Mary Ann Moon

Variants in the LRP5 gene are associated with both bone mineral density and fracture risk, researchers in the Genetic Markers for Osteoporosis (GENOMOS) consortium reported.

Two LRP5 variants were found to have “modest” effects that were very consistent across different populations and independent of subject sex or age.

Based on these findings, carriers of these polymorphisms may have a fracture risk that is 15%-20% higher than that for noncarriers, wrote Joyce van Meurs, Ph.D., of Erasmus Medical Center, Rotterdam (the Netherlands), and her associates.

The study involved 37,534 subjects who underwent genotyping and assessment of bone mineral density. A total of 8,932 subjects had fractures, including 2,146 vertebral fractures (JAMA 2008;299:1277-90).

Members of the GENOMOS consortium—18 research teams in Europe and North America—performed prospective genotyping for several polymorphisms of the LRP5 gene that are thought to be related to osteoporosis. “Some scattered studies have tested this association, but results have not been conclusive due to limited sample size,” the researchers wrote.

“The current collaborative study has the potential to answer this question more definitively because of its large sample size and therefore large power to observe the expected modest associations,” Dr. van Meurs and her associates explained.

“Although any single marker explains only a small portion of the phenotype risk, identification of several such osteoporosis risk variants may eventually help in improving clinical prediction,” they wrote.

“Single genetic risk variants may also offer useful insights about mechanisms and pathways that may be useful in drug development.” The investigators cautioned that their results may not apply to Asian or African populations, since the study subjects were predominantly whites of European descent.

Variants in the LRP5 gene are associated with both bone mineral density and fracture risk, researchers in the Genetic Markers for Osteoporosis (GENOMOS) consortium reported.

Two LRP5 variants were found to have “modest” effects that were very consistent across different populations and independent of subject sex or age.

Based on these findings, carriers of these polymorphisms may have a fracture risk that is 15%-20% higher than that for noncarriers, wrote Joyce van Meurs, Ph.D., of Erasmus Medical Center, Rotterdam (the Netherlands), and her associates.

The study involved 37,534 subjects who underwent genotyping and assessment of bone mineral density. A total of 8,932 subjects had fractures, including 2,146 vertebral fractures (JAMA 2008;299:1277-90).

Members of the GENOMOS consortium—18 research teams in Europe and North America—performed prospective genotyping for several polymorphisms of the LRP5 gene that are thought to be related to osteoporosis. “Some scattered studies have tested this association, but results have not been conclusive due to limited sample size,” the researchers wrote.

“The current collaborative study has the potential to answer this question more definitively because of its large sample size and therefore large power to observe the expected modest associations,” Dr. van Meurs and her associates explained.

“Although any single marker explains only a small portion of the phenotype risk, identification of several such osteoporosis risk variants may eventually help in improving clinical prediction,” they wrote.

“Single genetic risk variants may also offer useful insights about mechanisms and pathways that may be useful in drug development.” The investigators cautioned that their results may not apply to Asian or African populations, since the study subjects were predominantly whites of European descent.

Variants in the LRP5 gene are associated with both bone mineral density and fracture risk, researchers in the Genetic Markers for Osteoporosis (GENOMOS) consortium reported.

Two LRP5 variants were found to have “modest” effects that were very consistent across different populations and independent of subject sex or age.

Based on these findings, carriers of these polymorphisms may have a fracture risk that is 15%-20% higher than that for noncarriers, wrote Joyce van Meurs, Ph.D., of Erasmus Medical Center, Rotterdam (the Netherlands), and her associates.

The study involved 37,534 subjects who underwent genotyping and assessment of bone mineral density. A total of 8,932 subjects had fractures, including 2,146 vertebral fractures (JAMA 2008;299:1277-90).

Members of the GENOMOS consortium—18 research teams in Europe and North America—performed prospective genotyping for several polymorphisms of the LRP5 gene that are thought to be related to osteoporosis. “Some scattered studies have tested this association, but results have not been conclusive due to limited sample size,” the researchers wrote.

“The current collaborative study has the potential to answer this question more definitively because of its large sample size and therefore large power to observe the expected modest associations,” Dr. van Meurs and her associates explained.

“Although any single marker explains only a small portion of the phenotype risk, identification of several such osteoporosis risk variants may eventually help in improving clinical prediction,” they wrote.

“Single genetic risk variants may also offer useful insights about mechanisms and pathways that may be useful in drug development.” The investigators cautioned that their results may not apply to Asian or African populations, since the study subjects were predominantly whites of European descent.

It may not be necessary to withhold tissue plasminogen activator from patients with acute ischemic stroke who are already taking antiplatelet therapy, researchers reported.

The antiplatelet therapy does put these patients at increased risk of developing symptomatic intracerebral hemorrhage when they receive tissue plasminogen activator (TPA). But despite this risk, “prior antiplatelet therapy increased the odds of a favorable outcome” in a single-center observational study involving 301 patients.

The question of whether TPA treatment is safe in patients taking antiplatelet therapy is important because many people who develop acute ischemic stroke have a history of vascular events and are taking the drugs as preventative therapy when a stroke occurs. Many previous studies of the issue have yielded conflicting results, according to Dr. Maarten Uyttenboogaart and his associates at the University of Groningen, the Netherlands.

Dr. Uyttenboogaart and his colleagues studied 301 consecutive patients with acute ischemic stroke given TPA at the university medical center during 2002–2006. Eighty-nine (30%) were already taking aspirin, dipyridamole, combined aspirin plus dipyridamole, or clopidogrel as preventatives.

Symptomatic intracerebral hemorrhage occurred in 18 patients (6%), of whom 12 were receiving antiplatelet drugs, and 6 were not. “The absolute risk difference of approximately 10% translates into 1 additional [hemorrhage] in every tenth patient receiving thrombolysis and prior antiplatelet therapy,” the investigators said.

Half of the patients on prior antiplatelet therapy had a favorable outcome after TPA administration, compared with 45% of those who were not taking antiplatelet drugs (Arch. Neurol. 2008 March 10 [Epub doi:10.1001/archneur.65.5.noc70077]).

Since patients taking antiplatelet therapy were more likely to be older, to have a higher prevalence of vascular risk factors, and to have more previous vascular events than those not taking the agents, the data were adjusted to account for these differences and then reanalyzed. Prior antiplatelet therapy continued to be associated with a favorable outcome after TPA treatment.

“A possible mechanism behind this beneficial effect is that aspirin remains biologically active for 4–6 days and might prevent early reocclusion after TPA treatment,” the investigators noted.

Patients in this study were offered TPA for up to 4.5 hours following stroke onset, even though the treatment is approved for use only up to 3 hours after the event. A subgroup analysis of the 188 patients treated within this 3-hour window showed the same results as that for the entire cohort.

It may not be necessary to withhold tissue plasminogen activator from patients with acute ischemic stroke who are already taking antiplatelet therapy, researchers reported.

The antiplatelet therapy does put these patients at increased risk of developing symptomatic intracerebral hemorrhage when they receive tissue plasminogen activator (TPA). But despite this risk, “prior antiplatelet therapy increased the odds of a favorable outcome” in a single-center observational study involving 301 patients.

The question of whether TPA treatment is safe in patients taking antiplatelet therapy is important because many people who develop acute ischemic stroke have a history of vascular events and are taking the drugs as preventative therapy when a stroke occurs. Many previous studies of the issue have yielded conflicting results, according to Dr. Maarten Uyttenboogaart and his associates at the University of Groningen, the Netherlands.

Dr. Uyttenboogaart and his colleagues studied 301 consecutive patients with acute ischemic stroke given TPA at the university medical center during 2002–2006. Eighty-nine (30%) were already taking aspirin, dipyridamole, combined aspirin plus dipyridamole, or clopidogrel as preventatives.

Symptomatic intracerebral hemorrhage occurred in 18 patients (6%), of whom 12 were receiving antiplatelet drugs, and 6 were not. “The absolute risk difference of approximately 10% translates into 1 additional [hemorrhage] in every tenth patient receiving thrombolysis and prior antiplatelet therapy,” the investigators said.

Half of the patients on prior antiplatelet therapy had a favorable outcome after TPA administration, compared with 45% of those who were not taking antiplatelet drugs (Arch. Neurol. 2008 March 10 [Epub doi:10.1001/archneur.65.5.noc70077]).

Since patients taking antiplatelet therapy were more likely to be older, to have a higher prevalence of vascular risk factors, and to have more previous vascular events than those not taking the agents, the data were adjusted to account for these differences and then reanalyzed. Prior antiplatelet therapy continued to be associated with a favorable outcome after TPA treatment.

“A possible mechanism behind this beneficial effect is that aspirin remains biologically active for 4–6 days and might prevent early reocclusion after TPA treatment,” the investigators noted.

Patients in this study were offered TPA for up to 4.5 hours following stroke onset, even though the treatment is approved for use only up to 3 hours after the event. A subgroup analysis of the 188 patients treated within this 3-hour window showed the same results as that for the entire cohort.

It may not be necessary to withhold tissue plasminogen activator from patients with acute ischemic stroke who are already taking antiplatelet therapy, researchers reported.

