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Risks scream caution for catheter-directed thrombolysis for proximal DVT
Catheter-directed thrombolysis plus anticoagulation is no more effective than anticoagulation alone in preventing in-hospital death among adults who have lower-extremity proximal deep vein thrombosis, according to a nationwide observational study reported online July 21 in JAMA Internal Medicine.
However, catheter-directed thrombolysis carries higher risks, particularly serious bleeding risks such as intracranial hemorrhage, than does anticoagulation alone, and it costs nearly three times as much money. These findings highlight the need for randomized trials "to evaluate the magnitude of the effect of catheter-directed thrombolysis on ... mortality, postthrombotic syndrome, and recurrence of DVT [deep vein thrombosis]. In the absence of such data, it may be reasonable to restrict this form of therapy to those patients who have a low bleeding risk and a high risk for postthrombotic syndrome, such as patients with iliofemoral DVT," said Dr. Riyaz Bashir of the division of cardiovascular diseases, Temple University, Philadelphia, and his associates.
Conflicting data from several small studies as to the safety and effectiveness of catheter-directed thrombolysis have led professional societies to devise conflicting recommendations for its use: the American College of Chest Physicians advises against using the procedure, while the American Heart Association recommends it as a first-line therapy for certain patients. "We sought to assess real-world comparative-safety outcomes in patients proximal and caval DVT who underwent catheter-directed thrombolysis plus anticoagulation with a group treated with anticoagulation alone using risk-adjusted propensity-score matching," the investigators said.
They analyzed data from an Agency for Healthcare Research and Quality administrative database of patient discharges from approximately 1,000 nonfederal acute-care hospitals per year for a 6-year period. They identified 90,618 patients with a discharge diagnosis of proximal DVT; propensity-score matching yielded 3,594 well-matched patients in each study group. In-hospital mortality was not significantly different between patients who had catheter-directed thrombolysis plus anticoagulation (1.2%) and those who had anticoagulation alone (0.9%), Dr. Bashir and his associates wrote (JAMA Intern. Med. 2014 July 21 [doi:10.1001/jamainternmed.2014.3415]).
However, rates of blood transfusion (11.1% vs. 6.5%), pulmonary embolism (17.9% vs 11.4%), and intracranial hemorrhage (0.9% vs 0.3%) were significantly higher with the invasive intervention. And patients in the catheter-directed thrombolysis group required significantly longer hospitalizations (7.2 vs. 5.0 days) and incurred significantly higher hospital expenses ($85,094 vs. $28,164). "It is imperative that the magnitude of benefit from catheter-directed therapy be substantial to justify the increased initial resource utilization and bleeding risks of this therapy," the investigators noted.
Catheter-directed thrombolysis plus anticoagulation is no more effective than anticoagulation alone in preventing in-hospital death among adults who have lower-extremity proximal deep vein thrombosis, according to a nationwide observational study reported online July 21 in JAMA Internal Medicine.
However, catheter-directed thrombolysis carries higher risks, particularly serious bleeding risks such as intracranial hemorrhage, than does anticoagulation alone, and it costs nearly three times as much money. These findings highlight the need for randomized trials "to evaluate the magnitude of the effect of catheter-directed thrombolysis on ... mortality, postthrombotic syndrome, and recurrence of DVT [deep vein thrombosis]. In the absence of such data, it may be reasonable to restrict this form of therapy to those patients who have a low bleeding risk and a high risk for postthrombotic syndrome, such as patients with iliofemoral DVT," said Dr. Riyaz Bashir of the division of cardiovascular diseases, Temple University, Philadelphia, and his associates.
Conflicting data from several small studies as to the safety and effectiveness of catheter-directed thrombolysis have led professional societies to devise conflicting recommendations for its use: the American College of Chest Physicians advises against using the procedure, while the American Heart Association recommends it as a first-line therapy for certain patients. "We sought to assess real-world comparative-safety outcomes in patients proximal and caval DVT who underwent catheter-directed thrombolysis plus anticoagulation with a group treated with anticoagulation alone using risk-adjusted propensity-score matching," the investigators said.
They analyzed data from an Agency for Healthcare Research and Quality administrative database of patient discharges from approximately 1,000 nonfederal acute-care hospitals per year for a 6-year period. They identified 90,618 patients with a discharge diagnosis of proximal DVT; propensity-score matching yielded 3,594 well-matched patients in each study group. In-hospital mortality was not significantly different between patients who had catheter-directed thrombolysis plus anticoagulation (1.2%) and those who had anticoagulation alone (0.9%), Dr. Bashir and his associates wrote (JAMA Intern. Med. 2014 July 21 [doi:10.1001/jamainternmed.2014.3415]).
However, rates of blood transfusion (11.1% vs. 6.5%), pulmonary embolism (17.9% vs 11.4%), and intracranial hemorrhage (0.9% vs 0.3%) were significantly higher with the invasive intervention. And patients in the catheter-directed thrombolysis group required significantly longer hospitalizations (7.2 vs. 5.0 days) and incurred significantly higher hospital expenses ($85,094 vs. $28,164). "It is imperative that the magnitude of benefit from catheter-directed therapy be substantial to justify the increased initial resource utilization and bleeding risks of this therapy," the investigators noted.
Catheter-directed thrombolysis plus anticoagulation is no more effective than anticoagulation alone in preventing in-hospital death among adults who have lower-extremity proximal deep vein thrombosis, according to a nationwide observational study reported online July 21 in JAMA Internal Medicine.
However, catheter-directed thrombolysis carries higher risks, particularly serious bleeding risks such as intracranial hemorrhage, than does anticoagulation alone, and it costs nearly three times as much money. These findings highlight the need for randomized trials "to evaluate the magnitude of the effect of catheter-directed thrombolysis on ... mortality, postthrombotic syndrome, and recurrence of DVT [deep vein thrombosis]. In the absence of such data, it may be reasonable to restrict this form of therapy to those patients who have a low bleeding risk and a high risk for postthrombotic syndrome, such as patients with iliofemoral DVT," said Dr. Riyaz Bashir of the division of cardiovascular diseases, Temple University, Philadelphia, and his associates.
Conflicting data from several small studies as to the safety and effectiveness of catheter-directed thrombolysis have led professional societies to devise conflicting recommendations for its use: the American College of Chest Physicians advises against using the procedure, while the American Heart Association recommends it as a first-line therapy for certain patients. "We sought to assess real-world comparative-safety outcomes in patients proximal and caval DVT who underwent catheter-directed thrombolysis plus anticoagulation with a group treated with anticoagulation alone using risk-adjusted propensity-score matching," the investigators said.
They analyzed data from an Agency for Healthcare Research and Quality administrative database of patient discharges from approximately 1,000 nonfederal acute-care hospitals per year for a 6-year period. They identified 90,618 patients with a discharge diagnosis of proximal DVT; propensity-score matching yielded 3,594 well-matched patients in each study group. In-hospital mortality was not significantly different between patients who had catheter-directed thrombolysis plus anticoagulation (1.2%) and those who had anticoagulation alone (0.9%), Dr. Bashir and his associates wrote (JAMA Intern. Med. 2014 July 21 [doi:10.1001/jamainternmed.2014.3415]).
However, rates of blood transfusion (11.1% vs. 6.5%), pulmonary embolism (17.9% vs 11.4%), and intracranial hemorrhage (0.9% vs 0.3%) were significantly higher with the invasive intervention. And patients in the catheter-directed thrombolysis group required significantly longer hospitalizations (7.2 vs. 5.0 days) and incurred significantly higher hospital expenses ($85,094 vs. $28,164). "It is imperative that the magnitude of benefit from catheter-directed therapy be substantial to justify the increased initial resource utilization and bleeding risks of this therapy," the investigators noted.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Catheter-directed thrombolysis carries higher risks and may not improve outcomes for proximal DVT patients.
Major finding: In-hospital mortality was not significantly different between patients who had catheter-directed thrombolysis plus anticoagulation (1.2%) and those who had anticoagulation alone (0.9%), but rates of blood transfusion (11.1% vs 6.5%), pulmonary embolism (17.9% vs 11.4%), and intracranial hemorrhage (0.9% vs 0.3%) were significantly higher with the invasive intervention.
Data source: A propensity-matched analysis comparing the effectiveness and safety profiles between catheter-directed thrombolysis plus anticoagulation and anticoagulation alone in 3,594 adults across the country hospitalized with lower-extremity proximal DVT during a 6-year period.
Disclosures: This study was supported by Temple University Hospital, Philadelphia. Dr. Bashir reported no financial conflicts of interest; his associates reported ties to Covidien, Health Systems Networks, and Insight Telehealth.
Risks scream caution for catheter-directed thrombolysis for proximal DVT
Catheter-directed thrombolysis plus anticoagulation is no more effective than anticoagulation alone in preventing in-hospital death among adults who have lower-extremity proximal deep vein thrombosis, according to a nationwide observational study reported online July 21 in JAMA Internal Medicine.
However, catheter-directed thrombolysis carries higher risks, particularly serious bleeding risks such as intracranial hemorrhage, than does anticoagulation alone, and it costs nearly three times as much money. These findings highlight the need for randomized trials "to evaluate the magnitude of the effect of catheter-directed thrombolysis on ... mortality, postthrombotic syndrome, and recurrence of DVT [deep vein thrombosis]. In the absence of such data, it may be reasonable to restrict this form of therapy to those patients who have a low bleeding risk and a high risk for postthrombotic syndrome, such as patients with iliofemoral DVT," said Dr. Riyaz Bashir of the division of cardiovascular diseases, Temple University, Philadelphia, and his associates.
Conflicting data from several small studies as to the safety and effectiveness of catheter-directed thrombolysis have led professional societies to devise conflicting recommendations for its use: the American College of Chest Physicians advises against using the procedure, while the American Heart Association recommends it as a first-line therapy for certain patients. "We sought to assess real-world comparative-safety outcomes in patients proximal and caval DVT who underwent catheter-directed thrombolysis plus anticoagulation with a group treated with anticoagulation alone using risk-adjusted propensity-score matching," the investigators said.
They analyzed data from an Agency for Healthcare Research and Quality administrative database of patient discharges from approximately 1,000 nonfederal acute-care hospitals per year for a 6-year period. They identified 90,618 patients with a discharge diagnosis of proximal DVT; propensity-score matching yielded 3,594 well-matched patients in each study group. In-hospital mortality was not significantly different between patients who had catheter-directed thrombolysis plus anticoagulation (1.2%) and those who had anticoagulation alone (0.9%), Dr. Bashir and his associates wrote (JAMA Intern. Med. 2014 July 21 [doi:10.1001/jamainternmed.2014.3415]).
However, rates of blood transfusion (11.1% vs. 6.5%), pulmonary embolism (17.9% vs 11.4%), and intracranial hemorrhage (0.9% vs 0.3%) were significantly higher with the invasive intervention. And patients in the catheter-directed thrombolysis group required significantly longer hospitalizations (7.2 vs. 5.0 days) and incurred significantly higher hospital expenses ($85,094 vs. $28,164). "It is imperative that the magnitude of benefit from catheter-directed therapy be substantial to justify the increased initial resource utilization and bleeding risks of this therapy," the investigators noted.
Catheter-directed thrombolysis plus anticoagulation is no more effective than anticoagulation alone in preventing in-hospital death among adults who have lower-extremity proximal deep vein thrombosis, according to a nationwide observational study reported online July 21 in JAMA Internal Medicine.
However, catheter-directed thrombolysis carries higher risks, particularly serious bleeding risks such as intracranial hemorrhage, than does anticoagulation alone, and it costs nearly three times as much money. These findings highlight the need for randomized trials "to evaluate the magnitude of the effect of catheter-directed thrombolysis on ... mortality, postthrombotic syndrome, and recurrence of DVT [deep vein thrombosis]. In the absence of such data, it may be reasonable to restrict this form of therapy to those patients who have a low bleeding risk and a high risk for postthrombotic syndrome, such as patients with iliofemoral DVT," said Dr. Riyaz Bashir of the division of cardiovascular diseases, Temple University, Philadelphia, and his associates.
