Pulmonary Health Hub

CVS Pharmacy will stop selling cigarettes and other tobacco products by October of this year, the company announced Feb. 5.

CVS President and Chief Executive Officer Larry Merlo said in a statement that the sale of tobacco products is contrary to CVS’s responsibility to help patients manage chronic diseases such as high blood pressure, high cholesterol, and diabetes. "All of these conditions are made worse by smoking," he said. "Tobacco products have no place in a setting where health care is delivered."

In addition to pulling cigarettes from its shelves, CVS also plans to launch a national smoking cessation program in the spring for those trying to quit, Mr. Merlo added.

Dr. Troyen A. Brennan, CVS executive vice president and chief medical officer, and Dr. Steven A. Schroeder, of the Smoking Cessation Leadership Center at the University of California, San Francisco, further explained the decision in a JAMA commentary (JAMA 2014 Feb. 5 [doi:10.1001/jama.2014.686]). "This action may not lead many people to stop smoking; smokers will probably simply go elsewhere to buy cigarettes," they wrote. "But if other retailers follow this lead, tobacco products will become much more difficult to obtain."

Corund/Fotalia.com

U.S. Department of Health and Human Services secretary Kathleen Sebelius praised the effort in a statement, calling the move an "unprecedented step in the retail industry" that would contribute to positive health effects for the next generation.

"Nearly 500,000 Americans die early each year due to smoking, and smoking costs us $289 billion annually," she said, citing the recently released 50th Anniversary Surgeon General Report on smoking and health. "If we fail to reverse course, 5.6 million American children alive today will die prematurely due to smoking."

CVS’s decision also drew support from the American Medical Association. AMA president Dr. Ardis Dee Hoven said in a statement that she applauds the company’s decision to put public health first and recognize the importance of "supporting health and wellness instead of contributing to disease and death caused by tobacco use." Dr. Hoven also said she hoped the change would inspire other pharmacies to follow suit by ending cigarette sales in stores.

Dr. W. Michael Alberts, chief medical officer at Moffitt Cancer Center in Tampa, also voiced approval. "This is a major decision by CVS," he said in an interview. "It may even be a watershed moment akin to the decision to ban smoking on airplanes. Let’s hope such decisions become commonplace in corporate boardrooms."

mrajaraman@frontlinemedcom.com

CVS Pharmacy will stop selling cigarettes and other tobacco products by October of this year, the company announced Feb. 5.

CVS President and Chief Executive Officer Larry Merlo said in a statement that the sale of tobacco products is contrary to CVS’s responsibility to help patients manage chronic diseases such as high blood pressure, high cholesterol, and diabetes. "All of these conditions are made worse by smoking," he said. "Tobacco products have no place in a setting where health care is delivered."

In addition to pulling cigarettes from its shelves, CVS also plans to launch a national smoking cessation program in the spring for those trying to quit, Mr. Merlo added.

Dr. Troyen A. Brennan, CVS executive vice president and chief medical officer, and Dr. Steven A. Schroeder, of the Smoking Cessation Leadership Center at the University of California, San Francisco, further explained the decision in a JAMA commentary (JAMA 2014 Feb. 5 [doi:10.1001/jama.2014.686]). "This action may not lead many people to stop smoking; smokers will probably simply go elsewhere to buy cigarettes," they wrote. "But if other retailers follow this lead, tobacco products will become much more difficult to obtain."

Corund/Fotalia.com

U.S. Department of Health and Human Services secretary Kathleen Sebelius praised the effort in a statement, calling the move an "unprecedented step in the retail industry" that would contribute to positive health effects for the next generation.

"Nearly 500,000 Americans die early each year due to smoking, and smoking costs us $289 billion annually," she said, citing the recently released 50th Anniversary Surgeon General Report on smoking and health. "If we fail to reverse course, 5.6 million American children alive today will die prematurely due to smoking."

CVS’s decision also drew support from the American Medical Association. AMA president Dr. Ardis Dee Hoven said in a statement that she applauds the company’s decision to put public health first and recognize the importance of "supporting health and wellness instead of contributing to disease and death caused by tobacco use." Dr. Hoven also said she hoped the change would inspire other pharmacies to follow suit by ending cigarette sales in stores.

Dr. W. Michael Alberts, chief medical officer at Moffitt Cancer Center in Tampa, also voiced approval. "This is a major decision by CVS," he said in an interview. "It may even be a watershed moment akin to the decision to ban smoking on airplanes. Let’s hope such decisions become commonplace in corporate boardrooms."

mrajaraman@frontlinemedcom.com

CVS Pharmacy will stop selling cigarettes and other tobacco products by October of this year, the company announced Feb. 5.

CVS President and Chief Executive Officer Larry Merlo said in a statement that the sale of tobacco products is contrary to CVS’s responsibility to help patients manage chronic diseases such as high blood pressure, high cholesterol, and diabetes. "All of these conditions are made worse by smoking," he said. "Tobacco products have no place in a setting where health care is delivered."

In addition to pulling cigarettes from its shelves, CVS also plans to launch a national smoking cessation program in the spring for those trying to quit, Mr. Merlo added.

Dr. Troyen A. Brennan, CVS executive vice president and chief medical officer, and Dr. Steven A. Schroeder, of the Smoking Cessation Leadership Center at the University of California, San Francisco, further explained the decision in a JAMA commentary (JAMA 2014 Feb. 5 [doi:10.1001/jama.2014.686]). "This action may not lead many people to stop smoking; smokers will probably simply go elsewhere to buy cigarettes," they wrote. "But if other retailers follow this lead, tobacco products will become much more difficult to obtain."

Corund/Fotalia.com

U.S. Department of Health and Human Services secretary Kathleen Sebelius praised the effort in a statement, calling the move an "unprecedented step in the retail industry" that would contribute to positive health effects for the next generation.

"Nearly 500,000 Americans die early each year due to smoking, and smoking costs us $289 billion annually," she said, citing the recently released 50th Anniversary Surgeon General Report on smoking and health. "If we fail to reverse course, 5.6 million American children alive today will die prematurely due to smoking."

CVS’s decision also drew support from the American Medical Association. AMA president Dr. Ardis Dee Hoven said in a statement that she applauds the company’s decision to put public health first and recognize the importance of "supporting health and wellness instead of contributing to disease and death caused by tobacco use." Dr. Hoven also said she hoped the change would inspire other pharmacies to follow suit by ending cigarette sales in stores.

Dr. W. Michael Alberts, chief medical officer at Moffitt Cancer Center in Tampa, also voiced approval. "This is a major decision by CVS," he said in an interview. "It may even be a watershed moment akin to the decision to ban smoking on airplanes. Let’s hope such decisions become commonplace in corporate boardrooms."

mrajaraman@frontlinemedcom.com

PRACTICE CHANGER

Prescribe a five-day regimen of glucocorticoid therapy for acute exacerbations of chronic obstructive pulmonary disease (COPD); the shorter course of treatment appears to be as effective as a 14-day regimen.¹

Strength of ­recommendation

B: Based on a single well-­designed randomized controlled trial (RCT).¹

ILLUSTRATIVE CASE

A 55-year-old man with COPD presents to the emergency department (ED) with progressive shortness of breath, cough, and sputum production in the past four days. He is diagnosed with a COPD exacerbation, treated with corticosteroids, and admitted to the hospital. His inpatient treatment includes antibiotics, inhaled albuterol and ipratropium, supplemental oxygen, and oral corticosteroids.

How many days should he take oral steroids?

Severe exacerbations of COPD are independently associated with mortality,² regardless of baseline severity. Guidelines and systematic reviews highlight the importance of using oral glucocorticoids in the management of acute COPD exacerbations, as the drugs have been found to shorten recovery time and length of hospital stay, improve lung function, and reduce the risk for early relapse and treatment failure.^3-5 What is not clear is how long the course of oral steroids should be.

What we know (and don’t know) about duration

Data supporting a 14-day course of steroids versus a longer (eight-week) duration come from the Systemic Corticosteroids in COPD Exacerbations trial.⁶ Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria suggest a 10- to 14-day regimen (30 to 40 mg/d) but acknowledge that there is a lack of data from clinical and observational studies to support this recommendation.³ A recent Cochrane review compared a short course of treatment (three to seven days) with a longer regimen (10 to 15 days) and found that the evidence to support a clinical practice change was inconclusive.⁵

The study detailed in this PURL—a double-blind RCT comparing five-day with 14-day oral steroid treatment in patients ­hospitalized for acute COPD exacerbation—had more definitive results.¹

Continue reading for the study summary...

STUDY SUMMARY

Shorter and longer regimens produce equal results

Leuppi et al¹ used noninferiority methodology to compare a five- and a 14-day course of prednisone 40 mg/d to treat patients with COPD exacerbations. A patient was considered to have an exacerbation if he or she had a change from baseline in two or more of the following: dyspnea, cough, sputum quantity, or purulence.

Participants were patients who presented to the EDs of five Swiss teaching hospitals between March 2006 and February 2011. To be eligible, individuals had to be 40 or older and have at least 20 pack-years of smoking. Exclusion criteria included asthma, mild obstruction (FEV₁/FVC > 70%), pneumonia, an estimated survival of less than six months, pregnancy, and lactation.

All the participants (N = 311) received 40 mg methylprednisolone intravenously on day 1, followed by prednisone 40 mg orally on days 2 through 5. The researchers then randomly divided participants into two groups: One group continued to take prednisone 40 mg/d and the other group received a matching placebo for an additional nine days. Participants in both groups also received antibiotics for seven days, twice-daily inhaled steroids, daily tiotropium, and nebulized albuterol, as needed; additional oral glucocorticoids could be administered, as well, at the discretion of the treating physicians.

The primary outcome was the time to the next COPD exacerbation, up to 180 days. Noninferiority between the groups was defined as no more than a 15% absolute increase in exacerbations. The dropout rate was 5.7%, evenly divided between groups. Intention to treat and per-protocol analyses were conducted, and hazard ratios (HRs) were calculated using the Kaplan-Meier method and Cox proportional hazards models.

The time to next COPD exacerbation did not differ between the study groups: 56 days for those on the five-day steroid regimen versus 57 days for those on the
14-day regimen in the intention-to-treat analysis (HR, 0.95). Sensitivity analyses adjusting for baseline characteristics provided similar results, as did the per-protocol analysis.