The antiplatelet therapy does put these patients at increased risk of developing symptomatic intracerebral hemorrhage when they receive tissue plasminogen activator (TPA). But despite this risk, “prior antiplatelet therapy increased the odds of a favorable outcome” in a single-center observational study involving 301 patients.

The question of whether TPA treatment is safe in patients taking antiplatelet therapy is important because many people who develop acute ischemic stroke have a history of vascular events and are taking the drugs as preventative therapy when a stroke occurs. Many previous studies of the issue have yielded conflicting results, according to Dr. Maarten Uyttenboogaart and his associates at the University of Groningen, the Netherlands.

Dr. Uyttenboogaart and his colleagues studied 301 consecutive patients with acute ischemic stroke given TPA at the university medical center during 2002–2006. Eighty-nine (30%) were already taking aspirin, dipyridamole, combined aspirin plus dipyridamole, or clopidogrel as preventatives.

Symptomatic intracerebral hemorrhage occurred in 18 patients (6%), of whom 12 were receiving antiplatelet drugs, and 6 were not. “The absolute risk difference of approximately 10% translates into 1 additional [hemorrhage] in every tenth patient receiving thrombolysis and prior antiplatelet therapy,” the investigators said.

Half of the patients on prior antiplatelet therapy had a favorable outcome after TPA administration, compared with 45% of those who were not taking antiplatelet drugs (Arch. Neurol. 2008 March 10 [Epub doi:10.1001/archneur.65.5.noc70077]).

Since patients taking antiplatelet therapy were more likely to be older, to have a higher prevalence of vascular risk factors, and to have more previous vascular events than those not taking the agents, the data were adjusted to account for these differences and then reanalyzed. Prior antiplatelet therapy continued to be associated with a favorable outcome after TPA treatment.

“A possible mechanism behind this beneficial effect is that aspirin remains biologically active for 4–6 days and might prevent early reocclusion after TPA treatment,” the investigators noted.

Patients in this study were offered TPA for up to 4.5 hours following stroke onset, even though the treatment is approved for use only up to 3 hours after the event. A subgroup analysis of the 188 patients treated within this 3-hour window showed the same results as that for the entire cohort.

Patients who present with cocaine-associated chest pain or myocardial infarction should be treated similarly to patients with traditional acute coronary syndromes, with some exceptions, according to Dr. Jim McCord and his associates on the American Heart Association's acute cardiac care committee.

The committee reviewed the literature and issued a scientific statement in the March 17 online version of Circulation, with the aim of guiding diagnostic and therapeutic interventions for this subset of patients with acute chest pain.

Chest pain related to cocaine use is rarely caused by myocardial infarction, which develops in only 2%–6% of cases.

Therefore, risk stratification using well-established criteria, including electrocardiographic changes and a positive cardiac troponin test, “is feasible and safe.” But cocaine use can cause rhabdomyolysis and attendant abnormalities in creatine kinase and myoglobin levels, so those diagnostic tests may not be useful, said Dr. McCord of Henry Ford Hospital, Detroit, and his associates.

“In the absence of ischemic ECG changes or positive cardiac markers, intermediate- and low-risk patients can be safely managed in a chest pain observation unit for 9–12 hours, which can obviate the need for hospital admission in the majority of these patients,” they added.

Unlike patients with acute coronary syndrome unrelated to cocaine use, those with cocaine-associated chest pain should receive benzodiazepines immediately to relieve the pain, improve hemodynamics, and manage any neuropsychiatric manifestations that may accompany cocaine toxicity.

Also in contrast to ACS patients, those with cocaine-associated chest pain who do not have definite cardiac involvement may not need direct treatment of any hypertension and tachycardia they exhibit. Resolution of their anxiety with a benzodiazepine will often resolve the hypertension and tachycardia as well. If it doesn't, these can be managed with sodium nitroprusside, nitroglycerin, or intravenous phentolamine, the committee statement said.

For the few patients whose cocaine-associated chest pain is caused by ST-segment elevation myocardial infarction, percutaneous coronary intervention clearly is preferable to fibrinolysis.

There are few data regarding the use of drug-eluting stents in this patient population. Because most of these patients continue to use cocaine, they may have poor compliance with any long-term antiplatelet regimens. “Therefore, we recommend very careful consideration of the probability of long-term compliance before a drug-eluting stent is used in cocaine-associated MI,” the committee said.

β-Blockers should not be given in STEMI precipitated by cocaine use, because it may exacerbate coronary spasm. Whether calcium channel blockers are beneficial in this patient population is uncertain at best. Therefore, they should not be given as first-line treatment but can be considered for patients who don't respond to benzodiazepines and nitroglycerin, Dr. McCord and his associates said (doi: 10.1161/circulationaha.107.188950).

Antiplatelet and antithrombin therapies haven't been well studied for cocaine-related chest pain, but they may be beneficial, because cocaine injures the vascular epithelium, raises platelet aggregation, and impairs normal fibrinolysis. “We recommend aspirin be routinely administered and unfractionated heparin or low-molecular-weight heparin be given… unless there is a contraindication,” they said.

Finally, recidivism is common, with 60% of patients in one study admitting to continued cocaine use 1 year after being hospitalized for chest pain.

“Preliminary data suggest that a combination of intensive group and individual drug counseling has the greatest impact on recurrent cocaine use,” so these approaches should be recommended to these patients, the AHA committee said.

Chest pain associated with cocaine use is rarely caused by myocardial infarction. ©PhotoDisc

Patients who present with cocaine-associated chest pain or myocardial infarction should be treated similarly to patients with traditional acute coronary syndromes, with some exceptions, according to Dr. Jim McCord and his associates on the American Heart Association's acute cardiac care committee.

The committee reviewed the literature and issued a scientific statement in the March 17 online version of Circulation, with the aim of guiding diagnostic and therapeutic interventions for this subset of patients with acute chest pain.

Chest pain related to cocaine use is rarely caused by myocardial infarction, which develops in only 2%–6% of cases.

Therefore, risk stratification using well-established criteria, including electrocardiographic changes and a positive cardiac troponin test, “is feasible and safe.” But cocaine use can cause rhabdomyolysis and attendant abnormalities in creatine kinase and myoglobin levels, so those diagnostic tests may not be useful, said Dr. McCord of Henry Ford Hospital, Detroit, and his associates.

“In the absence of ischemic ECG changes or positive cardiac markers, intermediate- and low-risk patients can be safely managed in a chest pain observation unit for 9–12 hours, which can obviate the need for hospital admission in the majority of these patients,” they added.

Unlike patients with acute coronary syndrome unrelated to cocaine use, those with cocaine-associated chest pain should receive benzodiazepines immediately to relieve the pain, improve hemodynamics, and manage any neuropsychiatric manifestations that may accompany cocaine toxicity.

Also in contrast to ACS patients, those with cocaine-associated chest pain who do not have definite cardiac involvement may not need direct treatment of any hypertension and tachycardia they exhibit. Resolution of their anxiety with a benzodiazepine will often resolve the hypertension and tachycardia as well. If it doesn't, these can be managed with sodium nitroprusside, nitroglycerin, or intravenous phentolamine, the committee statement said.

For the few patients whose cocaine-associated chest pain is caused by ST-segment elevation myocardial infarction, percutaneous coronary intervention clearly is preferable to fibrinolysis.

There are few data regarding the use of drug-eluting stents in this patient population. Because most of these patients continue to use cocaine, they may have poor compliance with any long-term antiplatelet regimens. “Therefore, we recommend very careful consideration of the probability of long-term compliance before a drug-eluting stent is used in cocaine-associated MI,” the committee said.

β-Blockers should not be given in STEMI precipitated by cocaine use, because it may exacerbate coronary spasm. Whether calcium channel blockers are beneficial in this patient population is uncertain at best. Therefore, they should not be given as first-line treatment but can be considered for patients who don't respond to benzodiazepines and nitroglycerin, Dr. McCord and his associates said (doi: 10.1161/circulationaha.107.188950).

Antiplatelet and antithrombin therapies haven't been well studied for cocaine-related chest pain, but they may be beneficial, because cocaine injures the vascular epithelium, raises platelet aggregation, and impairs normal fibrinolysis. “We recommend aspirin be routinely administered and unfractionated heparin or low-molecular-weight heparin be given… unless there is a contraindication,” they said.

Finally, recidivism is common, with 60% of patients in one study admitting to continued cocaine use 1 year after being hospitalized for chest pain.

“Preliminary data suggest that a combination of intensive group and individual drug counseling has the greatest impact on recurrent cocaine use,” so these approaches should be recommended to these patients, the AHA committee said.

Chest pain associated with cocaine use is rarely caused by myocardial infarction. ©PhotoDisc

Patients who present with cocaine-associated chest pain or myocardial infarction should be treated similarly to patients with traditional acute coronary syndromes, with some exceptions, according to Dr. Jim McCord and his associates on the American Heart Association's acute cardiac care committee.

The committee reviewed the literature and issued a scientific statement in the March 17 online version of Circulation, with the aim of guiding diagnostic and therapeutic interventions for this subset of patients with acute chest pain.

