other chromosomal abnormalities were identified, but they did not affect the analysis of risk for trisomy 18 or 21, Dr. Norton and her associates noted.

The test involved collecting 20 mL of blood from each patient before she underwent any invasive diagnostic testing procedure. DNA samples were classified as high risk or low risk based on a predefined cutoff value of 1% based on previous analyses. Results from the DANSR assay were compared with results from invasive tests as a reference.

"With the methods reported here, the higher throughput and lower cost make this technique potentially scalable for population screening," Dr. Norton and her associates wrote. However, even the high detection rates achieved in the study do not compare with those obtained with invasive diagnoses and may not provide much in the way of additional information for women who then have invasive tests, they noted.

"Further experience in larger populations of average-risk women is needed to clarify the role and utility of cfDNA in clinical practice," they said.

Dr. Norton said she had no relevant financial disclosures. The study was funded by Ariosa Diagnostics, which makes the test used in the study. Several of her coauthors are employees, consultants, or board members of Ariosa Diagnostics.

A noninvasive DNA screening test effectively detected chromosome abnormalities in fetuses of women with singleton pregnancies, based on data from approximately 3,000 women published online in June in the American Journal of Obstetrics and Gynecology.

Data from previous case-control studies have shown that the Digital Analysis of Selected Regions (DANSR) assay can identify chromosome abnormalities by evaluating specific fragments of maternal cell-free DNA (cfDNA), said Dr. Mary E. Norton of Stanford (Calif.) University and her colleagues.

In this multicenter, prospective cohort study, the researchers included pregnant women aged 18-50 years with singleton pregnancies who were planning to undergo invasive prenatal diagnostic testing for any reason. Women with multiples, those with known chromosome abnormalities, or those who had already undergone an invasive prenatal test in the current pregnancy were excluded. The final analysis included samples from 3,228 women with a mean maternal age of 34 years and a mean gestational age of 17 weeks (Am. J. Obstet. Gynecol. 2012 [doi:10.1016/j.ajog.2012.05.021]).

The sensitivity of the test was 100% for trisomy 21 malformations. A total of 81 cases of trisomy 21 were identified and all were classified as high risk, with one false positive out of 2,888 normal cases, for a false positive rate of 0.3% (specificity 99.97%). Similarly, the sensitivity was 97% for trisomy 18. A total of 38 cases of trisomy 18 were identified, and 37 were classified as high-risk, with 2 false positives for a false positive rate of 0.07% (specificity 99.93%).

The positive predictive values for trisomy 21 and trisomy 18 were 98.8% and 94.9%, respectively. The negative predictive values for trisomy 21 and trisomy 18 were 100% and 99.96%, respectively.

Another 73 cases of other chromosomal abnormalities were identified, but they did not affect the analysis of risk for trisomy 18 or 21, Dr. Norton and her associates noted.

The test involved collecting 20 mL of blood from each patient before she underwent any invasive diagnostic testing procedure. DNA samples were classified as high risk or low risk based on a predefined cutoff value of 1% based on previous analyses. Results from the DANSR assay were compared with results from invasive tests as a reference.

"With the methods reported here, the higher throughput and lower cost make this technique potentially scalable for population screening," Dr. Norton and her associates wrote. However, even the high detection rates achieved in the study do not compare with those obtained with invasive diagnoses and may not provide much in the way of additional information for women who then have invasive tests, they noted.

"Further experience in larger populations of average-risk women is needed to clarify the role and utility of cfDNA in clinical practice," they said.

Dr. Norton said she had no relevant financial disclosures. The study was funded by Ariosa Diagnostics, which makes the test used in the study. Several of her coauthors are employees, consultants, or board members of Ariosa Diagnostics.

A noninvasive DNA screening test effectively detected chromosome abnormalities in fetuses of women with singleton pregnancies, based on data from approximately 3,000 women published online in June in the American Journal of Obstetrics and Gynecology.

Data from previous case-control studies have shown that the Digital Analysis of Selected Regions (DANSR) assay can identify chromosome abnormalities by evaluating specific fragments of maternal cell-free DNA (cfDNA), said Dr. Mary E. Norton of Stanford (Calif.) University and her colleagues.

In this multicenter, prospective cohort study, the researchers included pregnant women aged 18-50 years with singleton pregnancies who were planning to undergo invasive prenatal diagnostic testing for any reason. Women with multiples, those with known chromosome abnormalities, or those who had already undergone an invasive prenatal test in the current pregnancy were excluded. The final analysis included samples from 3,228 women with a mean maternal age of 34 years and a mean gestational age of 17 weeks (Am. J. Obstet. Gynecol. 2012 [doi:10.1016/j.ajog.2012.05.021]).

The sensitivity of the test was 100% for trisomy 21 malformations. A total of 81 cases of trisomy 21 were identified and all were classified as high risk, with one false positive out of 2,888 normal cases, for a false positive rate of 0.3% (specificity 99.97%). Similarly, the sensitivity was 97% for trisomy 18. A total of 38 cases of trisomy 18 were identified, and 37 were classified as high-risk, with 2 false positives for a false positive rate of 0.07% (specificity 99.93%).

The positive predictive values for trisomy 21 and trisomy 18 were 98.8% and 94.9%, respectively. The negative predictive values for trisomy 21 and trisomy 18 were 100% and 99.96%, respectively.

Another 73 cases of other chromosomal abnormalities were identified, but they did not affect the analysis of risk for trisomy 18 or 21, Dr. Norton and her associates noted.

The test involved collecting 20 mL of blood from each patient before she underwent any invasive diagnostic testing procedure. DNA samples were classified as high risk or low risk based on a predefined cutoff value of 1% based on previous analyses. Results from the DANSR assay were compared with results from invasive tests as a reference.

"With the methods reported here, the higher throughput and lower cost make this technique potentially scalable for population screening," Dr. Norton and her associates wrote. However, even the high detection rates achieved in the study do not compare with those obtained with invasive diagnoses and may not provide much in the way of additional information for women who then have invasive tests, they noted.

"Further experience in larger populations of average-risk women is needed to clarify the role and utility of cfDNA in clinical practice," they said.

Dr. Norton said she had no relevant financial disclosures. The study was funded by Ariosa Diagnostics, which makes the test used in the study. Several of her coauthors are employees, consultants, or board members of Ariosa Diagnostics.

Approximately one in eight Alzheimer’s disease patients who develop delirium while hospitalized will suffer at least one adverse outcome, based on data from 771 adults. The findings were published in Annals of Internal Medicine on June 18.

Previous studies have shown that delirium can increase the rate of cognitive decline in AD patients, but the impact of hospitalization and delirium has not been well studied, said Dr. Tamara G. Fong of the Aging Brain Center, Boston, and her colleagues. Adults with Alzheimer’s disease (AD) are three times more likely to be hospitalized than are those without AD, the researchers noted.

To assess the adverse outcomes of death, institutionalization, and cognitive decline associated with hospitalization and delirium, Dr. Fong and her colleagues followed 771 community-dwelling adults aged 65 years and older with a clinical diagnosis of AD. The mean follow-up was 2 years, and outcomes were assessed at 1 year after an initial hospitalization. A total of 367 individuals (48%) were hospitalized, and 194 of these patients (25%) developed delirium while hospitalized (Ann. Intern. Med. 2012;156:848-56).

At least one adverse outcome occurred in 32% of nonhospitalized patients, 55% of hospitalized patients without delirium, and 79% of hospitalized patients with delirium.

In the hospitalized patients, 6% of deaths, 15% of institutionalizations, and 21% of cases of cognitive decline were associated with delirium, the researchers said.