Secondary outcomes (overall survival; need for mechanical ventilation; need for additional corticosteroids; and clinical performance measures, such as dyspnea score and quality of life) also did not differ between groups. Nor were there differences in hyperglycemia, worsening hypertension, infection, or other adverse effects typically associated with glucocorticoid use. The active treatment group took more than 400 mg more prednisone than the placebo group (mean, 793 mg vs 379 mg, respectively).

WHAT’S NEW?

Now we know: five days is enough

While randomized trials have found that glucocorticoids improve COPD symptoms, the optimal treatment dose and duration were not known. Indeed, current guidelines recommend treatment for more than five days.³ This trial clearly demonstrated that 40-mg prednisone for five days is at least as good as a 14-day treatment course. Furthermore, it is un­necessary to taper the short-course therapy, which simplifies the regimen.

CAVEATS

Will the results apply to those less severely ill?

More than 80% of patients with acute COPD exacerbations can be managed in an outpatient setting.³ However, participants in this trial were hospitalized for a median of 8.5 days, and most had severe or very severe COPD—and thus, were not fully representative of COPD patients typically seen in an outpatient practice. Yet patients with less severe disease should be at least as likely to ­respond to short-course steroids as those whose COPD is more ­severe.

It is important to note that participants in this study all received optimal guideline-based therapies during hospitalization, which may be difficult to achieve for some patients treated in an outpatient setting. Finally, treatment adherence observed during the hospitalization period in this trial is unlikely to be replicated in the outpatient setting.

CHALLENGES TO IMPLEMENTATION

Identifying patients who need steroids for a longer duration

For patients with new COPD exacerbations or those successfully treated using short-course therapy in the past, a five-day regimen may be appropriate. For those in whom prior attempts at short-course treatment have failed, however, a 14-day course of treatment may be more advisable. That said, no guidelines are available to help us determine which patients previously treated with a longer regimen will find the shorter course of treatment unsuccessful.

Continue for references...

REFERENCES

1. Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309:2223-2231.

2. Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60:925-931.

3. Global Initiative for Chronic Obstructive Lung Disease, Inc. The global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. www.goldcopd.org. Accessed January 9, 2014.

4. Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2008;133:756-766.

5. Walters JA, Wang W, Morley C, et al. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011; (10):CD006897.

6. Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 1999;340:1941-1947.

ACKNOWLEDGEMENT

The PURLs Surveillance System is supported in part by Grant Number UL 1RR 024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(1):29-30, 32.

PRACTICE CHANGER

Prescribe a five-day regimen of glucocorticoid therapy for acute exacerbations of chronic obstructive pulmonary disease (COPD); the shorter course of treatment appears to be as effective as a 14-day regimen.¹

Strength of ­recommendation

B: Based on a single well-­designed randomized controlled trial (RCT).¹

ILLUSTRATIVE CASE

A 55-year-old man with COPD presents to the emergency department (ED) with progressive shortness of breath, cough, and sputum production in the past four days. He is diagnosed with a COPD exacerbation, treated with corticosteroids, and admitted to the hospital. His inpatient treatment includes antibiotics, inhaled albuterol and ipratropium, supplemental oxygen, and oral corticosteroids.

How many days should he take oral steroids?

Severe exacerbations of COPD are independently associated with mortality,² regardless of baseline severity. Guidelines and systematic reviews highlight the importance of using oral glucocorticoids in the management of acute COPD exacerbations, as the drugs have been found to shorten recovery time and length of hospital stay, improve lung function, and reduce the risk for early relapse and treatment failure.^3-5 What is not clear is how long the course of oral steroids should be.

What we know (and don’t know) about duration

Data supporting a 14-day course of steroids versus a longer (eight-week) duration come from the Systemic Corticosteroids in COPD Exacerbations trial.⁶ Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria suggest a 10- to 14-day regimen (30 to 40 mg/d) but acknowledge that there is a lack of data from clinical and observational studies to support this recommendation.³ A recent Cochrane review compared a short course of treatment (three to seven days) with a longer regimen (10 to 15 days) and found that the evidence to support a clinical practice change was inconclusive.⁵

The study detailed in this PURL—a double-blind RCT comparing five-day with 14-day oral steroid treatment in patients ­hospitalized for acute COPD exacerbation—had more definitive results.¹

Continue reading for the study summary...

STUDY SUMMARY

Shorter and longer regimens produce equal results

Leuppi et al¹ used noninferiority methodology to compare a five- and a 14-day course of prednisone 40 mg/d to treat patients with COPD exacerbations. A patient was considered to have an exacerbation if he or she had a change from baseline in two or more of the following: dyspnea, cough, sputum quantity, or purulence.

Participants were patients who presented to the EDs of five Swiss teaching hospitals between March 2006 and February 2011. To be eligible, individuals had to be 40 or older and have at least 20 pack-years of smoking. Exclusion criteria included asthma, mild obstruction (FEV₁/FVC > 70%), pneumonia, an estimated survival of less than six months, pregnancy, and lactation.

All the participants (N = 311) received 40 mg methylprednisolone intravenously on day 1, followed by prednisone 40 mg orally on days 2 through 5. The researchers then randomly divided participants into two groups: One group continued to take prednisone 40 mg/d and the other group received a matching placebo for an additional nine days. Participants in both groups also received antibiotics for seven days, twice-daily inhaled steroids, daily tiotropium, and nebulized albuterol, as needed; additional oral glucocorticoids could be administered, as well, at the discretion of the treating physicians.

The primary outcome was the time to the next COPD exacerbation, up to 180 days. Noninferiority between the groups was defined as no more than a 15% absolute increase in exacerbations. The dropout rate was 5.7%, evenly divided between groups. Intention to treat and per-protocol analyses were conducted, and hazard ratios (HRs) were calculated using the Kaplan-Meier method and Cox proportional hazards models.

The time to next COPD exacerbation did not differ between the study groups: 56 days for those on the five-day steroid regimen versus 57 days for those on the
14-day regimen in the intention-to-treat analysis (HR, 0.95). Sensitivity analyses adjusting for baseline characteristics provided similar results, as did the per-protocol analysis.

Secondary outcomes (overall survival; need for mechanical ventilation; need for additional corticosteroids; and clinical performance measures, such as dyspnea score and quality of life) also did not differ between groups. Nor were there differences in hyperglycemia, worsening hypertension, infection, or other adverse effects typically associated with glucocorticoid use. The active treatment group took more than 400 mg more prednisone than the placebo group (mean, 793 mg vs 379 mg, respectively).

WHAT’S NEW?

Now we know: five days is enough

While randomized trials have found that glucocorticoids improve COPD symptoms, the optimal treatment dose and duration were not known. Indeed, current guidelines recommend treatment for more than five days.³ This trial clearly demonstrated that 40-mg prednisone for five days is at least as good as a 14-day treatment course. Furthermore, it is un­necessary to taper the short-course therapy, which simplifies the regimen.

CAVEATS

Will the results apply to those less severely ill?

More than 80% of patients with acute COPD exacerbations can be managed in an outpatient setting.³ However, participants in this trial were hospitalized for a median of 8.5 days, and most had severe or very severe COPD—and thus, were not fully representative of COPD patients typically seen in an outpatient practice. Yet patients with less severe disease should be at least as likely to ­respond to short-course steroids as those whose COPD is more ­severe.

It is important to note that participants in this study all received optimal guideline-based therapies during hospitalization, which may be difficult to achieve for some patients treated in an outpatient setting. Finally, treatment adherence observed during the hospitalization period in this trial is unlikely to be replicated in the outpatient setting.

CHALLENGES TO IMPLEMENTATION

Identifying patients who need steroids for a longer duration

For patients with new COPD exacerbations or those successfully treated using short-course therapy in the past, a five-day regimen may be appropriate. For those in whom prior attempts at short-course treatment have failed, however, a 14-day course of treatment may be more advisable. That said, no guidelines are available to help us determine which patients previously treated with a longer regimen will find the shorter course of treatment unsuccessful.

Continue for references...

REFERENCES

1. Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309:2223-2231.

2. Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60:925-931.

3. Global Initiative for Chronic Obstructive Lung Disease, Inc. The global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. www.goldcopd.org. Accessed January 9, 2014.

4. Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2008;133:756-766.

5. Walters JA, Wang W, Morley C, et al. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011; (10):CD006897.

6. Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 1999;340:1941-1947.

ACKNOWLEDGEMENT

The PURLs Surveillance System is supported in part by Grant Number UL 1RR 024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(1):29-30, 32.

PRACTICE CHANGER

Prescribe a five-day regimen of glucocorticoid therapy for acute exacerbations of chronic obstructive pulmonary disease (COPD); the shorter course of treatment appears to be as effective as a 14-day regimen.¹

Strength of ­recommendation

B: Based on a single well-­designed randomized controlled trial (RCT).¹

ILLUSTRATIVE CASE

A 55-year-old man with COPD presents to the emergency department (ED) with progressive shortness of breath, cough, and sputum production in the past four days. He is diagnosed with a COPD exacerbation, treated with corticosteroids, and admitted to the hospital. His inpatient treatment includes antibiotics, inhaled albuterol and ipratropium, supplemental oxygen, and oral corticosteroids.

How many days should he take oral steroids?

Severe exacerbations of COPD are independently associated with mortality,² regardless of baseline severity. Guidelines and systematic reviews highlight the importance of using oral glucocorticoids in the management of acute COPD exacerbations, as the drugs have been found to shorten recovery time and length of hospital stay, improve lung function, and reduce the risk for early relapse and treatment failure.^3-5 What is not clear is how long the course of oral steroids should be.

What we know (and don’t know) about duration

Data supporting a 14-day course of steroids versus a longer (eight-week) duration come from the Systemic Corticosteroids in COPD Exacerbations trial.⁶ Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria suggest a 10- to 14-day regimen (30 to 40 mg/d) but acknowledge that there is a lack of data from clinical and observational studies to support this recommendation.³ A recent Cochrane review compared a short course of treatment (three to seven days) with a longer regimen (10 to 15 days) and found that the evidence to support a clinical practice change was inconclusive.⁵

The study detailed in this PURL—a double-blind RCT comparing five-day with 14-day oral steroid treatment in patients ­hospitalized for acute COPD exacerbation—had more definitive results.¹

Continue reading for the study summary...