Chest pain related to cocaine use is rarely caused by myocardial infarction, which develops in only 2%–6% of cases.

Therefore, risk stratification using well-established criteria, including electrocardiographic changes and a positive cardiac troponin test, “is feasible and safe.” But cocaine use can cause rhabdomyolysis and attendant abnormalities in creatine kinase and myoglobin levels, so those diagnostic tests may not be useful, said Dr. McCord of Henry Ford Hospital, Detroit, and his associates.

“In the absence of ischemic ECG changes or positive cardiac markers, intermediate- and low-risk patients can be safely managed in a chest pain observation unit for 9–12 hours, which can obviate the need for hospital admission in the majority of these patients,” they added.

Unlike patients with acute coronary syndrome unrelated to cocaine use, those with cocaine-associated chest pain should receive benzodiazepines immediately to relieve the pain, improve hemodynamics, and manage any neuropsychiatric manifestations that may accompany cocaine toxicity.

Also in contrast to ACS patients, those with cocaine-associated chest pain who do not have definite cardiac involvement may not need direct treatment of any hypertension and tachycardia they exhibit. Resolution of their anxiety with a benzodiazepine will often resolve the hypertension and tachycardia as well. If it doesn't, these can be managed with sodium nitroprusside, nitroglycerin, or intravenous phentolamine, the committee statement said.

For the few patients whose cocaine-associated chest pain is caused by ST-segment elevation myocardial infarction, percutaneous coronary intervention clearly is preferable to fibrinolysis.

There are few data regarding the use of drug-eluting stents in this patient population. Because most of these patients continue to use cocaine, they may have poor compliance with any long-term antiplatelet regimens. “Therefore, we recommend very careful consideration of the probability of long-term compliance before a drug-eluting stent is used in cocaine-associated MI,” the committee said.

β-Blockers should not be given in STEMI precipitated by cocaine use, because it may exacerbate coronary spasm. Whether calcium channel blockers are beneficial in this patient population is uncertain at best. Therefore, they should not be given as first-line treatment but can be considered for patients who don't respond to benzodiazepines and nitroglycerin, Dr. McCord and his associates said (doi: 10.1161/circulationaha.107.188950).

Antiplatelet and antithrombin therapies haven't been well studied for cocaine-related chest pain, but they may be beneficial, because cocaine injures the vascular epithelium, raises platelet aggregation, and impairs normal fibrinolysis. “We recommend aspirin be routinely administered and unfractionated heparin or low-molecular-weight heparin be given… unless there is a contraindication,” they said.

Finally, recidivism is common, with 60% of patients in one study admitting to continued cocaine use 1 year after being hospitalized for chest pain.

“Preliminary data suggest that a combination of intensive group and individual drug counseling has the greatest impact on recurrent cocaine use,” so these approaches should be recommended to these patients, the AHA committee said.

Chest pain associated with cocaine use is rarely caused by myocardial infarction. ©PhotoDisc

Saline nasal wash significantly improved symptoms in children with acute common colds or respiratory flu, and also reduced recurrences, researchers reported.

An isotonic saline nasal wash made from processed seawater thinned and reduced nasal secretions as well as relieved nasal obstruction and sore throat in a study of 401 patients aged 6–10 years. Treated children showed significantly less use of cold medications than did controls, had fewer school absences, and had fewer complications such as otitis media and sinusitis.

The treated children also showed greater improvement in overall health status and fewer recurrences of upper respiratory tract infection when they continued using the nasal spray as a preventive after the acute illness had resolved, according to Dr. Ivo Slapak of Teaching Hospital Brno (Czech Republic).

The study was funded by Laboratoires Goëmar, Saint-Malo (France), which supplied the nasal wash. The manufacturing process of this commercially available product “preserves the concentrations of ions and trace elements to levels comparable with those of seawater,” Dr. Slapak and his associates said.

Saline has anti-inflammatory activity, but the product's mechanism of action is not known. “It is not clear whether the effect is predominantly mechanical, based on clearing mucus, or whether salts and trace elements in seawater solutions play a significant role,” they added.

Several guidelines mention the potential benefit of saline nasal wash in treating colds and flu, although “evidence of its efficacy is rather poor,” the investigators noted. A large study in adults showed that the treatment had no effect.

In what they described as the first prospective study to assess the adjunctive treatment in children, Dr. Slapak and his associates at eight pediatric outpatient clinics randomly assigned patients to receive standard treatment either alone (101 subjects) or with open-label adjunctive nasal wash at one of three strengths: medium jet flow (100 subjects), fine spray (100 patients), or a dual eye-and-nose formula with a fine spray (100 subjects).

The saline wash was administered six times per day during the acute illness and three times per day during the prevention phase of the study. Standard treatment included antipyretics, decongestants, mucolytics, and systemic antibiotics, all given at the treating physician's discretion.

All the patients were followed for 12 weeks during cold season, from the onset of their acute illness until spring.

Acute nasal symptoms cleared more quickly in the children who received the nasal wash at any strength, and those subjects also used significantly fewer medications both acutely and during follow-up. Unblinded physicians and parents both rated the children's health status as significantly better in the treatment groups than in the control group. (See box.)

“Results were robust, consistent, and statistically significant, in contrast to the few published articles that do not clearly show the benefits of nasal wash to treat the common cold,” the investigators said (Arch. Otolaryngol. Head Neck Surg. 2008;134:67–74).

Significantly fewer subjects who used long-term nasal wash reported days of illness, absences from school, or complications. (See box.)

The researchers disclosed that they had received speakers' honoraria from various pharmaceutical firms, and some have worked or will work on projects for commercial drug laboratories.

ELSEVIER GLOBAL MEDICAL NEWS

Saline nasal wash significantly improved symptoms in children with acute common colds or respiratory flu, and also reduced recurrences, researchers reported.

An isotonic saline nasal wash made from processed seawater thinned and reduced nasal secretions as well as relieved nasal obstruction and sore throat in a study of 401 patients aged 6–10 years. Treated children showed significantly less use of cold medications than did controls, had fewer school absences, and had fewer complications such as otitis media and sinusitis.

The treated children also showed greater improvement in overall health status and fewer recurrences of upper respiratory tract infection when they continued using the nasal spray as a preventive after the acute illness had resolved, according to Dr. Ivo Slapak of Teaching Hospital Brno (Czech Republic).

The study was funded by Laboratoires Goëmar, Saint-Malo (France), which supplied the nasal wash. The manufacturing process of this commercially available product “preserves the concentrations of ions and trace elements to levels comparable with those of seawater,” Dr. Slapak and his associates said.

Saline has anti-inflammatory activity, but the product's mechanism of action is not known. “It is not clear whether the effect is predominantly mechanical, based on clearing mucus, or whether salts and trace elements in seawater solutions play a significant role,” they added.

Several guidelines mention the potential benefit of saline nasal wash in treating colds and flu, although “evidence of its efficacy is rather poor,” the investigators noted. A large study in adults showed that the treatment had no effect.

In what they described as the first prospective study to assess the adjunctive treatment in children, Dr. Slapak and his associates at eight pediatric outpatient clinics randomly assigned patients to receive standard treatment either alone (101 subjects) or with open-label adjunctive nasal wash at one of three strengths: medium jet flow (100 subjects), fine spray (100 patients), or a dual eye-and-nose formula with a fine spray (100 subjects).

The saline wash was administered six times per day during the acute illness and three times per day during the prevention phase of the study. Standard treatment included antipyretics, decongestants, mucolytics, and systemic antibiotics, all given at the treating physician's discretion.

All the patients were followed for 12 weeks during cold season, from the onset of their acute illness until spring.

Acute nasal symptoms cleared more quickly in the children who received the nasal wash at any strength, and those subjects also used significantly fewer medications both acutely and during follow-up. Unblinded physicians and parents both rated the children's health status as significantly better in the treatment groups than in the control group. (See box.)

“Results were robust, consistent, and statistically significant, in contrast to the few published articles that do not clearly show the benefits of nasal wash to treat the common cold,” the investigators said (Arch. Otolaryngol. Head Neck Surg. 2008;134:67–74).

Significantly fewer subjects who used long-term nasal wash reported days of illness, absences from school, or complications. (See box.)

The researchers disclosed that they had received speakers' honoraria from various pharmaceutical firms, and some have worked or will work on projects for commercial drug laboratories.

ELSEVIER GLOBAL MEDICAL NEWS

Saline nasal wash significantly improved symptoms in children with acute common colds or respiratory flu, and also reduced recurrences, researchers reported.

An isotonic saline nasal wash made from processed seawater thinned and reduced nasal secretions as well as relieved nasal obstruction and sore throat in a study of 401 patients aged 6–10 years. Treated children showed significantly less use of cold medications than did controls, had fewer school absences, and had fewer complications such as otitis media and sinusitis.

The treated children also showed greater improvement in overall health status and fewer recurrences of upper respiratory tract infection when they continued using the nasal spray as a preventive after the acute illness had resolved, according to Dr. Ivo Slapak of Teaching Hospital Brno (Czech Republic).