Death occurred in 15% of hospitalized patients with delirium, compared with 9% of hospitalized patients without delirium and 2% of nonhospitalized patients.

The hospitalized patients with delirium had an increased risk for death, institutionalization, and cognitive decline, compared with the other groups, with adjusted risk ratios of 5.4, 9.3, and 1.6, respectively. Hospitalized patients with no delirium had a slightly smaller increase in the risk of death (adjusted risk ratio 4.7) and institutionalization (adjusted risk ratio 6.9).

The mean age of the patients was 77 years, 57% were women, and 95% were white.

The results were limited by several factors, including the observational nature of the study and the incomplete data on the cognitive outcome and functional status of some patients, the researchers wrote. But the findings show "the important and incremental associations of hospitalization and delirium with 1-year outcomes," they said.

Additional research is needed to determine whether preventing hospitalization and delirium in AD patients can reduce their risk for death, institutionalization, and cognitive decline, they noted.

Dr. Fong had no financial conflicts to disclose. The study was funded by the National Institute on Aging and the Massachusetts Alzheimer’s Disease Research Center.

Approximately one in eight Alzheimer’s disease patients who develop delirium while hospitalized will suffer at least one adverse outcome, based on data from 771 adults. The findings were published in Annals of Internal Medicine on June 18.

Previous studies have shown that delirium can increase the rate of cognitive decline in AD patients, but the impact of hospitalization and delirium has not been well studied, said Dr. Tamara G. Fong of the Aging Brain Center, Boston, and her colleagues. Adults with Alzheimer’s disease (AD) are three times more likely to be hospitalized than are those without AD, the researchers noted.

To assess the adverse outcomes of death, institutionalization, and cognitive decline associated with hospitalization and delirium, Dr. Fong and her colleagues followed 771 community-dwelling adults aged 65 years and older with a clinical diagnosis of AD. The mean follow-up was 2 years, and outcomes were assessed at 1 year after an initial hospitalization. A total of 367 individuals (48%) were hospitalized, and 194 of these patients (25%) developed delirium while hospitalized (Ann. Intern. Med. 2012;156:848-56).

At least one adverse outcome occurred in 32% of nonhospitalized patients, 55% of hospitalized patients without delirium, and 79% of hospitalized patients with delirium.

In the hospitalized patients, 6% of deaths, 15% of institutionalizations, and 21% of cases of cognitive decline were associated with delirium, the researchers said.

Death occurred in 15% of hospitalized patients with delirium, compared with 9% of hospitalized patients without delirium and 2% of nonhospitalized patients.

The hospitalized patients with delirium had an increased risk for death, institutionalization, and cognitive decline, compared with the other groups, with adjusted risk ratios of 5.4, 9.3, and 1.6, respectively. Hospitalized patients with no delirium had a slightly smaller increase in the risk of death (adjusted risk ratio 4.7) and institutionalization (adjusted risk ratio 6.9).

The mean age of the patients was 77 years, 57% were women, and 95% were white.

The results were limited by several factors, including the observational nature of the study and the incomplete data on the cognitive outcome and functional status of some patients, the researchers wrote. But the findings show "the important and incremental associations of hospitalization and delirium with 1-year outcomes," they said.

Additional research is needed to determine whether preventing hospitalization and delirium in AD patients can reduce their risk for death, institutionalization, and cognitive decline, they noted.

Dr. Fong had no financial conflicts to disclose. The study was funded by the National Institute on Aging and the Massachusetts Alzheimer’s Disease Research Center.

Approximately one in eight Alzheimer’s disease patients who develop delirium while hospitalized will suffer at least one adverse outcome, based on data from 771 adults. The findings were published in Annals of Internal Medicine on June 18.

Previous studies have shown that delirium can increase the rate of cognitive decline in AD patients, but the impact of hospitalization and delirium has not been well studied, said Dr. Tamara G. Fong of the Aging Brain Center, Boston, and her colleagues. Adults with Alzheimer’s disease (AD) are three times more likely to be hospitalized than are those without AD, the researchers noted.

To assess the adverse outcomes of death, institutionalization, and cognitive decline associated with hospitalization and delirium, Dr. Fong and her colleagues followed 771 community-dwelling adults aged 65 years and older with a clinical diagnosis of AD. The mean follow-up was 2 years, and outcomes were assessed at 1 year after an initial hospitalization. A total of 367 individuals (48%) were hospitalized, and 194 of these patients (25%) developed delirium while hospitalized (Ann. Intern. Med. 2012;156:848-56).

At least one adverse outcome occurred in 32% of nonhospitalized patients, 55% of hospitalized patients without delirium, and 79% of hospitalized patients with delirium.

In the hospitalized patients, 6% of deaths, 15% of institutionalizations, and 21% of cases of cognitive decline were associated with delirium, the researchers said.

Death occurred in 15% of hospitalized patients with delirium, compared with 9% of hospitalized patients without delirium and 2% of nonhospitalized patients.

The hospitalized patients with delirium had an increased risk for death, institutionalization, and cognitive decline, compared with the other groups, with adjusted risk ratios of 5.4, 9.3, and 1.6, respectively. Hospitalized patients with no delirium had a slightly smaller increase in the risk of death (adjusted risk ratio 4.7) and institutionalization (adjusted risk ratio 6.9).

The mean age of the patients was 77 years, 57% were women, and 95% were white.

The results were limited by several factors, including the observational nature of the study and the incomplete data on the cognitive outcome and functional status of some patients, the researchers wrote. But the findings show "the important and incremental associations of hospitalization and delirium with 1-year outcomes," they said.

Additional research is needed to determine whether preventing hospitalization and delirium in AD patients can reduce their risk for death, institutionalization, and cognitive decline, they noted.

Dr. Fong had no financial conflicts to disclose. The study was funded by the National Institute on Aging and the Massachusetts Alzheimer’s Disease Research Center.

A pilot telepsychiatry program for children significantly improved symptoms and cut emergency department visits in half, based on data from more than 8,000 patients over 2 years.

Health care costs will continue to rise, so new mechanisms are needed to combat the shortfalls in primary care medicine – including the limited number of child psychiatrists, said Alexander Vo, Ph.D., who presented the results in a webinar June 12.

"Telemedicine is the use of technology to deliver health care from a distance," said Dr. Vo of the University of Texas Medical Branch at Galveston. Faced with a shortage of pediatric psychiatrists in Texas and given a mandate to provide access to quality mental health and medical care, the University of Texas received a grant to develop pediatric psychiatry clinics for telemedicine.

"The goal of the project was to increase access to mental health care," Dr. Vo said. "Over a 2-year period we served approximately 8,000 patients with approximately 12,000 clinical appointments."

Then after the 2-year period, Dr. Vo and his colleagues surveyed 530 parents whose children were involved in the telemedicine program. Overall, 89% of the parents said the program made it easier for their children to receive services from a specialist, and more than 60% of parents reported dramatic improvements in their children’s functional behavior or symptoms.

One of the most striking findings was a 51% reduction in emergency department visits from baseline to the end of year 2, said Dr. Vo. "We effectively diverted these individuals from the [ED], and probably indicated that a lot of the [ED] use by this population was inappropriate," he said. "This is a very big finding for us."

In addition, 89% of the families said they would use telepsychiatry again in the future if it was available to them. "This speaks to the potential that using technology to deliver health care has; people want this kind of service if they are not able to go in person," he said.

Several factors crucial to the success of the project included establishing partnerships with existing community mental health centers where patients could go for their telemedicine visits. The project also involved establishing broadband internet access where needed. "That allowed us to have the ability to deliver quality care by providing expert guidance via real time consultation and monitoring," Dr. Vo said.