STUDY SUMMARY

Shorter and longer regimens produce equal results

Leuppi et al¹ used noninferiority methodology to compare a five- and a 14-day course of prednisone 40 mg/d to treat patients with COPD exacerbations. A patient was considered to have an exacerbation if he or she had a change from baseline in two or more of the following: dyspnea, cough, sputum quantity, or purulence.

Participants were patients who presented to the EDs of five Swiss teaching hospitals between March 2006 and February 2011. To be eligible, individuals had to be 40 or older and have at least 20 pack-years of smoking. Exclusion criteria included asthma, mild obstruction (FEV₁/FVC > 70%), pneumonia, an estimated survival of less than six months, pregnancy, and lactation.

All the participants (N = 311) received 40 mg methylprednisolone intravenously on day 1, followed by prednisone 40 mg orally on days 2 through 5. The researchers then randomly divided participants into two groups: One group continued to take prednisone 40 mg/d and the other group received a matching placebo for an additional nine days. Participants in both groups also received antibiotics for seven days, twice-daily inhaled steroids, daily tiotropium, and nebulized albuterol, as needed; additional oral glucocorticoids could be administered, as well, at the discretion of the treating physicians.

The primary outcome was the time to the next COPD exacerbation, up to 180 days. Noninferiority between the groups was defined as no more than a 15% absolute increase in exacerbations. The dropout rate was 5.7%, evenly divided between groups. Intention to treat and per-protocol analyses were conducted, and hazard ratios (HRs) were calculated using the Kaplan-Meier method and Cox proportional hazards models.

The time to next COPD exacerbation did not differ between the study groups: 56 days for those on the five-day steroid regimen versus 57 days for those on the
14-day regimen in the intention-to-treat analysis (HR, 0.95). Sensitivity analyses adjusting for baseline characteristics provided similar results, as did the per-protocol analysis.

Secondary outcomes (overall survival; need for mechanical ventilation; need for additional corticosteroids; and clinical performance measures, such as dyspnea score and quality of life) also did not differ between groups. Nor were there differences in hyperglycemia, worsening hypertension, infection, or other adverse effects typically associated with glucocorticoid use. The active treatment group took more than 400 mg more prednisone than the placebo group (mean, 793 mg vs 379 mg, respectively).

WHAT’S NEW?

Now we know: five days is enough

While randomized trials have found that glucocorticoids improve COPD symptoms, the optimal treatment dose and duration were not known. Indeed, current guidelines recommend treatment for more than five days.³ This trial clearly demonstrated that 40-mg prednisone for five days is at least as good as a 14-day treatment course. Furthermore, it is un­necessary to taper the short-course therapy, which simplifies the regimen.

CAVEATS

Will the results apply to those less severely ill?

More than 80% of patients with acute COPD exacerbations can be managed in an outpatient setting.³ However, participants in this trial were hospitalized for a median of 8.5 days, and most had severe or very severe COPD—and thus, were not fully representative of COPD patients typically seen in an outpatient practice. Yet patients with less severe disease should be at least as likely to ­respond to short-course steroids as those whose COPD is more ­severe.

It is important to note that participants in this study all received optimal guideline-based therapies during hospitalization, which may be difficult to achieve for some patients treated in an outpatient setting. Finally, treatment adherence observed during the hospitalization period in this trial is unlikely to be replicated in the outpatient setting.

CHALLENGES TO IMPLEMENTATION

Identifying patients who need steroids for a longer duration

For patients with new COPD exacerbations or those successfully treated using short-course therapy in the past, a five-day regimen may be appropriate. For those in whom prior attempts at short-course treatment have failed, however, a 14-day course of treatment may be more advisable. That said, no guidelines are available to help us determine which patients previously treated with a longer regimen will find the shorter course of treatment unsuccessful.

Continue for references...

REFERENCES

1. Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309:2223-2231.

2. Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60:925-931.

3. Global Initiative for Chronic Obstructive Lung Disease, Inc. The global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. www.goldcopd.org. Accessed January 9, 2014.

4. Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2008;133:756-766.

5. Walters JA, Wang W, Morley C, et al. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011; (10):CD006897.

6. Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 1999;340:1941-1947.

ACKNOWLEDGEMENT

The PURLs Surveillance System is supported in part by Grant Number UL 1RR 024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(1):29-30, 32.

Exam-room posters declaring a clinician’s commitment to make appropriate antibiotics prescriptions may be a simple, low-cost approach to reducing inappropriate use of antibiotics for acute respiratory infections, according to a report published online Jan. 27 in JAMA Internal Medicine.

Compared with standard practice, the intervention reduced inappropriate prescribing by 20% but had no effect on appropriate prescribing of antibiotics among 11 physicians and three nurse practitioners treating acute respiratory infection at five outpatient primary care clinics. The improvement is comparable to that reported previously for more intensive and expensive interventions, said Daniella Meeker, Ph.D., of RAND Corp., Santa Monica, Calif., and her associates (JAMA Intern. Med. 2014 [doi:10.1001/jamainternmed.2013.14191]).

© Fuse/Thinkstock

If these results were extrapolated to the entire United States, the intervention "could eliminate 2.6 million unnecessary antibiotic prescriptions and save $70.4 million annually on drug costs alone," the investigators noted.

"To encourage more judicious use of antibiotics, we designed an intervention that takes advantage of clinicians’ desire to be consistent with their pubic commitments," Dr. Meeker and her colleagues said. "We developed a ... behavioral ‘nudge’ in the form of a public commitment device: a poster-sized letter signed by clinicians and posted in their examination rooms indicating their commitment to reducing inappropriate antibiotic use for acute respiratory infections."

"Public commitment" is a psychological principle that holds that people are much more likely to follow a course of action if they and others have publicly stated that they will do so. It was hoped that an intervention that taps into existing internal motivations would be a more subtle and effective approach than external "reeducation" programs or heavy-handed penalties such as withholding reimbursement for writing too many prescriptions.

Other public commitment approaches have proved successful at increasing participation in recycling programs, getting hotel guests to reuse their towels, increasing donations to organizations serving the disabled, and raising voting rates in elections.

The intervention was a form letter written at the eighth-grade reading level in both English and Spanish and displayed on a poster hung in the exam room. The poster explained why antibiotics were not appropriate for many acute respiratory infections, and it emphasized the clinician’s commitment to follow guidelines for appropriate prescribing. The poster included a photo of the clinician and his or her signature on the letter.

For this study, the posters were used for 12-week periods by clinicians at five Los Angeles community clinics and were used in such a way that an entire 1-year flu cycle was covered. The medical records, including antibiotic prescriptions, were reviewed for all adults seen by the participating clinicians and diagnosed as having an acute respiratory infection for which antibiotics may or may not have been appropriate.

The 14 participating clinicians were randomly assigned to either the intervention (7 using the study condition) or to standard practice (7 control subjects). Eleven of these clinicians were women, and 3 were men. The mean age was 54 years, and the mean duration in practice was 18 years.

A total of 449 patients were included in the intervention group and 505 in the control group. Most (77%) were women, and their mean age was 48 years. Approximately 43% were uninsured.

Diagnoses included acute nasopharyngitis (12 visits), acute laryngitis without obstruction (4 visits), acute laryngopharyngitis (3 visits), acute bronchitis (125 visits), acute upper respiratory tract infections of other sites (10 visits) acute upper respiratory tract infections not otherwise specified (448 visits), bronchitis not specified as acute or chronic (181 visits), nonstreptococcal pharyngitis (161 visits), and influenza with other respiratory manifestations (10 visits).

At baseline, before the intervention was employed, the inappropriate-prescribing rate was 43.5% for clinicians in the intervention group and 42.8% for those in the control group, a nonsignificant difference. During the 12-week intervention period, the inappropriate-prescribing rate dropped to 33.7% for the intervention group but rose to 52.7% for the control group.

That represents a 19.7% reduction for the intervention group, compared with the control group, Dr. Meeker and her associates said.

There was no evidence that the participating clinicians may have undermined the intervention by shifting diagnosis codes away from those that don’t require antibiotics and toward those that might. Diagnostic codes did not change appreciably between baseline and intervention periods in either study group, the researchers said.

Moreover, the rate of appropriate antibiotic prescribing did not change during the intervention period, indicating that clinicians continued to prescribe antibiotics when they were indicated and only stopped prescribing them when they were truly unnecessary.

The intervention, based on a psychological principle, was more effective at curtailing inappropriate prescription of antibiotics than are many others currently in use. Those others typically are based on a model holding that clinicians will change their behavior simply because it makes rational sense to do so, and they use techniques such as education, awareness training, electronic alerts or reminders, and financial incentives, the researchers explained.

"[Our] findings support an alternative model suggesting that clinicians are influenced by interpersonal factors within the context of patient care – in particular, a desire to remain consistent with a prior public commitment," Dr. Meeker and her associates said.

They added that their study was limited because it covered a relatively small geographic area, involved a small number of clinicians, and was of short duration. Moreover, even though the intervention succeeded in reducing inappropriate prescribing significantly, the rate of inappropriate prescribing still remained high among the study participants.

The National Institutes of Health and the National Institute on Aging funded the study. Dr. Meeker and her associates reported no relevant financial conflicts of interest.

Exam-room posters declaring a clinician’s commitment to make appropriate antibiotics prescriptions may be a simple, low-cost approach to reducing inappropriate use of antibiotics for acute respiratory infections, according to a report published online Jan. 27 in JAMA Internal Medicine.

Compared with standard practice, the intervention reduced inappropriate prescribing by 20% but had no effect on appropriate prescribing of antibiotics among 11 physicians and three nurse practitioners treating acute respiratory infection at five outpatient primary care clinics. The improvement is comparable to that reported previously for more intensive and expensive interventions, said Daniella Meeker, Ph.D., of RAND Corp., Santa Monica, Calif., and her associates (JAMA Intern. Med. 2014 [doi:10.1001/jamainternmed.2013.14191]).

