Sharon Worcester

philadelphia – Treatment with ergocalciferol (vitamin D2) normalized circulating 25-hydroxyvitamin D levels within 3 months in hemodialysis patients with 25-hydroxyvitamin D deficiency, but this did not translate to clinical benefit with respect to a number of measures in a 6-month randomized, double-blind, placebo-controlled trial.

Levels of 25-hydroxyvitamin D in 276 hemodialysis patients with vitamin D deficiency who were randomized to receive either ergocalciferol treatment for 6 months or placebo were 16.0 vs. 16.9 ng/ml at baseline, 41.0 vs. 17.3 ng/ml at 3 months, and 39.2 vs. 17.5 ng/ml at 6 months, respectively, Dr. Dana Miskulin reported at Kidney Week 2014.

Parathyroid hormone (PTH) level was the only measure that showed a significant difference between the placebo and treatment groups. PTH levels dropped with treatment at 6 months (decreasing from 475 pg/ml at baseline to 450 pg/ml), but levels rose in the placebo group (440 to 505 pg/ml). No significant differences were seen at 6 months between the two groups in the primary outcomes measure of Epoetin alfa (Epogen) dose (5,400 vs. 5,800 units per week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively). There also were no differences between the groups in calcium levels, phosphorus levels, C-reactive protein levels, 1,25-dihydroxyvitamin D dose, cinacalcet dose, infection rate, or all-cause or infection-related hospitalization, Dr. Miskulin of Tufts Medical Center, Boston said at the meeting, which was sponsored by the American Society of Nephrology.

Study participants had a mean age of 61 years, median dialysis vintage of 3.5 years, and 25-hydroxyvitamin D levels less than 30 ng/ml. A majority (60%) were back, 45% were women, and 46% had diabetes as the cause of end stage renal disease. The treatment and placebo groups were similar with respect to clinical factors at baseline.

Treatment was given at 50,000 IU weekly for 6 months in patients with 25-hydroxyvitamin D levels less than 16 ng/ml and 50,000 IU weekly for 3 months followed by 50,000 IU monthly for 3 months in those with levels of 16-30 ng/ml, she said.

Vitamin D deficiency has been linked to numerous health problems, including cardiovascular events and mortality, infections, immune disorders, diabetes, cancers, and skin diseases, and about 80% of dialysis patients have 25-hydroxyvitamin D levels less than 30 ng/ml, Dr. Miskulin said.

The current findings suggest that while supplementation with at least 50,000 units of ergocalciferol every 2 weeks achieves and maintains vitamin D levels greater than 30 ng/ml without hypercalcemia or hyperphosphatemia in most hemodialysis patients, the benefits of supplementation are questionable. Although she agreed that without clinical benefit there is no need to provide supplementation, she also acknowledged that longer follow-up is needed to determine the effects of vitamin D supplementation.

This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.

philadelphia – Treatment with ergocalciferol (vitamin D2) normalized circulating 25-hydroxyvitamin D levels within 3 months in hemodialysis patients with 25-hydroxyvitamin D deficiency, but this did not translate to clinical benefit with respect to a number of measures in a 6-month randomized, double-blind, placebo-controlled trial.

Levels of 25-hydroxyvitamin D in 276 hemodialysis patients with vitamin D deficiency who were randomized to receive either ergocalciferol treatment for 6 months or placebo were 16.0 vs. 16.9 ng/ml at baseline, 41.0 vs. 17.3 ng/ml at 3 months, and 39.2 vs. 17.5 ng/ml at 6 months, respectively, Dr. Dana Miskulin reported at Kidney Week 2014.

Parathyroid hormone (PTH) level was the only measure that showed a significant difference between the placebo and treatment groups. PTH levels dropped with treatment at 6 months (decreasing from 475 pg/ml at baseline to 450 pg/ml), but levels rose in the placebo group (440 to 505 pg/ml). No significant differences were seen at 6 months between the two groups in the primary outcomes measure of Epoetin alfa (Epogen) dose (5,400 vs. 5,800 units per week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively). There also were no differences between the groups in calcium levels, phosphorus levels, C-reactive protein levels, 1,25-dihydroxyvitamin D dose, cinacalcet dose, infection rate, or all-cause or infection-related hospitalization, Dr. Miskulin of Tufts Medical Center, Boston said at the meeting, which was sponsored by the American Society of Nephrology.

Study participants had a mean age of 61 years, median dialysis vintage of 3.5 years, and 25-hydroxyvitamin D levels less than 30 ng/ml. A majority (60%) were back, 45% were women, and 46% had diabetes as the cause of end stage renal disease. The treatment and placebo groups were similar with respect to clinical factors at baseline.

Treatment was given at 50,000 IU weekly for 6 months in patients with 25-hydroxyvitamin D levels less than 16 ng/ml and 50,000 IU weekly for 3 months followed by 50,000 IU monthly for 3 months in those with levels of 16-30 ng/ml, she said.

Vitamin D deficiency has been linked to numerous health problems, including cardiovascular events and mortality, infections, immune disorders, diabetes, cancers, and skin diseases, and about 80% of dialysis patients have 25-hydroxyvitamin D levels less than 30 ng/ml, Dr. Miskulin said.

The current findings suggest that while supplementation with at least 50,000 units of ergocalciferol every 2 weeks achieves and maintains vitamin D levels greater than 30 ng/ml without hypercalcemia or hyperphosphatemia in most hemodialysis patients, the benefits of supplementation are questionable. Although she agreed that without clinical benefit there is no need to provide supplementation, she also acknowledged that longer follow-up is needed to determine the effects of vitamin D supplementation.

This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.

philadelphia – Treatment with ergocalciferol (vitamin D2) normalized circulating 25-hydroxyvitamin D levels within 3 months in hemodialysis patients with 25-hydroxyvitamin D deficiency, but this did not translate to clinical benefit with respect to a number of measures in a 6-month randomized, double-blind, placebo-controlled trial.

Levels of 25-hydroxyvitamin D in 276 hemodialysis patients with vitamin D deficiency who were randomized to receive either ergocalciferol treatment for 6 months or placebo were 16.0 vs. 16.9 ng/ml at baseline, 41.0 vs. 17.3 ng/ml at 3 months, and 39.2 vs. 17.5 ng/ml at 6 months, respectively, Dr. Dana Miskulin reported at Kidney Week 2014.

Parathyroid hormone (PTH) level was the only measure that showed a significant difference between the placebo and treatment groups. PTH levels dropped with treatment at 6 months (decreasing from 475 pg/ml at baseline to 450 pg/ml), but levels rose in the placebo group (440 to 505 pg/ml). No significant differences were seen at 6 months between the two groups in the primary outcomes measure of Epoetin alfa (Epogen) dose (5,400 vs. 5,800 units per week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively). There also were no differences between the groups in calcium levels, phosphorus levels, C-reactive protein levels, 1,25-dihydroxyvitamin D dose, cinacalcet dose, infection rate, or all-cause or infection-related hospitalization, Dr. Miskulin of Tufts Medical Center, Boston said at the meeting, which was sponsored by the American Society of Nephrology.

Study participants had a mean age of 61 years, median dialysis vintage of 3.5 years, and 25-hydroxyvitamin D levels less than 30 ng/ml. A majority (60%) were back, 45% were women, and 46% had diabetes as the cause of end stage renal disease. The treatment and placebo groups were similar with respect to clinical factors at baseline.

Treatment was given at 50,000 IU weekly for 6 months in patients with 25-hydroxyvitamin D levels less than 16 ng/ml and 50,000 IU weekly for 3 months followed by 50,000 IU monthly for 3 months in those with levels of 16-30 ng/ml, she said.

Vitamin D deficiency has been linked to numerous health problems, including cardiovascular events and mortality, infections, immune disorders, diabetes, cancers, and skin diseases, and about 80% of dialysis patients have 25-hydroxyvitamin D levels less than 30 ng/ml, Dr. Miskulin said.

The current findings suggest that while supplementation with at least 50,000 units of ergocalciferol every 2 weeks achieves and maintains vitamin D levels greater than 30 ng/ml without hypercalcemia or hyperphosphatemia in most hemodialysis patients, the benefits of supplementation are questionable. Although she agreed that without clinical benefit there is no need to provide supplementation, she also acknowledged that longer follow-up is needed to determine the effects of vitamin D supplementation.

This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.

PHILADELPHIA – Patients with type 2 diabetes, chronic kidney disease, and a high risk of obstructive sleep apnea have more rapid loss of kidney function than do similar patients with a low risk of sleep apnea, findings from a retrospective cohort study suggest.