The program also involved the creation of a secure portal to share patient information among the different clinics, which had varying levels of technology for medical records, he said.

The take-home messages for clinicians are that telemedicine is a very viable medium for delivering care in psychiatry, it is accepted by patients, and it is effective for controlling costs, increasing access to care, and improving clinical outcomes, according to Dr. Vo.

"One of the hot topics is the use of in-home telemedicine," he added. Telemedicine from a patient’s home has the added advantages of convenience, privacy, and the avoidance of stigma, he said.

For providers who want to get into telemedicine, "this is an emerging market," he said. Potential barriers to expanding telepsychiatry include licensure and reimbursement issues. Specifically, providers may want to know whether they can still be paid at the same rate as an in-person visit, said Dr. Vo. Lack of broadband connectivity in some areas is a problem as well, he noted.

However, the findings from the University of Texas program suggest that telemedicine is here to stay. "Telemedicine transcends rural or geographic barriers," said Dr. Vo. In the future, telemedicine could expand to include telemonitoring of patients, especially those in urban areas who have mobile devices, he said.

The webinar was hosted by Internet Innovation Alliance (IIA) and Colorado Access, a nonprofit health plan that provides access to behavioral and physical health services. Dr. Vo had no financial conflicts to disclose.

A pilot telepsychiatry program for children significantly improved symptoms and cut emergency department visits in half, based on data from more than 8,000 patients over 2 years.

Health care costs will continue to rise, so new mechanisms are needed to combat the shortfalls in primary care medicine – including the limited number of child psychiatrists, said Alexander Vo, Ph.D., who presented the results in a webinar June 12.

"Telemedicine is the use of technology to deliver health care from a distance," said Dr. Vo of the University of Texas Medical Branch at Galveston. Faced with a shortage of pediatric psychiatrists in Texas and given a mandate to provide access to quality mental health and medical care, the University of Texas received a grant to develop pediatric psychiatry clinics for telemedicine.

"The goal of the project was to increase access to mental health care," Dr. Vo said. "Over a 2-year period we served approximately 8,000 patients with approximately 12,000 clinical appointments."

Then after the 2-year period, Dr. Vo and his colleagues surveyed 530 parents whose children were involved in the telemedicine program. Overall, 89% of the parents said the program made it easier for their children to receive services from a specialist, and more than 60% of parents reported dramatic improvements in their children’s functional behavior or symptoms.

One of the most striking findings was a 51% reduction in emergency department visits from baseline to the end of year 2, said Dr. Vo. "We effectively diverted these individuals from the [ED], and probably indicated that a lot of the [ED] use by this population was inappropriate," he said. "This is a very big finding for us."

In addition, 89% of the families said they would use telepsychiatry again in the future if it was available to them. "This speaks to the potential that using technology to deliver health care has; people want this kind of service if they are not able to go in person," he said.

Several factors crucial to the success of the project included establishing partnerships with existing community mental health centers where patients could go for their telemedicine visits. The project also involved establishing broadband internet access where needed. "That allowed us to have the ability to deliver quality care by providing expert guidance via real time consultation and monitoring," Dr. Vo said.

The program also involved the creation of a secure portal to share patient information among the different clinics, which had varying levels of technology for medical records, he said.

The take-home messages for clinicians are that telemedicine is a very viable medium for delivering care in psychiatry, it is accepted by patients, and it is effective for controlling costs, increasing access to care, and improving clinical outcomes, according to Dr. Vo.

"One of the hot topics is the use of in-home telemedicine," he added. Telemedicine from a patient’s home has the added advantages of convenience, privacy, and the avoidance of stigma, he said.

For providers who want to get into telemedicine, "this is an emerging market," he said. Potential barriers to expanding telepsychiatry include licensure and reimbursement issues. Specifically, providers may want to know whether they can still be paid at the same rate as an in-person visit, said Dr. Vo. Lack of broadband connectivity in some areas is a problem as well, he noted.

However, the findings from the University of Texas program suggest that telemedicine is here to stay. "Telemedicine transcends rural or geographic barriers," said Dr. Vo. In the future, telemedicine could expand to include telemonitoring of patients, especially those in urban areas who have mobile devices, he said.

The webinar was hosted by Internet Innovation Alliance (IIA) and Colorado Access, a nonprofit health plan that provides access to behavioral and physical health services. Dr. Vo had no financial conflicts to disclose.

A pilot telepsychiatry program for children significantly improved symptoms and cut emergency department visits in half, based on data from more than 8,000 patients over 2 years.

Health care costs will continue to rise, so new mechanisms are needed to combat the shortfalls in primary care medicine – including the limited number of child psychiatrists, said Alexander Vo, Ph.D., who presented the results in a webinar June 12.

"Telemedicine is the use of technology to deliver health care from a distance," said Dr. Vo of the University of Texas Medical Branch at Galveston. Faced with a shortage of pediatric psychiatrists in Texas and given a mandate to provide access to quality mental health and medical care, the University of Texas received a grant to develop pediatric psychiatry clinics for telemedicine.

"The goal of the project was to increase access to mental health care," Dr. Vo said. "Over a 2-year period we served approximately 8,000 patients with approximately 12,000 clinical appointments."

Then after the 2-year period, Dr. Vo and his colleagues surveyed 530 parents whose children were involved in the telemedicine program. Overall, 89% of the parents said the program made it easier for their children to receive services from a specialist, and more than 60% of parents reported dramatic improvements in their children’s functional behavior or symptoms.

One of the most striking findings was a 51% reduction in emergency department visits from baseline to the end of year 2, said Dr. Vo. "We effectively diverted these individuals from the [ED], and probably indicated that a lot of the [ED] use by this population was inappropriate," he said. "This is a very big finding for us."

In addition, 89% of the families said they would use telepsychiatry again in the future if it was available to them. "This speaks to the potential that using technology to deliver health care has; people want this kind of service if they are not able to go in person," he said.

Several factors crucial to the success of the project included establishing partnerships with existing community mental health centers where patients could go for their telemedicine visits. The project also involved establishing broadband internet access where needed. "That allowed us to have the ability to deliver quality care by providing expert guidance via real time consultation and monitoring," Dr. Vo said.

The program also involved the creation of a secure portal to share patient information among the different clinics, which had varying levels of technology for medical records, he said.

The take-home messages for clinicians are that telemedicine is a very viable medium for delivering care in psychiatry, it is accepted by patients, and it is effective for controlling costs, increasing access to care, and improving clinical outcomes, according to Dr. Vo.

"One of the hot topics is the use of in-home telemedicine," he added. Telemedicine from a patient’s home has the added advantages of convenience, privacy, and the avoidance of stigma, he said.

For providers who want to get into telemedicine, "this is an emerging market," he said. Potential barriers to expanding telepsychiatry include licensure and reimbursement issues. Specifically, providers may want to know whether they can still be paid at the same rate as an in-person visit, said Dr. Vo. Lack of broadband connectivity in some areas is a problem as well, he noted.

However, the findings from the University of Texas program suggest that telemedicine is here to stay. "Telemedicine transcends rural or geographic barriers," said Dr. Vo. In the future, telemedicine could expand to include telemonitoring of patients, especially those in urban areas who have mobile devices, he said.

The webinar was hosted by Internet Innovation Alliance (IIA) and Colorado Access, a nonprofit health plan that provides access to behavioral and physical health services. Dr. Vo had no financial conflicts to disclose.

