Mary Ann Moon

Whether patients with rheumatoid arthritis receive appropriate antirheumatic medications varies widely and depends on their age, sex, race, income, the neighborhood and area of the country where they reside, and their health care plan, according to a study in the Feb. 2 issue of JAMA.

"Although RA was once an inevitably deforming and disabling condition, the development of new DMARDs [disease-modifying antirheumatic drugs] and support for their early use has dramatically improved clinical outcomes for many patients. This study suggests that one mechanism for the sociodemographic disparities in RA outcomes in the United States may relate to differences in DMARD receipt," wrote Dr. Gabriela Schmajuk of Stanford (Calif.) University and her associates.

Recent population-based studies have shown consistently low rates of DMARD use, even though evidence-based guidelines recommend early and aggressive treatment. Dr. Schmajuk and her colleagues assessed medication use in a cohort of 93,143 RA patients enrolled in Medicare managed care plans during a recent 4-year period; the cohort comprises a nationally representative sample of the managed care population aged 65 years and older.

Overall, 37% of patients were not receiving DMARDs. These include abatacept, adalimumab, anakinra, azathioprine, cyclophosphamide, cyclosporine, etanercept, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, penicillamine, rituximab, staphylococcal protein A, and sulfasalazine.

In some cases, patients may have declined DMARD treatment, may have had quiescent disease that didn't require treatment, or may have had contraindications to all 17 of these drugs.

The greatest variation in the rate of DMARD use occurred by patient age: Only 42% of patients aged 85 years or older received DMARDs, compared with 72% of those aged 65-69 years. While it is possible that older patients had more comorbidities limiting their ability to use these drugs, it also is possible that age bias played a role in this result, the investigators said.

Men had slightly lower rates of use than women, and patients self-identified as black or "other" had lower rates of use (57% and 58%, respectively) than white patients (64%).

The rate of DMARD use was 55% among patients with a low personal income, compared with 64% among those with higher incomes. Similarly, patients who lived in neighborhoods of low socioeconomic status were less likely to be taking DMARDs than patients living in neighborhoods with higher socioeconomic status. It is possible that some of these patients don’t get DMARDs because they are unable to afford copayments or other forms of cost sharing, the investigators said.

Patients living in the South Atlantic and Middle Atlantic regions of the country had rates of use that were 10% lower than those living in other regions.

The use of DMARDs was 6% lower among patients enrolled in for-profit health plans than among those enrolled in not-for-profit plans, a difference that was small but statistically significant.

However, variability by health plan was much greater than that statistic alone would convey. Rates of use of DMARDs varied from a low of 16% in one health plan to a high of 87% in another, even after the data had been adjusted to account for differences in case mix. This finding is "concerning," Dr. Schmajuk and her associates said (JAMA 2011;305:480-86).

It is unknown whether this 70-point difference is due to differences in the availability or accessibility of specialty care within some health plans or differences in allowances on prescription drug benefits between health plans. It may even reflect in part inaccurate reporting on the forms used to collect the data, they added.

Whatever the explanations, the large variations in DMARD use are "unacceptable," the researchers said.

"Targeting educational and quality improvement interventions to patients who are underusing DMARDs and their clinicians will be important to eliminate these disparities," they said.

This study was supported by the American College of Rheumatology, National Center for Research Resources, Rosalind Russell Medical Research Centers for Arthritis, National Institutes of Health, State of California Lupus Fund, Arthritis Foundation, Agency for Healthcare Research and Quality, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. An associate of Dr. Schmajuk reported financial ties to Merck and the Pfizer Foundation.

Whether patients with rheumatoid arthritis receive appropriate antirheumatic medications varies widely and depends on their age, sex, race, income, the neighborhood and area of the country where they reside, and their health care plan, according to a study in the Feb. 2 issue of JAMA.

"Although RA was once an inevitably deforming and disabling condition, the development of new DMARDs [disease-modifying antirheumatic drugs] and support for their early use has dramatically improved clinical outcomes for many patients. This study suggests that one mechanism for the sociodemographic disparities in RA outcomes in the United States may relate to differences in DMARD receipt," wrote Dr. Gabriela Schmajuk of Stanford (Calif.) University and her associates.

Recent population-based studies have shown consistently low rates of DMARD use, even though evidence-based guidelines recommend early and aggressive treatment. Dr. Schmajuk and her colleagues assessed medication use in a cohort of 93,143 RA patients enrolled in Medicare managed care plans during a recent 4-year period; the cohort comprises a nationally representative sample of the managed care population aged 65 years and older.

Overall, 37% of patients were not receiving DMARDs. These include abatacept, adalimumab, anakinra, azathioprine, cyclophosphamide, cyclosporine, etanercept, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, penicillamine, rituximab, staphylococcal protein A, and sulfasalazine.

In some cases, patients may have declined DMARD treatment, may have had quiescent disease that didn't require treatment, or may have had contraindications to all 17 of these drugs.

The greatest variation in the rate of DMARD use occurred by patient age: Only 42% of patients aged 85 years or older received DMARDs, compared with 72% of those aged 65-69 years. While it is possible that older patients had more comorbidities limiting their ability to use these drugs, it also is possible that age bias played a role in this result, the investigators said.

Men had slightly lower rates of use than women, and patients self-identified as black or "other" had lower rates of use (57% and 58%, respectively) than white patients (64%).