© Fuse/Thinkstock

If these results were extrapolated to the entire United States, the intervention "could eliminate 2.6 million unnecessary antibiotic prescriptions and save $70.4 million annually on drug costs alone," the investigators noted.

"To encourage more judicious use of antibiotics, we designed an intervention that takes advantage of clinicians’ desire to be consistent with their pubic commitments," Dr. Meeker and her colleagues said. "We developed a ... behavioral ‘nudge’ in the form of a public commitment device: a poster-sized letter signed by clinicians and posted in their examination rooms indicating their commitment to reducing inappropriate antibiotic use for acute respiratory infections."

"Public commitment" is a psychological principle that holds that people are much more likely to follow a course of action if they and others have publicly stated that they will do so. It was hoped that an intervention that taps into existing internal motivations would be a more subtle and effective approach than external "reeducation" programs or heavy-handed penalties such as withholding reimbursement for writing too many prescriptions.

Other public commitment approaches have proved successful at increasing participation in recycling programs, getting hotel guests to reuse their towels, increasing donations to organizations serving the disabled, and raising voting rates in elections.

The intervention was a form letter written at the eighth-grade reading level in both English and Spanish and displayed on a poster hung in the exam room. The poster explained why antibiotics were not appropriate for many acute respiratory infections, and it emphasized the clinician’s commitment to follow guidelines for appropriate prescribing. The poster included a photo of the clinician and his or her signature on the letter.

For this study, the posters were used for 12-week periods by clinicians at five Los Angeles community clinics and were used in such a way that an entire 1-year flu cycle was covered. The medical records, including antibiotic prescriptions, were reviewed for all adults seen by the participating clinicians and diagnosed as having an acute respiratory infection for which antibiotics may or may not have been appropriate.

The 14 participating clinicians were randomly assigned to either the intervention (7 using the study condition) or to standard practice (7 control subjects). Eleven of these clinicians were women, and 3 were men. The mean age was 54 years, and the mean duration in practice was 18 years.

A total of 449 patients were included in the intervention group and 505 in the control group. Most (77%) were women, and their mean age was 48 years. Approximately 43% were uninsured.

Diagnoses included acute nasopharyngitis (12 visits), acute laryngitis without obstruction (4 visits), acute laryngopharyngitis (3 visits), acute bronchitis (125 visits), acute upper respiratory tract infections of other sites (10 visits) acute upper respiratory tract infections not otherwise specified (448 visits), bronchitis not specified as acute or chronic (181 visits), nonstreptococcal pharyngitis (161 visits), and influenza with other respiratory manifestations (10 visits).

At baseline, before the intervention was employed, the inappropriate-prescribing rate was 43.5% for clinicians in the intervention group and 42.8% for those in the control group, a nonsignificant difference. During the 12-week intervention period, the inappropriate-prescribing rate dropped to 33.7% for the intervention group but rose to 52.7% for the control group.

That represents a 19.7% reduction for the intervention group, compared with the control group, Dr. Meeker and her associates said.

There was no evidence that the participating clinicians may have undermined the intervention by shifting diagnosis codes away from those that don’t require antibiotics and toward those that might. Diagnostic codes did not change appreciably between baseline and intervention periods in either study group, the researchers said.

Moreover, the rate of appropriate antibiotic prescribing did not change during the intervention period, indicating that clinicians continued to prescribe antibiotics when they were indicated and only stopped prescribing them when they were truly unnecessary.

The intervention, based on a psychological principle, was more effective at curtailing inappropriate prescription of antibiotics than are many others currently in use. Those others typically are based on a model holding that clinicians will change their behavior simply because it makes rational sense to do so, and they use techniques such as education, awareness training, electronic alerts or reminders, and financial incentives, the researchers explained.

"[Our] findings support an alternative model suggesting that clinicians are influenced by interpersonal factors within the context of patient care – in particular, a desire to remain consistent with a prior public commitment," Dr. Meeker and her associates said.

They added that their study was limited because it covered a relatively small geographic area, involved a small number of clinicians, and was of short duration. Moreover, even though the intervention succeeded in reducing inappropriate prescribing significantly, the rate of inappropriate prescribing still remained high among the study participants.

The National Institutes of Health and the National Institute on Aging funded the study. Dr. Meeker and her associates reported no relevant financial conflicts of interest.

Exam-room posters declaring a clinician’s commitment to make appropriate antibiotics prescriptions may be a simple, low-cost approach to reducing inappropriate use of antibiotics for acute respiratory infections, according to a report published online Jan. 27 in JAMA Internal Medicine.

Compared with standard practice, the intervention reduced inappropriate prescribing by 20% but had no effect on appropriate prescribing of antibiotics among 11 physicians and three nurse practitioners treating acute respiratory infection at five outpatient primary care clinics. The improvement is comparable to that reported previously for more intensive and expensive interventions, said Daniella Meeker, Ph.D., of RAND Corp., Santa Monica, Calif., and her associates (JAMA Intern. Med. 2014 [doi:10.1001/jamainternmed.2013.14191]).

© Fuse/Thinkstock

If these results were extrapolated to the entire United States, the intervention "could eliminate 2.6 million unnecessary antibiotic prescriptions and save $70.4 million annually on drug costs alone," the investigators noted.

"To encourage more judicious use of antibiotics, we designed an intervention that takes advantage of clinicians’ desire to be consistent with their pubic commitments," Dr. Meeker and her colleagues said. "We developed a ... behavioral ‘nudge’ in the form of a public commitment device: a poster-sized letter signed by clinicians and posted in their examination rooms indicating their commitment to reducing inappropriate antibiotic use for acute respiratory infections."

"Public commitment" is a psychological principle that holds that people are much more likely to follow a course of action if they and others have publicly stated that they will do so. It was hoped that an intervention that taps into existing internal motivations would be a more subtle and effective approach than external "reeducation" programs or heavy-handed penalties such as withholding reimbursement for writing too many prescriptions.

Other public commitment approaches have proved successful at increasing participation in recycling programs, getting hotel guests to reuse their towels, increasing donations to organizations serving the disabled, and raising voting rates in elections.

The intervention was a form letter written at the eighth-grade reading level in both English and Spanish and displayed on a poster hung in the exam room. The poster explained why antibiotics were not appropriate for many acute respiratory infections, and it emphasized the clinician’s commitment to follow guidelines for appropriate prescribing. The poster included a photo of the clinician and his or her signature on the letter.

For this study, the posters were used for 12-week periods by clinicians at five Los Angeles community clinics and were used in such a way that an entire 1-year flu cycle was covered. The medical records, including antibiotic prescriptions, were reviewed for all adults seen by the participating clinicians and diagnosed as having an acute respiratory infection for which antibiotics may or may not have been appropriate.

The 14 participating clinicians were randomly assigned to either the intervention (7 using the study condition) or to standard practice (7 control subjects). Eleven of these clinicians were women, and 3 were men. The mean age was 54 years, and the mean duration in practice was 18 years.

A total of 449 patients were included in the intervention group and 505 in the control group. Most (77%) were women, and their mean age was 48 years. Approximately 43% were uninsured.

Diagnoses included acute nasopharyngitis (12 visits), acute laryngitis without obstruction (4 visits), acute laryngopharyngitis (3 visits), acute bronchitis (125 visits), acute upper respiratory tract infections of other sites (10 visits) acute upper respiratory tract infections not otherwise specified (448 visits), bronchitis not specified as acute or chronic (181 visits), nonstreptococcal pharyngitis (161 visits), and influenza with other respiratory manifestations (10 visits).

At baseline, before the intervention was employed, the inappropriate-prescribing rate was 43.5% for clinicians in the intervention group and 42.8% for those in the control group, a nonsignificant difference. During the 12-week intervention period, the inappropriate-prescribing rate dropped to 33.7% for the intervention group but rose to 52.7% for the control group.

That represents a 19.7% reduction for the intervention group, compared with the control group, Dr. Meeker and her associates said.

There was no evidence that the participating clinicians may have undermined the intervention by shifting diagnosis codes away from those that don’t require antibiotics and toward those that might. Diagnostic codes did not change appreciably between baseline and intervention periods in either study group, the researchers said.

Moreover, the rate of appropriate antibiotic prescribing did not change during the intervention period, indicating that clinicians continued to prescribe antibiotics when they were indicated and only stopped prescribing them when they were truly unnecessary.

The intervention, based on a psychological principle, was more effective at curtailing inappropriate prescription of antibiotics than are many others currently in use. Those others typically are based on a model holding that clinicians will change their behavior simply because it makes rational sense to do so, and they use techniques such as education, awareness training, electronic alerts or reminders, and financial incentives, the researchers explained.

"[Our] findings support an alternative model suggesting that clinicians are influenced by interpersonal factors within the context of patient care – in particular, a desire to remain consistent with a prior public commitment," Dr. Meeker and her associates said.

They added that their study was limited because it covered a relatively small geographic area, involved a small number of clinicians, and was of short duration. Moreover, even though the intervention succeeded in reducing inappropriate prescribing significantly, the rate of inappropriate prescribing still remained high among the study participants.

The National Institutes of Health and the National Institute on Aging funded the study. Dr. Meeker and her associates reported no relevant financial conflicts of interest.

Patients who undergo external beam radiation therapy for prostate cancer and smoke or have smoked have increased mortality and increased risk of complications, according to Dr. Emily Steinberger and her associates.

©Valeriy Kirsanov/fotolia.com

Current smoking significantly increased the risk of prostate-specific antigen relapse, distant metastases, and prostate cancer–related death. Current and former smokers were also at a higher risk of external beam radiation therapy–related genitourinary disorders. Smoking did not increase gastrointestinal toxicity, the researchers reported.

Oncologists should encourage patients to participate in smoking-cessation programs before therapy to potentially lower their risk, the researchers recommended.

Read the full article at BJU International (doi:10.1111/bju.12969).

Patients who undergo external beam radiation therapy for prostate cancer and smoke or have smoked have increased mortality and increased risk of complications, according to Dr. Emily Steinberger and her associates.

©Valeriy Kirsanov/fotolia.com

Current smoking significantly increased the risk of prostate-specific antigen relapse, distant metastases, and prostate cancer–related death. Current and former smokers were also at a higher risk of external beam radiation therapy–related genitourinary disorders. Smoking did not increase gastrointestinal toxicity, the researchers reported.