WASHINGTON – A two-part behavioral, educational intervention reduced rates of postpartum depression in black and Hispanic women by approximately one-third for up to 6 months, based on data from a randomized trial of 540 new mothers.

"The burden of postpartum depressive symptoms is especially high in low-income black and Latina women," Dr. Elizabeth Howell of Mount Sinai Medical Center in New York said.

Previous studies have suggested that factors such as poor social support, overload from the demands of daily life, and physical symptoms contribute to postpartum depression, she said at the annual meeting of the Society for Prevention Research.

In this study, Dr. Howell and her colleagues developed a behavioral, educational intervention to reduce postpartum depression in a high-risk population of minority women. The intervention included a 15-minute review of a patient-education booklet and partner summary sheet with a trained bilingual social worker before the women left the hospital. The second part of the intervention was a phone call from the social worker at 2 weeks post partum to assess the women’s symptoms, symptom management skills, and other issues. When needed, the social worker helped the 270 women in this group develop action plans to manage symptoms and access community resources. The findings also were published in the May issue of Obstetrics & Gynecology (2012;119:942-9).

"The burden of postpartum depressive symptoms is especially high in low-income black and Latina women," Dr. Elizabeth Howell said.

The educational pamphlet presented possible triggers of postpartum depression as normal elements of the postpartum experience, such as hair loss, bleeding, back pain, incision pain or episiotomy site pain, infant colic, and feeling sad or blue.

The 270 in the control group received a list of community resources instead of the detailed pamphlet, and a 2-week control phone call.

The study participants were evaluated for depression (defined as a score of 10 or greater on the Edinburgh Postnatal Depression Scale) before randomization and at 3 weeks, 3 months, and 6 months.

Overall, positive depression scores were significantly less common in the intervention group, compared with the controls, at 3 weeks (9% and 15%, respectively). Depression scores remained less common in the intervention group, compared with controls, at 3 months (8% vs. 13%) and 6 months (9% vs. 14%), although these differences did not reach statistical significance.

In an intent to treat analysis, mothers in the intervention group had a 33% reduced risk of screening positive for depression for up to 6 months post partum.

The mean age of the women was 28 years, 62% were Hispanic, and 41% were having their first child.

The study was limited by the relatively low rate of positive depressive symptoms, compared with data from other studies of high-risk minority women, the researchers noted. However, the results suggest that factors reported to contribute to postpartum depression can be addressed and modified.

"It is important to note that the effect during the first 6 months post partum would likely benefit the infant, mother, and family," they added.

Dr. Howell had no financial conflicts to disclose. The study was funded by the National Institutes of Health.

WASHINGTON – A two-part behavioral, educational intervention reduced rates of postpartum depression in black and Hispanic women by approximately one-third for up to 6 months, based on data from a randomized trial of 540 new mothers.

"The burden of postpartum depressive symptoms is especially high in low-income black and Latina women," Dr. Elizabeth Howell of Mount Sinai Medical Center in New York said.

Previous studies have suggested that factors such as poor social support, overload from the demands of daily life, and physical symptoms contribute to postpartum depression, she said at the annual meeting of the Society for Prevention Research.

In this study, Dr. Howell and her colleagues developed a behavioral, educational intervention to reduce postpartum depression in a high-risk population of minority women. The intervention included a 15-minute review of a patient-education booklet and partner summary sheet with a trained bilingual social worker before the women left the hospital. The second part of the intervention was a phone call from the social worker at 2 weeks post partum to assess the women’s symptoms, symptom management skills, and other issues. When needed, the social worker helped the 270 women in this group develop action plans to manage symptoms and access community resources. The findings also were published in the May issue of Obstetrics & Gynecology (2012;119:942-9).

"The burden of postpartum depressive symptoms is especially high in low-income black and Latina women," Dr. Elizabeth Howell said.

The educational pamphlet presented possible triggers of postpartum depression as normal elements of the postpartum experience, such as hair loss, bleeding, back pain, incision pain or episiotomy site pain, infant colic, and feeling sad or blue.

The 270 in the control group received a list of community resources instead of the detailed pamphlet, and a 2-week control phone call.

The study participants were evaluated for depression (defined as a score of 10 or greater on the Edinburgh Postnatal Depression Scale) before randomization and at 3 weeks, 3 months, and 6 months.

Overall, positive depression scores were significantly less common in the intervention group, compared with the controls, at 3 weeks (9% and 15%, respectively). Depression scores remained less common in the intervention group, compared with controls, at 3 months (8% vs. 13%) and 6 months (9% vs. 14%), although these differences did not reach statistical significance.

In an intent to treat analysis, mothers in the intervention group had a 33% reduced risk of screening positive for depression for up to 6 months post partum.

The mean age of the women was 28 years, 62% were Hispanic, and 41% were having their first child.

The study was limited by the relatively low rate of positive depressive symptoms, compared with data from other studies of high-risk minority women, the researchers noted. However, the results suggest that factors reported to contribute to postpartum depression can be addressed and modified.

"It is important to note that the effect during the first 6 months post partum would likely benefit the infant, mother, and family," they added.

Dr. Howell had no financial conflicts to disclose. The study was funded by the National Institutes of Health.

WASHINGTON – A two-part behavioral, educational intervention reduced rates of postpartum depression in black and Hispanic women by approximately one-third for up to 6 months, based on data from a randomized trial of 540 new mothers.

"The burden of postpartum depressive symptoms is especially high in low-income black and Latina women," Dr. Elizabeth Howell of Mount Sinai Medical Center in New York said.

Previous studies have suggested that factors such as poor social support, overload from the demands of daily life, and physical symptoms contribute to postpartum depression, she said at the annual meeting of the Society for Prevention Research.

In this study, Dr. Howell and her colleagues developed a behavioral, educational intervention to reduce postpartum depression in a high-risk population of minority women. The intervention included a 15-minute review of a patient-education booklet and partner summary sheet with a trained bilingual social worker before the women left the hospital. The second part of the intervention was a phone call from the social worker at 2 weeks post partum to assess the women’s symptoms, symptom management skills, and other issues. When needed, the social worker helped the 270 women in this group develop action plans to manage symptoms and access community resources. The findings also were published in the May issue of Obstetrics & Gynecology (2012;119:942-9).

"The burden of postpartum depressive symptoms is especially high in low-income black and Latina women," Dr. Elizabeth Howell said.

The educational pamphlet presented possible triggers of postpartum depression as normal elements of the postpartum experience, such as hair loss, bleeding, back pain, incision pain or episiotomy site pain, infant colic, and feeling sad or blue.

The 270 in the control group received a list of community resources instead of the detailed pamphlet, and a 2-week control phone call.

The study participants were evaluated for depression (defined as a score of 10 or greater on the Edinburgh Postnatal Depression Scale) before randomization and at 3 weeks, 3 months, and 6 months.

Overall, positive depression scores were significantly less common in the intervention group, compared with the controls, at 3 weeks (9% and 15%, respectively). Depression scores remained less common in the intervention group, compared with controls, at 3 months (8% vs. 13%) and 6 months (9% vs. 14%), although these differences did not reach statistical significance.

In an intent to treat analysis, mothers in the intervention group had a 33% reduced risk of screening positive for depression for up to 6 months post partum.

The mean age of the women was 28 years, 62% were Hispanic, and 41% were having their first child.

The study was limited by the relatively low rate of positive depressive symptoms, compared with data from other studies of high-risk minority women, the researchers noted. However, the results suggest that factors reported to contribute to postpartum depression can be addressed and modified.

"It is important to note that the effect during the first 6 months post partum would likely benefit the infant, mother, and family," they added.