The rate of DMARD use was 55% among patients with a low personal income, compared with 64% among those with higher incomes. Similarly, patients who lived in neighborhoods of low socioeconomic status were less likely to be taking DMARDs than patients living in neighborhoods with higher socioeconomic status. It is possible that some of these patients don’t get DMARDs because they are unable to afford copayments or other forms of cost sharing, the investigators said.

Patients living in the South Atlantic and Middle Atlantic regions of the country had rates of use that were 10% lower than those living in other regions.

The use of DMARDs was 6% lower among patients enrolled in for-profit health plans than among those enrolled in not-for-profit plans, a difference that was small but statistically significant.

However, variability by health plan was much greater than that statistic alone would convey. Rates of use of DMARDs varied from a low of 16% in one health plan to a high of 87% in another, even after the data had been adjusted to account for differences in case mix. This finding is "concerning," Dr. Schmajuk and her associates said (JAMA 2011;305:480-86).

It is unknown whether this 70-point difference is due to differences in the availability or accessibility of specialty care within some health plans or differences in allowances on prescription drug benefits between health plans. It may even reflect in part inaccurate reporting on the forms used to collect the data, they added.

Whatever the explanations, the large variations in DMARD use are "unacceptable," the researchers said.

"Targeting educational and quality improvement interventions to patients who are underusing DMARDs and their clinicians will be important to eliminate these disparities," they said.

This study was supported by the American College of Rheumatology, National Center for Research Resources, Rosalind Russell Medical Research Centers for Arthritis, National Institutes of Health, State of California Lupus Fund, Arthritis Foundation, Agency for Healthcare Research and Quality, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. An associate of Dr. Schmajuk reported financial ties to Merck and the Pfizer Foundation.

Whether patients with rheumatoid arthritis receive appropriate antirheumatic medications varies widely and depends on their age, sex, race, income, the neighborhood and area of the country where they reside, and their health care plan, according to a study in the Feb. 2 issue of JAMA.

"Although RA was once an inevitably deforming and disabling condition, the development of new DMARDs [disease-modifying antirheumatic drugs] and support for their early use has dramatically improved clinical outcomes for many patients. This study suggests that one mechanism for the sociodemographic disparities in RA outcomes in the United States may relate to differences in DMARD receipt," wrote Dr. Gabriela Schmajuk of Stanford (Calif.) University and her associates.

Recent population-based studies have shown consistently low rates of DMARD use, even though evidence-based guidelines recommend early and aggressive treatment. Dr. Schmajuk and her colleagues assessed medication use in a cohort of 93,143 RA patients enrolled in Medicare managed care plans during a recent 4-year period; the cohort comprises a nationally representative sample of the managed care population aged 65 years and older.

Overall, 37% of patients were not receiving DMARDs. These include abatacept, adalimumab, anakinra, azathioprine, cyclophosphamide, cyclosporine, etanercept, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, penicillamine, rituximab, staphylococcal protein A, and sulfasalazine.

In some cases, patients may have declined DMARD treatment, may have had quiescent disease that didn't require treatment, or may have had contraindications to all 17 of these drugs.

The greatest variation in the rate of DMARD use occurred by patient age: Only 42% of patients aged 85 years or older received DMARDs, compared with 72% of those aged 65-69 years. While it is possible that older patients had more comorbidities limiting their ability to use these drugs, it also is possible that age bias played a role in this result, the investigators said.

Men had slightly lower rates of use than women, and patients self-identified as black or "other" had lower rates of use (57% and 58%, respectively) than white patients (64%).

The rate of DMARD use was 55% among patients with a low personal income, compared with 64% among those with higher incomes. Similarly, patients who lived in neighborhoods of low socioeconomic status were less likely to be taking DMARDs than patients living in neighborhoods with higher socioeconomic status. It is possible that some of these patients don’t get DMARDs because they are unable to afford copayments or other forms of cost sharing, the investigators said.

Patients living in the South Atlantic and Middle Atlantic regions of the country had rates of use that were 10% lower than those living in other regions.

The use of DMARDs was 6% lower among patients enrolled in for-profit health plans than among those enrolled in not-for-profit plans, a difference that was small but statistically significant.

However, variability by health plan was much greater than that statistic alone would convey. Rates of use of DMARDs varied from a low of 16% in one health plan to a high of 87% in another, even after the data had been adjusted to account for differences in case mix. This finding is "concerning," Dr. Schmajuk and her associates said (JAMA 2011;305:480-86).

It is unknown whether this 70-point difference is due to differences in the availability or accessibility of specialty care within some health plans or differences in allowances on prescription drug benefits between health plans. It may even reflect in part inaccurate reporting on the forms used to collect the data, they added.

Whatever the explanations, the large variations in DMARD use are "unacceptable," the researchers said.

"Targeting educational and quality improvement interventions to patients who are underusing DMARDs and their clinicians will be important to eliminate these disparities," they said.

This study was supported by the American College of Rheumatology, National Center for Research Resources, Rosalind Russell Medical Research Centers for Arthritis, National Institutes of Health, State of California Lupus Fund, Arthritis Foundation, Agency for Healthcare Research and Quality, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. An associate of Dr. Schmajuk reported financial ties to Merck and the Pfizer Foundation.

For a variety of advanced solid tumors, the incidence of fatal adverse effects is significantly higher when bevacizumab is added to chemotherapy than when chemotherapy is used alone, according to a meta-analysis published in the Feb. 2 issue of JAMA.

The most common fatal adverse effects associated with bevacizumab (Avastin), a monoclonal antibody targeting the vascular endothelial growth factor (VEGF), were hemorrhage, neutropenia, and gastrointestinal tract perforation, said Dr. Vishal Ranpura and associates at Stony Brook (N.Y.) University Medical Center.