Oncologists should encourage patients to participate in smoking-cessation programs before therapy to potentially lower their risk, the researchers recommended.

Read the full article at BJU International (doi:10.1111/bju.12969).

Patients who undergo external beam radiation therapy for prostate cancer and smoke or have smoked have increased mortality and increased risk of complications, according to Dr. Emily Steinberger and her associates.

©Valeriy Kirsanov/fotolia.com

Current smoking significantly increased the risk of prostate-specific antigen relapse, distant metastases, and prostate cancer–related death. Current and former smokers were also at a higher risk of external beam radiation therapy–related genitourinary disorders. Smoking did not increase gastrointestinal toxicity, the researchers reported.

Oncologists should encourage patients to participate in smoking-cessation programs before therapy to potentially lower their risk, the researchers recommended.

Read the full article at BJU International (doi:10.1111/bju.12969).

Zinc was recognized as an element in 1509 and as an essential mineral much later. In 1961, zinc deficiency was linked with hypogonadism. Zinc is included in almost all over-the-counter daily vitamins and mineral supplements, typically in the form of zinc oxide, zinc acetate, and zinc gluconate. Zinc is absorbed through the small bowel with an efficiency of 20%-40%. It is the second most important metal in the body after iron and is present in virtually 100% of proteins.

Zinc inhibits viral replication. Because of this, it has been investigated as a way to decrease the duration of symptoms from the common cold. With some evidence suggesting that it works, we know little about the right dose for zinc to exert its magical effects.

In a recently published systematic review, Singh and Das updated a previous Cochrane systematic review and, once again, evaluated the efficacy of zinc in reducing the incidence, severity, and duration of common cold symptoms (Cochrane Database Syst. Rev. 2013;6:CD001364). Studies were included if they were randomized, double-blind, placebo-controlled trials using zinc for at least 5 days for treatment or 5 months for prevention of the common cold.

Sixteen therapeutic trails involving a total of 1,387 people, and two preventive trials with 394 participants were included in the meta-analysis. Zinc came in the form of syrup, lozenges, or tablets. Zinc was associated with statistically significant reductions in the duration but not the severity of symptoms. The mean difference in reduction duration was 1 day (95% confidence interval, –1.72 to –0.34). After 7 days of treatment, significantly fewer subjects had symptoms. Zinc was associated with a reduced incidence of colds, absences from school, and receipt of antibiotics. Bad taste and nausea were significantly higher in patients treated with zinc. The authors suggested that there is a significant reduction in the duration of cold symptoms at a dose of at least 75 mg/day in the lozenge form.

Inhaled zinc can cause permanent anosmia, and so this delivery route was not investigated. Lozenges may be the best bet, since we know the daily dose should be at least 75 mg for treatment. For patients interested in using zinc for prevention, no clear dosage recommendations can be made. Megadose supplementation or high zinc intake has been associated with abdominal pain, diarrhea, nausea, and vomiting. Zinc may interfere with copper absorption, and high zinc intake (greater than 150 mg/day) can lead to copper deficiency and should be avoided.

Dr. Ebbert is professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no conflicts of interest.

Zinc was recognized as an element in 1509 and as an essential mineral much later. In 1961, zinc deficiency was linked with hypogonadism. Zinc is included in almost all over-the-counter daily vitamins and mineral supplements, typically in the form of zinc oxide, zinc acetate, and zinc gluconate. Zinc is absorbed through the small bowel with an efficiency of 20%-40%. It is the second most important metal in the body after iron and is present in virtually 100% of proteins.

Zinc inhibits viral replication. Because of this, it has been investigated as a way to decrease the duration of symptoms from the common cold. With some evidence suggesting that it works, we know little about the right dose for zinc to exert its magical effects.

In a recently published systematic review, Singh and Das updated a previous Cochrane systematic review and, once again, evaluated the efficacy of zinc in reducing the incidence, severity, and duration of common cold symptoms (Cochrane Database Syst. Rev. 2013;6:CD001364). Studies were included if they were randomized, double-blind, placebo-controlled trials using zinc for at least 5 days for treatment or 5 months for prevention of the common cold.

Sixteen therapeutic trails involving a total of 1,387 people, and two preventive trials with 394 participants were included in the meta-analysis. Zinc came in the form of syrup, lozenges, or tablets. Zinc was associated with statistically significant reductions in the duration but not the severity of symptoms. The mean difference in reduction duration was 1 day (95% confidence interval, –1.72 to –0.34). After 7 days of treatment, significantly fewer subjects had symptoms. Zinc was associated with a reduced incidence of colds, absences from school, and receipt of antibiotics. Bad taste and nausea were significantly higher in patients treated with zinc. The authors suggested that there is a significant reduction in the duration of cold symptoms at a dose of at least 75 mg/day in the lozenge form.

Inhaled zinc can cause permanent anosmia, and so this delivery route was not investigated. Lozenges may be the best bet, since we know the daily dose should be at least 75 mg for treatment. For patients interested in using zinc for prevention, no clear dosage recommendations can be made. Megadose supplementation or high zinc intake has been associated with abdominal pain, diarrhea, nausea, and vomiting. Zinc may interfere with copper absorption, and high zinc intake (greater than 150 mg/day) can lead to copper deficiency and should be avoided.

Dr. Ebbert is professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no conflicts of interest.

Zinc was recognized as an element in 1509 and as an essential mineral much later. In 1961, zinc deficiency was linked with hypogonadism. Zinc is included in almost all over-the-counter daily vitamins and mineral supplements, typically in the form of zinc oxide, zinc acetate, and zinc gluconate. Zinc is absorbed through the small bowel with an efficiency of 20%-40%. It is the second most important metal in the body after iron and is present in virtually 100% of proteins.

Zinc inhibits viral replication. Because of this, it has been investigated as a way to decrease the duration of symptoms from the common cold. With some evidence suggesting that it works, we know little about the right dose for zinc to exert its magical effects.

In a recently published systematic review, Singh and Das updated a previous Cochrane systematic review and, once again, evaluated the efficacy of zinc in reducing the incidence, severity, and duration of common cold symptoms (Cochrane Database Syst. Rev. 2013;6:CD001364). Studies were included if they were randomized, double-blind, placebo-controlled trials using zinc for at least 5 days for treatment or 5 months for prevention of the common cold.

Sixteen therapeutic trails involving a total of 1,387 people, and two preventive trials with 394 participants were included in the meta-analysis. Zinc came in the form of syrup, lozenges, or tablets. Zinc was associated with statistically significant reductions in the duration but not the severity of symptoms. The mean difference in reduction duration was 1 day (95% confidence interval, –1.72 to –0.34). After 7 days of treatment, significantly fewer subjects had symptoms. Zinc was associated with a reduced incidence of colds, absences from school, and receipt of antibiotics. Bad taste and nausea were significantly higher in patients treated with zinc. The authors suggested that there is a significant reduction in the duration of cold symptoms at a dose of at least 75 mg/day in the lozenge form.

Inhaled zinc can cause permanent anosmia, and so this delivery route was not investigated. Lozenges may be the best bet, since we know the daily dose should be at least 75 mg for treatment. For patients interested in using zinc for prevention, no clear dosage recommendations can be made. Megadose supplementation or high zinc intake has been associated with abdominal pain, diarrhea, nausea, and vomiting. Zinc may interfere with copper absorption, and high zinc intake (greater than 150 mg/day) can lead to copper deficiency and should be avoided.

Dr. Ebbert is professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no conflicts of interest.

New York has the highest cigarette excise tax in the United States and Missouri has the lowest, with a difference of more than $4 in between, the American Lung Association said in a report released Jan. 22.

New York currently adds $4.35 to the price of each pack of cigarettes sold in the state, compared with Missouri’s lowest-in-the-nation rate of 17 cents per pack. Massachusetts has the second-highest tax at $3.51, while Virginia is second lowest at 30 cents. The U.S. average is $1.53 per pack, according to the association’s "State of Tobacco Control 2014" report.

The report noted a general lack of progress among states in smoking cessation and prevention in 2013, with only two states – Massachusetts and Minnesota – passing significant tax increases, "no states approving comprehensive smokefree workplace laws," and two states – Alaska and North Dakota – funding their tobacco prevention programs "at or above levels" recommended by the Centers for Disease Control and Prevention."

rfranki@frontlinemedcom.com

New York has the highest cigarette excise tax in the United States and Missouri has the lowest, with a difference of more than $4 in between, the American Lung Association said in a report released Jan. 22.

New York currently adds $4.35 to the price of each pack of cigarettes sold in the state, compared with Missouri’s lowest-in-the-nation rate of 17 cents per pack. Massachusetts has the second-highest tax at $3.51, while Virginia is second lowest at 30 cents. The U.S. average is $1.53 per pack, according to the association’s "State of Tobacco Control 2014" report.

The report noted a general lack of progress among states in smoking cessation and prevention in 2013, with only two states – Massachusetts and Minnesota – passing significant tax increases, "no states approving comprehensive smokefree workplace laws," and two states – Alaska and North Dakota – funding their tobacco prevention programs "at or above levels" recommended by the Centers for Disease Control and Prevention."

rfranki@frontlinemedcom.com

New York has the highest cigarette excise tax in the United States and Missouri has the lowest, with a difference of more than $4 in between, the American Lung Association said in a report released Jan. 22.

New York currently adds $4.35 to the price of each pack of cigarettes sold in the state, compared with Missouri’s lowest-in-the-nation rate of 17 cents per pack. Massachusetts has the second-highest tax at $3.51, while Virginia is second lowest at 30 cents. The U.S. average is $1.53 per pack, according to the association’s "State of Tobacco Control 2014" report.

The report noted a general lack of progress among states in smoking cessation and prevention in 2013, with only two states – Massachusetts and Minnesota – passing significant tax increases, "no states approving comprehensive smokefree workplace laws," and two states – Alaska and North Dakota – funding their tobacco prevention programs "at or above levels" recommended by the Centers for Disease Control and Prevention."

rfranki@frontlinemedcom.com

Adverse events decreased over the last decade for Medicare inpatients with acute myocardial infarction or heart failure but barely changed for those with pneumonia or conditions requiring surgery, according to an analysis of a Medicare database.