Dr. Howell had no financial conflicts to disclose. The study was funded by the National Institutes of Health.

Ustekinumab at 45-mg and 90-mg doses significantly improved arthritis symptoms, physical function, and inflammation in adults with psoriatic arthritis, compared with placebo, after 24 weeks of treatment, according to findings presented by Dr. Iain B. McInnes at the annual European Congress of Rheumatology.

These findings come from the PSUMMIT I study, a multicenter, randomized trial of 615 patients. Participants were patients whose psoriatic arthritis (PsA) remained persistent, despite treatment with NSAIDS or disease-modifying antirheumatic drugs (DMARDs). They were randomized to 45 mg of ustekinumab, 90 mg of ustekinumab, or a placebo. Patients who had been treated with anti–tumor necrosis factor (anti-TNF) agents were excluded from the study.

After 24 weeks, approximately half of the patients in the 45 mg–dose (42%) and 90 mg–dose (50%) groups achieved an ACR 20 response (that is, a 20% improvement based on certain parameters specified by the American College of Rheumatology); the percentages for both groups were significantly greater than that of the placebo group (23%).

"These findings are in line with our expectations from the original phase II trial published a short number of years ago and with the success already enjoyed in using this medicine in treating the skin component of the psoriasis/psoriatic arthritis spectrum," said Dr. McInnes, director of the Institute for Infection, Inflammation, and Immunity at the University of Glascow (Scotland). The findings are also gratifying, he added. "There has been some evidence elsewhere to suggest that the cytokines that are targeted by ustekinumab might be of importance in psoriasis and psoriatic arthritis pathogenesis – these clinical data are compatible with those ideas," he noted.

Significantly more patients in both ustekinumab groups achieved ACR 50 and ACR 70 responses, compared with the placebo patients. In addition, ustekinumab patients had clinically meaningful changes from baseline Health Assessment Questionnaire Disability Index scores (defined as a change greater than or equal to 0.3), compared with placebo patients. Approximately twice as many patients in the two treatment groups demonstrated this change, compared with the placebo patients (48% vs. 28%, respectively).

The median change in enthesitis scores were 43% in the 45-mg ustekinumab group and 50% in the 90-mg ustekinumab group, compared with no change in the placebo group.

So far, no substantial differences in adverse events between the treatment and placebo groups have emerged, Dr. McInnes said in an interview. However, "this is a small trial – in comparison to the larger phase III and postmarketing datasets for this agent in the psoriasis field – and as such we need to be conservative in our interpretation of adverse events," he emphasized. "Continued vigilance will be the key here, and follow-up is ongoing," he said.

If the findings are confirmed in other studies, "we may be able to offer this agent to provide a new mode of action for the treatment of psoriatic arthritis, a disease for which we currently have too few options available," said Dr. McInnes. However, "it is too early to determine at which stage in the patient journey such use would be optimally employed," he said.

"It seems self-evident that use of ustekinumab would be after conventional drugs have been tried, and then, most likely it would be used after a TNF inhibitor because that has been the order of discovery. This reflects the RA treatment paradigm.

"But this might not be the best course; in fact, we might get similar results with different modes of action. So without head-to-head data we would make our decision based on the extent of safety data available. There is considerable safety evidence for ustekinumab in the skin literature; however, right now there is a challenge to work out where this drug will be used if it is marketed" said Dr. McInnes.

Approximately half of the patients were using methotrexate at baseline, but this did not impact the effect of ustekinumab vs. placebo.

Dr. McInnes reported financial support from Janssen Research and Development.

Ustekinumab at 45-mg and 90-mg doses significantly improved arthritis symptoms, physical function, and inflammation in adults with psoriatic arthritis, compared with placebo, after 24 weeks of treatment, according to findings presented by Dr. Iain B. McInnes at the annual European Congress of Rheumatology.

These findings come from the PSUMMIT I study, a multicenter, randomized trial of 615 patients. Participants were patients whose psoriatic arthritis (PsA) remained persistent, despite treatment with NSAIDS or disease-modifying antirheumatic drugs (DMARDs). They were randomized to 45 mg of ustekinumab, 90 mg of ustekinumab, or a placebo. Patients who had been treated with anti–tumor necrosis factor (anti-TNF) agents were excluded from the study.

After 24 weeks, approximately half of the patients in the 45 mg–dose (42%) and 90 mg–dose (50%) groups achieved an ACR 20 response (that is, a 20% improvement based on certain parameters specified by the American College of Rheumatology); the percentages for both groups were significantly greater than that of the placebo group (23%).

"These findings are in line with our expectations from the original phase II trial published a short number of years ago and with the success already enjoyed in using this medicine in treating the skin component of the psoriasis/psoriatic arthritis spectrum," said Dr. McInnes, director of the Institute for Infection, Inflammation, and Immunity at the University of Glascow (Scotland). The findings are also gratifying, he added. "There has been some evidence elsewhere to suggest that the cytokines that are targeted by ustekinumab might be of importance in psoriasis and psoriatic arthritis pathogenesis – these clinical data are compatible with those ideas," he noted.

Significantly more patients in both ustekinumab groups achieved ACR 50 and ACR 70 responses, compared with the placebo patients. In addition, ustekinumab patients had clinically meaningful changes from baseline Health Assessment Questionnaire Disability Index scores (defined as a change greater than or equal to 0.3), compared with placebo patients. Approximately twice as many patients in the two treatment groups demonstrated this change, compared with the placebo patients (48% vs. 28%, respectively).

The median change in enthesitis scores were 43% in the 45-mg ustekinumab group and 50% in the 90-mg ustekinumab group, compared with no change in the placebo group.

So far, no substantial differences in adverse events between the treatment and placebo groups have emerged, Dr. McInnes said in an interview. However, "this is a small trial – in comparison to the larger phase III and postmarketing datasets for this agent in the psoriasis field – and as such we need to be conservative in our interpretation of adverse events," he emphasized. "Continued vigilance will be the key here, and follow-up is ongoing," he said.

If the findings are confirmed in other studies, "we may be able to offer this agent to provide a new mode of action for the treatment of psoriatic arthritis, a disease for which we currently have too few options available," said Dr. McInnes. However, "it is too early to determine at which stage in the patient journey such use would be optimally employed," he said.

"It seems self-evident that use of ustekinumab would be after conventional drugs have been tried, and then, most likely it would be used after a TNF inhibitor because that has been the order of discovery. This reflects the RA treatment paradigm.

"But this might not be the best course; in fact, we might get similar results with different modes of action. So without head-to-head data we would make our decision based on the extent of safety data available. There is considerable safety evidence for ustekinumab in the skin literature; however, right now there is a challenge to work out where this drug will be used if it is marketed" said Dr. McInnes.

Approximately half of the patients were using methotrexate at baseline, but this did not impact the effect of ustekinumab vs. placebo.

Dr. McInnes reported financial support from Janssen Research and Development.

Ustekinumab at 45-mg and 90-mg doses significantly improved arthritis symptoms, physical function, and inflammation in adults with psoriatic arthritis, compared with placebo, after 24 weeks of treatment, according to findings presented by Dr. Iain B. McInnes at the annual European Congress of Rheumatology.

These findings come from the PSUMMIT I study, a multicenter, randomized trial of 615 patients. Participants were patients whose psoriatic arthritis (PsA) remained persistent, despite treatment with NSAIDS or disease-modifying antirheumatic drugs (DMARDs). They were randomized to 45 mg of ustekinumab, 90 mg of ustekinumab, or a placebo. Patients who had been treated with anti–tumor necrosis factor (anti-TNF) agents were excluded from the study.