Of 56 patients with diabetic nephropathy who underwent screening for obstructive sleep apnea, 34 (61%) were at high risk. Compared with 22 patients with a low risk score, the high-risk patients had a significantly greater loss of estimated glomerular filtration rate over time (median loss of -3.4 vs. 1.5 ml/min/1.73 m² per year for the high- vs. low-risk patients, respectively), Dr. Roberto Pisoni reported in a poster at the annual meeting of the American Society of Nephrology.

This finding was despite comparable blood pressure for the high- and low-risk groups (systolic: 141.7 and 143.7 mm Hg; diastolic: 72.0 and 72.4 mm Hg, respectively), proteinuria upon admission to a chronic kidney disease clinic (urinary protein/creatinine ratio, 1.9 and 1.6 g/g, respectively), and time spent in clinic (1.9 vs. 2.1 years, respectively), said Dr. Pisoni of the Medical University of South Carolina, Charleston.

Patients in the high- and low-risk groups also had similar baseline gender, body mass index, use of renin-angiotensin-aldosterone system blockers, eGFR, and co-morbidities, he noted.

Data used for this study were from the University of Alabama at Birmingham Chronic Kidney Disease Database. Patients had completed the Berlin questionnaire to assess for sleep apnea during a 9-month study period.

Obstructive sleep apnea is common in patients with type 2 diabetes and is also associated with glomerular hyperfiltration and proteinuria in patients with normal renal function, which raised the question of whether it might be related to chronic kidney disease progression, Dr. Pisoni explained. He noted that the association between obstructive sleep apnea and diabetic nephropathy has not been fully investigated.

The study demonstrated that the “simple approach” of assessing obstructive sleep apnea risk identifies patients who are also at increased risk of CKD progression, he said, adding that the findings require replication in a prospective cohort.

Dr. Pisoni reported having no disclosures.

PHILADELPHIA – Patients with type 2 diabetes, chronic kidney disease, and a high risk of obstructive sleep apnea have more rapid loss of kidney function than do similar patients with a low risk of sleep apnea, findings from a retrospective cohort study suggest.

Of 56 patients with diabetic nephropathy who underwent screening for obstructive sleep apnea, 34 (61%) were at high risk. Compared with 22 patients with a low risk score, the high-risk patients had a significantly greater loss of estimated glomerular filtration rate over time (median loss of -3.4 vs. 1.5 ml/min/1.73 m² per year for the high- vs. low-risk patients, respectively), Dr. Roberto Pisoni reported in a poster at the annual meeting of the American Society of Nephrology.

This finding was despite comparable blood pressure for the high- and low-risk groups (systolic: 141.7 and 143.7 mm Hg; diastolic: 72.0 and 72.4 mm Hg, respectively), proteinuria upon admission to a chronic kidney disease clinic (urinary protein/creatinine ratio, 1.9 and 1.6 g/g, respectively), and time spent in clinic (1.9 vs. 2.1 years, respectively), said Dr. Pisoni of the Medical University of South Carolina, Charleston.

Patients in the high- and low-risk groups also had similar baseline gender, body mass index, use of renin-angiotensin-aldosterone system blockers, eGFR, and co-morbidities, he noted.

Data used for this study were from the University of Alabama at Birmingham Chronic Kidney Disease Database. Patients had completed the Berlin questionnaire to assess for sleep apnea during a 9-month study period.

Obstructive sleep apnea is common in patients with type 2 diabetes and is also associated with glomerular hyperfiltration and proteinuria in patients with normal renal function, which raised the question of whether it might be related to chronic kidney disease progression, Dr. Pisoni explained. He noted that the association between obstructive sleep apnea and diabetic nephropathy has not been fully investigated.

The study demonstrated that the “simple approach” of assessing obstructive sleep apnea risk identifies patients who are also at increased risk of CKD progression, he said, adding that the findings require replication in a prospective cohort.

Dr. Pisoni reported having no disclosures.

PHILADELPHIA – Patients with type 2 diabetes, chronic kidney disease, and a high risk of obstructive sleep apnea have more rapid loss of kidney function than do similar patients with a low risk of sleep apnea, findings from a retrospective cohort study suggest.

Of 56 patients with diabetic nephropathy who underwent screening for obstructive sleep apnea, 34 (61%) were at high risk. Compared with 22 patients with a low risk score, the high-risk patients had a significantly greater loss of estimated glomerular filtration rate over time (median loss of -3.4 vs. 1.5 ml/min/1.73 m² per year for the high- vs. low-risk patients, respectively), Dr. Roberto Pisoni reported in a poster at the annual meeting of the American Society of Nephrology.

This finding was despite comparable blood pressure for the high- and low-risk groups (systolic: 141.7 and 143.7 mm Hg; diastolic: 72.0 and 72.4 mm Hg, respectively), proteinuria upon admission to a chronic kidney disease clinic (urinary protein/creatinine ratio, 1.9 and 1.6 g/g, respectively), and time spent in clinic (1.9 vs. 2.1 years, respectively), said Dr. Pisoni of the Medical University of South Carolina, Charleston.

Patients in the high- and low-risk groups also had similar baseline gender, body mass index, use of renin-angiotensin-aldosterone system blockers, eGFR, and co-morbidities, he noted.

Data used for this study were from the University of Alabama at Birmingham Chronic Kidney Disease Database. Patients had completed the Berlin questionnaire to assess for sleep apnea during a 9-month study period.

Obstructive sleep apnea is common in patients with type 2 diabetes and is also associated with glomerular hyperfiltration and proteinuria in patients with normal renal function, which raised the question of whether it might be related to chronic kidney disease progression, Dr. Pisoni explained. He noted that the association between obstructive sleep apnea and diabetic nephropathy has not been fully investigated.

The study demonstrated that the “simple approach” of assessing obstructive sleep apnea risk identifies patients who are also at increased risk of CKD progression, he said, adding that the findings require replication in a prospective cohort.

Dr. Pisoni reported having no disclosures.

AUSTIN, TEX. – Inhaled corticosteroids can be successfully withdrawn without increasing the risk of exacerbations in patients who have chronic obstructive pulmonary disease and are receiving dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta₂-agonist (LABA), according to findings from the WISDOM study.

However, inhaled corticosteroid (ICS) withdrawal should be conducted with caution, as a small but statistically significantly greater decrease in lung function occurred in patients who withdrew completely, compared with those who did not during the 12-month, double-blind, parallel-group study, Dr. Helgo Magnussen reported at the annual meeting of the American College of Chest Physicians.

“In patients with severe but stable COPD who are receiving combination therapy with tiotropium, salmeterol and ICS, a stepwise withdrawal of ICS was noninferior to continuation of ICS with respect to the risk of moderate or severe exacerbations. Despite this, if you do [withdraw ICS] – and we believe you can try to withdraw ICS – please observe the symptoms and lung function, because we found this signal [for decreased lung function],” he said.

Study subjects were 2,485 adults over age 40 years with severe or very severe COPD and a history of exacerbations. All patients received triple therapy with the LAMA tiotropium at 18 mcg four times daily, the LABA salmeterol at 50 mcg twice daily, and the ICS fluticasone at 500 mcg twice daily for a 6-week run-in period.

The patients were randomized to continue the triple therapy or to undergo ICS withdrawal over 12 weeks, with a dose reduction every 6 weeks.

ICS withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval, compared with continued ICS with respect to moderate or severe COPD exacerbation (hazard ratio, 1.06), but the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second (FEV₁) at week 18 was 38 mL greater in the ICS withdrawal group, said Dr. Magnussen of the Pulmonary Research Institute at Lung Clinic Grosshansdorf (Germany), Airway Research Center North.

A similar between-group difference of 43 mL was seen at week 52, he said, noting that this did not differ significantly from the difference seen at week 18, demonstrating that there is no further decline in lung function after complete ICS withdrawal at week 18.

Also, the decline in lung function – even at the peak decrease in function at week 18, was not associated with an increase in dyspnea; the difference in change from baseline in the modified Medical Research Council (mMRC) dyspnea scale was nonsignificant for ICS withdrawal, compared with ICS continuation at week 18 or week 52. The change from baseline in the St. George’s Respiratory Questionnaire (SGRQ) total score was 0.55 with ICS withdrawal, compared with –0.42 with ICS at week 27, and 1.15, compared with –0.07 for withdrawal vs. continuation, respectively, at week 52. This difference, though statistically significant, was not considered clinically relevant, Dr. Magnussen said.

ICS treatment is recommended along with long-acting bronchodilators in patients with frequent exacerbations of severe COPD, but the benefits of ICS use in addition to dual bronchodilator therapy have not been fully elucidated, he said.