The improvements likely translated to 81,000 fewer adverse events for patients with acute MI (AMI) and heart failure (HF) from 2010 to 2011 alone, according to the study published Jan. 22 in the New England Journal of Medicine.

"Although this suggests that national efforts focused on patient safety have made some inroads, the lack of reductions across the board is disappointing," Yun Wang, Ph.D., of the Harvard School of Public Health, Boston, and his colleagues wrote.

The researchers examined whether hospitalized patients are any better off in light of the current focus on patient safety, including the launch of initiatives such as the American College of Surgeons’ National Surgical Quality Improvement Program and the federal government’s Surgical Infection Prevention Project.

They used three composite outcomes measures: the rate of occurrence for adverse events for which patients were at risk (for instance, only patients receiving warfarin were at risk for warfarin-related events); the proportion of patients with one or more adverse events; and the number of adverse events per 1,000 hospitalizations. They analyzed data on 61,523 patients who were discharged from 4,372 hospitals; the data were extracted from the Medicare Patient Safety Monitoring System database (N. Engl. J. Med. 2014:370;341-51).

The 61,523 patients included 11,399 with AMI, 15,374 with HF, 18,269 with pneumonia, and 16,481 with conditions requiring surgery. Postsurgical patients largely were being treated for joint replacement procedures and other osteoarthritis-related conditions, femur fracture, colon cancer, post-AMI procedures, or other forms of chronic ischemic heart disease.

From 2005-2006 to 2010-2011, AMI and HF patients saw a 1.3 percentage point decline in the rate of adverse events, from 5% to 3.7%. The proportion who had one or more such events decreased from 26% to 19%. The number of adverse events per 1,000 hospitalizations declined from 402 to 262 for AMI patients and from 235 to 167 for HF patients.

Infection-related and drug-related adverse events declined significantly in heart attack and HF patients. There was also a substantial improvement in postprocedure events in HF patients.

Postsurgical patients experienced slight increases in all three outcomes measures, in particular, increases in infection-related and postprocedural events such as venous thromboembolism, and cardiac and catheter-related events. The number of events per 1,000 hospitalizations for pneumonia patients increased insignificantly from 216 to 223. For postsurgical patients, the number of events increased insignificantly from 352/1,000 to 368/1,000.

Patients who had adverse events had significantly longer hospital stays and were at higher risk for death. As the number of adverse events increased, so did the risk of death.

The authors noted that declines in events for AMI and HF patients might be a reflection of the numerous efforts and initiatives to improve care in those two conditions.

But they also found that concerted efforts to improve safety did not necessarily work. There was an increase in pressure ulcers in postsurgical patients, and no decline in ventilator-associated pneumonia in most patients, even though there have been initiatives focused on those conditions.

"Our finding of an increased adverse-event rate among surgical patients indicates a continuing challenge and identifies an important target for patient-safety initiatives," the researchers said.

The study was supported by the Agency for Healthcare Research and Quality as well as academic and federal grants. Dr. Wang was a consultant to and other researchers were employees of the research firm Qualidigm and participated in the analysis. One of the researchers, Dr. Harlan M. Krumholz, disclosed being on a scientific advisory board for UnitedHealthcare and receiving grant money from Medtronic.

aault@frontlinemedcom.com

On Twitter @aliciaault

Adverse events decreased over the last decade for Medicare inpatients with acute myocardial infarction or heart failure but barely changed for those with pneumonia or conditions requiring surgery, according to an analysis of a Medicare database.

The improvements likely translated to 81,000 fewer adverse events for patients with acute MI (AMI) and heart failure (HF) from 2010 to 2011 alone, according to the study published Jan. 22 in the New England Journal of Medicine.

"Although this suggests that national efforts focused on patient safety have made some inroads, the lack of reductions across the board is disappointing," Yun Wang, Ph.D., of the Harvard School of Public Health, Boston, and his colleagues wrote.

The researchers examined whether hospitalized patients are any better off in light of the current focus on patient safety, including the launch of initiatives such as the American College of Surgeons’ National Surgical Quality Improvement Program and the federal government’s Surgical Infection Prevention Project.

They used three composite outcomes measures: the rate of occurrence for adverse events for which patients were at risk (for instance, only patients receiving warfarin were at risk for warfarin-related events); the proportion of patients with one or more adverse events; and the number of adverse events per 1,000 hospitalizations. They analyzed data on 61,523 patients who were discharged from 4,372 hospitals; the data were extracted from the Medicare Patient Safety Monitoring System database (N. Engl. J. Med. 2014:370;341-51).

The 61,523 patients included 11,399 with AMI, 15,374 with HF, 18,269 with pneumonia, and 16,481 with conditions requiring surgery. Postsurgical patients largely were being treated for joint replacement procedures and other osteoarthritis-related conditions, femur fracture, colon cancer, post-AMI procedures, or other forms of chronic ischemic heart disease.

From 2005-2006 to 2010-2011, AMI and HF patients saw a 1.3 percentage point decline in the rate of adverse events, from 5% to 3.7%. The proportion who had one or more such events decreased from 26% to 19%. The number of adverse events per 1,000 hospitalizations declined from 402 to 262 for AMI patients and from 235 to 167 for HF patients.

Infection-related and drug-related adverse events declined significantly in heart attack and HF patients. There was also a substantial improvement in postprocedure events in HF patients.

Postsurgical patients experienced slight increases in all three outcomes measures, in particular, increases in infection-related and postprocedural events such as venous thromboembolism, and cardiac and catheter-related events. The number of events per 1,000 hospitalizations for pneumonia patients increased insignificantly from 216 to 223. For postsurgical patients, the number of events increased insignificantly from 352/1,000 to 368/1,000.

Patients who had adverse events had significantly longer hospital stays and were at higher risk for death. As the number of adverse events increased, so did the risk of death.

The authors noted that declines in events for AMI and HF patients might be a reflection of the numerous efforts and initiatives to improve care in those two conditions.

But they also found that concerted efforts to improve safety did not necessarily work. There was an increase in pressure ulcers in postsurgical patients, and no decline in ventilator-associated pneumonia in most patients, even though there have been initiatives focused on those conditions.

"Our finding of an increased adverse-event rate among surgical patients indicates a continuing challenge and identifies an important target for patient-safety initiatives," the researchers said.

The study was supported by the Agency for Healthcare Research and Quality as well as academic and federal grants. Dr. Wang was a consultant to and other researchers were employees of the research firm Qualidigm and participated in the analysis. One of the researchers, Dr. Harlan M. Krumholz, disclosed being on a scientific advisory board for UnitedHealthcare and receiving grant money from Medtronic.

aault@frontlinemedcom.com

On Twitter @aliciaault

Adverse events decreased over the last decade for Medicare inpatients with acute myocardial infarction or heart failure but barely changed for those with pneumonia or conditions requiring surgery, according to an analysis of a Medicare database.

The improvements likely translated to 81,000 fewer adverse events for patients with acute MI (AMI) and heart failure (HF) from 2010 to 2011 alone, according to the study published Jan. 22 in the New England Journal of Medicine.

"Although this suggests that national efforts focused on patient safety have made some inroads, the lack of reductions across the board is disappointing," Yun Wang, Ph.D., of the Harvard School of Public Health, Boston, and his colleagues wrote.

The researchers examined whether hospitalized patients are any better off in light of the current focus on patient safety, including the launch of initiatives such as the American College of Surgeons’ National Surgical Quality Improvement Program and the federal government’s Surgical Infection Prevention Project.

They used three composite outcomes measures: the rate of occurrence for adverse events for which patients were at risk (for instance, only patients receiving warfarin were at risk for warfarin-related events); the proportion of patients with one or more adverse events; and the number of adverse events per 1,000 hospitalizations. They analyzed data on 61,523 patients who were discharged from 4,372 hospitals; the data were extracted from the Medicare Patient Safety Monitoring System database (N. Engl. J. Med. 2014:370;341-51).

The 61,523 patients included 11,399 with AMI, 15,374 with HF, 18,269 with pneumonia, and 16,481 with conditions requiring surgery. Postsurgical patients largely were being treated for joint replacement procedures and other osteoarthritis-related conditions, femur fracture, colon cancer, post-AMI procedures, or other forms of chronic ischemic heart disease.

From 2005-2006 to 2010-2011, AMI and HF patients saw a 1.3 percentage point decline in the rate of adverse events, from 5% to 3.7%. The proportion who had one or more such events decreased from 26% to 19%. The number of adverse events per 1,000 hospitalizations declined from 402 to 262 for AMI patients and from 235 to 167 for HF patients.

Infection-related and drug-related adverse events declined significantly in heart attack and HF patients. There was also a substantial improvement in postprocedure events in HF patients.

Postsurgical patients experienced slight increases in all three outcomes measures, in particular, increases in infection-related and postprocedural events such as venous thromboembolism, and cardiac and catheter-related events. The number of events per 1,000 hospitalizations for pneumonia patients increased insignificantly from 216 to 223. For postsurgical patients, the number of events increased insignificantly from 352/1,000 to 368/1,000.

Patients who had adverse events had significantly longer hospital stays and were at higher risk for death. As the number of adverse events increased, so did the risk of death.

The authors noted that declines in events for AMI and HF patients might be a reflection of the numerous efforts and initiatives to improve care in those two conditions.

But they also found that concerted efforts to improve safety did not necessarily work. There was an increase in pressure ulcers in postsurgical patients, and no decline in ventilator-associated pneumonia in most patients, even though there have been initiatives focused on those conditions.

"Our finding of an increased adverse-event rate among surgical patients indicates a continuing challenge and identifies an important target for patient-safety initiatives," the researchers said.

The study was supported by the Agency for Healthcare Research and Quality as well as academic and federal grants. Dr. Wang was a consultant to and other researchers were employees of the research firm Qualidigm and participated in the analysis. One of the researchers, Dr. Harlan M. Krumholz, disclosed being on a scientific advisory board for UnitedHealthcare and receiving grant money from Medtronic.

aault@frontlinemedcom.com

On Twitter @aliciaault

HOLLYWOOD, FLA. – The benefits of short-term trial immunosuppressive therapy outweigh the risks in inflammatory bowel disease, but certain patient populations require more vigilance than others, Dr. James D. Lewis said at the 2013 Advances in IBD meeting.