After 24 weeks, approximately half of the patients in the 45 mg–dose (42%) and 90 mg–dose (50%) groups achieved an ACR 20 response (that is, a 20% improvement based on certain parameters specified by the American College of Rheumatology); the percentages for both groups were significantly greater than that of the placebo group (23%).

"These findings are in line with our expectations from the original phase II trial published a short number of years ago and with the success already enjoyed in using this medicine in treating the skin component of the psoriasis/psoriatic arthritis spectrum," said Dr. McInnes, director of the Institute for Infection, Inflammation, and Immunity at the University of Glascow (Scotland). The findings are also gratifying, he added. "There has been some evidence elsewhere to suggest that the cytokines that are targeted by ustekinumab might be of importance in psoriasis and psoriatic arthritis pathogenesis – these clinical data are compatible with those ideas," he noted.

Significantly more patients in both ustekinumab groups achieved ACR 50 and ACR 70 responses, compared with the placebo patients. In addition, ustekinumab patients had clinically meaningful changes from baseline Health Assessment Questionnaire Disability Index scores (defined as a change greater than or equal to 0.3), compared with placebo patients. Approximately twice as many patients in the two treatment groups demonstrated this change, compared with the placebo patients (48% vs. 28%, respectively).

The median change in enthesitis scores were 43% in the 45-mg ustekinumab group and 50% in the 90-mg ustekinumab group, compared with no change in the placebo group.

So far, no substantial differences in adverse events between the treatment and placebo groups have emerged, Dr. McInnes said in an interview. However, "this is a small trial – in comparison to the larger phase III and postmarketing datasets for this agent in the psoriasis field – and as such we need to be conservative in our interpretation of adverse events," he emphasized. "Continued vigilance will be the key here, and follow-up is ongoing," he said.

If the findings are confirmed in other studies, "we may be able to offer this agent to provide a new mode of action for the treatment of psoriatic arthritis, a disease for which we currently have too few options available," said Dr. McInnes. However, "it is too early to determine at which stage in the patient journey such use would be optimally employed," he said.

"It seems self-evident that use of ustekinumab would be after conventional drugs have been tried, and then, most likely it would be used after a TNF inhibitor because that has been the order of discovery. This reflects the RA treatment paradigm.

"But this might not be the best course; in fact, we might get similar results with different modes of action. So without head-to-head data we would make our decision based on the extent of safety data available. There is considerable safety evidence for ustekinumab in the skin literature; however, right now there is a challenge to work out where this drug will be used if it is marketed" said Dr. McInnes.

Approximately half of the patients were using methotrexate at baseline, but this did not impact the effect of ustekinumab vs. placebo.

Dr. McInnes reported financial support from Janssen Research and Development.

Teen deaths due to car crashes dropped significantly over the past decade, owing to an improvement in risky behaviors such as not wearing a seat belt, according to data from the 2011 Youth Risk Behavior Surveillance System Survey.

"The most notable finding is this report is the significant reduction in the number of motor vehicle crashes, which are the leading cause of death among youth in the United States," Howell Wechsler, Ed.D., M.P.H., director of the Centers for Disease Control and Prevention’s Division of Adolescent and School Health, said in a telebriefing sponsored by the CDC on June 7.

In particular, the percentage of students who said they never or rarely wore seat belts dropped from 26% in 1991 to 8% in 2011, said Dr. Wechsler. In addition, the percentage of students who said they rode in a car with a drunk driver dropped from 40% to 24% between 1991 and 2011, and the percentage who said they had driven while drunk declined from 17% to 8% between 1997 and 2011.

"We would urge clinicians to ... give [their patients] good advice related to distracted driving and texting while driving."

Although these findings are encouraging, this year’s survey results also recognized the role of technology in creating new risky behaviors for teens by including questions about texting or emailing while driving, Dr. Wechsler said.

"For the first time, the use of technology is resulting in new risks," he said. Overall, 1 in 3 students said they had texted or emailed while driving within the past 30 days, and 1 in 6 students reported being the victims of cyberbullying during the past 12 months.

Texting or emailing while driving is especially dangerous, because it takes the drivers’ attention away from driving more often and for longer periods than other distractions, and inexperienced teen drivers are at increased risk for accidents resulting from inattention, Dr. Wechsler said.

"While we are pleased to see improvements in many behaviors related to motor vehicle crashes, naturally we are alarmed by some of the new findings, especially those involving distracted driving," Dr. Wechsler noted. The CDC is developing programs to improve and promote safe driving among teens, but health professionals have a role to play as well, he said.

"We would urge clinicians to counsel their patients and give them good advice related to distracted driving and texting while driving, and to also address the electronic bullying issue," he said.

Additional data from the survey showed no significant reduction in teen smoking and an increase in marijuana use since the last survey in 2009. Data for the Youth Risk Behavior Surveillance System Survey came from a nationally representative sample of more than 15,000 students in public and private high schools in the United States (MMWR 2012:61;SS-4).

Visit the CDC website for the complete report.

Teen deaths due to car crashes dropped significantly over the past decade, owing to an improvement in risky behaviors such as not wearing a seat belt, according to data from the 2011 Youth Risk Behavior Surveillance System Survey.

"The most notable finding is this report is the significant reduction in the number of motor vehicle crashes, which are the leading cause of death among youth in the United States," Howell Wechsler, Ed.D., M.P.H., director of the Centers for Disease Control and Prevention’s Division of Adolescent and School Health, said in a telebriefing sponsored by the CDC on June 7.

In particular, the percentage of students who said they never or rarely wore seat belts dropped from 26% in 1991 to 8% in 2011, said Dr. Wechsler. In addition, the percentage of students who said they rode in a car with a drunk driver dropped from 40% to 24% between 1991 and 2011, and the percentage who said they had driven while drunk declined from 17% to 8% between 1997 and 2011.

"We would urge clinicians to ... give [their patients] good advice related to distracted driving and texting while driving."

Although these findings are encouraging, this year’s survey results also recognized the role of technology in creating new risky behaviors for teens by including questions about texting or emailing while driving, Dr. Wechsler said.

"For the first time, the use of technology is resulting in new risks," he said. Overall, 1 in 3 students said they had texted or emailed while driving within the past 30 days, and 1 in 6 students reported being the victims of cyberbullying during the past 12 months.

Texting or emailing while driving is especially dangerous, because it takes the drivers’ attention away from driving more often and for longer periods than other distractions, and inexperienced teen drivers are at increased risk for accidents resulting from inattention, Dr. Wechsler said.

"While we are pleased to see improvements in many behaviors related to motor vehicle crashes, naturally we are alarmed by some of the new findings, especially those involving distracted driving," Dr. Wechsler noted. The CDC is developing programs to improve and promote safe driving among teens, but health professionals have a role to play as well, he said.

"We would urge clinicians to counsel their patients and give them good advice related to distracted driving and texting while driving, and to also address the electronic bullying issue," he said.

Additional data from the survey showed no significant reduction in teen smoking and an increase in marijuana use since the last survey in 2009. Data for the Youth Risk Behavior Surveillance System Survey came from a nationally representative sample of more than 15,000 students in public and private high schools in the United States (MMWR 2012:61;SS-4).

Visit the CDC website for the complete report.

Teen deaths due to car crashes dropped significantly over the past decade, owing to an improvement in risky behaviors such as not wearing a seat belt, according to data from the 2011 Youth Risk Behavior Surveillance System Survey.

"The most notable finding is this report is the significant reduction in the number of motor vehicle crashes, which are the leading cause of death among youth in the United States," Howell Wechsler, Ed.D., M.P.H., director of the Centers for Disease Control and Prevention’s Division of Adolescent and School Health, said in a telebriefing sponsored by the CDC on June 7.