The investigators conducted the meta-analysis because data from clinical trials have been conflicting, and bevacizumab’s role in fatal events in cancer patients "has not been definitively established." VEGF is key to vascular function and angiogenesis, and its inhibition by bevacizumab has been linked to wound dehiscence, bleeding, thromboembolic events, and bowel perforation.

The researchers scanned 385 potentially relevant clinical studies and chose 16 randomized controlled trials for inclusion in the meta-analysis. These comprised phase II and phase III trials involving 10,217 patients given either bevacizumab (5,589 subjects) or a placebo or control agent (4,628 subjects), in addition to standard chemotherapy, for the treatment of advanced colorectal, breast, renal cell, pancreatic, prostate, or non–small-cell lung cancer.

There were 148 fatal adverse events. The incidence was 2.5% among patients receiving bevacizumab, compared with 1.7% in the control patients. The summary relative risk was 1.46, indicating a significantly increased risk of fatal adverse events when bevacizumab was added to conventional chemotherapy.

Approximately 45% of the bevacizumab-associated fatalities were attributed to specific causes, chiefly hemorrhage, perforation of the gastrointestinal tract, and neutropenia. Fatal pulmonary hemorrhage was especially common, perhaps because bleeding in the lungs "is difficult to control and can cause immediate respiratory failure and death," Dr. Ranpura and colleagues said (JAMA 2011;305:487-94).

Treatment with taxanes and platinum agents appeared to raise the risk of fatal events associated with bevacizumab. This may reflect an interaction between these classes of drugs and bevacizumab, the researchers said.

Similarly, the risk of fatal events appeared to vary according to tumor type and bevacizumab dose, but these associations did not reach statistical significance, perhaps because the sample size was not large enough to detect a difference.

These results indicate that patients treated with bevacizumab should be monitored carefully so that potentially fatal adverse events can be quickly identified and treated, they noted.

This study was funded in part by the Research Foundation of the State University of New York at Stony Brook. An associate of Dr. Ranpura reported ties to Onyx, Novartis, Pfizer, Amgen, and Genentech.

For a variety of advanced solid tumors, the incidence of fatal adverse effects is significantly higher when bevacizumab is added to chemotherapy than when chemotherapy is used alone, according to a meta-analysis published in the Feb. 2 issue of JAMA.

The most common fatal adverse effects associated with bevacizumab (Avastin), a monoclonal antibody targeting the vascular endothelial growth factor (VEGF), were hemorrhage, neutropenia, and gastrointestinal tract perforation, said Dr. Vishal Ranpura and associates at Stony Brook (N.Y.) University Medical Center.

The investigators conducted the meta-analysis because data from clinical trials have been conflicting, and bevacizumab’s role in fatal events in cancer patients "has not been definitively established." VEGF is key to vascular function and angiogenesis, and its inhibition by bevacizumab has been linked to wound dehiscence, bleeding, thromboembolic events, and bowel perforation.

The researchers scanned 385 potentially relevant clinical studies and chose 16 randomized controlled trials for inclusion in the meta-analysis. These comprised phase II and phase III trials involving 10,217 patients given either bevacizumab (5,589 subjects) or a placebo or control agent (4,628 subjects), in addition to standard chemotherapy, for the treatment of advanced colorectal, breast, renal cell, pancreatic, prostate, or non–small-cell lung cancer.

There were 148 fatal adverse events. The incidence was 2.5% among patients receiving bevacizumab, compared with 1.7% in the control patients. The summary relative risk was 1.46, indicating a significantly increased risk of fatal adverse events when bevacizumab was added to conventional chemotherapy.

Approximately 45% of the bevacizumab-associated fatalities were attributed to specific causes, chiefly hemorrhage, perforation of the gastrointestinal tract, and neutropenia. Fatal pulmonary hemorrhage was especially common, perhaps because bleeding in the lungs "is difficult to control and can cause immediate respiratory failure and death," Dr. Ranpura and colleagues said (JAMA 2011;305:487-94).

Treatment with taxanes and platinum agents appeared to raise the risk of fatal events associated with bevacizumab. This may reflect an interaction between these classes of drugs and bevacizumab, the researchers said.

Similarly, the risk of fatal events appeared to vary according to tumor type and bevacizumab dose, but these associations did not reach statistical significance, perhaps because the sample size was not large enough to detect a difference.

These results indicate that patients treated with bevacizumab should be monitored carefully so that potentially fatal adverse events can be quickly identified and treated, they noted.

This study was funded in part by the Research Foundation of the State University of New York at Stony Brook. An associate of Dr. Ranpura reported ties to Onyx, Novartis, Pfizer, Amgen, and Genentech.

For a variety of advanced solid tumors, the incidence of fatal adverse effects is significantly higher when bevacizumab is added to chemotherapy than when chemotherapy is used alone, according to a meta-analysis published in the Feb. 2 issue of JAMA.

The most common fatal adverse effects associated with bevacizumab (Avastin), a monoclonal antibody targeting the vascular endothelial growth factor (VEGF), were hemorrhage, neutropenia, and gastrointestinal tract perforation, said Dr. Vishal Ranpura and associates at Stony Brook (N.Y.) University Medical Center.

The investigators conducted the meta-analysis because data from clinical trials have been conflicting, and bevacizumab’s role in fatal events in cancer patients "has not been definitively established." VEGF is key to vascular function and angiogenesis, and its inhibition by bevacizumab has been linked to wound dehiscence, bleeding, thromboembolic events, and bowel perforation.