"We can probably all agree that thiopurines increase the risk of lymphoma," said Dr. Lewis, of the University of Pennsylvania, Philadelphia, at the conference on inflammatory bowel diseases. "But I’ve gone from ‘probably’ to ‘possibly’ when it comes to using anti-TNF [anti–tumor necrosis factor] therapy. I believe that a short trial of biologics therapy can really inform the risk-benefit balance, moving the conversation from ‘it might make a patient better’ to either it did or it didn’t."

In young males and the elderly, the benefit of combination therapy might not prove worth the risks of the treatment, said Dr. Lewis, "but in the middle ground, I think we have a sweet spot."

Overall, unless ineffective treatment is justifiable for other reasons such as the prevention of antibody formation, it should be discontinued, he said.

Results from the CESAME study, published in 2009, reinforce previously published data, indicating the risk of lymphoma is up to five times higher in IBD patients exposed to thiopurines than in the general population (Lancet 2009;374:1617-25).

"The most important data from CESAME, however, was that patients who discontinued thiopurines had a lymphoma incidence rate that went back to that of the general population," Dr. Lewis said at the meeting, sponsored by the Crohn’s & Colitis Foundation of America.

The link between lymphoma and anti-TNF treatment is harder to establish in IBD patients, because many in this cohort also have been exposed to thiopurines as part of combination therapies, he said.

Combination therapy is possibly associated with a higher risk of lymphoma than thiopurine monotherapy, and it has been shown to lead to a higher incidence rate than biologics monotherapy, said Dr. Lewis.

If you counsel patients that there is a 1 in 2,000 risk of lymphoma per year, he said, but it takes only a quarter of a year to figure out if the drugs are going to work, then the short-term risk is 1.25 per 10,000 that an additional lymphoma would develop because of that 3-month treatment. "And if you stop the treatment, presumably that risk goes away."

The risk-to-benefit ratio would therefore be favorable for most patients who took thiopurines versus those who did not, he said. "The caveat being, the older you get, the more marginal that risk-benefit balance becomes, probably because as you age, your baseline risk for lymphoma is going up."

Regarding the risk of hepatosplenic T-cell lymphoma in patients exposed to immunosuppressive therapy, Dr. Lewis said that when he pooled the risk in person-years from two studies, he "did some back-of-the-envelope calculations and found that in males, the risk might be on the order of 11 in 100,000 person-years of thiopurine exposure."

That means the number needed to harm is about 9,000 patients, which when combined with the possible risk of developing other lymphomas, the number needed to harm is about 6,000 young males for 1 lymphoma death per year, according to Dr. Lewis.

"But I want to caution you that I am almost sure this is an overestimate of the risk, because if this is true, then it means in young males treated with thiopurines who get lymphoma, a third of them would be hepatosplenic lymphomas, and that seems unlikely," he said.

The ultimate magnitude of risk for adding thiopurine therapy for patients, particularly young males, is on par with that of the risk of death from annual use of automobiles, which Dr. Lewis said was approximately 1 in 9,090.

Since "a substantial proportion" of lymphomas associated with immunosuppression are related to the Epstein-Barr virus, according to Dr. Lewis, aside from minimizing unnecessary treatment, which can be hard to define, clinicians might consider discontinuing just thiopurine therapy, or all therapy in the setting of long-term remission. "I’m not endorsing that," he said. "I am saying that is a question for you to consider."

Other considerations include determining the minimum dose of thiopurine or methotrexate necessary to augment the effectiveness of anti-TNF treatment, as well as whether methotrexate is as effective as thiopurines without having an increased lymphoma risk, although only "indirect evidence" currently exists. "It would be nice to see a head-to-head comparison of those," he said.

As for using Epstein-Barr virus serology to help stratify risk, Dr. Lewis said that currently there are no guidelines for it in IBD, and he does not have a set rule to recommend it.

Dr. Lewis disclosed that he consults for AbbVie, Janssen, Prometheus, and Millennium and has received research funding from Centocor and Takeda.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – The benefits of short-term trial immunosuppressive therapy outweigh the risks in inflammatory bowel disease, but certain patient populations require more vigilance than others, Dr. James D. Lewis said at the 2013 Advances in IBD meeting.

"We can probably all agree that thiopurines increase the risk of lymphoma," said Dr. Lewis, of the University of Pennsylvania, Philadelphia, at the conference on inflammatory bowel diseases. "But I’ve gone from ‘probably’ to ‘possibly’ when it comes to using anti-TNF [anti–tumor necrosis factor] therapy. I believe that a short trial of biologics therapy can really inform the risk-benefit balance, moving the conversation from ‘it might make a patient better’ to either it did or it didn’t."

In young males and the elderly, the benefit of combination therapy might not prove worth the risks of the treatment, said Dr. Lewis, "but in the middle ground, I think we have a sweet spot."

Overall, unless ineffective treatment is justifiable for other reasons such as the prevention of antibody formation, it should be discontinued, he said.

Results from the CESAME study, published in 2009, reinforce previously published data, indicating the risk of lymphoma is up to five times higher in IBD patients exposed to thiopurines than in the general population (Lancet 2009;374:1617-25).

"The most important data from CESAME, however, was that patients who discontinued thiopurines had a lymphoma incidence rate that went back to that of the general population," Dr. Lewis said at the meeting, sponsored by the Crohn’s & Colitis Foundation of America.

The link between lymphoma and anti-TNF treatment is harder to establish in IBD patients, because many in this cohort also have been exposed to thiopurines as part of combination therapies, he said.

Combination therapy is possibly associated with a higher risk of lymphoma than thiopurine monotherapy, and it has been shown to lead to a higher incidence rate than biologics monotherapy, said Dr. Lewis.

If you counsel patients that there is a 1 in 2,000 risk of lymphoma per year, he said, but it takes only a quarter of a year to figure out if the drugs are going to work, then the short-term risk is 1.25 per 10,000 that an additional lymphoma would develop because of that 3-month treatment. "And if you stop the treatment, presumably that risk goes away."

The risk-to-benefit ratio would therefore be favorable for most patients who took thiopurines versus those who did not, he said. "The caveat being, the older you get, the more marginal that risk-benefit balance becomes, probably because as you age, your baseline risk for lymphoma is going up."

Regarding the risk of hepatosplenic T-cell lymphoma in patients exposed to immunosuppressive therapy, Dr. Lewis said that when he pooled the risk in person-years from two studies, he "did some back-of-the-envelope calculations and found that in males, the risk might be on the order of 11 in 100,000 person-years of thiopurine exposure."

That means the number needed to harm is about 9,000 patients, which when combined with the possible risk of developing other lymphomas, the number needed to harm is about 6,000 young males for 1 lymphoma death per year, according to Dr. Lewis.

"But I want to caution you that I am almost sure this is an overestimate of the risk, because if this is true, then it means in young males treated with thiopurines who get lymphoma, a third of them would be hepatosplenic lymphomas, and that seems unlikely," he said.

The ultimate magnitude of risk for adding thiopurine therapy for patients, particularly young males, is on par with that of the risk of death from annual use of automobiles, which Dr. Lewis said was approximately 1 in 9,090.

Since "a substantial proportion" of lymphomas associated with immunosuppression are related to the Epstein-Barr virus, according to Dr. Lewis, aside from minimizing unnecessary treatment, which can be hard to define, clinicians might consider discontinuing just thiopurine therapy, or all therapy in the setting of long-term remission. "I’m not endorsing that," he said. "I am saying that is a question for you to consider."

Other considerations include determining the minimum dose of thiopurine or methotrexate necessary to augment the effectiveness of anti-TNF treatment, as well as whether methotrexate is as effective as thiopurines without having an increased lymphoma risk, although only "indirect evidence" currently exists. "It would be nice to see a head-to-head comparison of those," he said.

As for using Epstein-Barr virus serology to help stratify risk, Dr. Lewis said that currently there are no guidelines for it in IBD, and he does not have a set rule to recommend it.

Dr. Lewis disclosed that he consults for AbbVie, Janssen, Prometheus, and Millennium and has received research funding from Centocor and Takeda.

wmcknight@frontlinemedcom.com

HOLLYWOOD, FLA. – The benefits of short-term trial immunosuppressive therapy outweigh the risks in inflammatory bowel disease, but certain patient populations require more vigilance than others, Dr. James D. Lewis said at the 2013 Advances in IBD meeting.

"We can probably all agree that thiopurines increase the risk of lymphoma," said Dr. Lewis, of the University of Pennsylvania, Philadelphia, at the conference on inflammatory bowel diseases. "But I’ve gone from ‘probably’ to ‘possibly’ when it comes to using anti-TNF [anti–tumor necrosis factor] therapy. I believe that a short trial of biologics therapy can really inform the risk-benefit balance, moving the conversation from ‘it might make a patient better’ to either it did or it didn’t."

In young males and the elderly, the benefit of combination therapy might not prove worth the risks of the treatment, said Dr. Lewis, "but in the middle ground, I think we have a sweet spot."

Overall, unless ineffective treatment is justifiable for other reasons such as the prevention of antibody formation, it should be discontinued, he said.

Results from the CESAME study, published in 2009, reinforce previously published data, indicating the risk of lymphoma is up to five times higher in IBD patients exposed to thiopurines than in the general population (Lancet 2009;374:1617-25).

"The most important data from CESAME, however, was that patients who discontinued thiopurines had a lymphoma incidence rate that went back to that of the general population," Dr. Lewis said at the meeting, sponsored by the Crohn’s & Colitis Foundation of America.

The link between lymphoma and anti-TNF treatment is harder to establish in IBD patients, because many in this cohort also have been exposed to thiopurines as part of combination therapies, he said.

Combination therapy is possibly associated with a higher risk of lymphoma than thiopurine monotherapy, and it has been shown to lead to a higher incidence rate than biologics monotherapy, said Dr. Lewis.

If you counsel patients that there is a 1 in 2,000 risk of lymphoma per year, he said, but it takes only a quarter of a year to figure out if the drugs are going to work, then the short-term risk is 1.25 per 10,000 that an additional lymphoma would develop because of that 3-month treatment. "And if you stop the treatment, presumably that risk goes away."