The study was funded by Laboratoires Goëmar, Saint-Malo (France), which supplied the nasal wash. The manufacturing process of this commercially available product “preserves the concentrations of ions and trace elements to levels comparable with those of seawater,” Dr. Slapak and his associates said.

Saline has anti-inflammatory activity, but the product's mechanism of action is not known. “It is not clear whether the effect is predominantly mechanical, based on clearing mucus, or whether salts and trace elements in seawater solutions play a significant role,” they added.

Several guidelines mention the potential benefit of saline nasal wash in treating colds and flu, although “evidence of its efficacy is rather poor,” the investigators noted. A large study in adults showed that the treatment had no effect.

In what they described as the first prospective study to assess the adjunctive treatment in children, Dr. Slapak and his associates at eight pediatric outpatient clinics randomly assigned patients to receive standard treatment either alone (101 subjects) or with open-label adjunctive nasal wash at one of three strengths: medium jet flow (100 subjects), fine spray (100 patients), or a dual eye-and-nose formula with a fine spray (100 subjects).

The saline wash was administered six times per day during the acute illness and three times per day during the prevention phase of the study. Standard treatment included antipyretics, decongestants, mucolytics, and systemic antibiotics, all given at the treating physician's discretion.

All the patients were followed for 12 weeks during cold season, from the onset of their acute illness until spring.

Acute nasal symptoms cleared more quickly in the children who received the nasal wash at any strength, and those subjects also used significantly fewer medications both acutely and during follow-up. Unblinded physicians and parents both rated the children's health status as significantly better in the treatment groups than in the control group. (See box.)

“Results were robust, consistent, and statistically significant, in contrast to the few published articles that do not clearly show the benefits of nasal wash to treat the common cold,” the investigators said (Arch. Otolaryngol. Head Neck Surg. 2008;134:67–74).

Significantly fewer subjects who used long-term nasal wash reported days of illness, absences from school, or complications. (See box.)

The researchers disclosed that they had received speakers' honoraria from various pharmaceutical firms, and some have worked or will work on projects for commercial drug laboratories.

ELSEVIER GLOBAL MEDICAL NEWS

Use of the aromatase inhibitor letrozole was linked to a significant 63% reduction in disease recurrence in women with early-stage breast cancer who completed 5 years of tamoxifen therapy 1 to 7 years earlier, results of a phase III study suggest.

“It appears that most cancers remain estrogen dependent for long periods in follow-up and that their clinical courses can be improved by the judicious use of aromatase inhibitors, even very late in follow-up,” study investigators reported online in the Journal of Clinical Oncology.

Until now providers, regulatory agencies, and health care funders have restricted the use of letrozole to women who were within 3 months of discontinuing tamoxifen, because the evidence supported its use only in these cases.

But many, if not most, breast cancer survivors have been off tamoxifen for more than 3 months. They have never been offered letrozole even though they might benefit from it, wrote Dr. Paul E. Goss of Massachusetts General Hospital Cancer Center, Boston, and his associates in the National Cancer Institute of Canada Clinical Trials Group MA.17 study.

Ideally, the question would be settled by a randomized clinical trial. Such a study is under consideration, but even if it proves feasible, the results will not be available for years. In the meantime, assessing outcomes in a subgroup of women in the NCIC MA.17 trial “provides a unique opportunity to determine whether a later intervention with the aromatase inhibitor” is beneficial. These findings “provide the only available information that can be used to inform the decision these women and their physicians face,” Dr. Goss and his associates said.

In the MA.17 trial, more than 5,000 postmenopausal women within 3 months of completing approximately 5 years of adjuvant tamoxifen therapy were randomly assigned to receive letrozole or placebo and were to be followed for another 5 years. But an interim analysis after a median of 2.4 years showed a distinct advantage with letrozole, so the trial was unblinded and the placebo group was offered letrozole for the remaining 2.6 years of the trial.

A total of 1,579 women switched to letrozole, and 804 elected no further treatment after unblinding. Of those who switched to letrozole, 31 (2%) developed recurrences, compared with 39 (5%) who did not take letrozole. The drug was associated with an adjusted hazard ratio of 0.37, corresponding to a 63% drop in disease recurrence (J. Clin. Oncol. 2008;26 [doi:10.1200/jco.2007.11.6798]).

Distant metastases occurred in 1% of women who switched to letrozole, compared with 2.4% of those who didn't take letrozole; a significant 61% reduction in the risk of developing distant metastases was reported. Similarly, mortality was lower with letrozole than without it (1.3% vs. 4.5%).

Interpreting these results is complicated by the fact that these study subjects self-selected for letrozole therapy or no further therapy. The patients who chose letrozole were at greater risk of recurrence because of tumor characteristics, however.

“The fact that women who would have been expected to have a higher rate of recurrence actually did better on letrozole strongly suggests that letrozole was responsible for the reduced frequency of breast cancer events in these patients,” Dr. Goss and his associates said.

Women who took letrozole were at increased risk of developing fractures or osteoporosis, known adverse effects of long-term exposure to letrozole. It is possible, however, that these complications could be prevented with bisphosphonates, vitamin D, and calcium replacement therapy, they added.

In addition to the National Cancer Institute of Canada's funding, this study was supported by the Pharmacia Corp, a Pfizer company, and Novartis Pharmaceuticals Canada Inc.

Use of the aromatase inhibitor letrozole was linked to a significant 63% reduction in disease recurrence in women with early-stage breast cancer who completed 5 years of tamoxifen therapy 1 to 7 years earlier, results of a phase III study suggest.

“It appears that most cancers remain estrogen dependent for long periods in follow-up and that their clinical courses can be improved by the judicious use of aromatase inhibitors, even very late in follow-up,” study investigators reported online in the Journal of Clinical Oncology.

Until now providers, regulatory agencies, and health care funders have restricted the use of letrozole to women who were within 3 months of discontinuing tamoxifen, because the evidence supported its use only in these cases.

But many, if not most, breast cancer survivors have been off tamoxifen for more than 3 months. They have never been offered letrozole even though they might benefit from it, wrote Dr. Paul E. Goss of Massachusetts General Hospital Cancer Center, Boston, and his associates in the National Cancer Institute of Canada Clinical Trials Group MA.17 study.

Ideally, the question would be settled by a randomized clinical trial. Such a study is under consideration, but even if it proves feasible, the results will not be available for years. In the meantime, assessing outcomes in a subgroup of women in the NCIC MA.17 trial “provides a unique opportunity to determine whether a later intervention with the aromatase inhibitor” is beneficial. These findings “provide the only available information that can be used to inform the decision these women and their physicians face,” Dr. Goss and his associates said.

In the MA.17 trial, more than 5,000 postmenopausal women within 3 months of completing approximately 5 years of adjuvant tamoxifen therapy were randomly assigned to receive letrozole or placebo and were to be followed for another 5 years. But an interim analysis after a median of 2.4 years showed a distinct advantage with letrozole, so the trial was unblinded and the placebo group was offered letrozole for the remaining 2.6 years of the trial.

A total of 1,579 women switched to letrozole, and 804 elected no further treatment after unblinding. Of those who switched to letrozole, 31 (2%) developed recurrences, compared with 39 (5%) who did not take letrozole. The drug was associated with an adjusted hazard ratio of 0.37, corresponding to a 63% drop in disease recurrence (J. Clin. Oncol. 2008;26 [doi:10.1200/jco.2007.11.6798]).

Distant metastases occurred in 1% of women who switched to letrozole, compared with 2.4% of those who didn't take letrozole; a significant 61% reduction in the risk of developing distant metastases was reported. Similarly, mortality was lower with letrozole than without it (1.3% vs. 4.5%).

Interpreting these results is complicated by the fact that these study subjects self-selected for letrozole therapy or no further therapy. The patients who chose letrozole were at greater risk of recurrence because of tumor characteristics, however.

“The fact that women who would have been expected to have a higher rate of recurrence actually did better on letrozole strongly suggests that letrozole was responsible for the reduced frequency of breast cancer events in these patients,” Dr. Goss and his associates said.

Women who took letrozole were at increased risk of developing fractures or osteoporosis, known adverse effects of long-term exposure to letrozole. It is possible, however, that these complications could be prevented with bisphosphonates, vitamin D, and calcium replacement therapy, they added.

In addition to the National Cancer Institute of Canada's funding, this study was supported by the Pharmacia Corp, a Pfizer company, and Novartis Pharmaceuticals Canada Inc.

Use of the aromatase inhibitor letrozole was linked to a significant 63% reduction in disease recurrence in women with early-stage breast cancer who completed 5 years of tamoxifen therapy 1 to 7 years earlier, results of a phase III study suggest.

“It appears that most cancers remain estrogen dependent for long periods in follow-up and that their clinical courses can be improved by the judicious use of aromatase inhibitors, even very late in follow-up,” study investigators reported online in the Journal of Clinical Oncology.

Until now providers, regulatory agencies, and health care funders have restricted the use of letrozole to women who were within 3 months of discontinuing tamoxifen, because the evidence supported its use only in these cases.