Conflicting data from several small studies as to the safety and effectiveness of catheter-directed thrombolysis have led professional societies to devise conflicting recommendations for its use: the American College of Chest Physicians advises against using the procedure, while the American Heart Association recommends it as a first-line therapy for certain patients. "We sought to assess real-world comparative-safety outcomes in patients proximal and caval DVT who underwent catheter-directed thrombolysis plus anticoagulation with a group treated with anticoagulation alone using risk-adjusted propensity-score matching," the investigators said.
They analyzed data from an Agency for Healthcare Research and Quality administrative database of patient discharges from approximately 1,000 nonfederal acute-care hospitals per year for a 6-year period. They identified 90,618 patients with a discharge diagnosis of proximal DVT; propensity-score matching yielded 3,594 well-matched patients in each study group. In-hospital mortality was not significantly different between patients who had catheter-directed thrombolysis plus anticoagulation (1.2%) and those who had anticoagulation alone (0.9%), Dr. Bashir and his associates wrote (JAMA Intern. Med. 2014 July 21 [doi:10.1001/jamainternmed.2014.3415]).
However, rates of blood transfusion (11.1% vs. 6.5%), pulmonary embolism (17.9% vs 11.4%), and intracranial hemorrhage (0.9% vs 0.3%) were significantly higher with the invasive intervention. And patients in the catheter-directed thrombolysis group required significantly longer hospitalizations (7.2 vs. 5.0 days) and incurred significantly higher hospital expenses ($85,094 vs. $28,164). "It is imperative that the magnitude of benefit from catheter-directed therapy be substantial to justify the increased initial resource utilization and bleeding risks of this therapy," the investigators noted.
Catheter-directed thrombolysis plus anticoagulation is no more effective than anticoagulation alone in preventing in-hospital death among adults who have lower-extremity proximal deep vein thrombosis, according to a nationwide observational study reported online July 21 in JAMA Internal Medicine.
However, catheter-directed thrombolysis carries higher risks, particularly serious bleeding risks such as intracranial hemorrhage, than does anticoagulation alone, and it costs nearly three times as much money. These findings highlight the need for randomized trials "to evaluate the magnitude of the effect of catheter-directed thrombolysis on ... mortality, postthrombotic syndrome, and recurrence of DVT [deep vein thrombosis]. In the absence of such data, it may be reasonable to restrict this form of therapy to those patients who have a low bleeding risk and a high risk for postthrombotic syndrome, such as patients with iliofemoral DVT," said Dr. Riyaz Bashir of the division of cardiovascular diseases, Temple University, Philadelphia, and his associates.
Conflicting data from several small studies as to the safety and effectiveness of catheter-directed thrombolysis have led professional societies to devise conflicting recommendations for its use: the American College of Chest Physicians advises against using the procedure, while the American Heart Association recommends it as a first-line therapy for certain patients. "We sought to assess real-world comparative-safety outcomes in patients proximal and caval DVT who underwent catheter-directed thrombolysis plus anticoagulation with a group treated with anticoagulation alone using risk-adjusted propensity-score matching," the investigators said.
They analyzed data from an Agency for Healthcare Research and Quality administrative database of patient discharges from approximately 1,000 nonfederal acute-care hospitals per year for a 6-year period. They identified 90,618 patients with a discharge diagnosis of proximal DVT; propensity-score matching yielded 3,594 well-matched patients in each study group. In-hospital mortality was not significantly different between patients who had catheter-directed thrombolysis plus anticoagulation (1.2%) and those who had anticoagulation alone (0.9%), Dr. Bashir and his associates wrote (JAMA Intern. Med. 2014 July 21 [doi:10.1001/jamainternmed.2014.3415]).
However, rates of blood transfusion (11.1% vs. 6.5%), pulmonary embolism (17.9% vs 11.4%), and intracranial hemorrhage (0.9% vs 0.3%) were significantly higher with the invasive intervention. And patients in the catheter-directed thrombolysis group required significantly longer hospitalizations (7.2 vs. 5.0 days) and incurred significantly higher hospital expenses ($85,094 vs. $28,164). "It is imperative that the magnitude of benefit from catheter-directed therapy be substantial to justify the increased initial resource utilization and bleeding risks of this therapy," the investigators noted.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Catheter-directed thrombolysis carries higher risks and may not improve outcomes for proximal DVT patients.
Major finding: In-hospital mortality was not significantly different between patients who had catheter-directed thrombolysis plus anticoagulation (1.2%) and those who had anticoagulation alone (0.9%), but rates of blood transfusion (11.1% vs 6.5%), pulmonary embolism (17.9% vs 11.4%), and intracranial hemorrhage (0.9% vs 0.3%) were significantly higher with the invasive intervention.
Data source: A propensity-matched analysis comparing the effectiveness and safety profiles between catheter-directed thrombolysis plus anticoagulation and anticoagulation alone in 3,594 adults across the country hospitalized with lower-extremity proximal DVT during a 6-year period.
Disclosures: This study was supported by Temple University Hospital, Philadelphia. Dr. Bashir reported no financial conflicts of interest; his associates reported ties to Covidien, Health Systems Networks, and Insight Telehealth.
Serum albumin, creatinine predicted survival in ALS
Serum levels of both albumin and creatinine proved to be independent biomarkers of disease severity in men and women with amyotrophic lateral sclerosis, with lower levels denoting more serious disease and a shorter survival time, according to a report published online July 21 in JAMA Neurology.
To identify any potential correlations between hematologic biomarkers and ALS severity, researchers analyzed data concerning 638 patients from a regional registry of people diagnosed during 2007-2011 in the Piemonte and Valle d’Aosta areas of Italy. The 352 men and 286 women underwent complete physical examinations at the time of diagnosis, which included tests for 17 serum biomarkers. The only two serum biomarkers found to correlate with ALS severity were albumin level, which reflected inflammation, and creatinine, which reflected muscle wasting, said Dr. Adriano Chio, professor of neuroscience, University of Torino, Turin, Italy, and his associates.
Both biomarkers showed an inverse dose-response relationship with clinical function at diagnosis in men and women. Both had sensitivity and specificity values at predicting 1-year mortality that were similar to those of "the best established prognostic factors" for ALS, such as forced vital capacity, age, and scores on the ALS Functional Rating Scale-Revised, the investigators said (JAMA Neurol. 2014 July 21 [doi:10.1001/jamaneurol.2014.1129]).
Dr. Chio and his colleagues performed a validation study in a cohort of 122 patients (54 men, 68 women) at all stages of ALS who were treated at an ALS tertiary care center in another area of Italy. This study confirmed the findings from the discovery cohort. "Both creatinine and albumin are reliable and easily detectable blood markers of the severity of motor dysfunction in ALS and could be used in defining patients’ prognosis at the time of diagnosis," they said.
This study was supported by the Italian Ministry of Health and the European Community’s Health Seventh Framework Programme. Dr. Chio reported serving on scientific advisory board for Biogen Idec and Cytokinetics
Serum levels of both albumin and creatinine proved to be independent biomarkers of disease severity in men and women with amyotrophic lateral sclerosis, with lower levels denoting more serious disease and a shorter survival time, according to a report published online July 21 in JAMA Neurology.
To identify any potential correlations between hematologic biomarkers and ALS severity, researchers analyzed data concerning 638 patients from a regional registry of people diagnosed during 2007-2011 in the Piemonte and Valle d’Aosta areas of Italy. The 352 men and 286 women underwent complete physical examinations at the time of diagnosis, which included tests for 17 serum biomarkers. The only two serum biomarkers found to correlate with ALS severity were albumin level, which reflected inflammation, and creatinine, which reflected muscle wasting, said Dr. Adriano Chio, professor of neuroscience, University of Torino, Turin, Italy, and his associates.
Both biomarkers showed an inverse dose-response relationship with clinical function at diagnosis in men and women. Both had sensitivity and specificity values at predicting 1-year mortality that were similar to those of "the best established prognostic factors" for ALS, such as forced vital capacity, age, and scores on the ALS Functional Rating Scale-Revised, the investigators said (JAMA Neurol. 2014 July 21 [doi:10.1001/jamaneurol.2014.1129]).
Dr. Chio and his colleagues performed a validation study in a cohort of 122 patients (54 men, 68 women) at all stages of ALS who were treated at an ALS tertiary care center in another area of Italy. This study confirmed the findings from the discovery cohort. "Both creatinine and albumin are reliable and easily detectable blood markers of the severity of motor dysfunction in ALS and could be used in defining patients’ prognosis at the time of diagnosis," they said.
This study was supported by the Italian Ministry of Health and the European Community’s Health Seventh Framework Programme. Dr. Chio reported serving on scientific advisory board for Biogen Idec and Cytokinetics
Serum levels of both albumin and creatinine proved to be independent biomarkers of disease severity in men and women with amyotrophic lateral sclerosis, with lower levels denoting more serious disease and a shorter survival time, according to a report published online July 21 in JAMA Neurology.
To identify any potential correlations between hematologic biomarkers and ALS severity, researchers analyzed data concerning 638 patients from a regional registry of people diagnosed during 2007-2011 in the Piemonte and Valle d’Aosta areas of Italy. The 352 men and 286 women underwent complete physical examinations at the time of diagnosis, which included tests for 17 serum biomarkers. The only two serum biomarkers found to correlate with ALS severity were albumin level, which reflected inflammation, and creatinine, which reflected muscle wasting, said Dr. Adriano Chio, professor of neuroscience, University of Torino, Turin, Italy, and his associates.
Both biomarkers showed an inverse dose-response relationship with clinical function at diagnosis in men and women. Both had sensitivity and specificity values at predicting 1-year mortality that were similar to those of "the best established prognostic factors" for ALS, such as forced vital capacity, age, and scores on the ALS Functional Rating Scale-Revised, the investigators said (JAMA Neurol. 2014 July 21 [doi:10.1001/jamaneurol.2014.1129]).
Dr. Chio and his colleagues performed a validation study in a cohort of 122 patients (54 men, 68 women) at all stages of ALS who were treated at an ALS tertiary care center in another area of Italy. This study confirmed the findings from the discovery cohort. "Both creatinine and albumin are reliable and easily detectable blood markers of the severity of motor dysfunction in ALS and could be used in defining patients’ prognosis at the time of diagnosis," they said.
This study was supported by the Italian Ministry of Health and the European Community’s Health Seventh Framework Programme. Dr. Chio reported serving on scientific advisory board for Biogen Idec and Cytokinetics
FROM JAMA NEUROLOGY
Key clinical point: Serum levels of both albumin and creatinine were independent biomarkers of ALS severity.
Major finding: At diagnosis, serum levels of both albumin and creatinine showed an inverse dose-response relationship with clinical function in men and women, with sensitivity and specificity values at predicting 1-year mortality that were similar to those of "the best established prognostic factors" for ALS.
Data source: A population-based cohort study of serum biomarkers in 638 ALS patients registered in an Italian regional database, and a validation cohort study of 122 patients with different stages of ALS seen consecutively at an ALS tertiary care center in another area of Italy.
Disclosures: This study was supported by the Italian Ministry of Health and the European Community’s Health Seventh Framework Programme. Dr. Chio reported serving on scientific advisory board for Biogen Idec and Cytokinetics.
Daily inhaled corticosteroids marginally suppress children’s growth
Daily use of low- to medium-dose inhaled corticosteroids for mild to moderate persistent asthma suppresses growth to a "small" degree in children of all ages, according to a Cochrane review published online July 16 in the Cochrane Database of Systematic Reviews.
This level of use was associated with a mean reduction of 0.48 cm per year in linear growth velocity during the first year of treatment, against a background average growth rate of 6-9 cm per year. The growth suppression was less pronounced in subsequent years of treatment, and the magnitude of growth suppression was more strongly related to the particular drug used than to the dose or delivery device, said Dr. Linjie Zhang of the Federal University of Rio Grande (Brazil) and his associates.
"The evidence we reviewed suggests that children treated daily with inhaled corticosteroids may grow approximately half a centimeter less during the first year of treatment. But this effect is less pronounced in subsequent years, is not cumulative, and seems minor compared with the known benefits of the drugs for controlling asthma and ensuring full lung growth," Dr. Zhang said in a press statement accompanying the report.
The investigators undertook this comprehensive review of the literature and metaanalysis because of persistent concerns about possible adverse effects of inhaled corticosteroids on children’s growth and because several recent randomized trials have examined the issue and have assessed newly available agents and modes of delivery. They identified 25 good-quality, parallel-group, randomized clinical trials involving 8,471 children up to age 18, of whom 5,128 were treated with inhaled corticosteroids and 3,343 were treated with nonsteroidal anti-inflammatory drugs or placebo and served as controls.