The findings of the WISDOM study (N. Engl. J. Med. 2014;371:1285-94), suggest that ICS discontinuation is possible.This study was funded by Boehringer Ingelheim. Dr. Magnussen reported receiving consultant fees and/or serving on a speakers bureau or advisory committee for Almirall, Boehringer Ingelheim, Chiesi, Berli-Chemi, and Novartis. His employer, the Pulmonary Research Institute, received payments for conducting the study.

AUSTIN, TEX. – Inhaled corticosteroids can be successfully withdrawn without increasing the risk of exacerbations in patients who have chronic obstructive pulmonary disease and are receiving dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta₂-agonist (LABA), according to findings from the WISDOM study.

However, inhaled corticosteroid (ICS) withdrawal should be conducted with caution, as a small but statistically significantly greater decrease in lung function occurred in patients who withdrew completely, compared with those who did not during the 12-month, double-blind, parallel-group study, Dr. Helgo Magnussen reported at the annual meeting of the American College of Chest Physicians.

“In patients with severe but stable COPD who are receiving combination therapy with tiotropium, salmeterol and ICS, a stepwise withdrawal of ICS was noninferior to continuation of ICS with respect to the risk of moderate or severe exacerbations. Despite this, if you do [withdraw ICS] – and we believe you can try to withdraw ICS – please observe the symptoms and lung function, because we found this signal [for decreased lung function],” he said.

Study subjects were 2,485 adults over age 40 years with severe or very severe COPD and a history of exacerbations. All patients received triple therapy with the LAMA tiotropium at 18 mcg four times daily, the LABA salmeterol at 50 mcg twice daily, and the ICS fluticasone at 500 mcg twice daily for a 6-week run-in period.

The patients were randomized to continue the triple therapy or to undergo ICS withdrawal over 12 weeks, with a dose reduction every 6 weeks.

ICS withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval, compared with continued ICS with respect to moderate or severe COPD exacerbation (hazard ratio, 1.06), but the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second (FEV₁) at week 18 was 38 mL greater in the ICS withdrawal group, said Dr. Magnussen of the Pulmonary Research Institute at Lung Clinic Grosshansdorf (Germany), Airway Research Center North.

A similar between-group difference of 43 mL was seen at week 52, he said, noting that this did not differ significantly from the difference seen at week 18, demonstrating that there is no further decline in lung function after complete ICS withdrawal at week 18.

Also, the decline in lung function – even at the peak decrease in function at week 18, was not associated with an increase in dyspnea; the difference in change from baseline in the modified Medical Research Council (mMRC) dyspnea scale was nonsignificant for ICS withdrawal, compared with ICS continuation at week 18 or week 52. The change from baseline in the St. George’s Respiratory Questionnaire (SGRQ) total score was 0.55 with ICS withdrawal, compared with –0.42 with ICS at week 27, and 1.15, compared with –0.07 for withdrawal vs. continuation, respectively, at week 52. This difference, though statistically significant, was not considered clinically relevant, Dr. Magnussen said.

ICS treatment is recommended along with long-acting bronchodilators in patients with frequent exacerbations of severe COPD, but the benefits of ICS use in addition to dual bronchodilator therapy have not been fully elucidated, he said.

The findings of the WISDOM study (N. Engl. J. Med. 2014;371:1285-94), suggest that ICS discontinuation is possible.This study was funded by Boehringer Ingelheim. Dr. Magnussen reported receiving consultant fees and/or serving on a speakers bureau or advisory committee for Almirall, Boehringer Ingelheim, Chiesi, Berli-Chemi, and Novartis. His employer, the Pulmonary Research Institute, received payments for conducting the study.

AUSTIN, TEX. – Inhaled corticosteroids can be successfully withdrawn without increasing the risk of exacerbations in patients who have chronic obstructive pulmonary disease and are receiving dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta₂-agonist (LABA), according to findings from the WISDOM study.

However, inhaled corticosteroid (ICS) withdrawal should be conducted with caution, as a small but statistically significantly greater decrease in lung function occurred in patients who withdrew completely, compared with those who did not during the 12-month, double-blind, parallel-group study, Dr. Helgo Magnussen reported at the annual meeting of the American College of Chest Physicians.

“In patients with severe but stable COPD who are receiving combination therapy with tiotropium, salmeterol and ICS, a stepwise withdrawal of ICS was noninferior to continuation of ICS with respect to the risk of moderate or severe exacerbations. Despite this, if you do [withdraw ICS] – and we believe you can try to withdraw ICS – please observe the symptoms and lung function, because we found this signal [for decreased lung function],” he said.

Study subjects were 2,485 adults over age 40 years with severe or very severe COPD and a history of exacerbations. All patients received triple therapy with the LAMA tiotropium at 18 mcg four times daily, the LABA salmeterol at 50 mcg twice daily, and the ICS fluticasone at 500 mcg twice daily for a 6-week run-in period.

The patients were randomized to continue the triple therapy or to undergo ICS withdrawal over 12 weeks, with a dose reduction every 6 weeks.

ICS withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval, compared with continued ICS with respect to moderate or severe COPD exacerbation (hazard ratio, 1.06), but the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second (FEV₁) at week 18 was 38 mL greater in the ICS withdrawal group, said Dr. Magnussen of the Pulmonary Research Institute at Lung Clinic Grosshansdorf (Germany), Airway Research Center North.

A similar between-group difference of 43 mL was seen at week 52, he said, noting that this did not differ significantly from the difference seen at week 18, demonstrating that there is no further decline in lung function after complete ICS withdrawal at week 18.

Also, the decline in lung function – even at the peak decrease in function at week 18, was not associated with an increase in dyspnea; the difference in change from baseline in the modified Medical Research Council (mMRC) dyspnea scale was nonsignificant for ICS withdrawal, compared with ICS continuation at week 18 or week 52. The change from baseline in the St. George’s Respiratory Questionnaire (SGRQ) total score was 0.55 with ICS withdrawal, compared with –0.42 with ICS at week 27, and 1.15, compared with –0.07 for withdrawal vs. continuation, respectively, at week 52. This difference, though statistically significant, was not considered clinically relevant, Dr. Magnussen said.

ICS treatment is recommended along with long-acting bronchodilators in patients with frequent exacerbations of severe COPD, but the benefits of ICS use in addition to dual bronchodilator therapy have not been fully elucidated, he said.

The findings of the WISDOM study (N. Engl. J. Med. 2014;371:1285-94), suggest that ICS discontinuation is possible.This study was funded by Boehringer Ingelheim. Dr. Magnussen reported receiving consultant fees and/or serving on a speakers bureau or advisory committee for Almirall, Boehringer Ingelheim, Chiesi, Berli-Chemi, and Novartis. His employer, the Pulmonary Research Institute, received payments for conducting the study.

AUSTIN, TEX. – Higher baseline alpha-1 proteinase inhibitor level, higher body mass index, and female gender may be associated with improved response to alpha-1 proteinase inhibitor augmentation therapy, according to an analysis of data from RAPID.

Better responses to therapy in the trial, as compared with placebo and as measured by mean computed tomography-assessed rate of change in adjusted P15 lung density at total lung capacity, occurred among the 79 female subjects (1.45 g/L per year), and among the 60, 58, and 59 patients with high functional, antigenic, or intermediate functional alpha-1 proteinase inhibitor (A_1-PI) levels, respectively (1.08, 1.23, and 1.38 g/L per year), Dr. James Stocks reported at the annual meeting of the American College of Chest Physicians.

The differences in the rate of change with treatment vs. placebo in these subgroups were statistically significant, said Dr. Stocks of the University of Texas Health Science Center at Tyler.

Greater differences in favor of A1-PI – with a trend toward statistical significance – were also seen in the 21 patients with a body mass index of 30 kg/m² or greater (2.21 g/L per year), the 86 patients under age 54 years (0.96 g/L year), the 87 patients with a carbon monoxide diffusion capacity at or below the median at baseline (0.90 g/L per year), the 8 patients with lower exercise capacity, defined by 400 m or less walked (0.99 g/L per year), and the 88 patients with St. George’s Respiratory Questionnaire symptoms scores at or below the median at baseline (0.93 g/L per year), he said.

RAPID (Randomized, Placebo-Controlled Trial in Alpha-1 Proteinase Inhibitor Deficiency) – the single largest clinical trial of A_1-PI augmentation therapy – included 180 A_1-PI–deficient patients and demonstrated that weekly intravenous A_1-PI therapy at a dose of 60 g/kg per week for 2 years slows progression of emphysema. The annual rate of decline in CT-measured lung density was 34%, compared with placebo. Those findings were reported in May 2013.

According to the current analysis, A_1-PI augmentation appears to be efficacious across a wide range of subgroups, Dr. Stocks said. Those with higher BMI may have experienced greater benefit because of receiving a greater amount of A_1-PI as a result of weight-based dosing. Younger patients may have experienced greater benefit because of being in the earlier stages of disease, with less emphysematous lung damage and lung density loss.