But many, if not most, breast cancer survivors have been off tamoxifen for more than 3 months. They have never been offered letrozole even though they might benefit from it, wrote Dr. Paul E. Goss of Massachusetts General Hospital Cancer Center, Boston, and his associates in the National Cancer Institute of Canada Clinical Trials Group MA.17 study.

Ideally, the question would be settled by a randomized clinical trial. Such a study is under consideration, but even if it proves feasible, the results will not be available for years. In the meantime, assessing outcomes in a subgroup of women in the NCIC MA.17 trial “provides a unique opportunity to determine whether a later intervention with the aromatase inhibitor” is beneficial. These findings “provide the only available information that can be used to inform the decision these women and their physicians face,” Dr. Goss and his associates said.

In the MA.17 trial, more than 5,000 postmenopausal women within 3 months of completing approximately 5 years of adjuvant tamoxifen therapy were randomly assigned to receive letrozole or placebo and were to be followed for another 5 years. But an interim analysis after a median of 2.4 years showed a distinct advantage with letrozole, so the trial was unblinded and the placebo group was offered letrozole for the remaining 2.6 years of the trial.

A total of 1,579 women switched to letrozole, and 804 elected no further treatment after unblinding. Of those who switched to letrozole, 31 (2%) developed recurrences, compared with 39 (5%) who did not take letrozole. The drug was associated with an adjusted hazard ratio of 0.37, corresponding to a 63% drop in disease recurrence (J. Clin. Oncol. 2008;26 [doi:10.1200/jco.2007.11.6798]).

Distant metastases occurred in 1% of women who switched to letrozole, compared with 2.4% of those who didn't take letrozole; a significant 61% reduction in the risk of developing distant metastases was reported. Similarly, mortality was lower with letrozole than without it (1.3% vs. 4.5%).

Interpreting these results is complicated by the fact that these study subjects self-selected for letrozole therapy or no further therapy. The patients who chose letrozole were at greater risk of recurrence because of tumor characteristics, however.

“The fact that women who would have been expected to have a higher rate of recurrence actually did better on letrozole strongly suggests that letrozole was responsible for the reduced frequency of breast cancer events in these patients,” Dr. Goss and his associates said.

Women who took letrozole were at increased risk of developing fractures or osteoporosis, known adverse effects of long-term exposure to letrozole. It is possible, however, that these complications could be prevented with bisphosphonates, vitamin D, and calcium replacement therapy, they added.

In addition to the National Cancer Institute of Canada's funding, this study was supported by the Pharmacia Corp, a Pfizer company, and Novartis Pharmaceuticals Canada Inc.

In the 3 years after the Women's Health Initiative clinical trial was halted early, risks and benefits related to hormone therapy changed rapidly in those who stopped taking the medication, according to WHI investigators.

Despite these alterations, the overall assessment of health risks and benefits associated with combined HT (conjugated equine estrogens plus medroxyprogesterone acetate) “continues to be weighted toward risk,” said Dr. Gerardo Heiss of the University of North Carolina, Chapel Hill, and his WHIassociates.

But representatives of Wyeth Pharmaceuticals, manufacturer of Prempro, the combination HT product used in the study, said during a company-sponsored teleconference that the study does not reflect the current, lower HT dosages doctors recommend for typical HT users, who are younger, newly menopausal women.

Dr. Gary Stiles, executive vice president and chief medical officer for Wyeth, said the findings were an “ad hoc analysis without providing the full context.” He noted that today's patients were “more than a decade” younger than the WHI participants, who had a mean age of 63 years at baseline. The company encourages doctors to provide lower dosages of HT drugs for the shortest time possible, he added.

The portion of the WHI trial that dealt with combined hormone therapy (HT) was stopped in 2002 at a mean of 5.6 years of follow-up because an interim analysis showed the therapy increased the risk of invasive breast cancer and failed to yield any overall health benefit. Analysis of the results accumulated to that date showed those who took HT (0.625 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate daily) for menopausal symptoms also had higher risks of cardiovascular disease, coronary heart disease, stroke, and venous thromboembolism, along with lower risks of fracture and of colorectal cancer, compared with those not on HT.

Most of the subjects were followed through the planned 8-year duration of the WHI. Results are now available on 15,730 of these women for a further 2.4 years of follow-up after discontinuation. (See box.)

The increased risk of cardiovascular disease-related events noted in the interim analysis did not persist after stopping HT, and the risk of deep vein thrombosis and pulmonary embolism also “disappeared.”

But the risk of all malignancies increased, probably due to a rise in the rate of cancers other than breast and colorectal, primarily lung cancers.

The increased risk of breast cancer noted at the interim analysis did not persist after discontinuing HT, but neither did the decreased risk of colorectal cancer.

HT's protective effect against fractures also dissipated after discontinuation. Women who had taken and then stopped HT showed the same risk of hip, vertebral, and other fractures as did those who had taken placebo.

During the intervention phase of the WHI, all-cause mortality was virtually identical between subjects taking HT and those taking placebo. But in the postintervention phase, mortality was 15% higher in women who had taken and then discontinued HT.

Although this difference did not reach statistical significance because of the small number of deaths, it suggests that all-cause mortality increased after HT, the researchers said (JAMA 2008;299:1036–45).

Associate editor Lorinda Bullock contributed to this article.

ELSEVIER GLOBAL MEDICAL NEWS

In the 3 years after the Women's Health Initiative clinical trial was halted early, risks and benefits related to hormone therapy changed rapidly in those who stopped taking the medication, according to WHI investigators.

Despite these alterations, the overall assessment of health risks and benefits associated with combined HT (conjugated equine estrogens plus medroxyprogesterone acetate) “continues to be weighted toward risk,” said Dr. Gerardo Heiss of the University of North Carolina, Chapel Hill, and his WHIassociates.

But representatives of Wyeth Pharmaceuticals, manufacturer of Prempro, the combination HT product used in the study, said during a company-sponsored teleconference that the study does not reflect the current, lower HT dosages doctors recommend for typical HT users, who are younger, newly menopausal women.

Dr. Gary Stiles, executive vice president and chief medical officer for Wyeth, said the findings were an “ad hoc analysis without providing the full context.” He noted that today's patients were “more than a decade” younger than the WHI participants, who had a mean age of 63 years at baseline. The company encourages doctors to provide lower dosages of HT drugs for the shortest time possible, he added.

The portion of the WHI trial that dealt with combined hormone therapy (HT) was stopped in 2002 at a mean of 5.6 years of follow-up because an interim analysis showed the therapy increased the risk of invasive breast cancer and failed to yield any overall health benefit. Analysis of the results accumulated to that date showed those who took HT (0.625 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate daily) for menopausal symptoms also had higher risks of cardiovascular disease, coronary heart disease, stroke, and venous thromboembolism, along with lower risks of fracture and of colorectal cancer, compared with those not on HT.

Most of the subjects were followed through the planned 8-year duration of the WHI. Results are now available on 15,730 of these women for a further 2.4 years of follow-up after discontinuation. (See box.)

The increased risk of cardiovascular disease-related events noted in the interim analysis did not persist after stopping HT, and the risk of deep vein thrombosis and pulmonary embolism also “disappeared.”

But the risk of all malignancies increased, probably due to a rise in the rate of cancers other than breast and colorectal, primarily lung cancers.

The increased risk of breast cancer noted at the interim analysis did not persist after discontinuing HT, but neither did the decreased risk of colorectal cancer.

HT's protective effect against fractures also dissipated after discontinuation. Women who had taken and then stopped HT showed the same risk of hip, vertebral, and other fractures as did those who had taken placebo.

During the intervention phase of the WHI, all-cause mortality was virtually identical between subjects taking HT and those taking placebo. But in the postintervention phase, mortality was 15% higher in women who had taken and then discontinued HT.

Although this difference did not reach statistical significance because of the small number of deaths, it suggests that all-cause mortality increased after HT, the researchers said (JAMA 2008;299:1036–45).

Associate editor Lorinda Bullock contributed to this article.

ELSEVIER GLOBAL MEDICAL NEWS

In the 3 years after the Women's Health Initiative clinical trial was halted early, risks and benefits related to hormone therapy changed rapidly in those who stopped taking the medication, according to WHI investigators.

Despite these alterations, the overall assessment of health risks and benefits associated with combined HT (conjugated equine estrogens plus medroxyprogesterone acetate) “continues to be weighted toward risk,” said Dr. Gerardo Heiss of the University of North Carolina, Chapel Hill, and his WHIassociates.

But representatives of Wyeth Pharmaceuticals, manufacturer of Prempro, the combination HT product used in the study, said during a company-sponsored teleconference that the study does not reflect the current, lower HT dosages doctors recommend for typical HT users, who are younger, newly menopausal women.

Dr. Gary Stiles, executive vice president and chief medical officer for Wyeth, said the findings were an “ad hoc analysis without providing the full context.” He noted that today's patients were “more than a decade” younger than the WHI participants, who had a mean age of 63 years at baseline. The company encourages doctors to provide lower dosages of HT drugs for the shortest time possible, he added.