Most of the trials were blinded, and most were multicenter. Seventeen of the 25 were funded by pharmaceutical companies.
The participating children used beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, or mometasone, delivered by any type of inhalation device, and were followed for 3 months to 6 years.
All six inhaled corticosteroids were found to suppress linear growth velocity during 1 year of treatment, which was the primary outcome of interest. They all also suppressed growth as measured by the secondary outcomes of change in height standard deviation score over time and change from baseline in height over time. These effects were less pronounced in subsequent years of treatment, but persisted until patients reached their adult height.
The one study that followed prepubescent participants into adulthood showed that those who used inhaled corticosteroids had a mean reduction of 1.2 cm in adult height, compared with those who did not.
Daily dose, delivery device, and patient age had had no significant impact on the magnitude of growth suppression. A small number of studies that compared the various corticosteroids against each other showed that beclomethasone and budesonide were somewhat more potent growth suppressors, compared with the other four agents. However, a meta-analysis is not the best method for exploring these issues, and data from more head-to-head randomized trials are required to confirm these findings, Dr. Zhang and his associates noted (Cochrane Database Systematic Rev. 2014 July 16 [doi:10.1002/I4651858.CD009471.pub2]).
Their findings indicate that inhaled corticosteroids should be prescribed at the lowest effective dose. "Moreover, it is prudent to monitor linear growth in children treated with inhaled corticosteroids, given that individual susceptibility to these drugs may vary considerably," the investigators added.
Daily use of low- to medium-dose inhaled corticosteroids for mild to moderate persistent asthma suppresses growth to a "small" degree in children of all ages, according to a Cochrane review published online July 16 in the Cochrane Database of Systematic Reviews.
This level of use was associated with a mean reduction of 0.48 cm per year in linear growth velocity during the first year of treatment, against a background average growth rate of 6-9 cm per year. The growth suppression was less pronounced in subsequent years of treatment, and the magnitude of growth suppression was more strongly related to the particular drug used than to the dose or delivery device, said Dr. Linjie Zhang of the Federal University of Rio Grande (Brazil) and his associates.
"The evidence we reviewed suggests that children treated daily with inhaled corticosteroids may grow approximately half a centimeter less during the first year of treatment. But this effect is less pronounced in subsequent years, is not cumulative, and seems minor compared with the known benefits of the drugs for controlling asthma and ensuring full lung growth," Dr. Zhang said in a press statement accompanying the report.
The investigators undertook this comprehensive review of the literature and metaanalysis because of persistent concerns about possible adverse effects of inhaled corticosteroids on children’s growth and because several recent randomized trials have examined the issue and have assessed newly available agents and modes of delivery. They identified 25 good-quality, parallel-group, randomized clinical trials involving 8,471 children up to age 18, of whom 5,128 were treated with inhaled corticosteroids and 3,343 were treated with nonsteroidal anti-inflammatory drugs or placebo and served as controls.
Most of the trials were blinded, and most were multicenter. Seventeen of the 25 were funded by pharmaceutical companies.
The participating children used beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, or mometasone, delivered by any type of inhalation device, and were followed for 3 months to 6 years.
All six inhaled corticosteroids were found to suppress linear growth velocity during 1 year of treatment, which was the primary outcome of interest. They all also suppressed growth as measured by the secondary outcomes of change in height standard deviation score over time and change from baseline in height over time. These effects were less pronounced in subsequent years of treatment, but persisted until patients reached their adult height.
The one study that followed prepubescent participants into adulthood showed that those who used inhaled corticosteroids had a mean reduction of 1.2 cm in adult height, compared with those who did not.
Daily dose, delivery device, and patient age had had no significant impact on the magnitude of growth suppression. A small number of studies that compared the various corticosteroids against each other showed that beclomethasone and budesonide were somewhat more potent growth suppressors, compared with the other four agents. However, a meta-analysis is not the best method for exploring these issues, and data from more head-to-head randomized trials are required to confirm these findings, Dr. Zhang and his associates noted (Cochrane Database Systematic Rev. 2014 July 16 [doi:10.1002/I4651858.CD009471.pub2]).
Their findings indicate that inhaled corticosteroids should be prescribed at the lowest effective dose. "Moreover, it is prudent to monitor linear growth in children treated with inhaled corticosteroids, given that individual susceptibility to these drugs may vary considerably," the investigators added.
Daily use of low- to medium-dose inhaled corticosteroids for mild to moderate persistent asthma suppresses growth to a "small" degree in children of all ages, according to a Cochrane review published online July 16 in the Cochrane Database of Systematic Reviews.
This level of use was associated with a mean reduction of 0.48 cm per year in linear growth velocity during the first year of treatment, against a background average growth rate of 6-9 cm per year. The growth suppression was less pronounced in subsequent years of treatment, and the magnitude of growth suppression was more strongly related to the particular drug used than to the dose or delivery device, said Dr. Linjie Zhang of the Federal University of Rio Grande (Brazil) and his associates.
"The evidence we reviewed suggests that children treated daily with inhaled corticosteroids may grow approximately half a centimeter less during the first year of treatment. But this effect is less pronounced in subsequent years, is not cumulative, and seems minor compared with the known benefits of the drugs for controlling asthma and ensuring full lung growth," Dr. Zhang said in a press statement accompanying the report.
The investigators undertook this comprehensive review of the literature and metaanalysis because of persistent concerns about possible adverse effects of inhaled corticosteroids on children’s growth and because several recent randomized trials have examined the issue and have assessed newly available agents and modes of delivery. They identified 25 good-quality, parallel-group, randomized clinical trials involving 8,471 children up to age 18, of whom 5,128 were treated with inhaled corticosteroids and 3,343 were treated with nonsteroidal anti-inflammatory drugs or placebo and served as controls.
Most of the trials were blinded, and most were multicenter. Seventeen of the 25 were funded by pharmaceutical companies.
The participating children used beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, or mometasone, delivered by any type of inhalation device, and were followed for 3 months to 6 years.
All six inhaled corticosteroids were found to suppress linear growth velocity during 1 year of treatment, which was the primary outcome of interest. They all also suppressed growth as measured by the secondary outcomes of change in height standard deviation score over time and change from baseline in height over time. These effects were less pronounced in subsequent years of treatment, but persisted until patients reached their adult height.
The one study that followed prepubescent participants into adulthood showed that those who used inhaled corticosteroids had a mean reduction of 1.2 cm in adult height, compared with those who did not.
Daily dose, delivery device, and patient age had had no significant impact on the magnitude of growth suppression. A small number of studies that compared the various corticosteroids against each other showed that beclomethasone and budesonide were somewhat more potent growth suppressors, compared with the other four agents. However, a meta-analysis is not the best method for exploring these issues, and data from more head-to-head randomized trials are required to confirm these findings, Dr. Zhang and his associates noted (Cochrane Database Systematic Rev. 2014 July 16 [doi:10.1002/I4651858.CD009471.pub2]).
Their findings indicate that inhaled corticosteroids should be prescribed at the lowest effective dose. "Moreover, it is prudent to monitor linear growth in children treated with inhaled corticosteroids, given that individual susceptibility to these drugs may vary considerably," the investigators added.
FROM THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS
Major finding: All six inhaled corticosteroids in this review were found to suppress linear growth velocity during 1 year of treatment; they all also suppressed growth as measured by the secondary outcomes of change in height standard deviation score over time and change from baseline in height over time.
Data source: A comprehensive meta-analysis of 25 good-quality, parallel-group, randomized clinical trials involving 8,471 children of all ages with mild to moderate persistent asthma whose growth was assessed for up to 6 years of follow-up.
Disclosures: Dr. Zhang and his associates reported no financial conflicts of interest.
Niacin-laropiprant combo plus statin didn’t cut vascular events
Adding extended-release niacin plus laropiprant to effective statin-based LDL-lowering therapy failed to prevent major vascular events in patients with atherosclerotic vascular disease, but it did raise the rate of serious adverse events, according to a report published online July 16 in the New England Journal of Medicine.
"We believe that [our] findings are likely to be generalizable to all high-dose niacin formulations," and any potential benefits of the therapy must be weighed against those important hazards, reported Martin J. Landray, Ph.D., of the University of Oxford (England), and his associates in the HPS2-THRIVE (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events) clinical trial.
The study involved 25,673 high-risk men and women at 245 sites in the United Kingdom, Scandinavia, and China whose LDL cholesterol was already controlled by statins and who were randomly assigned to receive either oral niacin plus laropiprant (a prostaglandin-receptor antagonist that improves adherence to niacin by reducing flushing) or a matching placebo (N. Engl. J. Med. 2014;371:203-12).
The goal was to determine whether raising the HDL level with niacin would prevent major coronary events, stroke of any type, or revascularization procedures. Participants were followed for a median of 4 years.
Even though the study drug reduced LDL cholesterol by an average of 10 mg/dL, raised HDL by an average of 6 mg/dL, and reduced triglyceride levels by an average of 33 mg/dL, it failed to significantly decrease the incidence of major vascular events, compared with placebo (13.2% vs. 13.7%, respectively), either overall or in any of more than 30 subgroups of patients.
In fact, using the niacin-laropiprant combination raised the risk of death from any cause by 9%, compared with placebo, a difference that was not significant (P = .08), the investigators reported.
Niacin plus laropiprant was associated with numerous adverse events already linked to niacin therapy, such as serious gastrointestinal, musculoskeletal, and skin-related disorders. Of particular concern was the 55% increase in severe disturbances of metabolic control among patients who had concomitant diabetes (most of whom required hospitalization), and a 32% increase in new-onset diabetes. That contradicts previous assurances that niacin is safe for people who have diabetes, Dr. Landray and his associates noted.
Two serious adverse events that haven’t previously been associated with niacin or laropiprant also were identified: a wide range of infections affecting many body sites, and a similarly wide range of bleeding events, including intracranial hemorrhage and severe gastrointestinal bleeding.
HPS2-THRIVE was supported by Merck, maker of the study drugs; the U.K. Medical Research Council; the British Heart Foundation; and Cancer Research UK. Dr. Landray and several associates reported receiving grant support from Merck; no other relevant conflicts of interest were reported.
The findings of Dr. Landray’s study show that "niacin must be considered to have an unacceptable toxicity profile for the majority of patients, and it should not be used routinely," said Dr. Donald M. Lloyd-Jones. The findings also seriously undermine the hypothesis that HDL cholesterol plays a causal role in major atherosclerotic vascular events, he added.
Taken together with the failure of drugs such as torcetrapib and dalcetrapib in reducing cardiovascular risk despite markedly increasing HDL cholesterol levels, the HPS2-THRIVE results demonstrate that HDL level is solely a risk marker, not a risk factor that merits intervention.
"It is time to face the fact that increasing HDL cholesterol level in isolation" is unlikely to benefit most patients, Dr. Lloyd-Jones cautioned. However, niacin may still have a role in patients at very high risk for cardiovascular events who truly have contraindications to statins and other less toxic drugs, and as a possible fourth-line agent for patients with severe hypertriglyceridemia who are at risk for developing pancreatitis, he added.
Dr. Lloyd-Jones is in the department of preventive medicine and the division of cardiology at Northwestern University, Chicago. He reported no relevant financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Landray’s report (N. Engl. J. Med. 2014;371:271-3).
The findings of Dr. Landray’s study show that "niacin must be considered to have an unacceptable toxicity profile for the majority of patients, and it should not be used routinely," said Dr. Donald M. Lloyd-Jones. The findings also seriously undermine the hypothesis that HDL cholesterol plays a causal role in major atherosclerotic vascular events, he added.
Taken together with the failure of drugs such as torcetrapib and dalcetrapib in reducing cardiovascular risk despite markedly increasing HDL cholesterol levels, the HPS2-THRIVE results demonstrate that HDL level is solely a risk marker, not a risk factor that merits intervention.
"It is time to face the fact that increasing HDL cholesterol level in isolation" is unlikely to benefit most patients, Dr. Lloyd-Jones cautioned. However, niacin may still have a role in patients at very high risk for cardiovascular events who truly have contraindications to statins and other less toxic drugs, and as a possible fourth-line agent for patients with severe hypertriglyceridemia who are at risk for developing pancreatitis, he added.