“It is important to note that were no multiplicity adjustments made in the analysis, and no tests for interaction within a subgroup were significant, so no subgroup could be said to be particularly favored as being suitable for treatment with A_1-PI,” he said. It does appear, however, that earlier treatment may help to reduce overall progression of emphysema in affected patients, and that baseline factors such as higher baseline A_1-PI, BMI, and gender may impact treatment benefit, he said.

This study was funded by CSL Behring. Dr. Stocks reported receiving funds as an investigator for the commercially sponsored clinical trial.

AUSTIN, TEX. – Higher baseline alpha-1 proteinase inhibitor level, higher body mass index, and female gender may be associated with improved response to alpha-1 proteinase inhibitor augmentation therapy, according to an analysis of data from RAPID.

Better responses to therapy in the trial, as compared with placebo and as measured by mean computed tomography-assessed rate of change in adjusted P15 lung density at total lung capacity, occurred among the 79 female subjects (1.45 g/L per year), and among the 60, 58, and 59 patients with high functional, antigenic, or intermediate functional alpha-1 proteinase inhibitor (A_1-PI) levels, respectively (1.08, 1.23, and 1.38 g/L per year), Dr. James Stocks reported at the annual meeting of the American College of Chest Physicians.

The differences in the rate of change with treatment vs. placebo in these subgroups were statistically significant, said Dr. Stocks of the University of Texas Health Science Center at Tyler.

Greater differences in favor of A1-PI – with a trend toward statistical significance – were also seen in the 21 patients with a body mass index of 30 kg/m² or greater (2.21 g/L per year), the 86 patients under age 54 years (0.96 g/L year), the 87 patients with a carbon monoxide diffusion capacity at or below the median at baseline (0.90 g/L per year), the 8 patients with lower exercise capacity, defined by 400 m or less walked (0.99 g/L per year), and the 88 patients with St. George’s Respiratory Questionnaire symptoms scores at or below the median at baseline (0.93 g/L per year), he said.

RAPID (Randomized, Placebo-Controlled Trial in Alpha-1 Proteinase Inhibitor Deficiency) – the single largest clinical trial of A_1-PI augmentation therapy – included 180 A_1-PI–deficient patients and demonstrated that weekly intravenous A_1-PI therapy at a dose of 60 g/kg per week for 2 years slows progression of emphysema. The annual rate of decline in CT-measured lung density was 34%, compared with placebo. Those findings were reported in May 2013.

According to the current analysis, A_1-PI augmentation appears to be efficacious across a wide range of subgroups, Dr. Stocks said. Those with higher BMI may have experienced greater benefit because of receiving a greater amount of A_1-PI as a result of weight-based dosing. Younger patients may have experienced greater benefit because of being in the earlier stages of disease, with less emphysematous lung damage and lung density loss.

“It is important to note that were no multiplicity adjustments made in the analysis, and no tests for interaction within a subgroup were significant, so no subgroup could be said to be particularly favored as being suitable for treatment with A_1-PI,” he said. It does appear, however, that earlier treatment may help to reduce overall progression of emphysema in affected patients, and that baseline factors such as higher baseline A_1-PI, BMI, and gender may impact treatment benefit, he said.

This study was funded by CSL Behring. Dr. Stocks reported receiving funds as an investigator for the commercially sponsored clinical trial.

AUSTIN, TEX. – Higher baseline alpha-1 proteinase inhibitor level, higher body mass index, and female gender may be associated with improved response to alpha-1 proteinase inhibitor augmentation therapy, according to an analysis of data from RAPID.

Better responses to therapy in the trial, as compared with placebo and as measured by mean computed tomography-assessed rate of change in adjusted P15 lung density at total lung capacity, occurred among the 79 female subjects (1.45 g/L per year), and among the 60, 58, and 59 patients with high functional, antigenic, or intermediate functional alpha-1 proteinase inhibitor (A_1-PI) levels, respectively (1.08, 1.23, and 1.38 g/L per year), Dr. James Stocks reported at the annual meeting of the American College of Chest Physicians.

The differences in the rate of change with treatment vs. placebo in these subgroups were statistically significant, said Dr. Stocks of the University of Texas Health Science Center at Tyler.

Greater differences in favor of A1-PI – with a trend toward statistical significance – were also seen in the 21 patients with a body mass index of 30 kg/m² or greater (2.21 g/L per year), the 86 patients under age 54 years (0.96 g/L year), the 87 patients with a carbon monoxide diffusion capacity at or below the median at baseline (0.90 g/L per year), the 8 patients with lower exercise capacity, defined by 400 m or less walked (0.99 g/L per year), and the 88 patients with St. George’s Respiratory Questionnaire symptoms scores at or below the median at baseline (0.93 g/L per year), he said.

RAPID (Randomized, Placebo-Controlled Trial in Alpha-1 Proteinase Inhibitor Deficiency) – the single largest clinical trial of A_1-PI augmentation therapy – included 180 A_1-PI–deficient patients and demonstrated that weekly intravenous A_1-PI therapy at a dose of 60 g/kg per week for 2 years slows progression of emphysema. The annual rate of decline in CT-measured lung density was 34%, compared with placebo. Those findings were reported in May 2013.

According to the current analysis, A_1-PI augmentation appears to be efficacious across a wide range of subgroups, Dr. Stocks said. Those with higher BMI may have experienced greater benefit because of receiving a greater amount of A_1-PI as a result of weight-based dosing. Younger patients may have experienced greater benefit because of being in the earlier stages of disease, with less emphysematous lung damage and lung density loss.

“It is important to note that were no multiplicity adjustments made in the analysis, and no tests for interaction within a subgroup were significant, so no subgroup could be said to be particularly favored as being suitable for treatment with A_1-PI,” he said. It does appear, however, that earlier treatment may help to reduce overall progression of emphysema in affected patients, and that baseline factors such as higher baseline A_1-PI, BMI, and gender may impact treatment benefit, he said.

This study was funded by CSL Behring. Dr. Stocks reported receiving funds as an investigator for the commercially sponsored clinical trial.

PHILADELPHIA – A nurse- and respiratory therapist–led opt-out protocol for coordinated daily spontaneous awakening trials and spontaneous breathing trials was associated with significant reductions in hospital length of stay and ventilator-associated events in a multicenter quality improvement collaborative nested within a prospective study of ventilator-associated events.

The protocol led to significant increases – after adjustment for age, sex, Sequential Organ Failure Assessment score, reason for intubation, comorbidity score, and unit ID – in spontaneous awakening trials (SATs), spontaneous breathing trials (SBTs), and in the percentage of SBTs performed without sedation among 3,425 episodes and 22,991days of mechanical ventilation in the collaborative units, Dr. Deverick Anderson of Duke University Medical Center, Durham, N.C., reported at an annual scientific meeting on infectious diseases.

The SAT performance rate increased from 30% to 70% during the course of the study, and the SBT performance rate also increased, though more modestly, from about 55% to nearly 70%. The performance rate of SBTs performed with sedatives off – an intervention that improves the ability to be extubated – increased from nearly 55% to more than 95%.

The mean duration of mechanical ventilation decreased by 2.4 days, mean ICU stay decreased by 3 days, and mean hospital length of stay decreased by 6.3 days, Dr. Anderson said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Further, ventilator-associated conditions and infection-related ventilator-associated complications significantly decreased (odds ratio, 0.63 and 0.35, respectively). However, there was no decrease in possible or probable pneumonia (OR, 0.51).

Self-extubations increased (OR, 2.1, but there was no change in reintubations within 24 hours (OR, 0.96), Dr. Anderson said

“When we put all of this together, we were able to show a decrease in our rates of VAEs [ventilator-associated events] per 100 episodes. Over the course of the entire study, we calculated a 37% decrease in the risk of VAEs,” Dr. Anderson said.

However, the number of VAEs per 1,000 days didn’t change, because both the denominator and the numerator changed with the intervention. This finding raises questions about determining the right denominator to use. Based on the findings, it appears that ventilator episodes, rather than ventilator days, might be the best denominators, he said.

The study was conducted at 12 adult intensive care units at seven hospitals participating in the Centers for Disease Control and Prevention’s Prevention Epicenters Wake Up and Breathe Collaborative between November 2011 and May 2013. The collaborative was designed to prevent VAEs by decreasing patients’ sedative and ventilator exposures.

The collaborative was developed after early 2013 when the CDC replaced its ventilator-associated pneumonia (VAP) definitions with VAE definitions, expanding surveillance to VAEs in an effort to improve the objectivity of the definitions, to improve the ease of performing surveillance, and to try to improve the ability to make interhospital comparisons, Dr. Anderson explained, adding that VAEs include VAP, but also include pulmonary edema, atelectasis, and acute respiratory distress syndrome.