The researchers scanned 385 potentially relevant clinical studies and chose 16 randomized controlled trials for inclusion in the meta-analysis. These comprised phase II and phase III trials involving 10,217 patients given either bevacizumab (5,589 subjects) or a placebo or control agent (4,628 subjects), in addition to standard chemotherapy, for the treatment of advanced colorectal, breast, renal cell, pancreatic, prostate, or non–small-cell lung cancer.

There were 148 fatal adverse events. The incidence was 2.5% among patients receiving bevacizumab, compared with 1.7% in the control patients. The summary relative risk was 1.46, indicating a significantly increased risk of fatal adverse events when bevacizumab was added to conventional chemotherapy.

Approximately 45% of the bevacizumab-associated fatalities were attributed to specific causes, chiefly hemorrhage, perforation of the gastrointestinal tract, and neutropenia. Fatal pulmonary hemorrhage was especially common, perhaps because bleeding in the lungs "is difficult to control and can cause immediate respiratory failure and death," Dr. Ranpura and colleagues said (JAMA 2011;305:487-94).

Treatment with taxanes and platinum agents appeared to raise the risk of fatal events associated with bevacizumab. This may reflect an interaction between these classes of drugs and bevacizumab, the researchers said.

Similarly, the risk of fatal events appeared to vary according to tumor type and bevacizumab dose, but these associations did not reach statistical significance, perhaps because the sample size was not large enough to detect a difference.

These results indicate that patients treated with bevacizumab should be monitored carefully so that potentially fatal adverse events can be quickly identified and treated, they noted.

This study was funded in part by the Research Foundation of the State University of New York at Stony Brook. An associate of Dr. Ranpura reported ties to Onyx, Novartis, Pfizer, Amgen, and Genentech.

Budesonide was found noninferior to, but not better than, mesalamine for inducing remission of mildly to moderately active Crohn’s disease in an international phase III clinical trial, Dr. Andreas Tromm and his colleagues reported in the February issue of Gastroenterology.

In addition, once-daily dosing with 9 mg of budesonide was as effective as was the standard regimen of 3-mg doses taken three times daily. "From a clinical practice perspective, it would seem justified to recommend the budesonide 9 mg once-daily regimen, since this would be expected to improve adherence," said Dr. Tromm of Evangelisches Hospital Hattingen (Germany) and his associates (Gastroenterology 2011 February [doi:10.1053/j.gastro.2010.11.004]).

Recent guidelines from the European Crohn’s and Colitis Organisation recommend budesonide as more effective than mesalamine for mildly active, localized ileocecal Crohn’s disease, and also recommend that budesonide or systemic corticosteroids are preferable for treating moderately active localized ileocecal disease. Budesonide has a superior adverse effect profile and is better able to preserve adrenal function and bone mass, the authors wrote.

"However, only a single randomized study ... [involving only 182 subjects] a decade ago has directly compared the efficacy and safety of budesonide versus mesalamine for the management of active Crohn’s disease," they added. No studies have explored the use of different dosing regimens.

Dr. Tromm and his colleagues performed a double-blind phase III clinical trial in which adults with mildly to moderately active Crohn’s disease were randomly assigned to receive eudragit-L-coated mesalamine tablets 4.5 g/day (153 patients), 3-mg budesonide capsules three times per day (79 patients), or one 9-mg oral budesonide capsule once daily (77 patients), for 8 weeks. The study subjects were followed every 2 weeks at 46 gastroenterology clinics in Croatia, the Czech Republic, Germany, Greece, Hungary, Israel, and the Slovak Republic.

The mean Crohn’s Disease Activity Index (CDAI) score was higher in both budesonide groups than in the mesalamine group, and both budesonide groups had a higher proportion of patients with CDAI scores over 300. Also, both budesonide groups had more patients with extraintestinal manifestations of Crohn’s disease. Otherwise there were no meaningful differences among the study groups in clinical characteristics.

The primary efficacy end point was clinical remission (a CDAI score of 150 or less) at the conclusion of the trial. Remission occurred in 70% of the patients taking budesonide, compared with 62% of those taking mesalamine. This difference was not statistically significant but did meet the criteria for noninferiority in effectiveness.

More physicians rated budesonide as achieving "therapeutic success" or "therapeutic benefit" than mesalamine, but this difference also did not reach statistical significance.

Remission rates did not differ significantly between the once-daily (67%) and thrice-daily (72%) budesonide groups, nor did any other efficacy end points. "Although tested in only an exploratory sense, these data suggest that once-daily or thrice-daily administration does not affect the efficacy of budesonide," Dr. Tromm and his colleagues said.

The subgroup of female patients demonstrated a greater clinical response to budesonide (75% remission) than to mesalamine (57%). "Whether this finding reflects a genuine treatment effect remains uncertain, since other studies of budesonide for active Crohn’s disease have observed no gender-specific effects," they noted.

The greatest difference in treatment response was seen in the subgroups of patients who had high CDAI scores or high CRP levels at baseline, indicating greater severity of inflammation. Sixty-six percent of patients with high baseline CDAI scores remitted with budesonide, compared with only 49% of those with high CDAI scores who took mesalamine. The remission rate was 65% with budesonide for patients with high baseline CRP levels, compared with only 52% with mesalamine.

Median time to treatment response and median time to remission did not differ among the three treatment groups. Similarly, the median decrease in CDAI scores did not differ, and it was significant with all three drug regimens.