Dr. Lloyd-Jones is in the department of preventive medicine and the division of cardiology at Northwestern University, Chicago. He reported no relevant financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Landray’s report (N. Engl. J. Med. 2014;371:271-3).
The findings of Dr. Landray’s study show that "niacin must be considered to have an unacceptable toxicity profile for the majority of patients, and it should not be used routinely," said Dr. Donald M. Lloyd-Jones. The findings also seriously undermine the hypothesis that HDL cholesterol plays a causal role in major atherosclerotic vascular events, he added.
Taken together with the failure of drugs such as torcetrapib and dalcetrapib in reducing cardiovascular risk despite markedly increasing HDL cholesterol levels, the HPS2-THRIVE results demonstrate that HDL level is solely a risk marker, not a risk factor that merits intervention.
"It is time to face the fact that increasing HDL cholesterol level in isolation" is unlikely to benefit most patients, Dr. Lloyd-Jones cautioned. However, niacin may still have a role in patients at very high risk for cardiovascular events who truly have contraindications to statins and other less toxic drugs, and as a possible fourth-line agent for patients with severe hypertriglyceridemia who are at risk for developing pancreatitis, he added.
Dr. Lloyd-Jones is in the department of preventive medicine and the division of cardiology at Northwestern University, Chicago. He reported no relevant financial conflicts of interest. These remarks were taken from his editorial accompanying Dr. Landray’s report (N. Engl. J. Med. 2014;371:271-3).
Adding extended-release niacin plus laropiprant to effective statin-based LDL-lowering therapy failed to prevent major vascular events in patients with atherosclerotic vascular disease, but it did raise the rate of serious adverse events, according to a report published online July 16 in the New England Journal of Medicine.
"We believe that [our] findings are likely to be generalizable to all high-dose niacin formulations," and any potential benefits of the therapy must be weighed against those important hazards, reported Martin J. Landray, Ph.D., of the University of Oxford (England), and his associates in the HPS2-THRIVE (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events) clinical trial.
The study involved 25,673 high-risk men and women at 245 sites in the United Kingdom, Scandinavia, and China whose LDL cholesterol was already controlled by statins and who were randomly assigned to receive either oral niacin plus laropiprant (a prostaglandin-receptor antagonist that improves adherence to niacin by reducing flushing) or a matching placebo (N. Engl. J. Med. 2014;371:203-12).
The goal was to determine whether raising the HDL level with niacin would prevent major coronary events, stroke of any type, or revascularization procedures. Participants were followed for a median of 4 years.
Even though the study drug reduced LDL cholesterol by an average of 10 mg/dL, raised HDL by an average of 6 mg/dL, and reduced triglyceride levels by an average of 33 mg/dL, it failed to significantly decrease the incidence of major vascular events, compared with placebo (13.2% vs. 13.7%, respectively), either overall or in any of more than 30 subgroups of patients.
In fact, using the niacin-laropiprant combination raised the risk of death from any cause by 9%, compared with placebo, a difference that was not significant (P = .08), the investigators reported.
Niacin plus laropiprant was associated with numerous adverse events already linked to niacin therapy, such as serious gastrointestinal, musculoskeletal, and skin-related disorders. Of particular concern was the 55% increase in severe disturbances of metabolic control among patients who had concomitant diabetes (most of whom required hospitalization), and a 32% increase in new-onset diabetes. That contradicts previous assurances that niacin is safe for people who have diabetes, Dr. Landray and his associates noted.
Two serious adverse events that haven’t previously been associated with niacin or laropiprant also were identified: a wide range of infections affecting many body sites, and a similarly wide range of bleeding events, including intracranial hemorrhage and severe gastrointestinal bleeding.
HPS2-THRIVE was supported by Merck, maker of the study drugs; the U.K. Medical Research Council; the British Heart Foundation; and Cancer Research UK. Dr. Landray and several associates reported receiving grant support from Merck; no other relevant conflicts of interest were reported.
Adding extended-release niacin plus laropiprant to effective statin-based LDL-lowering therapy failed to prevent major vascular events in patients with atherosclerotic vascular disease, but it did raise the rate of serious adverse events, according to a report published online July 16 in the New England Journal of Medicine.
"We believe that [our] findings are likely to be generalizable to all high-dose niacin formulations," and any potential benefits of the therapy must be weighed against those important hazards, reported Martin J. Landray, Ph.D., of the University of Oxford (England), and his associates in the HPS2-THRIVE (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events) clinical trial.
The study involved 25,673 high-risk men and women at 245 sites in the United Kingdom, Scandinavia, and China whose LDL cholesterol was already controlled by statins and who were randomly assigned to receive either oral niacin plus laropiprant (a prostaglandin-receptor antagonist that improves adherence to niacin by reducing flushing) or a matching placebo (N. Engl. J. Med. 2014;371:203-12).
The goal was to determine whether raising the HDL level with niacin would prevent major coronary events, stroke of any type, or revascularization procedures. Participants were followed for a median of 4 years.
Even though the study drug reduced LDL cholesterol by an average of 10 mg/dL, raised HDL by an average of 6 mg/dL, and reduced triglyceride levels by an average of 33 mg/dL, it failed to significantly decrease the incidence of major vascular events, compared with placebo (13.2% vs. 13.7%, respectively), either overall or in any of more than 30 subgroups of patients.
In fact, using the niacin-laropiprant combination raised the risk of death from any cause by 9%, compared with placebo, a difference that was not significant (P = .08), the investigators reported.
Niacin plus laropiprant was associated with numerous adverse events already linked to niacin therapy, such as serious gastrointestinal, musculoskeletal, and skin-related disorders. Of particular concern was the 55% increase in severe disturbances of metabolic control among patients who had concomitant diabetes (most of whom required hospitalization), and a 32% increase in new-onset diabetes. That contradicts previous assurances that niacin is safe for people who have diabetes, Dr. Landray and his associates noted.
Two serious adverse events that haven’t previously been associated with niacin or laropiprant also were identified: a wide range of infections affecting many body sites, and a similarly wide range of bleeding events, including intracranial hemorrhage and severe gastrointestinal bleeding.
HPS2-THRIVE was supported by Merck, maker of the study drugs; the U.K. Medical Research Council; the British Heart Foundation; and Cancer Research UK. Dr. Landray and several associates reported receiving grant support from Merck; no other relevant conflicts of interest were reported.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Giving patients on statins high-dose niacin and laropiprant won’t reduce their risk of cardiovascular events.
Major finding: Niacin plus laropiprant reduced LDL cholesterol an additional 10 mg/dL, raised HDL an average of 6 mg/dL, and reduced triglyceride level an average of 33 mg/dL; but it failed to decrease the incidence of major vascular events, compared with placebo (13.2% vs. 13.7%, respectively).
Data source: An international randomized, double-blind clinical trial involving 25,673 high-risk adults with atherosclerotic vascular disease who received either niacin plus laropiprant or a matching placebo and were followed for a median of 4 years.
Disclosures: HPS2-THRIVE was supported by Merck, maker of the study drugs; the U.K. Medical Research Council; the British Heart Foundation; and Cancer Research UK. Dr. Landray and several associates reported receiving grant support from Merck; no other relevant conflicts of interest were reported.
Telecare intervention lessens chronic joint pain
A telecare intervention within the primary care practice setting elicited clinically meaningful and statistically significant improvements in long-standing chronic joint and other musculoskeletal pain, according to a report published online July 15 in JAMA.
A total of 250 adults with refractory, moderately severe regional (joints, limbs, back, or neck) or generalized (fibromyalgia or widespread) musculoskeletal pain of long duration participated in a randomized, blinded, 1-year clinical trial comparing the telecare intervention (124 patients) against usual chronic pain treatment (126 patients) in the primary care setting, reported Dr. Kurt Kroenke of the Veterans Affairs Center for Health Information and Communication, Roudebush VA Medical Center, Indianapolis, and his associates.
The intervention had three key components: frequent automated monitoring of patient symptoms using telephone or Internet voice recordings; nurse calls to patients who reported inadequate treatment response, adverse effects, or nonadherence; and analgesic management using a stepped-care algorithm, which was implemented by a nurse-manager who worked with a physician pain specialist, in collaboration with the primary care physician. The estimated total time spent per patient during the study year was 3-4 hours for the study nurse and 1 hour for the study physician.
Patients frequently checked in to the automated system to report their pain, anxiety, and depression symptoms; how difficult their pain made it for them to carry out usual activities; their adherence to medications; the degree of relief they obtained from pain medications; any change in pain, including the degree of improvement; adverse effects from their analgesics; and whether they wanted to change their medication regimen or speak to a nurse.
The medication algorithm called for the stepwise use of simple analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs); tricyclic antidepressants (amitriptyline and nortriptyline) and cyclobenzaprine; tramadol; gabapentoids (gabapentin and pregabalin); topical analgesics; and opioids.
After 1 year, patients in the intervention group showed significantly greater improvement than the control group in measures of total pain, pain severity, and pain interference with daily activities, along with significantly greater satisfaction with their medical care. They were nearly twice as likely to report a 30% improvement from baseline (51.7%) than were patients in the usual-care group (27.1%).
They also were much less likely to report worsening pain (19.2% vs. 36.0%), which indicates a reduced risk of deterioration of their condition because their pain therapy was optimized, and much more likely to rate their medication as "good to excellent" (73.9% vs. 50.9%). And they reported greater improvements in secondary outcomes such as depression, anxiety, somatization, sleep, and social functioning, the investigators reported (JAMA 2014;312:240-248).
Patients in the intervention group received a greater number of analgesics for a greater length of time and at a higher mean dose than did those in the control group. However, only six patients in the entire study population initiated opioid use, and the median daily dose for all patients taking opioids was identical at the end of the study to what it was at the beginning. The two study groups showed no differences in their use of health care services such as outpatient visits, emergency department visits, and hospitalizations.
This study was supported by the U.S. Department of Veterans Affairs’ Health Services Research and Development Service. Dr. Kroenke reported receiving honoraria from Eli Lilly for work unrelated to this study.
This promising intervention doesn’t require significant additional time or effort from primary care physicians and is simple enough that it could be implemented in most primary care settings, said Dr. Michael E. Ohl and Dr. Gary E. Rosenthal.
"The authors estimated that the intervention required 3-4 hours of nurse-manager time and 1 hour of physician time per patient during a 12-month period. Thus, a single nurse could potentially manage the care of 500-600 patients with the support of a 0.25 full-time equivalent physician pain specialist," they noted.
Dr. Ohl and Dr. Rosenthal are at the Iowa City VA Medical Center and in the department of internal medicine at the University of Iowa. Dr. Rosenthal is also at the Institute for Clinical and Translational Sciences at the university. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Kroenke’s report (JAMA 2014;312:235-6).
This promising intervention doesn’t require significant additional time or effort from primary care physicians and is simple enough that it could be implemented in most primary care settings, said Dr. Michael E. Ohl and Dr. Gary E. Rosenthal.
"The authors estimated that the intervention required 3-4 hours of nurse-manager time and 1 hour of physician time per patient during a 12-month period. Thus, a single nurse could potentially manage the care of 500-600 patients with the support of a 0.25 full-time equivalent physician pain specialist," they noted.
Dr. Ohl and Dr. Rosenthal are at the Iowa City VA Medical Center and in the department of internal medicine at the University of Iowa. Dr. Rosenthal is also at the Institute for Clinical and Translational Sciences at the university. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Kroenke’s report (JAMA 2014;312:235-6).
This promising intervention doesn’t require significant additional time or effort from primary care physicians and is simple enough that it could be implemented in most primary care settings, said Dr. Michael E. Ohl and Dr. Gary E. Rosenthal.
"The authors estimated that the intervention required 3-4 hours of nurse-manager time and 1 hour of physician time per patient during a 12-month period. Thus, a single nurse could potentially manage the care of 500-600 patients with the support of a 0.25 full-time equivalent physician pain specialist," they noted.
Dr. Ohl and Dr. Rosenthal are at the Iowa City VA Medical Center and in the department of internal medicine at the University of Iowa. Dr. Rosenthal is also at the Institute for Clinical and Translational Sciences at the university. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Kroenke’s report (JAMA 2014;312:235-6).