The portion of the WHI trial that dealt with combined hormone therapy (HT) was stopped in 2002 at a mean of 5.6 years of follow-up because an interim analysis showed the therapy increased the risk of invasive breast cancer and failed to yield any overall health benefit. Analysis of the results accumulated to that date showed those who took HT (0.625 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate daily) for menopausal symptoms also had higher risks of cardiovascular disease, coronary heart disease, stroke, and venous thromboembolism, along with lower risks of fracture and of colorectal cancer, compared with those not on HT.

Most of the subjects were followed through the planned 8-year duration of the WHI. Results are now available on 15,730 of these women for a further 2.4 years of follow-up after discontinuation. (See box.)

The increased risk of cardiovascular disease-related events noted in the interim analysis did not persist after stopping HT, and the risk of deep vein thrombosis and pulmonary embolism also “disappeared.”

But the risk of all malignancies increased, probably due to a rise in the rate of cancers other than breast and colorectal, primarily lung cancers.

The increased risk of breast cancer noted at the interim analysis did not persist after discontinuing HT, but neither did the decreased risk of colorectal cancer.

HT's protective effect against fractures also dissipated after discontinuation. Women who had taken and then stopped HT showed the same risk of hip, vertebral, and other fractures as did those who had taken placebo.

During the intervention phase of the WHI, all-cause mortality was virtually identical between subjects taking HT and those taking placebo. But in the postintervention phase, mortality was 15% higher in women who had taken and then discontinued HT.

Although this difference did not reach statistical significance because of the small number of deaths, it suggests that all-cause mortality increased after HT, the researchers said (JAMA 2008;299:1036–45).

Associate editor Lorinda Bullock contributed to this article.

ELSEVIER GLOBAL MEDICAL NEWS

Adolescents with depression that fails to respond to a selective serotonin reuptake inhibitor show more improvement with a switch to cognitive-behavioral therapy and another medication regimen than with a switch to a medication regimen alone, according to a multicenter study.

The Treatment of SSRI-Resistant Depression in Adolescents trial, funded by the National Institute of Mental Health, is the first to evaluate teens with the chronic symptoms and significant suicidal ideation that are typically seen in community practice but are excluded from most studies.

The 334 study subjects had failed to respond to at least 8 weeks of an initial SSRI (40 mg of fluoxetine or the equivalent of another agent), wrote Dr. David Brent of the University of Pittsburgh and colleagues.

The average age of the subjects was 16 years, and 82% were white. Most had moderately severe symptoms, with a median duration of 17 months. About 59% showed clinically significant suicidal ideation, and half had at least one comorbid disorder.

The subjects were randomly assigned to receive a different SSRI alone, venlafaxine (Effexor) alone, a different SSRI plus cognitive-behavioral therapy (CBT), or venlafaxine plus CBT. The CBT focused on “cognitive restructuring and behavior activation, emotion regulation, social skills, and problem solving” and included parent-child sessions as well.

After 12 weeks, 55% of those receiving CBT showed an adequate clinical response, compared with 41% of those who had not received it. There were no significant differences in response between a second SSRI or venlafaxine, nor were there differences in responses to the various SSRIs used, the authors said (JAMA 2008;299:901–13).

“The slightly higher rate of cardiovascular effects associated with venlafaxine and the relatively modest treatment effects in adolescent depression … support the choice of another SSRI over venlafaxine as a second-line antidepressant,” they added.

A significant difference was found in the response to CBT according to which study site administered it, a finding that will be further explored in a future report. However, the overall positive effect of CBT was robust in sensitivity analyses, even after controlling for site factors. The study limitations include the absence of ethnic diversity in the patients. Dr. Brent reported no financial disclosures.

ELSEVIER GLOBAL MEDICAL NEWS

Adolescents with depression that fails to respond to a selective serotonin reuptake inhibitor show more improvement with a switch to cognitive-behavioral therapy and another medication regimen than with a switch to a medication regimen alone, according to a multicenter study.

The Treatment of SSRI-Resistant Depression in Adolescents trial, funded by the National Institute of Mental Health, is the first to evaluate teens with the chronic symptoms and significant suicidal ideation that are typically seen in community practice but are excluded from most studies.

The 334 study subjects had failed to respond to at least 8 weeks of an initial SSRI (40 mg of fluoxetine or the equivalent of another agent), wrote Dr. David Brent of the University of Pittsburgh and colleagues.

The average age of the subjects was 16 years, and 82% were white. Most had moderately severe symptoms, with a median duration of 17 months. About 59% showed clinically significant suicidal ideation, and half had at least one comorbid disorder.

The subjects were randomly assigned to receive a different SSRI alone, venlafaxine (Effexor) alone, a different SSRI plus cognitive-behavioral therapy (CBT), or venlafaxine plus CBT. The CBT focused on “cognitive restructuring and behavior activation, emotion regulation, social skills, and problem solving” and included parent-child sessions as well.

After 12 weeks, 55% of those receiving CBT showed an adequate clinical response, compared with 41% of those who had not received it. There were no significant differences in response between a second SSRI or venlafaxine, nor were there differences in responses to the various SSRIs used, the authors said (JAMA 2008;299:901–13).

“The slightly higher rate of cardiovascular effects associated with venlafaxine and the relatively modest treatment effects in adolescent depression … support the choice of another SSRI over venlafaxine as a second-line antidepressant,” they added.

A significant difference was found in the response to CBT according to which study site administered it, a finding that will be further explored in a future report. However, the overall positive effect of CBT was robust in sensitivity analyses, even after controlling for site factors. The study limitations include the absence of ethnic diversity in the patients. Dr. Brent reported no financial disclosures.

ELSEVIER GLOBAL MEDICAL NEWS

Adolescents with depression that fails to respond to a selective serotonin reuptake inhibitor show more improvement with a switch to cognitive-behavioral therapy and another medication regimen than with a switch to a medication regimen alone, according to a multicenter study.

The Treatment of SSRI-Resistant Depression in Adolescents trial, funded by the National Institute of Mental Health, is the first to evaluate teens with the chronic symptoms and significant suicidal ideation that are typically seen in community practice but are excluded from most studies.

The 334 study subjects had failed to respond to at least 8 weeks of an initial SSRI (40 mg of fluoxetine or the equivalent of another agent), wrote Dr. David Brent of the University of Pittsburgh and colleagues.

The average age of the subjects was 16 years, and 82% were white. Most had moderately severe symptoms, with a median duration of 17 months. About 59% showed clinically significant suicidal ideation, and half had at least one comorbid disorder.

The subjects were randomly assigned to receive a different SSRI alone, venlafaxine (Effexor) alone, a different SSRI plus cognitive-behavioral therapy (CBT), or venlafaxine plus CBT. The CBT focused on “cognitive restructuring and behavior activation, emotion regulation, social skills, and problem solving” and included parent-child sessions as well.

After 12 weeks, 55% of those receiving CBT showed an adequate clinical response, compared with 41% of those who had not received it. There were no significant differences in response between a second SSRI or venlafaxine, nor were there differences in responses to the various SSRIs used, the authors said (JAMA 2008;299:901–13).

“The slightly higher rate of cardiovascular effects associated with venlafaxine and the relatively modest treatment effects in adolescent depression … support the choice of another SSRI over venlafaxine as a second-line antidepressant,” they added.

A significant difference was found in the response to CBT according to which study site administered it, a finding that will be further explored in a future report. However, the overall positive effect of CBT was robust in sensitivity analyses, even after controlling for site factors. The study limitations include the absence of ethnic diversity in the patients. Dr. Brent reported no financial disclosures.

ELSEVIER GLOBAL MEDICAL NEWS

The burden of depression is disproportionately higher among older women than older men because of their greater susceptibility to depression and–once depressed–their greater tendency to have persistent depression and their lower probability of death, suggest the results of a longitudinal study.

Clinically significant depressive symptoms affect 8%–20% of community-dwelling older people, and previous research has failed to explain the underlying gender differences, study investigators wrote.

Lisa C. Barry, Ph.D., of Yale University, New Haven, Conn., and her associates assessed those differences in the onset and persistence of depression, as well as in overall mortality. They used data from a 1998 longitudinal study of 754 residents of New Haven aged 70 years and older at baseline. The subjects were followed using detailed in-home assessments every 18 months for up to 6 years (Arch. Gen. Psychiatry 2008;65:172–8).

At baseline, the subjects were a mean age of 78 years. Sixty-five percent of them were women, and 91% were non-Hispanic whites. On average, subjects had a high school education, had two chronic conditions, and were cognitively intact.

A total of 269 subjects (36%) had depressive symptoms at some time during the 6-year study. The prevalence of depressive symptoms was substantially higher among women than men at all time points.

Compared with men, women showed a higher rate of making the transition from nondepressed to depressed status over time. In addition, women showed a higher rate of remaining depressed over time, and a lower rate of making the transition to nondepressed status or to death over time, the investigators said.

“Of course, older men generally have higher mortality rates than older women, irrespective of depression. Nevertheless, the mortality difference we observed by sex was marked, with a nearly threefold difference in the odds ratios for participants who were depressed, compared with those who were not depressed,” the researchers said.

Previous studies may have been unable to detect these patterns because they did not account for fluctuations in depression over time. Rather, they usually included only a single follow-up assessment of depression after a comparatively short interval, Dr. Barry and her associates noted.