Adverse events occurred in 39% of patients taking t.i.d. budesonide, 47% of those taking once-daily budesonide, and 47% of those taking mesalamine. The corresponding rates of adverse events suspected to be drug related were 10%, 12%, and 7%.

The rates of treatment cessation because of adverse events were 3% with budesonide and 5% with mesalamine.

The study was funded by Dr. Falk Pharma GmbH. Dr. Tromm disclosed receiving speakers’ honoraria and travel funding from Dr. Falk Pharma, and several authors are employees of the company, whereas other authors had no conflicts of interest to disclose.

Budesonide was found noninferior to, but not better than, mesalamine for inducing remission of mildly to moderately active Crohn’s disease in an international phase III clinical trial, Dr. Andreas Tromm and his colleagues reported in the February issue of Gastroenterology.

In addition, once-daily dosing with 9 mg of budesonide was as effective as was the standard regimen of 3-mg doses taken three times daily. "From a clinical practice perspective, it would seem justified to recommend the budesonide 9 mg once-daily regimen, since this would be expected to improve adherence," said Dr. Tromm of Evangelisches Hospital Hattingen (Germany) and his associates (Gastroenterology 2011 February [doi:10.1053/j.gastro.2010.11.004]).

Recent guidelines from the European Crohn’s and Colitis Organisation recommend budesonide as more effective than mesalamine for mildly active, localized ileocecal Crohn’s disease, and also recommend that budesonide or systemic corticosteroids are preferable for treating moderately active localized ileocecal disease. Budesonide has a superior adverse effect profile and is better able to preserve adrenal function and bone mass, the authors wrote.

"However, only a single randomized study ... [involving only 182 subjects] a decade ago has directly compared the efficacy and safety of budesonide versus mesalamine for the management of active Crohn’s disease," they added. No studies have explored the use of different dosing regimens.

Dr. Tromm and his colleagues performed a double-blind phase III clinical trial in which adults with mildly to moderately active Crohn’s disease were randomly assigned to receive eudragit-L-coated mesalamine tablets 4.5 g/day (153 patients), 3-mg budesonide capsules three times per day (79 patients), or one 9-mg oral budesonide capsule once daily (77 patients), for 8 weeks. The study subjects were followed every 2 weeks at 46 gastroenterology clinics in Croatia, the Czech Republic, Germany, Greece, Hungary, Israel, and the Slovak Republic.

The mean Crohn’s Disease Activity Index (CDAI) score was higher in both budesonide groups than in the mesalamine group, and both budesonide groups had a higher proportion of patients with CDAI scores over 300. Also, both budesonide groups had more patients with extraintestinal manifestations of Crohn’s disease. Otherwise there were no meaningful differences among the study groups in clinical characteristics.

The primary efficacy end point was clinical remission (a CDAI score of 150 or less) at the conclusion of the trial. Remission occurred in 70% of the patients taking budesonide, compared with 62% of those taking mesalamine. This difference was not statistically significant but did meet the criteria for noninferiority in effectiveness.

More physicians rated budesonide as achieving "therapeutic success" or "therapeutic benefit" than mesalamine, but this difference also did not reach statistical significance.

Remission rates did not differ significantly between the once-daily (67%) and thrice-daily (72%) budesonide groups, nor did any other efficacy end points. "Although tested in only an exploratory sense, these data suggest that once-daily or thrice-daily administration does not affect the efficacy of budesonide," Dr. Tromm and his colleagues said.

The subgroup of female patients demonstrated a greater clinical response to budesonide (75% remission) than to mesalamine (57%). "Whether this finding reflects a genuine treatment effect remains uncertain, since other studies of budesonide for active Crohn’s disease have observed no gender-specific effects," they noted.

The greatest difference in treatment response was seen in the subgroups of patients who had high CDAI scores or high CRP levels at baseline, indicating greater severity of inflammation. Sixty-six percent of patients with high baseline CDAI scores remitted with budesonide, compared with only 49% of those with high CDAI scores who took mesalamine. The remission rate was 65% with budesonide for patients with high baseline CRP levels, compared with only 52% with mesalamine.

Median time to treatment response and median time to remission did not differ among the three treatment groups. Similarly, the median decrease in CDAI scores did not differ, and it was significant with all three drug regimens.

Adverse events occurred in 39% of patients taking t.i.d. budesonide, 47% of those taking once-daily budesonide, and 47% of those taking mesalamine. The corresponding rates of adverse events suspected to be drug related were 10%, 12%, and 7%.

The rates of treatment cessation because of adverse events were 3% with budesonide and 5% with mesalamine.

The study was funded by Dr. Falk Pharma GmbH. Dr. Tromm disclosed receiving speakers’ honoraria and travel funding from Dr. Falk Pharma, and several authors are employees of the company, whereas other authors had no conflicts of interest to disclose.

Budesonide was found noninferior to, but not better than, mesalamine for inducing remission of mildly to moderately active Crohn’s disease in an international phase III clinical trial, Dr. Andreas Tromm and his colleagues reported in the February issue of Gastroenterology.

In addition, once-daily dosing with 9 mg of budesonide was as effective as was the standard regimen of 3-mg doses taken three times daily. "From a clinical practice perspective, it would seem justified to recommend the budesonide 9 mg once-daily regimen, since this would be expected to improve adherence," said Dr. Tromm of Evangelisches Hospital Hattingen (Germany) and his associates (Gastroenterology 2011 February [doi:10.1053/j.gastro.2010.11.004]).