A telecare intervention within the primary care practice setting elicited clinically meaningful and statistically significant improvements in long-standing chronic joint and other musculoskeletal pain, according to a report published online July 15 in JAMA.
A total of 250 adults with refractory, moderately severe regional (joints, limbs, back, or neck) or generalized (fibromyalgia or widespread) musculoskeletal pain of long duration participated in a randomized, blinded, 1-year clinical trial comparing the telecare intervention (124 patients) against usual chronic pain treatment (126 patients) in the primary care setting, reported Dr. Kurt Kroenke of the Veterans Affairs Center for Health Information and Communication, Roudebush VA Medical Center, Indianapolis, and his associates.
The intervention had three key components: frequent automated monitoring of patient symptoms using telephone or Internet voice recordings; nurse calls to patients who reported inadequate treatment response, adverse effects, or nonadherence; and analgesic management using a stepped-care algorithm, which was implemented by a nurse-manager who worked with a physician pain specialist, in collaboration with the primary care physician. The estimated total time spent per patient during the study year was 3-4 hours for the study nurse and 1 hour for the study physician.
Patients frequently checked in to the automated system to report their pain, anxiety, and depression symptoms; how difficult their pain made it for them to carry out usual activities; their adherence to medications; the degree of relief they obtained from pain medications; any change in pain, including the degree of improvement; adverse effects from their analgesics; and whether they wanted to change their medication regimen or speak to a nurse.
The medication algorithm called for the stepwise use of simple analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs); tricyclic antidepressants (amitriptyline and nortriptyline) and cyclobenzaprine; tramadol; gabapentoids (gabapentin and pregabalin); topical analgesics; and opioids.
After 1 year, patients in the intervention group showed significantly greater improvement than the control group in measures of total pain, pain severity, and pain interference with daily activities, along with significantly greater satisfaction with their medical care. They were nearly twice as likely to report a 30% improvement from baseline (51.7%) than were patients in the usual-care group (27.1%).
They also were much less likely to report worsening pain (19.2% vs. 36.0%), which indicates a reduced risk of deterioration of their condition because their pain therapy was optimized, and much more likely to rate their medication as "good to excellent" (73.9% vs. 50.9%). And they reported greater improvements in secondary outcomes such as depression, anxiety, somatization, sleep, and social functioning, the investigators reported (JAMA 2014;312:240-248).
Patients in the intervention group received a greater number of analgesics for a greater length of time and at a higher mean dose than did those in the control group. However, only six patients in the entire study population initiated opioid use, and the median daily dose for all patients taking opioids was identical at the end of the study to what it was at the beginning. The two study groups showed no differences in their use of health care services such as outpatient visits, emergency department visits, and hospitalizations.
This study was supported by the U.S. Department of Veterans Affairs’ Health Services Research and Development Service. Dr. Kroenke reported receiving honoraria from Eli Lilly for work unrelated to this study.
A telecare intervention within the primary care practice setting elicited clinically meaningful and statistically significant improvements in long-standing chronic joint and other musculoskeletal pain, according to a report published online July 15 in JAMA.
A total of 250 adults with refractory, moderately severe regional (joints, limbs, back, or neck) or generalized (fibromyalgia or widespread) musculoskeletal pain of long duration participated in a randomized, blinded, 1-year clinical trial comparing the telecare intervention (124 patients) against usual chronic pain treatment (126 patients) in the primary care setting, reported Dr. Kurt Kroenke of the Veterans Affairs Center for Health Information and Communication, Roudebush VA Medical Center, Indianapolis, and his associates.
The intervention had three key components: frequent automated monitoring of patient symptoms using telephone or Internet voice recordings; nurse calls to patients who reported inadequate treatment response, adverse effects, or nonadherence; and analgesic management using a stepped-care algorithm, which was implemented by a nurse-manager who worked with a physician pain specialist, in collaboration with the primary care physician. The estimated total time spent per patient during the study year was 3-4 hours for the study nurse and 1 hour for the study physician.
Patients frequently checked in to the automated system to report their pain, anxiety, and depression symptoms; how difficult their pain made it for them to carry out usual activities; their adherence to medications; the degree of relief they obtained from pain medications; any change in pain, including the degree of improvement; adverse effects from their analgesics; and whether they wanted to change their medication regimen or speak to a nurse.
The medication algorithm called for the stepwise use of simple analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs); tricyclic antidepressants (amitriptyline and nortriptyline) and cyclobenzaprine; tramadol; gabapentoids (gabapentin and pregabalin); topical analgesics; and opioids.
After 1 year, patients in the intervention group showed significantly greater improvement than the control group in measures of total pain, pain severity, and pain interference with daily activities, along with significantly greater satisfaction with their medical care. They were nearly twice as likely to report a 30% improvement from baseline (51.7%) than were patients in the usual-care group (27.1%).
They also were much less likely to report worsening pain (19.2% vs. 36.0%), which indicates a reduced risk of deterioration of their condition because their pain therapy was optimized, and much more likely to rate their medication as "good to excellent" (73.9% vs. 50.9%). And they reported greater improvements in secondary outcomes such as depression, anxiety, somatization, sleep, and social functioning, the investigators reported (JAMA 2014;312:240-248).
Patients in the intervention group received a greater number of analgesics for a greater length of time and at a higher mean dose than did those in the control group. However, only six patients in the entire study population initiated opioid use, and the median daily dose for all patients taking opioids was identical at the end of the study to what it was at the beginning. The two study groups showed no differences in their use of health care services such as outpatient visits, emergency department visits, and hospitalizations.
This study was supported by the U.S. Department of Veterans Affairs’ Health Services Research and Development Service. Dr. Kroenke reported receiving honoraria from Eli Lilly for work unrelated to this study.
FROM JAMA
Key clinical finding: A hands-off telecare approach helps patients with chronic joint and other musculoskeletal pain manage it.
Major finding: Patients in the intervention group showed significantly greater improvement than the control group in measures of total pain, pain severity, and pain interference with daily activities; they were nearly twice as likely to report a 30% improvement from baseline (51.7%) than were patients in the usual-care group (27.1%), much less likely to report worsening pain (19.2% vs. 36.0%), and much more likely to rate their medication as "good to excellent" (73.9% vs. 50.9%).
Data source: A 1-year randomized, controlled trial involving 250 adults with refractory, moderately severe, chronic musculoskeletal pain.
Disclosures: This study was supported by the U.S. Department of Veterans Affairs’ Health Services Research and Development Service.
Stroke incidence down in whites and blacks across the U.S.
The incidence of stroke has declined significantly since 1987 in both blacks and whites and in both men and women, according to a prospective cohort study of residents in four U.S. communities.
Several studies have documented a decline in stroke rates in many other countries over the past decade, but there have been persistent racial, ethnic, and gender disparities in stroke rates in the United States, according to Silvia Koton, Ph.D., of Johns Hopkins University School of Public Health, Baltimore, and Tel Aviv University.
The report was published online July 15 in JAMA.
To assess long-term temporal trends, Dr. Koton and her associates analyzed data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of nearly 16,000 residents who were aged 45-64 years at baseline in 1987-1989 in Minneapolis; Washington County, Md.; Forsyth County, N.C.; and Jackson, Miss. ARIC included a comparatively large sample of black participants, and more than half the study subjects were women.
The researchers assessed 14,357 ARIC participants with 282,097 person-years. A total of 1,051 (7%) had a stroke during a median follow-up of 22.5 years for a incidence rate ratio of 3.73 per 1,000 person-years. Over time, the incidence of stroke showed an absolute decrease of 1.16 per 1,000 person-years after adjustment for age, other demographic variables, and time-varying prevalence of risk factors.
The incidence of stroke declined in blacks and whites, as well as in men and women. The incidence was 2.96 per 1,000 person-years for whites and 6.02 for blacks, with absolute, age-adjusted reductions of 0.83 per 1,000 person-years and 1.75 per 1,000 person-years, respectively. However, the decrease occurred only in people aged 65 years and older; the incidence of stroke remained steady throughout the study period in younger adults, the investigators said (JAMA 2014;312:259-68).
The risk of stroke mortality significantly declined by 20% after adjustment for age, but the reduction shrank to a nonsignificant 10% after the researchers fully adjusted for age, sex, race, center (demographic variables), hypertension, diabetes, smoking, and cholesterol-lowering medication use. In contrast to the decrease in incidence, the decrease in mortality was observed primarily among patients younger than age 65.
Stroke incidence and mortality have declined across racial groups, but the disparity between blacks and whites still persists, Dr. Ralph L. Sacco and Dr. Chuanhui Dong of the department of neurology at the University of Miami wrote in an editorial (JAMA 2014;312:237-8).
"Unless health disparities are addressed and innovative strategies to change behavior are developed and adopted, the cerebrovascular health of the population will be unlikely to improve." In particular, younger segments of the population must protect their brain health – especially by managing controllable risk factors such as diet, exercise, smoking, and obesity – to enhance the chance of successful cognitive aging, they noted.
The study was not designed to determine why these trends occurred, but it is likely that these factors played a significant role: improvements in the control of risk factors such as hypertension, smoking, diabetes, dyslipidemia, and atrial fibrillation, and the use of reperfusion therapy and improved postacute management strategies, the researchers said.
This study was supported by the National Heart, Lung, and Blood Institute and the National Institutes of Health. Dr. Koton and her associates reported no financial conflicts of interest. Dr. Sacco and Dr. Dong had nothing to disclose.
The incidence of stroke has declined significantly since 1987 in both blacks and whites and in both men and women, according to a prospective cohort study of residents in four U.S. communities.
Several studies have documented a decline in stroke rates in many other countries over the past decade, but there have been persistent racial, ethnic, and gender disparities in stroke rates in the United States, according to Silvia Koton, Ph.D., of Johns Hopkins University School of Public Health, Baltimore, and Tel Aviv University.
The report was published online July 15 in JAMA.
To assess long-term temporal trends, Dr. Koton and her associates analyzed data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of nearly 16,000 residents who were aged 45-64 years at baseline in 1987-1989 in Minneapolis; Washington County, Md.; Forsyth County, N.C.; and Jackson, Miss. ARIC included a comparatively large sample of black participants, and more than half the study subjects were women.
The researchers assessed 14,357 ARIC participants with 282,097 person-years. A total of 1,051 (7%) had a stroke during a median follow-up of 22.5 years for a incidence rate ratio of 3.73 per 1,000 person-years. Over time, the incidence of stroke showed an absolute decrease of 1.16 per 1,000 person-years after adjustment for age, other demographic variables, and time-varying prevalence of risk factors.
The incidence of stroke declined in blacks and whites, as well as in men and women. The incidence was 2.96 per 1,000 person-years for whites and 6.02 for blacks, with absolute, age-adjusted reductions of 0.83 per 1,000 person-years and 1.75 per 1,000 person-years, respectively. However, the decrease occurred only in people aged 65 years and older; the incidence of stroke remained steady throughout the study period in younger adults, the investigators said (JAMA 2014;312:259-68).
The risk of stroke mortality significantly declined by 20% after adjustment for age, but the reduction shrank to a nonsignificant 10% after the researchers fully adjusted for age, sex, race, center (demographic variables), hypertension, diabetes, smoking, and cholesterol-lowering medication use. In contrast to the decrease in incidence, the decrease in mortality was observed primarily among patients younger than age 65.
Stroke incidence and mortality have declined across racial groups, but the disparity between blacks and whites still persists, Dr. Ralph L. Sacco and Dr. Chuanhui Dong of the department of neurology at the University of Miami wrote in an editorial (JAMA 2014;312:237-8).
"Unless health disparities are addressed and innovative strategies to change behavior are developed and adopted, the cerebrovascular health of the population will be unlikely to improve." In particular, younger segments of the population must protect their brain health – especially by managing controllable risk factors such as diet, exercise, smoking, and obesity – to enhance the chance of successful cognitive aging, they noted.
The study was not designed to determine why these trends occurred, but it is likely that these factors played a significant role: improvements in the control of risk factors such as hypertension, smoking, diabetes, dyslipidemia, and atrial fibrillation, and the use of reperfusion therapy and improved postacute management strategies, the researchers said.
This study was supported by the National Heart, Lung, and Blood Institute and the National Institutes of Health. Dr. Koton and her associates reported no financial conflicts of interest. Dr. Sacco and Dr. Dong had nothing to disclose.