Thus, interventions aimed simply at reducing VAP may not change the rate of VAEs, he said.

Patients with VAEs stay on ventilators longer, stay in the ICU longer, are exposed to more antibiotic, and have two- to threefold increased rates of mortality, compared with those on ventilators but without VAEs, but little is known about preventing VAEs.

A larger study suggested that about a third of cases might be preventable, but no intervention has been tested and found to have an effect on the rate of VAEs. The Wake Up and Breathe Collaborative was tasked with answering the question of whether VAEs are preventable, and the investigators thought the best opportunity for prevention was to decrease the amount of sedation that ventilated patients received, Dr. Anderson said.

“More specifically – to decrease sedation through daily SATs and SBTs,” he added.

The opt-out protocol called for SATs and SBTs in all ventilated patients unless they met specific safety criteria or a physician wrote a specific opt-out order.

Though limited by the quasi-experimental open label study design, the findings are consistent with those from prior studies of such protocols.

“We felt that our multicenter prospective collaborative study was a success. … putting it all together, we conclude that VAEs are preventable when we improve compliance with evidence-based practice for our ventilated patients,” he said.Dr. Anderson reported receiving royalties from UpToDate and receiving research support from the CDC and the National Institutes of Health/National Institute of Allergy and Infectious Diseases.

PHILADELPHIA – A nurse- and respiratory therapist–led opt-out protocol for coordinated daily spontaneous awakening trials and spontaneous breathing trials was associated with significant reductions in hospital length of stay and ventilator-associated events in a multicenter quality improvement collaborative nested within a prospective study of ventilator-associated events.

The protocol led to significant increases – after adjustment for age, sex, Sequential Organ Failure Assessment score, reason for intubation, comorbidity score, and unit ID – in spontaneous awakening trials (SATs), spontaneous breathing trials (SBTs), and in the percentage of SBTs performed without sedation among 3,425 episodes and 22,991days of mechanical ventilation in the collaborative units, Dr. Deverick Anderson of Duke University Medical Center, Durham, N.C., reported at an annual scientific meeting on infectious diseases.

The SAT performance rate increased from 30% to 70% during the course of the study, and the SBT performance rate also increased, though more modestly, from about 55% to nearly 70%. The performance rate of SBTs performed with sedatives off – an intervention that improves the ability to be extubated – increased from nearly 55% to more than 95%.

The mean duration of mechanical ventilation decreased by 2.4 days, mean ICU stay decreased by 3 days, and mean hospital length of stay decreased by 6.3 days, Dr. Anderson said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Further, ventilator-associated conditions and infection-related ventilator-associated complications significantly decreased (odds ratio, 0.63 and 0.35, respectively). However, there was no decrease in possible or probable pneumonia (OR, 0.51).

Self-extubations increased (OR, 2.1, but there was no change in reintubations within 24 hours (OR, 0.96), Dr. Anderson said

“When we put all of this together, we were able to show a decrease in our rates of VAEs [ventilator-associated events] per 100 episodes. Over the course of the entire study, we calculated a 37% decrease in the risk of VAEs,” Dr. Anderson said.

However, the number of VAEs per 1,000 days didn’t change, because both the denominator and the numerator changed with the intervention. This finding raises questions about determining the right denominator to use. Based on the findings, it appears that ventilator episodes, rather than ventilator days, might be the best denominators, he said.

The study was conducted at 12 adult intensive care units at seven hospitals participating in the Centers for Disease Control and Prevention’s Prevention Epicenters Wake Up and Breathe Collaborative between November 2011 and May 2013. The collaborative was designed to prevent VAEs by decreasing patients’ sedative and ventilator exposures.

The collaborative was developed after early 2013 when the CDC replaced its ventilator-associated pneumonia (VAP) definitions with VAE definitions, expanding surveillance to VAEs in an effort to improve the objectivity of the definitions, to improve the ease of performing surveillance, and to try to improve the ability to make interhospital comparisons, Dr. Anderson explained, adding that VAEs include VAP, but also include pulmonary edema, atelectasis, and acute respiratory distress syndrome.

Thus, interventions aimed simply at reducing VAP may not change the rate of VAEs, he said.

Patients with VAEs stay on ventilators longer, stay in the ICU longer, are exposed to more antibiotic, and have two- to threefold increased rates of mortality, compared with those on ventilators but without VAEs, but little is known about preventing VAEs.

A larger study suggested that about a third of cases might be preventable, but no intervention has been tested and found to have an effect on the rate of VAEs. The Wake Up and Breathe Collaborative was tasked with answering the question of whether VAEs are preventable, and the investigators thought the best opportunity for prevention was to decrease the amount of sedation that ventilated patients received, Dr. Anderson said.

“More specifically – to decrease sedation through daily SATs and SBTs,” he added.

The opt-out protocol called for SATs and SBTs in all ventilated patients unless they met specific safety criteria or a physician wrote a specific opt-out order.

Though limited by the quasi-experimental open label study design, the findings are consistent with those from prior studies of such protocols.

“We felt that our multicenter prospective collaborative study was a success. … putting it all together, we conclude that VAEs are preventable when we improve compliance with evidence-based practice for our ventilated patients,” he said.Dr. Anderson reported receiving royalties from UpToDate and receiving research support from the CDC and the National Institutes of Health/National Institute of Allergy and Infectious Diseases.

PHILADELPHIA – A nurse- and respiratory therapist–led opt-out protocol for coordinated daily spontaneous awakening trials and spontaneous breathing trials was associated with significant reductions in hospital length of stay and ventilator-associated events in a multicenter quality improvement collaborative nested within a prospective study of ventilator-associated events.

The protocol led to significant increases – after adjustment for age, sex, Sequential Organ Failure Assessment score, reason for intubation, comorbidity score, and unit ID – in spontaneous awakening trials (SATs), spontaneous breathing trials (SBTs), and in the percentage of SBTs performed without sedation among 3,425 episodes and 22,991days of mechanical ventilation in the collaborative units, Dr. Deverick Anderson of Duke University Medical Center, Durham, N.C., reported at an annual scientific meeting on infectious diseases.

The SAT performance rate increased from 30% to 70% during the course of the study, and the SBT performance rate also increased, though more modestly, from about 55% to nearly 70%. The performance rate of SBTs performed with sedatives off – an intervention that improves the ability to be extubated – increased from nearly 55% to more than 95%.

The mean duration of mechanical ventilation decreased by 2.4 days, mean ICU stay decreased by 3 days, and mean hospital length of stay decreased by 6.3 days, Dr. Anderson said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Further, ventilator-associated conditions and infection-related ventilator-associated complications significantly decreased (odds ratio, 0.63 and 0.35, respectively). However, there was no decrease in possible or probable pneumonia (OR, 0.51).

Self-extubations increased (OR, 2.1, but there was no change in reintubations within 24 hours (OR, 0.96), Dr. Anderson said

“When we put all of this together, we were able to show a decrease in our rates of VAEs [ventilator-associated events] per 100 episodes. Over the course of the entire study, we calculated a 37% decrease in the risk of VAEs,” Dr. Anderson said.

However, the number of VAEs per 1,000 days didn’t change, because both the denominator and the numerator changed with the intervention. This finding raises questions about determining the right denominator to use. Based on the findings, it appears that ventilator episodes, rather than ventilator days, might be the best denominators, he said.

The study was conducted at 12 adult intensive care units at seven hospitals participating in the Centers for Disease Control and Prevention’s Prevention Epicenters Wake Up and Breathe Collaborative between November 2011 and May 2013. The collaborative was designed to prevent VAEs by decreasing patients’ sedative and ventilator exposures.

The collaborative was developed after early 2013 when the CDC replaced its ventilator-associated pneumonia (VAP) definitions with VAE definitions, expanding surveillance to VAEs in an effort to improve the objectivity of the definitions, to improve the ease of performing surveillance, and to try to improve the ability to make interhospital comparisons, Dr. Anderson explained, adding that VAEs include VAP, but also include pulmonary edema, atelectasis, and acute respiratory distress syndrome.

Thus, interventions aimed simply at reducing VAP may not change the rate of VAEs, he said.

Patients with VAEs stay on ventilators longer, stay in the ICU longer, are exposed to more antibiotic, and have two- to threefold increased rates of mortality, compared with those on ventilators but without VAEs, but little is known about preventing VAEs.

A larger study suggested that about a third of cases might be preventable, but no intervention has been tested and found to have an effect on the rate of VAEs. The Wake Up and Breathe Collaborative was tasked with answering the question of whether VAEs are preventable, and the investigators thought the best opportunity for prevention was to decrease the amount of sedation that ventilated patients received, Dr. Anderson said.