In particular, the percentage of students who said they never or rarely wore seat belts dropped from 26% in 1991 to 8% in 2011, said Dr. Wechsler. In addition, the percentage of students who said they rode in a car with a drunk driver dropped from 40% to 24% between 1991 and 2011, and the percentage who said they had driven while drunk declined from 17% to 8% between 1997 and 2011.

"We would urge clinicians to ... give [their patients] good advice related to distracted driving and texting while driving."

Although these findings are encouraging, this year’s survey results also recognized the role of technology in creating new risky behaviors for teens by including questions about texting or emailing while driving, Dr. Wechsler said.

"For the first time, the use of technology is resulting in new risks," he said. Overall, 1 in 3 students said they had texted or emailed while driving within the past 30 days, and 1 in 6 students reported being the victims of cyberbullying during the past 12 months.

Texting or emailing while driving is especially dangerous, because it takes the drivers’ attention away from driving more often and for longer periods than other distractions, and inexperienced teen drivers are at increased risk for accidents resulting from inattention, Dr. Wechsler said.

"While we are pleased to see improvements in many behaviors related to motor vehicle crashes, naturally we are alarmed by some of the new findings, especially those involving distracted driving," Dr. Wechsler noted. The CDC is developing programs to improve and promote safe driving among teens, but health professionals have a role to play as well, he said.

"We would urge clinicians to counsel their patients and give them good advice related to distracted driving and texting while driving, and to also address the electronic bullying issue," he said.

Additional data from the survey showed no significant reduction in teen smoking and an increase in marijuana use since the last survey in 2009. Data for the Youth Risk Behavior Surveillance System Survey came from a nationally representative sample of more than 15,000 students in public and private high schools in the United States (MMWR 2012:61;SS-4).

Visit the CDC website for the complete report.

Adults with major depression were significantly less likely to discontinue treatment when they received telephone-administered cognitive behavioral therapy, compared with patients who received face-to-face CBT. However, at 6-months, those who received in-person therapy were comparatively less depressed, according to the findings of a randomized, controlled trial. The results were published June 6 in JAMA.

"The discrepancy between patients’ preference for psychotherapy and the low rates of initiation and adherence is likely due to access barriers," said David C. Mohr, Ph.D., of Northwestern University, Chicago, and colleagues. Telephone therapy has been tested as a tool to overcome barriers, but not for its effectiveness compared with face-to-face therapy, the researchers noted.

In this study, 325 adults with major depressive disorder who were being treated in primary care settings were randomized to 18 weekly sessions of telephone cognitive behavior therapy (T-CBT) or in-person CBT (JAMA 2012;307:2278-85).

Significantly fewer T-CBT patients discontinued therapy before the end of the study, compared with in-person CBT patients (21% vs. 33%). Early attrition (prior to 5 weeks) was significantly lower in the T-CBT patients compared with the in-person CBT patients (4% vs. 13%), but attrition rates were not significantly different between the two groups from 5 weeks to 18 weeks.

"The discrepancy between patients’ preference for psychotherapy and the low rates of initiation and adherence is likely due to access barriers," said David C. Mohr, Ph.D.

At study completion, there was no significant difference in the number of patients who met the key response-to-treatment criterion – a 50% decrease in scores on the Hamilton Depression Rating scale – between the T-CBT and in-person CBT groups (44% and 49%, respectively).

Although improvement in depressive symptoms compared with baseline was similar between the groups at the end of the treatment period, significantly more patients who received in-person therapy were fully remitted after 6 months (19% vs. 32%).

No significant adverse events – including suicide completions, suicide attempts, or psychiatric hospitalizations – were reported in either group.

The results were limited by the narrow focus on CBT for depression, which prevents generalization to other therapies and other mental health problems, the researchers noted.

There are pros and cons of telephone therapy, they said. Telephone therapy allows health care providers to reach more patients. "However, the increased adherence associated with T-CBT may come at the cost of some increased risk of poorer outcomes after treatment cessation," they added.

Dr. Mohr reported having no financial conflicts of interest. The study was funded by the National Institute of Mental Health.

Adults with major depression were significantly less likely to discontinue treatment when they received telephone-administered cognitive behavioral therapy, compared with patients who received face-to-face CBT. However, at 6-months, those who received in-person therapy were comparatively less depressed, according to the findings of a randomized, controlled trial. The results were published June 6 in JAMA.

"The discrepancy between patients’ preference for psychotherapy and the low rates of initiation and adherence is likely due to access barriers," said David C. Mohr, Ph.D., of Northwestern University, Chicago, and colleagues. Telephone therapy has been tested as a tool to overcome barriers, but not for its effectiveness compared with face-to-face therapy, the researchers noted.

In this study, 325 adults with major depressive disorder who were being treated in primary care settings were randomized to 18 weekly sessions of telephone cognitive behavior therapy (T-CBT) or in-person CBT (JAMA 2012;307:2278-85).

Significantly fewer T-CBT patients discontinued therapy before the end of the study, compared with in-person CBT patients (21% vs. 33%). Early attrition (prior to 5 weeks) was significantly lower in the T-CBT patients compared with the in-person CBT patients (4% vs. 13%), but attrition rates were not significantly different between the two groups from 5 weeks to 18 weeks.

"The discrepancy between patients’ preference for psychotherapy and the low rates of initiation and adherence is likely due to access barriers," said David C. Mohr, Ph.D.

At study completion, there was no significant difference in the number of patients who met the key response-to-treatment criterion – a 50% decrease in scores on the Hamilton Depression Rating scale – between the T-CBT and in-person CBT groups (44% and 49%, respectively).

Although improvement in depressive symptoms compared with baseline was similar between the groups at the end of the treatment period, significantly more patients who received in-person therapy were fully remitted after 6 months (19% vs. 32%).

No significant adverse events – including suicide completions, suicide attempts, or psychiatric hospitalizations – were reported in either group.

The results were limited by the narrow focus on CBT for depression, which prevents generalization to other therapies and other mental health problems, the researchers noted.

There are pros and cons of telephone therapy, they said. Telephone therapy allows health care providers to reach more patients. "However, the increased adherence associated with T-CBT may come at the cost of some increased risk of poorer outcomes after treatment cessation," they added.

Dr. Mohr reported having no financial conflicts of interest. The study was funded by the National Institute of Mental Health.

Adults with major depression were significantly less likely to discontinue treatment when they received telephone-administered cognitive behavioral therapy, compared with patients who received face-to-face CBT. However, at 6-months, those who received in-person therapy were comparatively less depressed, according to the findings of a randomized, controlled trial. The results were published June 6 in JAMA.

"The discrepancy between patients’ preference for psychotherapy and the low rates of initiation and adherence is likely due to access barriers," said David C. Mohr, Ph.D., of Northwestern University, Chicago, and colleagues. Telephone therapy has been tested as a tool to overcome barriers, but not for its effectiveness compared with face-to-face therapy, the researchers noted.

In this study, 325 adults with major depressive disorder who were being treated in primary care settings were randomized to 18 weekly sessions of telephone cognitive behavior therapy (T-CBT) or in-person CBT (JAMA 2012;307:2278-85).

Significantly fewer T-CBT patients discontinued therapy before the end of the study, compared with in-person CBT patients (21% vs. 33%). Early attrition (prior to 5 weeks) was significantly lower in the T-CBT patients compared with the in-person CBT patients (4% vs. 13%), but attrition rates were not significantly different between the two groups from 5 weeks to 18 weeks.