The incidence of stroke has declined significantly since 1987 in both blacks and whites and in both men and women, according to a prospective cohort study of residents in four U.S. communities.
Several studies have documented a decline in stroke rates in many other countries over the past decade, but there have been persistent racial, ethnic, and gender disparities in stroke rates in the United States, according to Silvia Koton, Ph.D., of Johns Hopkins University School of Public Health, Baltimore, and Tel Aviv University.
The report was published online July 15 in JAMA.
To assess long-term temporal trends, Dr. Koton and her associates analyzed data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of nearly 16,000 residents who were aged 45-64 years at baseline in 1987-1989 in Minneapolis; Washington County, Md.; Forsyth County, N.C.; and Jackson, Miss. ARIC included a comparatively large sample of black participants, and more than half the study subjects were women.
The researchers assessed 14,357 ARIC participants with 282,097 person-years. A total of 1,051 (7%) had a stroke during a median follow-up of 22.5 years for a incidence rate ratio of 3.73 per 1,000 person-years. Over time, the incidence of stroke showed an absolute decrease of 1.16 per 1,000 person-years after adjustment for age, other demographic variables, and time-varying prevalence of risk factors.
The incidence of stroke declined in blacks and whites, as well as in men and women. The incidence was 2.96 per 1,000 person-years for whites and 6.02 for blacks, with absolute, age-adjusted reductions of 0.83 per 1,000 person-years and 1.75 per 1,000 person-years, respectively. However, the decrease occurred only in people aged 65 years and older; the incidence of stroke remained steady throughout the study period in younger adults, the investigators said (JAMA 2014;312:259-68).
The risk of stroke mortality significantly declined by 20% after adjustment for age, but the reduction shrank to a nonsignificant 10% after the researchers fully adjusted for age, sex, race, center (demographic variables), hypertension, diabetes, smoking, and cholesterol-lowering medication use. In contrast to the decrease in incidence, the decrease in mortality was observed primarily among patients younger than age 65.
Stroke incidence and mortality have declined across racial groups, but the disparity between blacks and whites still persists, Dr. Ralph L. Sacco and Dr. Chuanhui Dong of the department of neurology at the University of Miami wrote in an editorial (JAMA 2014;312:237-8).
"Unless health disparities are addressed and innovative strategies to change behavior are developed and adopted, the cerebrovascular health of the population will be unlikely to improve." In particular, younger segments of the population must protect their brain health – especially by managing controllable risk factors such as diet, exercise, smoking, and obesity – to enhance the chance of successful cognitive aging, they noted.
The study was not designed to determine why these trends occurred, but it is likely that these factors played a significant role: improvements in the control of risk factors such as hypertension, smoking, diabetes, dyslipidemia, and atrial fibrillation, and the use of reperfusion therapy and improved postacute management strategies, the researchers said.
This study was supported by the National Heart, Lung, and Blood Institute and the National Institutes of Health. Dr. Koton and her associates reported no financial conflicts of interest. Dr. Sacco and Dr. Dong had nothing to disclose.
FROM JAMA
Key clinical point: The incidence of stroke in the United States has declined, but there is still a disparity in incidence between blacks and whites.
Major finding: Since 1987, the incidence of stroke showed an absolute decrease of 1.16 per 1,000 person-years.
Data source: A secondary analysis of data from the prospective Atherosclerosis Risk in Communities cohort study, involving 14,357 participants followed for a median of 22.5 years for the development of stroke.
Disclosures: This study was supported by the National Heart, Lung, and Blood Institute and the National Institutes of Health. Dr. Koton and her associates reported no financial conflicts of interest. Dr. Sacco and Dr. Dong had nothing to disclose.
High dietary omega-3 fatty acids are associated with lower ALS risk
Adults who consumed high levels of omega-3 polyunsaturated fatty acids showed a markedly reduced risk of developing amyotrophic lateral sclerosis in a pooled analysis of five large prospective cohort studies that assessed diet.
Diet-derived omega-3 polyunsaturated fatty acids (PUFAs) are known to have neuroprotective effects, and those present in neural plasma membranes can modulate oxidative stress, excitotoxicity, and inflammation. But no prospective studies have explored a possible relationship between omega-3 PUFA intake and amyotrophic lateral sclerosis (ALS) risk, according to Kathryn C. Fitzgerald of the department of nutrition, Harvard School of Public Health, Boston, and her associates.
In a study published July 14 in JAMA Neurology, Ms. Fitzgerald and her colleagues pooled data from the Health Professionals Follow-up Study, the Nurses’ Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study. A total of 995 ALS patients were identified among 1,002,082 participants in these studies. The five studies included detailed dietary information and tracked the occurrence of ALS in the study participants through the National Death Index.
Omega-3 PUFA intake in the highest quintile of consumption at a median of 2.11 g/day was associated with a 34% reduced risk of developing ALS, compared with the lowest quintile of consumption at a median of 0.94 g/day. This finding was consistent across all five studies. This means that adding 0.5% of energy from omega-3 PUFAs and maintaining a constant intake of omega-6 fatty acids while reducing the intake of other types of fat would reduce ALS risk by 34%. Consumption of alpha-linolenic acid, another PUFA, also was associated with significantly reduced risk of developing ALS. In contrast, consumption of omega-6 PUFAs, consumption of linolenic acid, total energy intake, and percentage of energy from other types of fat showed no association with ALS risk, the investigators said (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1214]).
Foods that are rich in omega-3 PUFAs include fatty fish (salmon, sardines, tuna, herring) and fish oils; vegetable oils (corn, safflower, canola, soy, and flaxseed oils); and nuts and seeds (walnuts, chia seeds, butternuts, and sunflower seeds). Further studies are needed to confirm this protective effect in ALS and to determine whether patients who already have the disease would benefit from the addition of omega-3 PUFAs to their diets, Ms. Fitzgerald and her associates added.
The findings from Ms. Fitzgerald and her associates are persuasive and consistent with earlier suggestions that PUFAs may play a role in other neurodegenerative conditions, Dr. Michael Swash said in a related editorial (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1894]).
"Ideas on long-term risk-susceptibility factors are very much welcomed in trying to unravel the mystery that is ALS. Now, in addition to genetic factors, there are the following five risk factors to work on: male sex, smoking status, BMI, physical exercise, and dietary intake of PUFAs," said Dr. Swash of the Royal London Hospital, Queen Mary University of London, and the Institute of Neuroscience at the University of Lisbon.
This study was supported by the National Institute of Neurological Diseases and Stroke, the National Cancer Institute, and the ALS Therapy Alliance Foundation. The study authors and Dr. Swash had no financial disclosures.
Adults who consumed high levels of omega-3 polyunsaturated fatty acids showed a markedly reduced risk of developing amyotrophic lateral sclerosis in a pooled analysis of five large prospective cohort studies that assessed diet.
Diet-derived omega-3 polyunsaturated fatty acids (PUFAs) are known to have neuroprotective effects, and those present in neural plasma membranes can modulate oxidative stress, excitotoxicity, and inflammation. But no prospective studies have explored a possible relationship between omega-3 PUFA intake and amyotrophic lateral sclerosis (ALS) risk, according to Kathryn C. Fitzgerald of the department of nutrition, Harvard School of Public Health, Boston, and her associates.
In a study published July 14 in JAMA Neurology, Ms. Fitzgerald and her colleagues pooled data from the Health Professionals Follow-up Study, the Nurses’ Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study. A total of 995 ALS patients were identified among 1,002,082 participants in these studies. The five studies included detailed dietary information and tracked the occurrence of ALS in the study participants through the National Death Index.
Omega-3 PUFA intake in the highest quintile of consumption at a median of 2.11 g/day was associated with a 34% reduced risk of developing ALS, compared with the lowest quintile of consumption at a median of 0.94 g/day. This finding was consistent across all five studies. This means that adding 0.5% of energy from omega-3 PUFAs and maintaining a constant intake of omega-6 fatty acids while reducing the intake of other types of fat would reduce ALS risk by 34%. Consumption of alpha-linolenic acid, another PUFA, also was associated with significantly reduced risk of developing ALS. In contrast, consumption of omega-6 PUFAs, consumption of linolenic acid, total energy intake, and percentage of energy from other types of fat showed no association with ALS risk, the investigators said (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1214]).
Foods that are rich in omega-3 PUFAs include fatty fish (salmon, sardines, tuna, herring) and fish oils; vegetable oils (corn, safflower, canola, soy, and flaxseed oils); and nuts and seeds (walnuts, chia seeds, butternuts, and sunflower seeds). Further studies are needed to confirm this protective effect in ALS and to determine whether patients who already have the disease would benefit from the addition of omega-3 PUFAs to their diets, Ms. Fitzgerald and her associates added.
The findings from Ms. Fitzgerald and her associates are persuasive and consistent with earlier suggestions that PUFAs may play a role in other neurodegenerative conditions, Dr. Michael Swash said in a related editorial (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1894]).
"Ideas on long-term risk-susceptibility factors are very much welcomed in trying to unravel the mystery that is ALS. Now, in addition to genetic factors, there are the following five risk factors to work on: male sex, smoking status, BMI, physical exercise, and dietary intake of PUFAs," said Dr. Swash of the Royal London Hospital, Queen Mary University of London, and the Institute of Neuroscience at the University of Lisbon.
This study was supported by the National Institute of Neurological Diseases and Stroke, the National Cancer Institute, and the ALS Therapy Alliance Foundation. The study authors and Dr. Swash had no financial disclosures.
Adults who consumed high levels of omega-3 polyunsaturated fatty acids showed a markedly reduced risk of developing amyotrophic lateral sclerosis in a pooled analysis of five large prospective cohort studies that assessed diet.
Diet-derived omega-3 polyunsaturated fatty acids (PUFAs) are known to have neuroprotective effects, and those present in neural plasma membranes can modulate oxidative stress, excitotoxicity, and inflammation. But no prospective studies have explored a possible relationship between omega-3 PUFA intake and amyotrophic lateral sclerosis (ALS) risk, according to Kathryn C. Fitzgerald of the department of nutrition, Harvard School of Public Health, Boston, and her associates.
In a study published July 14 in JAMA Neurology, Ms. Fitzgerald and her colleagues pooled data from the Health Professionals Follow-up Study, the Nurses’ Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study. A total of 995 ALS patients were identified among 1,002,082 participants in these studies. The five studies included detailed dietary information and tracked the occurrence of ALS in the study participants through the National Death Index.
Omega-3 PUFA intake in the highest quintile of consumption at a median of 2.11 g/day was associated with a 34% reduced risk of developing ALS, compared with the lowest quintile of consumption at a median of 0.94 g/day. This finding was consistent across all five studies. This means that adding 0.5% of energy from omega-3 PUFAs and maintaining a constant intake of omega-6 fatty acids while reducing the intake of other types of fat would reduce ALS risk by 34%. Consumption of alpha-linolenic acid, another PUFA, also was associated with significantly reduced risk of developing ALS. In contrast, consumption of omega-6 PUFAs, consumption of linolenic acid, total energy intake, and percentage of energy from other types of fat showed no association with ALS risk, the investigators said (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1214]).
Foods that are rich in omega-3 PUFAs include fatty fish (salmon, sardines, tuna, herring) and fish oils; vegetable oils (corn, safflower, canola, soy, and flaxseed oils); and nuts and seeds (walnuts, chia seeds, butternuts, and sunflower seeds). Further studies are needed to confirm this protective effect in ALS and to determine whether patients who already have the disease would benefit from the addition of omega-3 PUFAs to their diets, Ms. Fitzgerald and her associates added.
The findings from Ms. Fitzgerald and her associates are persuasive and consistent with earlier suggestions that PUFAs may play a role in other neurodegenerative conditions, Dr. Michael Swash said in a related editorial (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1894]).
"Ideas on long-term risk-susceptibility factors are very much welcomed in trying to unravel the mystery that is ALS. Now, in addition to genetic factors, there are the following five risk factors to work on: male sex, smoking status, BMI, physical exercise, and dietary intake of PUFAs," said Dr. Swash of the Royal London Hospital, Queen Mary University of London, and the Institute of Neuroscience at the University of Lisbon.
This study was supported by the National Institute of Neurological Diseases and Stroke, the National Cancer Institute, and the ALS Therapy Alliance Foundation. The study authors and Dr. Swash had no financial disclosures.