“More specifically – to decrease sedation through daily SATs and SBTs,” he added.

The opt-out protocol called for SATs and SBTs in all ventilated patients unless they met specific safety criteria or a physician wrote a specific opt-out order.

Though limited by the quasi-experimental open label study design, the findings are consistent with those from prior studies of such protocols.

“We felt that our multicenter prospective collaborative study was a success. … putting it all together, we conclude that VAEs are preventable when we improve compliance with evidence-based practice for our ventilated patients,” he said.Dr. Anderson reported receiving royalties from UpToDate and receiving research support from the CDC and the National Institutes of Health/National Institute of Allergy and Infectious Diseases.

AUSTIN, TEX. – Race, gender, and care setting appear to predict ventilator-associated pneumonia, according to an analysis of data from the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample.

The strongest predictor of ventilator-associated pneumonia (VAP) was mechanical ventilation for more than 96 hours (odds ratio, 13.64) in an analysis of 13,082 patients who developed the condition. The study subjects were among the 905,000 patients who required mechanical ventilation between 2008 and 2011 and who were available for analysis. The study was controlled for known VAP risk factors, including age, chronic lung disease, altered level of consciousness, acute respiratory distress syndrome, nasogastric tube, aspiration, comorbid conditions, chest surgery, hospital characteristics, and insurance status, Dr. Kathan Mehta of the University of Pittsburgh Medical Center, reported at the annual meeting of the American College of Chest Physicians.

Black patients, men, and those who were treated at a teaching hospital were also at significantly increased risk for VAP (OR, 1.23, 1.33, and 1.64, respectively), Dr. Mehta said.

VAP is an important cause of morbidity and mortality in hospitalized patients requiring mechanical ventilation. A number of risk factors have been associated with high incidence of VAP, but the role of epidemiologic factors in VAP development has been largely unknown, he said.

The current findings – from the one of the largest available comprehensive hospital discharge datasets on mechanical ventilation – have implications for preventing VAP and for improving the diagnosis and treatment of VAP. The at-risk population may benefit from higher suspicion for VAP for early diagnosis and treatment, and from aggressive measures to prevent VAP,” he said. Dr. Mehta reported having no disclosures.

AUSTIN, TEX. – Race, gender, and care setting appear to predict ventilator-associated pneumonia, according to an analysis of data from the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample.

The strongest predictor of ventilator-associated pneumonia (VAP) was mechanical ventilation for more than 96 hours (odds ratio, 13.64) in an analysis of 13,082 patients who developed the condition. The study subjects were among the 905,000 patients who required mechanical ventilation between 2008 and 2011 and who were available for analysis. The study was controlled for known VAP risk factors, including age, chronic lung disease, altered level of consciousness, acute respiratory distress syndrome, nasogastric tube, aspiration, comorbid conditions, chest surgery, hospital characteristics, and insurance status, Dr. Kathan Mehta of the University of Pittsburgh Medical Center, reported at the annual meeting of the American College of Chest Physicians.

Black patients, men, and those who were treated at a teaching hospital were also at significantly increased risk for VAP (OR, 1.23, 1.33, and 1.64, respectively), Dr. Mehta said.

VAP is an important cause of morbidity and mortality in hospitalized patients requiring mechanical ventilation. A number of risk factors have been associated with high incidence of VAP, but the role of epidemiologic factors in VAP development has been largely unknown, he said.

The current findings – from the one of the largest available comprehensive hospital discharge datasets on mechanical ventilation – have implications for preventing VAP and for improving the diagnosis and treatment of VAP. The at-risk population may benefit from higher suspicion for VAP for early diagnosis and treatment, and from aggressive measures to prevent VAP,” he said. Dr. Mehta reported having no disclosures.

AUSTIN, TEX. – Race, gender, and care setting appear to predict ventilator-associated pneumonia, according to an analysis of data from the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample.

The strongest predictor of ventilator-associated pneumonia (VAP) was mechanical ventilation for more than 96 hours (odds ratio, 13.64) in an analysis of 13,082 patients who developed the condition. The study subjects were among the 905,000 patients who required mechanical ventilation between 2008 and 2011 and who were available for analysis. The study was controlled for known VAP risk factors, including age, chronic lung disease, altered level of consciousness, acute respiratory distress syndrome, nasogastric tube, aspiration, comorbid conditions, chest surgery, hospital characteristics, and insurance status, Dr. Kathan Mehta of the University of Pittsburgh Medical Center, reported at the annual meeting of the American College of Chest Physicians.

Black patients, men, and those who were treated at a teaching hospital were also at significantly increased risk for VAP (OR, 1.23, 1.33, and 1.64, respectively), Dr. Mehta said.

VAP is an important cause of morbidity and mortality in hospitalized patients requiring mechanical ventilation. A number of risk factors have been associated with high incidence of VAP, but the role of epidemiologic factors in VAP development has been largely unknown, he said.

The current findings – from the one of the largest available comprehensive hospital discharge datasets on mechanical ventilation – have implications for preventing VAP and for improving the diagnosis and treatment of VAP. The at-risk population may benefit from higher suspicion for VAP for early diagnosis and treatment, and from aggressive measures to prevent VAP,” he said. Dr. Mehta reported having no disclosures.

Supplemental screening ultrasonography would add substantial costs while providing little clinical benefit after a negative screening mammography in women with dense breasts, according to three validated microsimulation models.

Adding ultrasound screening after a negative mammogram for women with heterogeneously or extremely dense breasts would cost more than $100,000 per quality-adjusted life-years (QALY) gained, compared with mammography screening alone, the models consistently showed.

Using simulated cohorts of women aged 50-74 years who were undergoing biennial mammography screening, the three models yielded similar results with respect to the estimated benefits and harms of three screening strategies: mammography alone, mammography plus screening ultrasonography after a negative mammography result in women with extremely dense breasts, and mammography plus handheld screening ultrasonography after a negative mammography result in women with heterogeneously or extremely dense breasts.

Courtesy University of Vermont College of Medicine

Brian L. Sprague, Ph.D., of the University of Vermont, Burlington, and his colleagues reported the findings in the Dec. 9 edition of Annals of Internal Medicine.

The findings could help influence the current national debate over breast density notification laws. At least 19 states have already enacted legislation that requires that women with dense breasts be informed about their breast density and about the availability of supplemental screening tests such as ultrasound. The high rate of false-negative mammograms in women with dense breasts is driving patient advocates to seek similar laws across the country. There’s even a bill under consideration at the national level.

The researchers found that mammography screening alone, across the models, reduced breast cancer deaths from 25.4 per 1,000 women in the absence of screening, to 19.7 per 1,000 women. There was an increase in total costs of approximately $1 million per 1,000 women.

Compared with biennial mammography screening alone, supplemental screening ultrasonography for women with extremely dense breasts would avert 0.30 additional breast cancer deaths and produce 1.1 additional QALY per 1,000 women, or about 9.6 hours per woman. These gains would come at a cost of 189 biopsies resulting from false-positive findings and $287,000 per 1,000 women with extremely dense breasts (a cost-effectiveness ratio of $246,000 per QALY gained).

In women with heterogeneously or extremely dense breasts, supplemental ultrasonography would avert 0.36 additional breast cancer deaths and produce 1.7 additional QALYs per 1,000 women. But these benefits would come at a cost of 354 biopsies resulting from a false-positive finding, and $560,000 per 1,000 women with heterogeneously or extremely dense breasts (a cost effectiveness ratio of $325,000/QALY gained), according to the study.

Restricting supplemental screening ultrasonography only to those with extremely dense breasts improved efficiency somewhat, but even this approach was not cost-effective by most standards.

The study used established, validated Cancer Intervention and Surveillance Modeling Network microsimulation breast cancer models, which incorporate evidence from clinical trials and observational studies.

“The models simulated life histories of women who were at risk for breast cancer, had screening, were treated for breast cancer diagnosed by screening or clinical detection, and were at risk for dying of breast cancer and other causes,” the researchers wrote, adding that the models differed in structure, but used common inputs.

The researchers called for further studies evaluating the potential role of other imaging methods, such as magnetic resonance imaging and digital breast tomosynthesis, in screening for women with dense breasts.

This study was funded by the National Cancer Institute. Dr. Sprague and several of the study authors reported receiving grant funds from the National Cancer Institute during the conduct of the study.

Supplemental screening ultrasonography would add substantial costs while providing little clinical benefit after a negative screening mammography in women with dense breasts, according to three validated microsimulation models.

Adding ultrasound screening after a negative mammogram for women with heterogeneously or extremely dense breasts would cost more than $100,000 per quality-adjusted life-years (QALY) gained, compared with mammography screening alone, the models consistently showed.