In contrast, “the consistency of our findings over four different time intervals provides strong evidence that depression is more likely to persist in older women than in men. [This] is somewhat surprising because women are more likely than men to receive pharmacologic and nonpharmacologic treatment for depression,” they said.

“Whether women are treated less aggressively than men for late-life depression or are less likely to respond to conventional treatment is not known, but should be the focus of future research,” the researchers said.

The investigators added that nearly 40% of the depressed subjects in this study showed symptoms during at least two (and often more) consecutive time points. This finding highlights “the need to initiate and potentially maintain antidepressant treatment after resolution of the initial depressive episode” in this patient population, Dr. Barry and her associates said.

They also pointed out that because African Americans have a higher prevalence of persistent depression than non-Hispanic whites, “future research should explore whether the relationship between sex and transitions across depression states is modified by race, using data that more closely reflect the racial composition” of older adults in the United States.

The study was supported by grants from the National Institute on Aging. The investigators reported no disclosures.

The burden of depression is disproportionately higher among older women than older men because of their greater susceptibility to depression and–once depressed–their greater tendency to have persistent depression and their lower probability of death, suggest the results of a longitudinal study.

Clinically significant depressive symptoms affect 8%–20% of community-dwelling older people, and previous research has failed to explain the underlying gender differences, study investigators wrote.

Lisa C. Barry, Ph.D., of Yale University, New Haven, Conn., and her associates assessed those differences in the onset and persistence of depression, as well as in overall mortality. They used data from a 1998 longitudinal study of 754 residents of New Haven aged 70 years and older at baseline. The subjects were followed using detailed in-home assessments every 18 months for up to 6 years (Arch. Gen. Psychiatry 2008;65:172–8).

At baseline, the subjects were a mean age of 78 years. Sixty-five percent of them were women, and 91% were non-Hispanic whites. On average, subjects had a high school education, had two chronic conditions, and were cognitively intact.

A total of 269 subjects (36%) had depressive symptoms at some time during the 6-year study. The prevalence of depressive symptoms was substantially higher among women than men at all time points.

Compared with men, women showed a higher rate of making the transition from nondepressed to depressed status over time. In addition, women showed a higher rate of remaining depressed over time, and a lower rate of making the transition to nondepressed status or to death over time, the investigators said.

“Of course, older men generally have higher mortality rates than older women, irrespective of depression. Nevertheless, the mortality difference we observed by sex was marked, with a nearly threefold difference in the odds ratios for participants who were depressed, compared with those who were not depressed,” the researchers said.

Previous studies may have been unable to detect these patterns because they did not account for fluctuations in depression over time. Rather, they usually included only a single follow-up assessment of depression after a comparatively short interval, Dr. Barry and her associates noted.

In contrast, “the consistency of our findings over four different time intervals provides strong evidence that depression is more likely to persist in older women than in men. [This] is somewhat surprising because women are more likely than men to receive pharmacologic and nonpharmacologic treatment for depression,” they said.

“Whether women are treated less aggressively than men for late-life depression or are less likely to respond to conventional treatment is not known, but should be the focus of future research,” the researchers said.

The investigators added that nearly 40% of the depressed subjects in this study showed symptoms during at least two (and often more) consecutive time points. This finding highlights “the need to initiate and potentially maintain antidepressant treatment after resolution of the initial depressive episode” in this patient population, Dr. Barry and her associates said.

They also pointed out that because African Americans have a higher prevalence of persistent depression than non-Hispanic whites, “future research should explore whether the relationship between sex and transitions across depression states is modified by race, using data that more closely reflect the racial composition” of older adults in the United States.

The study was supported by grants from the National Institute on Aging. The investigators reported no disclosures.

The burden of depression is disproportionately higher among older women than older men because of their greater susceptibility to depression and–once depressed–their greater tendency to have persistent depression and their lower probability of death, suggest the results of a longitudinal study.

Clinically significant depressive symptoms affect 8%–20% of community-dwelling older people, and previous research has failed to explain the underlying gender differences, study investigators wrote.

Lisa C. Barry, Ph.D., of Yale University, New Haven, Conn., and her associates assessed those differences in the onset and persistence of depression, as well as in overall mortality. They used data from a 1998 longitudinal study of 754 residents of New Haven aged 70 years and older at baseline. The subjects were followed using detailed in-home assessments every 18 months for up to 6 years (Arch. Gen. Psychiatry 2008;65:172–8).

At baseline, the subjects were a mean age of 78 years. Sixty-five percent of them were women, and 91% were non-Hispanic whites. On average, subjects had a high school education, had two chronic conditions, and were cognitively intact.

A total of 269 subjects (36%) had depressive symptoms at some time during the 6-year study. The prevalence of depressive symptoms was substantially higher among women than men at all time points.

Compared with men, women showed a higher rate of making the transition from nondepressed to depressed status over time. In addition, women showed a higher rate of remaining depressed over time, and a lower rate of making the transition to nondepressed status or to death over time, the investigators said.

“Of course, older men generally have higher mortality rates than older women, irrespective of depression. Nevertheless, the mortality difference we observed by sex was marked, with a nearly threefold difference in the odds ratios for participants who were depressed, compared with those who were not depressed,” the researchers said.

Previous studies may have been unable to detect these patterns because they did not account for fluctuations in depression over time. Rather, they usually included only a single follow-up assessment of depression after a comparatively short interval, Dr. Barry and her associates noted.

In contrast, “the consistency of our findings over four different time intervals provides strong evidence that depression is more likely to persist in older women than in men. [This] is somewhat surprising because women are more likely than men to receive pharmacologic and nonpharmacologic treatment for depression,” they said.

“Whether women are treated less aggressively than men for late-life depression or are less likely to respond to conventional treatment is not known, but should be the focus of future research,” the researchers said.

The investigators added that nearly 40% of the depressed subjects in this study showed symptoms during at least two (and often more) consecutive time points. This finding highlights “the need to initiate and potentially maintain antidepressant treatment after resolution of the initial depressive episode” in this patient population, Dr. Barry and her associates said.

They also pointed out that because African Americans have a higher prevalence of persistent depression than non-Hispanic whites, “future research should explore whether the relationship between sex and transitions across depression states is modified by race, using data that more closely reflect the racial composition” of older adults in the United States.

The study was supported by grants from the National Institute on Aging. The investigators reported no disclosures.

A prolonged QRS duration predicts high mortality and morbidity after discharge in patients hospitalized for heart failure who also have reduced left ventricular ejection fraction, according to an analysis of the EVEREST trial.

“This high morbidity and mortality was observed even though patients were well treated with standard medical therapy that included β-blockers and ACE inhibitors or angiotensin receptor blockers,” said Dr. Norman C. Wang of Northwestern University, Chicago, and his associates.

Measuring QRS duration on ECG is “relatively inexpensive, simple to perform, and yields an instant result,” the investigators noted.

The EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) investigators reported their main conclusions last year. They now report the results of a retrospective, post hoc analysis of data on a subset of 2,962 subjects hospitalized for heart failure at more than 350 medical centers around the world and followed for a median of 10 months. This study was supported by Otsuka Pharmaceutical Group.

Patients underwent ECG evaluation at admission and at several intervals during hospitalization. About 45% of the patients had a prolonged QRS (duration of 120 milliseconds or more).

A prolonged QRS on admission was associated with a significantly increased risk of death within 3 months (12% incidence) and at the end of follow-up (28% incidence), compared with a normal QRS on admission (7% and 19%, respectively). This represents a 24% increased risk of death with a prolonged QRS duration.

Similarly, the composite end point of cardiovascular death or rehospitalization for heart failure was significantly more common in patients with a prolonged QRS on admission, Dr. Wang and his associates said (JAMA 2008;299:2656–66).

Also, if a prolonged QRS developed during hospitalization, it was associated with increased event rates after discharge.

However, “one must be cautious in attributing mechanistic significance to the QRS widening itself” as study patients with a wide QRS consistently had a higher prevalence of many known risk factors, including older age, lower ejection fraction, faster heart rate, and higher serum blood urea nitrogen, creatinine, and brain natriuretic peptide levels, Dr. Barrie Massie said in an interview. “Importantly, they were less often treated with β-blockers and much more frequently receiving amiodarone,” added Dr. Massie, professor of medicine at the University of California, San Francisco, and chief of cardiology at the San Francisco VA Medical Center.

Most patients who died during follow-up succumbed to progressive heart failure or sudden cardiac death, Dr. Wang reported.

A prolonged QRS duration predicts high mortality and morbidity after discharge in patients hospitalized for heart failure who also have reduced left ventricular ejection fraction, according to an analysis of the EVEREST trial.

“This high morbidity and mortality was observed even though patients were well treated with standard medical therapy that included β-blockers and ACE inhibitors or angiotensin receptor blockers,” said Dr. Norman C. Wang of Northwestern University, Chicago, and his associates.

Measuring QRS duration on ECG is “relatively inexpensive, simple to perform, and yields an instant result,” the investigators noted.

The EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) investigators reported their main conclusions last year. They now report the results of a retrospective, post hoc analysis of data on a subset of 2,962 subjects hospitalized for heart failure at more than 350 medical centers around the world and followed for a median of 10 months. This study was supported by Otsuka Pharmaceutical Group.

Patients underwent ECG evaluation at admission and at several intervals during hospitalization. About 45% of the patients had a prolonged QRS (duration of 120 milliseconds or more).

A prolonged QRS on admission was associated with a significantly increased risk of death within 3 months (12% incidence) and at the end of follow-up (28% incidence), compared with a normal QRS on admission (7% and 19%, respectively). This represents a 24% increased risk of death with a prolonged QRS duration.

Similarly, the composite end point of cardiovascular death or rehospitalization for heart failure was significantly more common in patients with a prolonged QRS on admission, Dr. Wang and his associates said (JAMA 2008;299:2656–66).

Also, if a prolonged QRS developed during hospitalization, it was associated with increased event rates after discharge.

However, “one must be cautious in attributing mechanistic significance to the QRS widening itself” as study patients with a wide QRS consistently had a higher prevalence of many known risk factors, including older age, lower ejection fraction, faster heart rate, and higher serum blood urea nitrogen, creatinine, and brain natriuretic peptide levels, Dr. Barrie Massie said in an interview. “Importantly, they were less often treated with β-blockers and much more frequently receiving amiodarone,” added Dr. Massie, professor of medicine at the University of California, San Francisco, and chief of cardiology at the San Francisco VA Medical Center.

Most patients who died during follow-up succumbed to progressive heart failure or sudden cardiac death, Dr. Wang reported.

A prolonged QRS duration predicts high mortality and morbidity after discharge in patients hospitalized for heart failure who also have reduced left ventricular ejection fraction, according to an analysis of the EVEREST trial.

“This high morbidity and mortality was observed even though patients were well treated with standard medical therapy that included β-blockers and ACE inhibitors or angiotensin receptor blockers,” said Dr. Norman C. Wang of Northwestern University, Chicago, and his associates.

Measuring QRS duration on ECG is “relatively inexpensive, simple to perform, and yields an instant result,” the investigators noted.

The EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) investigators reported their main conclusions last year. They now report the results of a retrospective, post hoc analysis of data on a subset of 2,962 subjects hospitalized for heart failure at more than 350 medical centers around the world and followed for a median of 10 months. This study was supported by Otsuka Pharmaceutical Group.

Patients underwent ECG evaluation at admission and at several intervals during hospitalization. About 45% of the patients had a prolonged QRS (duration of 120 milliseconds or more).

A prolonged QRS on admission was associated with a significantly increased risk of death within 3 months (12% incidence) and at the end of follow-up (28% incidence), compared with a normal QRS on admission (7% and 19%, respectively). This represents a 24% increased risk of death with a prolonged QRS duration.

Similarly, the composite end point of cardiovascular death or rehospitalization for heart failure was significantly more common in patients with a prolonged QRS on admission, Dr. Wang and his associates said (JAMA 2008;299:2656–66).

Also, if a prolonged QRS developed during hospitalization, it was associated with increased event rates after discharge.

However, “one must be cautious in attributing mechanistic significance to the QRS widening itself” as study patients with a wide QRS consistently had a higher prevalence of many known risk factors, including older age, lower ejection fraction, faster heart rate, and higher serum blood urea nitrogen, creatinine, and brain natriuretic peptide levels, Dr. Barrie Massie said in an interview. “Importantly, they were less often treated with β-blockers and much more frequently receiving amiodarone,” added Dr. Massie, professor of medicine at the University of California, San Francisco, and chief of cardiology at the San Francisco VA Medical Center.

Most patients who died during follow-up succumbed to progressive heart failure or sudden cardiac death, Dr. Wang reported.

Patients with HIV who do not carry the HLA-B*5701 allele are at very low risk for a hypersensitivity reaction to the antiviral drug abacavir, researchers reported.

For that reason, a pharmacogenetic test—screening for the HLA-B*5701 variant—now can be used to prevent a specific toxic effect of a drug, according to Dr. Simon Mallal of Royal Perth (Australia) Hospital and his associates.

The investigators conducted the Prospective Randomised Evaluation of DNA Screening in a Clinical Trial (PREDICT-1) in 1,956 adults with HIV who were treated at 265 medical centers in 19 countries. A total of 847 patients who served as the control group began usual treatment with abacavir without HLA-B*5701 screening. Participants' mean age was 42 years, with a range of 18–76 years.

Another 803 patients first underwent HLA-B*5701 screening, and those who were found to carry the variant were excluded from abacavir therapy. Their mean age was 42 years, with a range of 18–77 years. The remaining HLA-B*5701-negative patients received abacavir. Both groups were observed over 6 weeks for hypersensitivity reactions.

No hypersensitivity reactions developed in patients who were not carriers of HLA-B*5701. In the control group, approximately half of the patients later found to be HLA-B*5701 carriers had a hypersensitivity reaction to the drug.

The HLA-B*5701 allele had a negative predictive value of 100% and a positive predictive value of 48%, Dr. Mallal and his associates said (N. Engl. J. Med. 2008;358:568–79).

“HLA-B*5701 carriage clearly demarcated a high-risk group of patients, accounting for approximately 6% of the population, from the remaining 94% who were at low risk for a hypersensitivity reaction to abacavir,” they said.

The study was supported by GlaxoSmithKline, and several of the investigators disclosed relationships with the company. Dr. Mallal disclosed that he is the sole shareholder for a company that has a patent pending for HLA-B*5701 testing.

Patients with HIV who do not carry the HLA-B*5701 allele are at very low risk for a hypersensitivity reaction to the antiviral drug abacavir, researchers reported.

For that reason, a pharmacogenetic test—screening for the HLA-B*5701 variant—now can be used to prevent a specific toxic effect of a drug, according to Dr. Simon Mallal of Royal Perth (Australia) Hospital and his associates.

The investigators conducted the Prospective Randomised Evaluation of DNA Screening in a Clinical Trial (PREDICT-1) in 1,956 adults with HIV who were treated at 265 medical centers in 19 countries. A total of 847 patients who served as the control group began usual treatment with abacavir without HLA-B*5701 screening. Participants' mean age was 42 years, with a range of 18–76 years.

Another 803 patients first underwent HLA-B*5701 screening, and those who were found to carry the variant were excluded from abacavir therapy. Their mean age was 42 years, with a range of 18–77 years. The remaining HLA-B*5701-negative patients received abacavir. Both groups were observed over 6 weeks for hypersensitivity reactions.

No hypersensitivity reactions developed in patients who were not carriers of HLA-B*5701. In the control group, approximately half of the patients later found to be HLA-B*5701 carriers had a hypersensitivity reaction to the drug.

The HLA-B*5701 allele had a negative predictive value of 100% and a positive predictive value of 48%, Dr. Mallal and his associates said (N. Engl. J. Med. 2008;358:568–79).

“HLA-B*5701 carriage clearly demarcated a high-risk group of patients, accounting for approximately 6% of the population, from the remaining 94% who were at low risk for a hypersensitivity reaction to abacavir,” they said.

The study was supported by GlaxoSmithKline, and several of the investigators disclosed relationships with the company. Dr. Mallal disclosed that he is the sole shareholder for a company that has a patent pending for HLA-B*5701 testing.

Patients with HIV who do not carry the HLA-B*5701 allele are at very low risk for a hypersensitivity reaction to the antiviral drug abacavir, researchers reported.

For that reason, a pharmacogenetic test—screening for the HLA-B*5701 variant—now can be used to prevent a specific toxic effect of a drug, according to Dr. Simon Mallal of Royal Perth (Australia) Hospital and his associates.

The investigators conducted the Prospective Randomised Evaluation of DNA Screening in a Clinical Trial (PREDICT-1) in 1,956 adults with HIV who were treated at 265 medical centers in 19 countries. A total of 847 patients who served as the control group began usual treatment with abacavir without HLA-B*5701 screening. Participants' mean age was 42 years, with a range of 18–76 years.

Another 803 patients first underwent HLA-B*5701 screening, and those who were found to carry the variant were excluded from abacavir therapy. Their mean age was 42 years, with a range of 18–77 years. The remaining HLA-B*5701-negative patients received abacavir. Both groups were observed over 6 weeks for hypersensitivity reactions.

No hypersensitivity reactions developed in patients who were not carriers of HLA-B*5701. In the control group, approximately half of the patients later found to be HLA-B*5701 carriers had a hypersensitivity reaction to the drug.

The HLA-B*5701 allele had a negative predictive value of 100% and a positive predictive value of 48%, Dr. Mallal and his associates said (N. Engl. J. Med. 2008;358:568–79).

“HLA-B*5701 carriage clearly demarcated a high-risk group of patients, accounting for approximately 6% of the population, from the remaining 94% who were at low risk for a hypersensitivity reaction to abacavir,” they said.

The study was supported by GlaxoSmithKline, and several of the investigators disclosed relationships with the company. Dr. Mallal disclosed that he is the sole shareholder for a company that has a patent pending for HLA-B*5701 testing.