FROM JAMA NEUROLOGY
Key clinical point: Eating more omega-3 PUFAs, maintaining a constant intake of omega-6 fatty acids, and reducing the intake of other types of fat is associated with a reduced risk of ALS.
Major finding: High omega-3 PUFA intake was associated with a 34% reduction in the relative risk of developing ALS.
Data source: A pooled analysis of five large prospective cohorts totaling 1,002,082 participants to explore any association between dietary intake of various fatty acids and ALS risk.
Disclosures: This study was supported by the National Institute of Neurological Diseases and Stroke, the National Cancer Institute, and the ALS Therapy Alliance Foundation. The study authors and Dr. Swash had no financial disclosures.
Specialists drive overtreatment of low-risk prostate cancer
Low-risk prostate cancer in older men is still being overtreated, according to two separate studies that examined the issue from different perspectives, both of which were published online July 14 in JAMA Internal Medicine.
One group of researchers found that primary androgen deprivation therapy fails to improve either overall or disease-specific survival in this patient population, yet it still is widely used as the initial treatment for localized disease. And another group found that urologists and radiation oncologists are the driving force behind the overly aggressive approach to low-risk prostate cancer in older men.
Both groups of investigators called for efforts to limit these harmful trends.
In the first study, Grace L. Lu-Yao, Ph.D., and her associates analyzed information on 66,717 cases of prostate cancer in the Surveillance, Epidemiology, and End Results (SEER) and Medicaid databases diagnosed in 1992-2009. All the patients were aged 66 years and older, and all had T1/T2 disease. There were 5,275 deaths from prostate cancer and 39,801 deaths from all causes during nearly 20 years of follow-up.
Primary androgen deprivation therapy failed to improve either overall or disease-specific survival at 5 years or 15 years. Further study using instrumental variable analysis to control for an imbalance in risk factors between users and nonusers of androgen deprivation therapy confirmed these results, as did several sensitivity analyses, "suggesting that our conclusions are robust" (JAMA Intern. Med. 2014 July 14 [doi: 10.1001/jamainternmed.2014.3028]).
"For patients with less aggressive cancers, deferred androgen deprivation therapy is safe and reduces the risks of treatment-associated adverse effects, such as osteoporosis, weight gain, decreased libido, decreased muscle tone, diabetes mellitus, and metabolic syndrome," wrote Dr. Lu-Yao of Rutgers Cancer Institute of New Jersey, New Brunswick, and her associates.
"Physicians and patients often believe that treatment is necessary and beneficial. Our data suggest that this may not be the case, at least for primary androgen deprivation therapy," they said.
In the other study, investigators examined physician and patient factors that influence treatment decisions in low-risk prostate cancer. They also analyzed SEER data, this time involving 12,068 men aged 66 years and older (median age, 72 years) who were diagnosed as having low-risk prostate adenocarcinoma in 2006-2009. These men were diagnosed by 2,145 urologists; 68% of them also consulted a radiation oncologist, said Dr. Karen E. Hoffman of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.
Fully 80% of the low-risk patients diagnosed by a urologist immediately received treatment; only 20% instead underwent observation, as is recommended. The use of observation varied markedly across urologists, with some performing observation for less than 5% of their patients and others performing observation for nearly 65%. Forty urologists (10.2%) had rates of observation that were significantly different from the mean.
In analyses that estimated the relative contributions of numerous factors to treatment decisions, "the diagnosing urologist was the most influential measured factor, responsible for 16.1% of the variance in management choice; just 7.9% of the variance was attributable to patient characteristics," Dr. Hoffman and her associates reported (JAMA Intern. Med. 2014 July 14 [doi: 10.1001/jamainternmed.2014.3021]).
Similarly, of the 7,554 men who consulted 870 radiation oncologists, a remarkable 91.5% underwent immediate treatment (usually radiotherapy), while only 8.5% underwent observation, as is recommended. The use of observation also varied markedly across radiation oncologists, with some advising observation for only 2% of their patients and others advising it for 47%. Again, the variance in treatment decisions attributable to radiation oncologists was at least double that attributable to patient factors.
"In our cohort, 70.0% of men aged 76-80 years and 55.1% of men older than 80 years still received up-front treatment," a striking proportion because the average life expectancy for men 77 years and older in the United States is less than 10 years. "Older men, especially those with multiple medical conditions, are not thought to gain a survival benefit from treatment of low-risk prostate cancer," Dr. Hoffman and her colleagues noted.
Their findings are important because most primary care physicians who refer their patients to specialists for prostate biopsy or consultation probably "assume that patients will receive similar management recommendations regardless of which [specialist] they see." These results demonstrate the opposite: Patients with low-risk prostate cancer could receive widely divergent treatment advice, solely depending on the specialists’ preferences.
Dr. Lu-Yao’s study was supported by the National Cancer Institute and the Cancer Institute of New Jersey. She reported ties to Merck and Schering-Plough, and one of her associates reported receiving research funding from Myriad. Dr. Hoffman’s study was supported by the Cancer Prevention and Research Institute of Texas, the National Cancer Institute, the American Cancer Society, the Duncan Family Institute, the University of Texas M.D. Anderson Cancer Center, and the National Institutes of Health. She reported no potential financial conflicts of interest, and one of her associates reported receiving research support from Varian Medical Systems.
Low-risk prostate cancer in older men is still being overtreated, according to two separate studies that examined the issue from different perspectives, both of which were published online July 14 in JAMA Internal Medicine.
One group of researchers found that primary androgen deprivation therapy fails to improve either overall or disease-specific survival in this patient population, yet it still is widely used as the initial treatment for localized disease. And another group found that urologists and radiation oncologists are the driving force behind the overly aggressive approach to low-risk prostate cancer in older men.
Both groups of investigators called for efforts to limit these harmful trends.
In the first study, Grace L. Lu-Yao, Ph.D., and her associates analyzed information on 66,717 cases of prostate cancer in the Surveillance, Epidemiology, and End Results (SEER) and Medicaid databases diagnosed in 1992-2009. All the patients were aged 66 years and older, and all had T1/T2 disease. There were 5,275 deaths from prostate cancer and 39,801 deaths from all causes during nearly 20 years of follow-up.
Primary androgen deprivation therapy failed to improve either overall or disease-specific survival at 5 years or 15 years. Further study using instrumental variable analysis to control for an imbalance in risk factors between users and nonusers of androgen deprivation therapy confirmed these results, as did several sensitivity analyses, "suggesting that our conclusions are robust" (JAMA Intern. Med. 2014 July 14 [doi: 10.1001/jamainternmed.2014.3028]).
"For patients with less aggressive cancers, deferred androgen deprivation therapy is safe and reduces the risks of treatment-associated adverse effects, such as osteoporosis, weight gain, decreased libido, decreased muscle tone, diabetes mellitus, and metabolic syndrome," wrote Dr. Lu-Yao of Rutgers Cancer Institute of New Jersey, New Brunswick, and her associates.
"Physicians and patients often believe that treatment is necessary and beneficial. Our data suggest that this may not be the case, at least for primary androgen deprivation therapy," they said.
In the other study, investigators examined physician and patient factors that influence treatment decisions in low-risk prostate cancer. They also analyzed SEER data, this time involving 12,068 men aged 66 years and older (median age, 72 years) who were diagnosed as having low-risk prostate adenocarcinoma in 2006-2009. These men were diagnosed by 2,145 urologists; 68% of them also consulted a radiation oncologist, said Dr. Karen E. Hoffman of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.
Fully 80% of the low-risk patients diagnosed by a urologist immediately received treatment; only 20% instead underwent observation, as is recommended. The use of observation varied markedly across urologists, with some performing observation for less than 5% of their patients and others performing observation for nearly 65%. Forty urologists (10.2%) had rates of observation that were significantly different from the mean.
In analyses that estimated the relative contributions of numerous factors to treatment decisions, "the diagnosing urologist was the most influential measured factor, responsible for 16.1% of the variance in management choice; just 7.9% of the variance was attributable to patient characteristics," Dr. Hoffman and her associates reported (JAMA Intern. Med. 2014 July 14 [doi: 10.1001/jamainternmed.2014.3021]).
Similarly, of the 7,554 men who consulted 870 radiation oncologists, a remarkable 91.5% underwent immediate treatment (usually radiotherapy), while only 8.5% underwent observation, as is recommended. The use of observation also varied markedly across radiation oncologists, with some advising observation for only 2% of their patients and others advising it for 47%. Again, the variance in treatment decisions attributable to radiation oncologists was at least double that attributable to patient factors.
"In our cohort, 70.0% of men aged 76-80 years and 55.1% of men older than 80 years still received up-front treatment," a striking proportion because the average life expectancy for men 77 years and older in the United States is less than 10 years. "Older men, especially those with multiple medical conditions, are not thought to gain a survival benefit from treatment of low-risk prostate cancer," Dr. Hoffman and her colleagues noted.
Their findings are important because most primary care physicians who refer their patients to specialists for prostate biopsy or consultation probably "assume that patients will receive similar management recommendations regardless of which [specialist] they see." These results demonstrate the opposite: Patients with low-risk prostate cancer could receive widely divergent treatment advice, solely depending on the specialists’ preferences.
Dr. Lu-Yao’s study was supported by the National Cancer Institute and the Cancer Institute of New Jersey. She reported ties to Merck and Schering-Plough, and one of her associates reported receiving research funding from Myriad. Dr. Hoffman’s study was supported by the Cancer Prevention and Research Institute of Texas, the National Cancer Institute, the American Cancer Society, the Duncan Family Institute, the University of Texas M.D. Anderson Cancer Center, and the National Institutes of Health. She reported no potential financial conflicts of interest, and one of her associates reported receiving research support from Varian Medical Systems.
Low-risk prostate cancer in older men is still being overtreated, according to two separate studies that examined the issue from different perspectives, both of which were published online July 14 in JAMA Internal Medicine.
One group of researchers found that primary androgen deprivation therapy fails to improve either overall or disease-specific survival in this patient population, yet it still is widely used as the initial treatment for localized disease. And another group found that urologists and radiation oncologists are the driving force behind the overly aggressive approach to low-risk prostate cancer in older men.
Both groups of investigators called for efforts to limit these harmful trends.
In the first study, Grace L. Lu-Yao, Ph.D., and her associates analyzed information on 66,717 cases of prostate cancer in the Surveillance, Epidemiology, and End Results (SEER) and Medicaid databases diagnosed in 1992-2009. All the patients were aged 66 years and older, and all had T1/T2 disease. There were 5,275 deaths from prostate cancer and 39,801 deaths from all causes during nearly 20 years of follow-up.
Primary androgen deprivation therapy failed to improve either overall or disease-specific survival at 5 years or 15 years. Further study using instrumental variable analysis to control for an imbalance in risk factors between users and nonusers of androgen deprivation therapy confirmed these results, as did several sensitivity analyses, "suggesting that our conclusions are robust" (JAMA Intern. Med. 2014 July 14 [doi: 10.1001/jamainternmed.2014.3028]).
"For patients with less aggressive cancers, deferred androgen deprivation therapy is safe and reduces the risks of treatment-associated adverse effects, such as osteoporosis, weight gain, decreased libido, decreased muscle tone, diabetes mellitus, and metabolic syndrome," wrote Dr. Lu-Yao of Rutgers Cancer Institute of New Jersey, New Brunswick, and her associates.
"Physicians and patients often believe that treatment is necessary and beneficial. Our data suggest that this may not be the case, at least for primary androgen deprivation therapy," they said.
In the other study, investigators examined physician and patient factors that influence treatment decisions in low-risk prostate cancer. They also analyzed SEER data, this time involving 12,068 men aged 66 years and older (median age, 72 years) who were diagnosed as having low-risk prostate adenocarcinoma in 2006-2009. These men were diagnosed by 2,145 urologists; 68% of them also consulted a radiation oncologist, said Dr. Karen E. Hoffman of the University of Texas M.D. Anderson Cancer Center, Houston, and her associates.
Fully 80% of the low-risk patients diagnosed by a urologist immediately received treatment; only 20% instead underwent observation, as is recommended. The use of observation varied markedly across urologists, with some performing observation for less than 5% of their patients and others performing observation for nearly 65%. Forty urologists (10.2%) had rates of observation that were significantly different from the mean.