Using simulated cohorts of women aged 50-74 years who were undergoing biennial mammography screening, the three models yielded similar results with respect to the estimated benefits and harms of three screening strategies: mammography alone, mammography plus screening ultrasonography after a negative mammography result in women with extremely dense breasts, and mammography plus handheld screening ultrasonography after a negative mammography result in women with heterogeneously or extremely dense breasts.

Courtesy University of Vermont College of Medicine

Brian L. Sprague, Ph.D., of the University of Vermont, Burlington, and his colleagues reported the findings in the Dec. 9 edition of Annals of Internal Medicine.

The findings could help influence the current national debate over breast density notification laws. At least 19 states have already enacted legislation that requires that women with dense breasts be informed about their breast density and about the availability of supplemental screening tests such as ultrasound. The high rate of false-negative mammograms in women with dense breasts is driving patient advocates to seek similar laws across the country. There’s even a bill under consideration at the national level.

The researchers found that mammography screening alone, across the models, reduced breast cancer deaths from 25.4 per 1,000 women in the absence of screening, to 19.7 per 1,000 women. There was an increase in total costs of approximately $1 million per 1,000 women.

Compared with biennial mammography screening alone, supplemental screening ultrasonography for women with extremely dense breasts would avert 0.30 additional breast cancer deaths and produce 1.1 additional QALY per 1,000 women, or about 9.6 hours per woman. These gains would come at a cost of 189 biopsies resulting from false-positive findings and $287,000 per 1,000 women with extremely dense breasts (a cost-effectiveness ratio of $246,000 per QALY gained).

In women with heterogeneously or extremely dense breasts, supplemental ultrasonography would avert 0.36 additional breast cancer deaths and produce 1.7 additional QALYs per 1,000 women. But these benefits would come at a cost of 354 biopsies resulting from a false-positive finding, and $560,000 per 1,000 women with heterogeneously or extremely dense breasts (a cost effectiveness ratio of $325,000/QALY gained), according to the study.

Restricting supplemental screening ultrasonography only to those with extremely dense breasts improved efficiency somewhat, but even this approach was not cost-effective by most standards.

The study used established, validated Cancer Intervention and Surveillance Modeling Network microsimulation breast cancer models, which incorporate evidence from clinical trials and observational studies.

“The models simulated life histories of women who were at risk for breast cancer, had screening, were treated for breast cancer diagnosed by screening or clinical detection, and were at risk for dying of breast cancer and other causes,” the researchers wrote, adding that the models differed in structure, but used common inputs.

The researchers called for further studies evaluating the potential role of other imaging methods, such as magnetic resonance imaging and digital breast tomosynthesis, in screening for women with dense breasts.

This study was funded by the National Cancer Institute. Dr. Sprague and several of the study authors reported receiving grant funds from the National Cancer Institute during the conduct of the study.

Supplemental screening ultrasonography would add substantial costs while providing little clinical benefit after a negative screening mammography in women with dense breasts, according to three validated microsimulation models.

Adding ultrasound screening after a negative mammogram for women with heterogeneously or extremely dense breasts would cost more than $100,000 per quality-adjusted life-years (QALY) gained, compared with mammography screening alone, the models consistently showed.

Using simulated cohorts of women aged 50-74 years who were undergoing biennial mammography screening, the three models yielded similar results with respect to the estimated benefits and harms of three screening strategies: mammography alone, mammography plus screening ultrasonography after a negative mammography result in women with extremely dense breasts, and mammography plus handheld screening ultrasonography after a negative mammography result in women with heterogeneously or extremely dense breasts.

Courtesy University of Vermont College of Medicine

Brian L. Sprague, Ph.D., of the University of Vermont, Burlington, and his colleagues reported the findings in the Dec. 9 edition of Annals of Internal Medicine.

The findings could help influence the current national debate over breast density notification laws. At least 19 states have already enacted legislation that requires that women with dense breasts be informed about their breast density and about the availability of supplemental screening tests such as ultrasound. The high rate of false-negative mammograms in women with dense breasts is driving patient advocates to seek similar laws across the country. There’s even a bill under consideration at the national level.

The researchers found that mammography screening alone, across the models, reduced breast cancer deaths from 25.4 per 1,000 women in the absence of screening, to 19.7 per 1,000 women. There was an increase in total costs of approximately $1 million per 1,000 women.

Compared with biennial mammography screening alone, supplemental screening ultrasonography for women with extremely dense breasts would avert 0.30 additional breast cancer deaths and produce 1.1 additional QALY per 1,000 women, or about 9.6 hours per woman. These gains would come at a cost of 189 biopsies resulting from false-positive findings and $287,000 per 1,000 women with extremely dense breasts (a cost-effectiveness ratio of $246,000 per QALY gained).

In women with heterogeneously or extremely dense breasts, supplemental ultrasonography would avert 0.36 additional breast cancer deaths and produce 1.7 additional QALYs per 1,000 women. But these benefits would come at a cost of 354 biopsies resulting from a false-positive finding, and $560,000 per 1,000 women with heterogeneously or extremely dense breasts (a cost effectiveness ratio of $325,000/QALY gained), according to the study.

Restricting supplemental screening ultrasonography only to those with extremely dense breasts improved efficiency somewhat, but even this approach was not cost-effective by most standards.

The study used established, validated Cancer Intervention and Surveillance Modeling Network microsimulation breast cancer models, which incorporate evidence from clinical trials and observational studies.

“The models simulated life histories of women who were at risk for breast cancer, had screening, were treated for breast cancer diagnosed by screening or clinical detection, and were at risk for dying of breast cancer and other causes,” the researchers wrote, adding that the models differed in structure, but used common inputs.

The researchers called for further studies evaluating the potential role of other imaging methods, such as magnetic resonance imaging and digital breast tomosynthesis, in screening for women with dense breasts.

This study was funded by the National Cancer Institute. Dr. Sprague and several of the study authors reported receiving grant funds from the National Cancer Institute during the conduct of the study.

PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.

Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.

An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.

“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.

Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.

“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.

“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.

An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.

As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.

Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.

“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.

Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.

In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm³, he said.

However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.

“It’s a low risk, but a real one,” he said.

The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.

Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.

“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.

If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.

Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.

A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.

He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.

If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.

“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.

Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.

Dr. Fine said he had no relevant financial disclosures.

PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.

Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.

An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.

“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.

Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.

“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.

“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.

An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.

As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.

Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.

“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.

Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.

In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm³, he said.

However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.

“It’s a low risk, but a real one,” he said.

The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.

Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.

“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.

If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.

Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.

A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.

He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.

If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.

“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.

Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.

Dr. Fine said he had no relevant financial disclosures.

PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.

Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.

An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.

“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.

Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.

“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.

“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.

An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.

As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.

Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.

“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.

Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.

In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm³, he said.

However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.

“It’s a low risk, but a real one,” he said.

The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.

Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.

“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.

If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.

Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.

A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.

He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.

If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.

“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.

Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.

Dr. Fine said he had no relevant financial disclosures.

The 2014-2015 flu season may be particularly severe, and the 2014-2015 vaccine will provide important, but limited protection, according to a health advisory from the Centers for Disease Control and Prevention that is based on early analyses of reported disease cases.

The advisory also stresses the importance of antiviral treatment in those with confirmed or suspected influenza, particularly those at risk of developing complications, including young children, adults aged 65 years and older, pregnant women, and those with chronic health conditions, such as asthma, diabetes, or heart, lung, or kidney disease.

Influenza A viruses, mainly H3N2, predominate thus far during the 2014-2015 flu season, comprising more than 91% of the specimens collected and analyzed, and only about half of those have been antigenically similar to H3N2 components included in the 2014-2015 vaccine, according to the advisory.

This doesn’t bode well for the effectiveness of the vaccine, which is particularly troubling given that H3N2-predominate seasons historically have been associated with up to twice the rate of overall and age-specific flu-related hospitalizations and deaths, CDC director Dr. Thomas R. Frieden explained during a press briefing.

Still, vaccination remains the best line of defense against infection, he said.

The vaccine will protect against circulating strains that have not undergone significant antigenic drift, including the influenza B viruses, which have comprised about 9% of those collected to date. In addition, the vaccine has been found to provide some protection against the antigenically drifted H3N2 viruses, he said.

“We continue to recommend flu vaccine as the single best way to protect yourself against the flu,” he said.

Dr. Frieden also stressed the importance of antiviral use.

“Antivirals aren’t a substitute for vaccinations … but they are an important second line of defense for treating the flu, and this year, treatment with antiviral drugs is especially important, particularly for people who are at high risk for serious flu complications or for people who are very sick with flu,” he said.

These agents are greatly underprescribed, with fewer than one in six severely ill patients receiving antiviral treatment, he noted.