Recent guidelines from the European Crohn’s and Colitis Organisation recommend budesonide as more effective than mesalamine for mildly active, localized ileocecal Crohn’s disease, and also recommend that budesonide or systemic corticosteroids are preferable for treating moderately active localized ileocecal disease. Budesonide has a superior adverse effect profile and is better able to preserve adrenal function and bone mass, the authors wrote.

"However, only a single randomized study ... [involving only 182 subjects] a decade ago has directly compared the efficacy and safety of budesonide versus mesalamine for the management of active Crohn’s disease," they added. No studies have explored the use of different dosing regimens.

Dr. Tromm and his colleagues performed a double-blind phase III clinical trial in which adults with mildly to moderately active Crohn’s disease were randomly assigned to receive eudragit-L-coated mesalamine tablets 4.5 g/day (153 patients), 3-mg budesonide capsules three times per day (79 patients), or one 9-mg oral budesonide capsule once daily (77 patients), for 8 weeks. The study subjects were followed every 2 weeks at 46 gastroenterology clinics in Croatia, the Czech Republic, Germany, Greece, Hungary, Israel, and the Slovak Republic.

The mean Crohn’s Disease Activity Index (CDAI) score was higher in both budesonide groups than in the mesalamine group, and both budesonide groups had a higher proportion of patients with CDAI scores over 300. Also, both budesonide groups had more patients with extraintestinal manifestations of Crohn’s disease. Otherwise there were no meaningful differences among the study groups in clinical characteristics.

The primary efficacy end point was clinical remission (a CDAI score of 150 or less) at the conclusion of the trial. Remission occurred in 70% of the patients taking budesonide, compared with 62% of those taking mesalamine. This difference was not statistically significant but did meet the criteria for noninferiority in effectiveness.

More physicians rated budesonide as achieving "therapeutic success" or "therapeutic benefit" than mesalamine, but this difference also did not reach statistical significance.

Remission rates did not differ significantly between the once-daily (67%) and thrice-daily (72%) budesonide groups, nor did any other efficacy end points. "Although tested in only an exploratory sense, these data suggest that once-daily or thrice-daily administration does not affect the efficacy of budesonide," Dr. Tromm and his colleagues said.

The subgroup of female patients demonstrated a greater clinical response to budesonide (75% remission) than to mesalamine (57%). "Whether this finding reflects a genuine treatment effect remains uncertain, since other studies of budesonide for active Crohn’s disease have observed no gender-specific effects," they noted.

The greatest difference in treatment response was seen in the subgroups of patients who had high CDAI scores or high CRP levels at baseline, indicating greater severity of inflammation. Sixty-six percent of patients with high baseline CDAI scores remitted with budesonide, compared with only 49% of those with high CDAI scores who took mesalamine. The remission rate was 65% with budesonide for patients with high baseline CRP levels, compared with only 52% with mesalamine.

Median time to treatment response and median time to remission did not differ among the three treatment groups. Similarly, the median decrease in CDAI scores did not differ, and it was significant with all three drug regimens.

Adverse events occurred in 39% of patients taking t.i.d. budesonide, 47% of those taking once-daily budesonide, and 47% of those taking mesalamine. The corresponding rates of adverse events suspected to be drug related were 10%, 12%, and 7%.

The rates of treatment cessation because of adverse events were 3% with budesonide and 5% with mesalamine.

The study was funded by Dr. Falk Pharma GmbH. Dr. Tromm disclosed receiving speakers’ honoraria and travel funding from Dr. Falk Pharma, and several authors are employees of the company, whereas other authors had no conflicts of interest to disclose.

Budesonide was found noninferior to, but not better than, mesalamine for inducing remission of mildly to moderately active Crohn’s disease in an international phase III clinical trial, Dr. Andreas Tromm and his colleagues reported in the February issue of Gastroenterology.

In addition, once-daily dosing with 9 mg of budesonide was as effective as was the standard regimen of 3-mg doses taken three times daily. "From a clinical practice perspective, it would seem justified to recommend the budesonide 9 mg once-daily regimen, since this would be expected to improve adherence," said Dr. Tromm of Evangelisches Hospital Hattingen (Germany) and his associates (Gastroenterology 2011 February [doi:10.1053/j.gastro.2010.11.004]).

Recent guidelines from the European Crohn’s and Colitis Organisation recommend budesonide as more effective than mesalamine for mildly active, localized ileocecal Crohn’s disease, and also recommend that budesonide or systemic corticosteroids are preferable for treating moderately active localized ileocecal disease. Budesonide has a superior adverse effect profile and is better able to preserve adrenal function and bone mass, the authors wrote.

"However, only a single randomized study ... [involving only 182 subjects] a decade ago has directly compared the efficacy and safety of budesonide versus mesalamine for the management of active Crohn’s disease," they added. No studies have explored the use of different dosing regimens.

Dr. Tromm and his colleagues performed a double-blind phase III clinical trial in which adults with mildly to moderately active Crohn’s disease were randomly assigned to receive eudragit-L-coated mesalamine tablets 4.5 g/day (153 patients), 3-mg budesonide capsules three times per day (79 patients), or one 9-mg oral budesonide capsule once daily (77 patients), for 8 weeks. The study subjects were followed every 2 weeks at 46 gastroenterology clinics in Croatia, the Czech Republic, Germany, Greece, Hungary, Israel, and the Slovak Republic.