"The discrepancy between patients’ preference for psychotherapy and the low rates of initiation and adherence is likely due to access barriers," said David C. Mohr, Ph.D.

At study completion, there was no significant difference in the number of patients who met the key response-to-treatment criterion – a 50% decrease in scores on the Hamilton Depression Rating scale – between the T-CBT and in-person CBT groups (44% and 49%, respectively).

Although improvement in depressive symptoms compared with baseline was similar between the groups at the end of the treatment period, significantly more patients who received in-person therapy were fully remitted after 6 months (19% vs. 32%).

No significant adverse events – including suicide completions, suicide attempts, or psychiatric hospitalizations – were reported in either group.

The results were limited by the narrow focus on CBT for depression, which prevents generalization to other therapies and other mental health problems, the researchers noted.

There are pros and cons of telephone therapy, they said. Telephone therapy allows health care providers to reach more patients. "However, the increased adherence associated with T-CBT may come at the cost of some increased risk of poorer outcomes after treatment cessation," they added.

Dr. Mohr reported having no financial conflicts of interest. The study was funded by the National Institute of Mental Health.

Median overall survival is approximately twice as long for patients with esophageal or esophagogastric-junction cancer who undergo chemoradiotherapy before surgery than for those treated with surgery alone, investigators reported.

In an intent-to-treat analysis of 366 patients, the median overall survival was 49 months in the chemoradiotherapy plus surgery group, versus 24 months in the surgery group (hazard ratio, 0.657; P = .003). The findings were published May 31 in the New England Journal of Medicine.

The overall survival rates in the chemoradiotherapy plus surgery group were higher than those in the surgery-only group throughout the study: 82% vs. 70% (year 1), 67% vs. 50% (year 2), 58% vs. 44% (year 3), and 47% vs. 34% (year 5).

Significantly more patients in the chemoradiotherapy plus surgery group achieved complete resection (defined as no tumor within 1 mm of the resection margins) compared with the surgery-only group (92% vs. 69%, P less than .001), wrote Dr. Pieter van Hagen of Erasmus University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Of 161 patients who underwent resection after chemoradiotherapy, 47 (29%) had a pathological complete response. Postoperative complications were similar between the two treatment groups, and in-hospital mortality was 4% in both groups (N. Engl. J. Med. 2012;366:2074-84).

Patients aged 18-75 years with tumors no larger than 8 cm in length and 5 cm in width were randomized to immediate surgery or surgery after a regimen of chemoradiotherapy. All patients met the World Health Organization (WHO) performance status score of 2 or lower, and had adequate pulmonary, hematologic, hepatic, and renal function.

Patients in the chemoradiotherapy group received an intravenous dose of carboplatin targeted at an area under the curve of 2 mg/mL per minute and paclitaxel at a dose of 50 mg per square meter of body surface area on days 1, 8, 15, 22, and 29. The patients were premedicated intravenously with dexamethasone, clemastine, ranitidine, and standard antiemetics.

For the radiation part of the treatment, they received a total radiation dose of 41.4 Gy delivered in 23 fractions of 1.8 Gy each. Five fractions were administered per week, starting on the first day of the first chemotherapy cycle. All patients were treated via external-beam radiation.

The study was supported by the Dutch Cancer Foundation. Dr. van Hagen had no relevant financial disclosures.

Median overall survival is approximately twice as long for patients with esophageal or esophagogastric-junction cancer who undergo chemoradiotherapy before surgery than for those treated with surgery alone, investigators reported.

In an intent-to-treat analysis of 366 patients, the median overall survival was 49 months in the chemoradiotherapy plus surgery group, versus 24 months in the surgery group (hazard ratio, 0.657; P = .003). The findings were published May 31 in the New England Journal of Medicine.

The overall survival rates in the chemoradiotherapy plus surgery group were higher than those in the surgery-only group throughout the study: 82% vs. 70% (year 1), 67% vs. 50% (year 2), 58% vs. 44% (year 3), and 47% vs. 34% (year 5).

Significantly more patients in the chemoradiotherapy plus surgery group achieved complete resection (defined as no tumor within 1 mm of the resection margins) compared with the surgery-only group (92% vs. 69%, P less than .001), wrote Dr. Pieter van Hagen of Erasmus University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Of 161 patients who underwent resection after chemoradiotherapy, 47 (29%) had a pathological complete response. Postoperative complications were similar between the two treatment groups, and in-hospital mortality was 4% in both groups (N. Engl. J. Med. 2012;366:2074-84).

Patients aged 18-75 years with tumors no larger than 8 cm in length and 5 cm in width were randomized to immediate surgery or surgery after a regimen of chemoradiotherapy. All patients met the World Health Organization (WHO) performance status score of 2 or lower, and had adequate pulmonary, hematologic, hepatic, and renal function.

Patients in the chemoradiotherapy group received an intravenous dose of carboplatin targeted at an area under the curve of 2 mg/mL per minute and paclitaxel at a dose of 50 mg per square meter of body surface area on days 1, 8, 15, 22, and 29. The patients were premedicated intravenously with dexamethasone, clemastine, ranitidine, and standard antiemetics.

For the radiation part of the treatment, they received a total radiation dose of 41.4 Gy delivered in 23 fractions of 1.8 Gy each. Five fractions were administered per week, starting on the first day of the first chemotherapy cycle. All patients were treated via external-beam radiation.

The study was supported by the Dutch Cancer Foundation. Dr. van Hagen had no relevant financial disclosures.

Median overall survival is approximately twice as long for patients with esophageal or esophagogastric-junction cancer who undergo chemoradiotherapy before surgery than for those treated with surgery alone, investigators reported.

In an intent-to-treat analysis of 366 patients, the median overall survival was 49 months in the chemoradiotherapy plus surgery group, versus 24 months in the surgery group (hazard ratio, 0.657; P = .003). The findings were published May 31 in the New England Journal of Medicine.

The overall survival rates in the chemoradiotherapy plus surgery group were higher than those in the surgery-only group throughout the study: 82% vs. 70% (year 1), 67% vs. 50% (year 2), 58% vs. 44% (year 3), and 47% vs. 34% (year 5).

Significantly more patients in the chemoradiotherapy plus surgery group achieved complete resection (defined as no tumor within 1 mm of the resection margins) compared with the surgery-only group (92% vs. 69%, P less than .001), wrote Dr. Pieter van Hagen of Erasmus University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Of 161 patients who underwent resection after chemoradiotherapy, 47 (29%) had a pathological complete response. Postoperative complications were similar between the two treatment groups, and in-hospital mortality was 4% in both groups (N. Engl. J. Med. 2012;366:2074-84).

Patients aged 18-75 years with tumors no larger than 8 cm in length and 5 cm in width were randomized to immediate surgery or surgery after a regimen of chemoradiotherapy. All patients met the World Health Organization (WHO) performance status score of 2 or lower, and had adequate pulmonary, hematologic, hepatic, and renal function.

Patients in the chemoradiotherapy group received an intravenous dose of carboplatin targeted at an area under the curve of 2 mg/mL per minute and paclitaxel at a dose of 50 mg per square meter of body surface area on days 1, 8, 15, 22, and 29. The patients were premedicated intravenously with dexamethasone, clemastine, ranitidine, and standard antiemetics.

For the radiation part of the treatment, they received a total radiation dose of 41.4 Gy delivered in 23 fractions of 1.8 Gy each. Five fractions were administered per week, starting on the first day of the first chemotherapy cycle. All patients were treated via external-beam radiation.

The study was supported by the Dutch Cancer Foundation. Dr. van Hagen had no relevant financial disclosures.