“It’s very important that we do better for people who are severely ill or who could become severely ill with influenza,” he said, adding that antiviral use is even more important during seasons such as this one when the circulating viruses are different from the vaccine viruses.

The two neuraminidase inhibitor antiviral medications currently approved for treating influenza – oseltamivir and zanamivir – shorten the duration of fever and illness symptoms by about a day and can reduce the risk of severe outcomes, he said.

Treatment should be provided withing 2 days of symptoms onset when possible, but it may also provide benefit to hospitalized patients even if taken later in the course of illness.

“We strongly recommend that if doctors suspect the flu in someone who may be severely ill from the flu, they don’t wait for the results of a flu test before starting antivirals,” he said.

“There is no way to predict with certainly what will happen. We have four different strains of flu circulating. The B strain, the H1 strain, the well-matched H3 strain, and the poorly matched H3 strain. Only time will tell which of them, if any, will predominate for the coming weeks and months of this year’s flu season,” he said.

However, already this season there have been five pediatric deaths from influenza, including three in patients with H3N2 disease, and one in a patient with influenza type B.

“We’ve also heard of outbreaks in schools and in nursing homes,” Dr. Frieden said, adding that “getting a vaccine, even if it doesn’t provide as good protection as we would hope, would be more important than ever, and remains the single most effective way to protect yourself against the flu.”

Physicians should continue to vaccinate patients, he said, noting that nearly 150 million doses have been distributed by manufacturers, and that the supply is expected to meet the demand. The supply of antiviral medications is also expected to be adequate.

Patients should also be advised to stay home when they are sick to avoid spreading influenza, and to seek treatment promptly for flu symptoms, including fever, cough, sore throat, runny or stuffy nose, body aches, headache, chills, and fatigue, he said.

The 2014-2015 flu season may be particularly severe, and the 2014-2015 vaccine will provide important, but limited protection, according to a health advisory from the Centers for Disease Control and Prevention that is based on early analyses of reported disease cases.

The advisory also stresses the importance of antiviral treatment in those with confirmed or suspected influenza, particularly those at risk of developing complications, including young children, adults aged 65 years and older, pregnant women, and those with chronic health conditions, such as asthma, diabetes, or heart, lung, or kidney disease.

Influenza A viruses, mainly H3N2, predominate thus far during the 2014-2015 flu season, comprising more than 91% of the specimens collected and analyzed, and only about half of those have been antigenically similar to H3N2 components included in the 2014-2015 vaccine, according to the advisory.

This doesn’t bode well for the effectiveness of the vaccine, which is particularly troubling given that H3N2-predominate seasons historically have been associated with up to twice the rate of overall and age-specific flu-related hospitalizations and deaths, CDC director Dr. Thomas R. Frieden explained during a press briefing.

Still, vaccination remains the best line of defense against infection, he said.

The vaccine will protect against circulating strains that have not undergone significant antigenic drift, including the influenza B viruses, which have comprised about 9% of those collected to date. In addition, the vaccine has been found to provide some protection against the antigenically drifted H3N2 viruses, he said.

“We continue to recommend flu vaccine as the single best way to protect yourself against the flu,” he said.

Dr. Frieden also stressed the importance of antiviral use.

“Antivirals aren’t a substitute for vaccinations … but they are an important second line of defense for treating the flu, and this year, treatment with antiviral drugs is especially important, particularly for people who are at high risk for serious flu complications or for people who are very sick with flu,” he said.

These agents are greatly underprescribed, with fewer than one in six severely ill patients receiving antiviral treatment, he noted.

“It’s very important that we do better for people who are severely ill or who could become severely ill with influenza,” he said, adding that antiviral use is even more important during seasons such as this one when the circulating viruses are different from the vaccine viruses.

The two neuraminidase inhibitor antiviral medications currently approved for treating influenza – oseltamivir and zanamivir – shorten the duration of fever and illness symptoms by about a day and can reduce the risk of severe outcomes, he said.

Treatment should be provided withing 2 days of symptoms onset when possible, but it may also provide benefit to hospitalized patients even if taken later in the course of illness.

“We strongly recommend that if doctors suspect the flu in someone who may be severely ill from the flu, they don’t wait for the results of a flu test before starting antivirals,” he said.

“There is no way to predict with certainly what will happen. We have four different strains of flu circulating. The B strain, the H1 strain, the well-matched H3 strain, and the poorly matched H3 strain. Only time will tell which of them, if any, will predominate for the coming weeks and months of this year’s flu season,” he said.

However, already this season there have been five pediatric deaths from influenza, including three in patients with H3N2 disease, and one in a patient with influenza type B.

“We’ve also heard of outbreaks in schools and in nursing homes,” Dr. Frieden said, adding that “getting a vaccine, even if it doesn’t provide as good protection as we would hope, would be more important than ever, and remains the single most effective way to protect yourself against the flu.”

Physicians should continue to vaccinate patients, he said, noting that nearly 150 million doses have been distributed by manufacturers, and that the supply is expected to meet the demand. The supply of antiviral medications is also expected to be adequate.

Patients should also be advised to stay home when they are sick to avoid spreading influenza, and to seek treatment promptly for flu symptoms, including fever, cough, sore throat, runny or stuffy nose, body aches, headache, chills, and fatigue, he said.

The 2014-2015 flu season may be particularly severe, and the 2014-2015 vaccine will provide important, but limited protection, according to a health advisory from the Centers for Disease Control and Prevention that is based on early analyses of reported disease cases.

The advisory also stresses the importance of antiviral treatment in those with confirmed or suspected influenza, particularly those at risk of developing complications, including young children, adults aged 65 years and older, pregnant women, and those with chronic health conditions, such as asthma, diabetes, or heart, lung, or kidney disease.

Influenza A viruses, mainly H3N2, predominate thus far during the 2014-2015 flu season, comprising more than 91% of the specimens collected and analyzed, and only about half of those have been antigenically similar to H3N2 components included in the 2014-2015 vaccine, according to the advisory.

This doesn’t bode well for the effectiveness of the vaccine, which is particularly troubling given that H3N2-predominate seasons historically have been associated with up to twice the rate of overall and age-specific flu-related hospitalizations and deaths, CDC director Dr. Thomas R. Frieden explained during a press briefing.

Still, vaccination remains the best line of defense against infection, he said.

The vaccine will protect against circulating strains that have not undergone significant antigenic drift, including the influenza B viruses, which have comprised about 9% of those collected to date. In addition, the vaccine has been found to provide some protection against the antigenically drifted H3N2 viruses, he said.

“We continue to recommend flu vaccine as the single best way to protect yourself against the flu,” he said.

Dr. Frieden also stressed the importance of antiviral use.

“Antivirals aren’t a substitute for vaccinations … but they are an important second line of defense for treating the flu, and this year, treatment with antiviral drugs is especially important, particularly for people who are at high risk for serious flu complications or for people who are very sick with flu,” he said.

These agents are greatly underprescribed, with fewer than one in six severely ill patients receiving antiviral treatment, he noted.

“It’s very important that we do better for people who are severely ill or who could become severely ill with influenza,” he said, adding that antiviral use is even more important during seasons such as this one when the circulating viruses are different from the vaccine viruses.

The two neuraminidase inhibitor antiviral medications currently approved for treating influenza – oseltamivir and zanamivir – shorten the duration of fever and illness symptoms by about a day and can reduce the risk of severe outcomes, he said.

Treatment should be provided withing 2 days of symptoms onset when possible, but it may also provide benefit to hospitalized patients even if taken later in the course of illness.

“We strongly recommend that if doctors suspect the flu in someone who may be severely ill from the flu, they don’t wait for the results of a flu test before starting antivirals,” he said.

“There is no way to predict with certainly what will happen. We have four different strains of flu circulating. The B strain, the H1 strain, the well-matched H3 strain, and the poorly matched H3 strain. Only time will tell which of them, if any, will predominate for the coming weeks and months of this year’s flu season,” he said.

However, already this season there have been five pediatric deaths from influenza, including three in patients with H3N2 disease, and one in a patient with influenza type B.

“We’ve also heard of outbreaks in schools and in nursing homes,” Dr. Frieden said, adding that “getting a vaccine, even if it doesn’t provide as good protection as we would hope, would be more important than ever, and remains the single most effective way to protect yourself against the flu.”

Physicians should continue to vaccinate patients, he said, noting that nearly 150 million doses have been distributed by manufacturers, and that the supply is expected to meet the demand. The supply of antiviral medications is also expected to be adequate.

Patients should also be advised to stay home when they are sick to avoid spreading influenza, and to seek treatment promptly for flu symptoms, including fever, cough, sore throat, runny or stuffy nose, body aches, headache, chills, and fatigue, he said.