The mean Crohn’s Disease Activity Index (CDAI) score was higher in both budesonide groups than in the mesalamine group, and both budesonide groups had a higher proportion of patients with CDAI scores over 300. Also, both budesonide groups had more patients with extraintestinal manifestations of Crohn’s disease. Otherwise there were no meaningful differences among the study groups in clinical characteristics.

The primary efficacy end point was clinical remission (a CDAI score of 150 or less) at the conclusion of the trial. Remission occurred in 70% of the patients taking budesonide, compared with 62% of those taking mesalamine. This difference was not statistically significant but did meet the criteria for noninferiority in effectiveness.

More physicians rated budesonide as achieving "therapeutic success" or "therapeutic benefit" than mesalamine, but this difference also did not reach statistical significance.

Remission rates did not differ significantly between the once-daily (67%) and thrice-daily (72%) budesonide groups, nor did any other efficacy end points. "Although tested in only an exploratory sense, these data suggest that once-daily or thrice-daily administration does not affect the efficacy of budesonide," Dr. Tromm and his colleagues said.

The subgroup of female patients demonstrated a greater clinical response to budesonide (75% remission) than to mesalamine (57%). "Whether this finding reflects a genuine treatment effect remains uncertain, since other studies of budesonide for active Crohn’s disease have observed no gender-specific effects," they noted.

The greatest difference in treatment response was seen in the subgroups of patients who had high CDAI scores or high CRP levels at baseline, indicating greater severity of inflammation. Sixty-six percent of patients with high baseline CDAI scores remitted with budesonide, compared with only 49% of those with high CDAI scores who took mesalamine. The remission rate was 65% with budesonide for patients with high baseline CRP levels, compared with only 52% with mesalamine.

Median time to treatment response and median time to remission did not differ among the three treatment groups. Similarly, the median decrease in CDAI scores did not differ, and it was significant with all three drug regimens.

Adverse events occurred in 39% of patients taking t.i.d. budesonide, 47% of those taking once-daily budesonide, and 47% of those taking mesalamine. The corresponding rates of adverse events suspected to be drug related were 10%, 12%, and 7%.

The rates of treatment cessation because of adverse events were 3% with budesonide and 5% with mesalamine.

The study was funded by Dr. Falk Pharma GmbH. Dr. Tromm disclosed receiving speakers’ honoraria and travel funding from Dr. Falk Pharma, and several authors are employees of the company, whereas other authors had no conflicts of interest to disclose.

Budesonide was found noninferior to, but not better than, mesalamine for inducing remission of mildly to moderately active Crohn’s disease in an international phase III clinical trial, Dr. Andreas Tromm and his colleagues reported in the February issue of Gastroenterology.

In addition, once-daily dosing with 9 mg of budesonide was as effective as was the standard regimen of 3-mg doses taken three times daily. "From a clinical practice perspective, it would seem justified to recommend the budesonide 9 mg once-daily regimen, since this would be expected to improve adherence," said Dr. Tromm of Evangelisches Hospital Hattingen (Germany) and his associates (Gastroenterology 2011 February [doi:10.1053/j.gastro.2010.11.004]).

Recent guidelines from the European Crohn’s and Colitis Organisation recommend budesonide as more effective than mesalamine for mildly active, localized ileocecal Crohn’s disease, and also recommend that budesonide or systemic corticosteroids are preferable for treating moderately active localized ileocecal disease. Budesonide has a superior adverse effect profile and is better able to preserve adrenal function and bone mass, the authors wrote.

"However, only a single randomized study ... [involving only 182 subjects] a decade ago has directly compared the efficacy and safety of budesonide versus mesalamine for the management of active Crohn’s disease," they added. No studies have explored the use of different dosing regimens.

Dr. Tromm and his colleagues performed a double-blind phase III clinical trial in which adults with mildly to moderately active Crohn’s disease were randomly assigned to receive eudragit-L-coated mesalamine tablets 4.5 g/day (153 patients), 3-mg budesonide capsules three times per day (79 patients), or one 9-mg oral budesonide capsule once daily (77 patients), for 8 weeks. The study subjects were followed every 2 weeks at 46 gastroenterology clinics in Croatia, the Czech Republic, Germany, Greece, Hungary, Israel, and the Slovak Republic.

The mean Crohn’s Disease Activity Index (CDAI) score was higher in both budesonide groups than in the mesalamine group, and both budesonide groups had a higher proportion of patients with CDAI scores over 300. Also, both budesonide groups had more patients with extraintestinal manifestations of Crohn’s disease. Otherwise there were no meaningful differences among the study groups in clinical characteristics.

The primary efficacy end point was clinical remission (a CDAI score of 150 or less) at the conclusion of the trial. Remission occurred in 70% of the patients taking budesonide, compared with 62% of those taking mesalamine. This difference was not statistically significant but did meet the criteria for noninferiority in effectiveness.

More physicians rated budesonide as achieving "therapeutic success" or "therapeutic benefit" than mesalamine, but this difference also did not reach statistical significance.

Remission rates did not differ significantly between the once-daily (67%) and thrice-daily (72%) budesonide groups, nor did any other efficacy end points. "Although tested in only an exploratory sense, these data suggest that once-daily or thrice-daily administration does not affect the efficacy of budesonide," Dr. Tromm and his colleagues said.

The subgroup of female patients demonstrated a greater clinical response to budesonide (75% remission) than to mesalamine (57%). "Whether this finding reflects a genuine treatment effect remains uncertain, since other studies of budesonide for active Crohn’s disease have observed no gender-specific effects," they noted.