In analyses that estimated the relative contributions of numerous factors to treatment decisions, "the diagnosing urologist was the most influential measured factor, responsible for 16.1% of the variance in management choice; just 7.9% of the variance was attributable to patient characteristics," Dr. Hoffman and her associates reported (JAMA Intern. Med. 2014 July 14 [doi: 10.1001/jamainternmed.2014.3021]).
Similarly, of the 7,554 men who consulted 870 radiation oncologists, a remarkable 91.5% underwent immediate treatment (usually radiotherapy), while only 8.5% underwent observation, as is recommended. The use of observation also varied markedly across radiation oncologists, with some advising observation for only 2% of their patients and others advising it for 47%. Again, the variance in treatment decisions attributable to radiation oncologists was at least double that attributable to patient factors.
"In our cohort, 70.0% of men aged 76-80 years and 55.1% of men older than 80 years still received up-front treatment," a striking proportion because the average life expectancy for men 77 years and older in the United States is less than 10 years. "Older men, especially those with multiple medical conditions, are not thought to gain a survival benefit from treatment of low-risk prostate cancer," Dr. Hoffman and her colleagues noted.
Their findings are important because most primary care physicians who refer their patients to specialists for prostate biopsy or consultation probably "assume that patients will receive similar management recommendations regardless of which [specialist] they see." These results demonstrate the opposite: Patients with low-risk prostate cancer could receive widely divergent treatment advice, solely depending on the specialists’ preferences.
Dr. Lu-Yao’s study was supported by the National Cancer Institute and the Cancer Institute of New Jersey. She reported ties to Merck and Schering-Plough, and one of her associates reported receiving research funding from Myriad. Dr. Hoffman’s study was supported by the Cancer Prevention and Research Institute of Texas, the National Cancer Institute, the American Cancer Society, the Duncan Family Institute, the University of Texas M.D. Anderson Cancer Center, and the National Institutes of Health. She reported no potential financial conflicts of interest, and one of her associates reported receiving research support from Varian Medical Systems.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Patients with low-risk prostate cancer receive widely divergent treatment advice, based on specialists’ preferences above patient characteristics or evidence.
Major finding: A large database analysis showed that primary androgen deprivation therapy failed to improve either overall or disease-specific survival at 5 years or 15 years in men with low-risk prostate cancer. In another study, 80% of low-risk men diagnosed by urologists received immediate treatment rather than undergoing observation as recommended, as did 91.5% of those who consulted radiation oncologists.
Data source: A population-based cohort study involving 66,717 men aged 66 years and older diagnosed as having low-risk prostate cancer in 1992-2009, and a population-based cohort study involving 12,068 men aged 66 and older who were similarly diagnosed in 2006-2009 by 2,145 urologists and who consulted with 870 radiation oncologists.
Disclosures: Dr. Lu-Yao’s study was supported by the National Cancer Institute and the Cancer Institute of New Jersey. She reported ties to Merck and Schering-Plough, and one of her associates reported receiving research funding from Myriad. Dr. Hoffman’s study was supported by the Cancer Prevention and Research Institute of Texas, the National Cancer Institute, the American Cancer Society, the Duncan Family Institute, the University of Texas M.D. Anderson Cancer Center, and the National Institutes of Health. She reported no potential financial conflicts of interest, and one of her associates reported receiving research support from Varian Medical Systems.
For stable PE, thrombolysis may reduce mortality
Thrombolytic therapy decreased all-cause mortality in patients with hemodynamically stable pulmonary embolism associated with right ventricular dysfunction – those at "intermediate risk," according to a meta-analysis published online June 17 in JAMA.
The investigators described their study of 16 randomized, controlled clinical trials involving 2,115 patients as "the first analysis of thrombolysis in PE that has sufficient statistical power to detect associations with a meaningful mortality reduction." If their findings are confirmed in future randomized clinical trials, "there may be a shift in the treatment of selected patients with intermediate-risk PE using thrombolytics."
However, "the optimism regarding this clinical advantage must be tempered by [our] finding of significantly increased risk of major bleeding and intracranial hemorrhage associated with thrombolytic therapy, particularly for patients older than 65 years," said Dr. Saurav Chatterjee of the division of cardiology, St. Luke’s-Roosevelt Hospital Center of the Mount Sinai Health System, New York, and his associates (JAMA 2014;311:2414-21).
The study population included 1,499 patients who had hemodynamically stable PE associated with right ventricular dysfunction, the largest subset of patients seen in clinical practice and the group for whom the risks and benefits of thrombolysis are the most unclear.
After a mean follow-up of 82 days, overall mortality was 2.17% in patients who received thrombolysis, compared with 3.89% in those who received anticoagulation. In addition, the risk of recurrent PE was significantly lower with thrombolytic therapy (1.17%) than with anticoagulation (3.04%).
However, the rate of major bleeding was 9.24% for thrombolytic therapy, compared with 3.42% for anticoagulation. And the rate of intracranial hemorrhage was 1.46% for thrombolysis, compared with 0.19% for anticoagulation, the investigators said.
The bleeding risk was especially high in patients aged 65 years and older. Attenuation of this risk in younger patients suggests that they may be considered stronger candidates for thrombolytic therapy, Dr. Chatterjee and his associates said.
Dr. Chatterjee reported no financial conflicts; his associates reported ties to AstraZeneca, Boston Scientific, Cardiostem, Cordis, EKOS Corporation, Embolitech, GenWay, Johnson & Johnson, Soteria, and Vascular Magnetics.
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Dr. Joshua A. Beckman comments: Dr. Chatterjee and his associates calculated the net clinical benefit of thrombolysis, and their result "suggests evidence of modest efficacy in intermediate-risk PE."
But their findings do not yet add up to a change in the standard of care. Each clinician must decide on an individualized basis which of these patients should receive thrombolytic therapy, based on clinical presentation, comorbid conditions, and both the physician’s and the patient’s tolerance of risk.
Dr. Beckman is in the cardiovascular division at Brigham and Women’s Hospital, Boston. He reported various ties to industry. These remarks were taken from his editorial accompanying Dr. Chatterjee’s report (JAMA 2014;311:2385-6).
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Dr. Joshua A. Beckman comments: Dr. Chatterjee and his associates calculated the net clinical benefit of thrombolysis, and their result "suggests evidence of modest efficacy in intermediate-risk PE."
But their findings do not yet add up to a change in the standard of care. Each clinician must decide on an individualized basis which of these patients should receive thrombolytic therapy, based on clinical presentation, comorbid conditions, and both the physician’s and the patient’s tolerance of risk.
Dr. Beckman is in the cardiovascular division at Brigham and Women’s Hospital, Boston. He reported various ties to industry. These remarks were taken from his editorial accompanying Dr. Chatterjee’s report (JAMA 2014;311:2385-6).
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Dr. Joshua A. Beckman comments: Dr. Chatterjee and his associates calculated the net clinical benefit of thrombolysis, and their result "suggests evidence of modest efficacy in intermediate-risk PE."
But their findings do not yet add up to a change in the standard of care. Each clinician must decide on an individualized basis which of these patients should receive thrombolytic therapy, based on clinical presentation, comorbid conditions, and both the physician’s and the patient’s tolerance of risk.
Dr. Beckman is in the cardiovascular division at Brigham and Women’s Hospital, Boston. He reported various ties to industry. These remarks were taken from his editorial accompanying Dr. Chatterjee’s report (JAMA 2014;311:2385-6).
Thrombolytic therapy decreased all-cause mortality in patients with hemodynamically stable pulmonary embolism associated with right ventricular dysfunction – those at "intermediate risk," according to a meta-analysis published online June 17 in JAMA.
The investigators described their study of 16 randomized, controlled clinical trials involving 2,115 patients as "the first analysis of thrombolysis in PE that has sufficient statistical power to detect associations with a meaningful mortality reduction." If their findings are confirmed in future randomized clinical trials, "there may be a shift in the treatment of selected patients with intermediate-risk PE using thrombolytics."
However, "the optimism regarding this clinical advantage must be tempered by [our] finding of significantly increased risk of major bleeding and intracranial hemorrhage associated with thrombolytic therapy, particularly for patients older than 65 years," said Dr. Saurav Chatterjee of the division of cardiology, St. Luke’s-Roosevelt Hospital Center of the Mount Sinai Health System, New York, and his associates (JAMA 2014;311:2414-21).
The study population included 1,499 patients who had hemodynamically stable PE associated with right ventricular dysfunction, the largest subset of patients seen in clinical practice and the group for whom the risks and benefits of thrombolysis are the most unclear.
After a mean follow-up of 82 days, overall mortality was 2.17% in patients who received thrombolysis, compared with 3.89% in those who received anticoagulation. In addition, the risk of recurrent PE was significantly lower with thrombolytic therapy (1.17%) than with anticoagulation (3.04%).
However, the rate of major bleeding was 9.24% for thrombolytic therapy, compared with 3.42% for anticoagulation. And the rate of intracranial hemorrhage was 1.46% for thrombolysis, compared with 0.19% for anticoagulation, the investigators said.
The bleeding risk was especially high in patients aged 65 years and older. Attenuation of this risk in younger patients suggests that they may be considered stronger candidates for thrombolytic therapy, Dr. Chatterjee and his associates said.
Dr. Chatterjee reported no financial conflicts; his associates reported ties to AstraZeneca, Boston Scientific, Cardiostem, Cordis, EKOS Corporation, Embolitech, GenWay, Johnson & Johnson, Soteria, and Vascular Magnetics.
Thrombolytic therapy decreased all-cause mortality in patients with hemodynamically stable pulmonary embolism associated with right ventricular dysfunction – those at "intermediate risk," according to a meta-analysis published online June 17 in JAMA.
The investigators described their study of 16 randomized, controlled clinical trials involving 2,115 patients as "the first analysis of thrombolysis in PE that has sufficient statistical power to detect associations with a meaningful mortality reduction." If their findings are confirmed in future randomized clinical trials, "there may be a shift in the treatment of selected patients with intermediate-risk PE using thrombolytics."
However, "the optimism regarding this clinical advantage must be tempered by [our] finding of significantly increased risk of major bleeding and intracranial hemorrhage associated with thrombolytic therapy, particularly for patients older than 65 years," said Dr. Saurav Chatterjee of the division of cardiology, St. Luke’s-Roosevelt Hospital Center of the Mount Sinai Health System, New York, and his associates (JAMA 2014;311:2414-21).
The study population included 1,499 patients who had hemodynamically stable PE associated with right ventricular dysfunction, the largest subset of patients seen in clinical practice and the group for whom the risks and benefits of thrombolysis are the most unclear.
After a mean follow-up of 82 days, overall mortality was 2.17% in patients who received thrombolysis, compared with 3.89% in those who received anticoagulation. In addition, the risk of recurrent PE was significantly lower with thrombolytic therapy (1.17%) than with anticoagulation (3.04%).
However, the rate of major bleeding was 9.24% for thrombolytic therapy, compared with 3.42% for anticoagulation. And the rate of intracranial hemorrhage was 1.46% for thrombolysis, compared with 0.19% for anticoagulation, the investigators said.
The bleeding risk was especially high in patients aged 65 years and older. Attenuation of this risk in younger patients suggests that they may be considered stronger candidates for thrombolytic therapy, Dr. Chatterjee and his associates said.
Dr. Chatterjee reported no financial conflicts; his associates reported ties to AstraZeneca, Boston Scientific, Cardiostem, Cordis, EKOS Corporation, Embolitech, GenWay, Johnson & Johnson, Soteria, and Vascular Magnetics.
Key clinical point: Thrombolysis may be a therapeutic alternative to anticoagulation in some patients with stable, intermediate-risk pulmonary embolism.
Major finding: Mortality was 2.17% in PE patients who received thrombolysis, compared with 3.89% in those who received anticoagulation; the risk of recurrent PE also was significantly lower with thrombolytic therapy (1.17%) than with anticoagulation (3.04%).
Data source: A meta-analysis of 16 randomized, controlled trials involving 2,115 patients with PE, including 1,499 with intermediate-risk PE, who were followed for a mean of 82 days.
Disclosures: Dr. Chatterjee reported no financial conflicts; his associates reported several industry ties.to AstraZeneca, Boston Scientific, Cardiostem, Cordis, EKOS Corporation, Embolitech, GenWay, Johnson & Johnson, Soteria, and Vascular Magnetics.