The greatest difference in treatment response was seen in the subgroups of patients who had high CDAI scores or high CRP levels at baseline, indicating greater severity of inflammation. Sixty-six percent of patients with high baseline CDAI scores remitted with budesonide, compared with only 49% of those with high CDAI scores who took mesalamine. The remission rate was 65% with budesonide for patients with high baseline CRP levels, compared with only 52% with mesalamine.

Median time to treatment response and median time to remission did not differ among the three treatment groups. Similarly, the median decrease in CDAI scores did not differ, and it was significant with all three drug regimens.

Adverse events occurred in 39% of patients taking t.i.d. budesonide, 47% of those taking once-daily budesonide, and 47% of those taking mesalamine. The corresponding rates of adverse events suspected to be drug related were 10%, 12%, and 7%.

The rates of treatment cessation because of adverse events were 3% with budesonide and 5% with mesalamine.

The study was funded by Dr. Falk Pharma GmbH. Dr. Tromm disclosed receiving speakers’ honoraria and travel funding from Dr. Falk Pharma, and several authors are employees of the company, whereas other authors had no conflicts of interest to disclose.

Budesonide was found noninferior to, but not better than, mesalamine for inducing remission of mildly to moderately active Crohn’s disease in an international phase III clinical trial, Dr. Andreas Tromm and his colleagues reported in the February issue of Gastroenterology.

In addition, once-daily dosing with 9 mg of budesonide was as effective as was the standard regimen of 3-mg doses taken three times daily. "From a clinical practice perspective, it would seem justified to recommend the budesonide 9 mg once-daily regimen, since this would be expected to improve adherence," said Dr. Tromm of Evangelisches Hospital Hattingen (Germany) and his associates (Gastroenterology 2011 February [doi:10.1053/j.gastro.2010.11.004]).

Recent guidelines from the European Crohn’s and Colitis Organisation recommend budesonide as more effective than mesalamine for mildly active, localized ileocecal Crohn’s disease, and also recommend that budesonide or systemic corticosteroids are preferable for treating moderately active localized ileocecal disease. Budesonide has a superior adverse effect profile and is better able to preserve adrenal function and bone mass, the authors wrote.

"However, only a single randomized study ... [involving only 182 subjects] a decade ago has directly compared the efficacy and safety of budesonide versus mesalamine for the management of active Crohn’s disease," they added. No studies have explored the use of different dosing regimens.

Dr. Tromm and his colleagues performed a double-blind phase III clinical trial in which adults with mildly to moderately active Crohn’s disease were randomly assigned to receive eudragit-L-coated mesalamine tablets 4.5 g/day (153 patients), 3-mg budesonide capsules three times per day (79 patients), or one 9-mg oral budesonide capsule once daily (77 patients), for 8 weeks. The study subjects were followed every 2 weeks at 46 gastroenterology clinics in Croatia, the Czech Republic, Germany, Greece, Hungary, Israel, and the Slovak Republic.

The mean Crohn’s Disease Activity Index (CDAI) score was higher in both budesonide groups than in the mesalamine group, and both budesonide groups had a higher proportion of patients with CDAI scores over 300. Also, both budesonide groups had more patients with extraintestinal manifestations of Crohn’s disease. Otherwise there were no meaningful differences among the study groups in clinical characteristics.

The primary efficacy end point was clinical remission (a CDAI score of 150 or less) at the conclusion of the trial. Remission occurred in 70% of the patients taking budesonide, compared with 62% of those taking mesalamine. This difference was not statistically significant but did meet the criteria for noninferiority in effectiveness.

More physicians rated budesonide as achieving "therapeutic success" or "therapeutic benefit" than mesalamine, but this difference also did not reach statistical significance.

Remission rates did not differ significantly between the once-daily (67%) and thrice-daily (72%) budesonide groups, nor did any other efficacy end points. "Although tested in only an exploratory sense, these data suggest that once-daily or thrice-daily administration does not affect the efficacy of budesonide," Dr. Tromm and his colleagues said.

The subgroup of female patients demonstrated a greater clinical response to budesonide (75% remission) than to mesalamine (57%). "Whether this finding reflects a genuine treatment effect remains uncertain, since other studies of budesonide for active Crohn’s disease have observed no gender-specific effects," they noted.

The greatest difference in treatment response was seen in the subgroups of patients who had high CDAI scores or high CRP levels at baseline, indicating greater severity of inflammation. Sixty-six percent of patients with high baseline CDAI scores remitted with budesonide, compared with only 49% of those with high CDAI scores who took mesalamine. The remission rate was 65% with budesonide for patients with high baseline CRP levels, compared with only 52% with mesalamine.

Median time to treatment response and median time to remission did not differ among the three treatment groups. Similarly, the median decrease in CDAI scores did not differ, and it was significant with all three drug regimens.

Adverse events occurred in 39% of patients taking t.i.d. budesonide, 47% of those taking once-daily budesonide, and 47% of those taking mesalamine. The corresponding rates of adverse events suspected to be drug related were 10%, 12%, and 7%.

The rates of treatment cessation because of adverse events were 3% with budesonide and 5% with mesalamine.

The study was funded by Dr. Falk Pharma GmbH. Dr. Tromm disclosed receiving speakers’ honoraria and travel funding from Dr. Falk Pharma, and several authors are employees of the company, whereas other authors had no conflicts of interest to disclose.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non-small cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, a study has shown.

In addition, because endosonography is minimally invasive, adding this step doesn't raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered (JAMA 2010;304:2245-52).

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said.

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

This study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.