The risk-to-benefit ratio would therefore be favorable for most patients who took thiopurines versus those who did not, he said. "The caveat being, the older you get, the more marginal that risk-benefit balance becomes, probably because as you age, your baseline risk for lymphoma is going up."

Regarding the risk of hepatosplenic T-cell lymphoma in patients exposed to immunosuppressive therapy, Dr. Lewis said that when he pooled the risk in person-years from two studies, he "did some back-of-the-envelope calculations and found that in males, the risk might be on the order of 11 in 100,000 person-years of thiopurine exposure."

That means the number needed to harm is about 9,000 patients, which when combined with the possible risk of developing other lymphomas, the number needed to harm is about 6,000 young males for 1 lymphoma death per year, according to Dr. Lewis.

"But I want to caution you that I am almost sure this is an overestimate of the risk, because if this is true, then it means in young males treated with thiopurines who get lymphoma, a third of them would be hepatosplenic lymphomas, and that seems unlikely," he said.

The ultimate magnitude of risk for adding thiopurine therapy for patients, particularly young males, is on par with that of the risk of death from annual use of automobiles, which Dr. Lewis said was approximately 1 in 9,090.

Since "a substantial proportion" of lymphomas associated with immunosuppression are related to the Epstein-Barr virus, according to Dr. Lewis, aside from minimizing unnecessary treatment, which can be hard to define, clinicians might consider discontinuing just thiopurine therapy, or all therapy in the setting of long-term remission. "I’m not endorsing that," he said. "I am saying that is a question for you to consider."

Other considerations include determining the minimum dose of thiopurine or methotrexate necessary to augment the effectiveness of anti-TNF treatment, as well as whether methotrexate is as effective as thiopurines without having an increased lymphoma risk, although only "indirect evidence" currently exists. "It would be nice to see a head-to-head comparison of those," he said.

As for using Epstein-Barr virus serology to help stratify risk, Dr. Lewis said that currently there are no guidelines for it in IBD, and he does not have a set rule to recommend it.

Dr. Lewis disclosed that he consults for AbbVie, Janssen, Prometheus, and Millennium and has received research funding from Centocor and Takeda.

wmcknight@frontlinemedcom.com

SAN DIEGO – About 30% of nodules detected by CT screening fit the criteria for an indeterminate pulmonary nodule. Very few of those nodules represent cancer, and the question is, what do you recommend for those patients in terms of follow-up?

"We’re encountering more and more patients with lung nodules in the clinic, and with the advance of screening, it will become even more of a problem. The numbers are tremendous," Dr. Pierre P. Massion stated at the Joint Conference on the Molecular Origins of Lung Cancer, sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Massion, the Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said it’s important to differentiate – early, accurately, and noninvasively – benign lesions from cancer. "There is a race for early diagnosis, because surgery is the best chance for cure ... but we also need to decrease the number of thoracotomies performed for benign disease."

Data from eight large trials of lung cancer screening examined the relationship between lesion size and the probability of lung cancer (Chest 2007;132[3 Suppl]:94S-107S). The probability of cancer was 0-1% for lesions less than 5 mm in diameter; 6%-28% for those 5-10 mm, 33%-60% for those 11-20 mm, and 64%-82% for those 21-30 mm.

"The bigger the nodule, the greater the probability of cancer. In fact, however, the number of large nodules is very small," Dr. Massion said. "The indeterminate ones are between 5 and 15 mm in diameter, and these are the ones we struggle with how best to handle." The probability of cancer from indeterminate pulmonary nodules ranges from 6% to 60%, which is a large range.

The shape of the nodule provides additional information, Dr. Massion said. Triangular shape abutting a fissure and central calcification are generally indicators of benign disease and typically do not require follow-up. Alternatively, solid, noncalcified spiculated nodules have a high likelihood of being cancer. Part solid nodules are "very worrisome," he said. "These are most likely to contain malignancy. Nonsolid lesions, also called ground-glass opacities, are troublesome and difficult to assess. They represent about a 20% probability of disease."

The rate of growth of small nodules over time "is probably one of the best imaging markers, [but] for small nodules such as those 5 mm in diameter, the volumetric analysis has a large coefficient of variance," he said.

Prediction models are important to the evaluation of lung nodules, yet even with existing tools "we’re wrong about 30% of the time," he said. The best three prediction models come from studies of patients at the Mayo Clinic (Arch. Intern. Med. 1997;157:849-55) and the Veterans Affairs department (Chest 2007;131:383-88), and from patients enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (N. Engl. J. Med. 2013;368:728-36). These prediction models are now recommended for use on nodules greater than 8 mm in diameter in the ACCP 2013 guidelines for evaluation of lung nodules (Chest 2013;143[5 Suppl]:e93S-120S).

"We have no models for never-smokers, which is a huge problem in the community at the moment."

Dr. Massion predicted that serum biomarkers might "come to the rescue" for deciding which patients with indeterminate pulmonary nodules might need to go for a biopsy or resection and which can be carefully watched over time.

In a separate study of 62 lung nodules that integrated clinical, imaging, and protein biomarker findings, clinical information alone resulted in about 50% sensitivity for predicting disease, "which is not great," said Dr. Massion, who was the principal investigator (Cancer Epidemiol. Biomarkers Prev. 2012;21:786-92). The addition of CT imaging increased the area under the curve to about 61%. Adding biomarkers in the blood raised the bar to about 69%.

"It’s not a panacea, but we show a trend toward improvement of classification of these nodules, which is where I think this field is going – integrating information from the clinic, imaging, and the discriminatory power of biomarkers."

Dr. Massion said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – About 30% of nodules detected by CT screening fit the criteria for an indeterminate pulmonary nodule. Very few of those nodules represent cancer, and the question is, what do you recommend for those patients in terms of follow-up?

"We’re encountering more and more patients with lung nodules in the clinic, and with the advance of screening, it will become even more of a problem. The numbers are tremendous," Dr. Pierre P. Massion stated at the Joint Conference on the Molecular Origins of Lung Cancer, sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Massion, the Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said it’s important to differentiate – early, accurately, and noninvasively – benign lesions from cancer. "There is a race for early diagnosis, because surgery is the best chance for cure ... but we also need to decrease the number of thoracotomies performed for benign disease."

Data from eight large trials of lung cancer screening examined the relationship between lesion size and the probability of lung cancer (Chest 2007;132[3 Suppl]:94S-107S). The probability of cancer was 0-1% for lesions less than 5 mm in diameter; 6%-28% for those 5-10 mm, 33%-60% for those 11-20 mm, and 64%-82% for those 21-30 mm.

"The bigger the nodule, the greater the probability of cancer. In fact, however, the number of large nodules is very small," Dr. Massion said. "The indeterminate ones are between 5 and 15 mm in diameter, and these are the ones we struggle with how best to handle." The probability of cancer from indeterminate pulmonary nodules ranges from 6% to 60%, which is a large range.

The shape of the nodule provides additional information, Dr. Massion said. Triangular shape abutting a fissure and central calcification are generally indicators of benign disease and typically do not require follow-up. Alternatively, solid, noncalcified spiculated nodules have a high likelihood of being cancer. Part solid nodules are "very worrisome," he said. "These are most likely to contain malignancy. Nonsolid lesions, also called ground-glass opacities, are troublesome and difficult to assess. They represent about a 20% probability of disease."

The rate of growth of small nodules over time "is probably one of the best imaging markers, [but] for small nodules such as those 5 mm in diameter, the volumetric analysis has a large coefficient of variance," he said.

Prediction models are important to the evaluation of lung nodules, yet even with existing tools "we’re wrong about 30% of the time," he said. The best three prediction models come from studies of patients at the Mayo Clinic (Arch. Intern. Med. 1997;157:849-55) and the Veterans Affairs department (Chest 2007;131:383-88), and from patients enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (N. Engl. J. Med. 2013;368:728-36). These prediction models are now recommended for use on nodules greater than 8 mm in diameter in the ACCP 2013 guidelines for evaluation of lung nodules (Chest 2013;143[5 Suppl]:e93S-120S).

"We have no models for never-smokers, which is a huge problem in the community at the moment."

Dr. Massion predicted that serum biomarkers might "come to the rescue" for deciding which patients with indeterminate pulmonary nodules might need to go for a biopsy or resection and which can be carefully watched over time.

In a separate study of 62 lung nodules that integrated clinical, imaging, and protein biomarker findings, clinical information alone resulted in about 50% sensitivity for predicting disease, "which is not great," said Dr. Massion, who was the principal investigator (Cancer Epidemiol. Biomarkers Prev. 2012;21:786-92). The addition of CT imaging increased the area under the curve to about 61%. Adding biomarkers in the blood raised the bar to about 69%.

"It’s not a panacea, but we show a trend toward improvement of classification of these nodules, which is where I think this field is going – integrating information from the clinic, imaging, and the discriminatory power of biomarkers."

Dr. Massion said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – About 30% of nodules detected by CT screening fit the criteria for an indeterminate pulmonary nodule. Very few of those nodules represent cancer, and the question is, what do you recommend for those patients in terms of follow-up?

"We’re encountering more and more patients with lung nodules in the clinic, and with the advance of screening, it will become even more of a problem. The numbers are tremendous," Dr. Pierre P. Massion stated at the Joint Conference on the Molecular Origins of Lung Cancer, sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Massion, the Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said it’s important to differentiate – early, accurately, and noninvasively – benign lesions from cancer. "There is a race for early diagnosis, because surgery is the best chance for cure ... but we also need to decrease the number of thoracotomies performed for benign disease."

Data from eight large trials of lung cancer screening examined the relationship between lesion size and the probability of lung cancer (Chest 2007;132[3 Suppl]:94S-107S). The probability of cancer was 0-1% for lesions less than 5 mm in diameter; 6%-28% for those 5-10 mm, 33%-60% for those 11-20 mm, and 64%-82% for those 21-30 mm.

"The bigger the nodule, the greater the probability of cancer. In fact, however, the number of large nodules is very small," Dr. Massion said. "The indeterminate ones are between 5 and 15 mm in diameter, and these are the ones we struggle with how best to handle." The probability of cancer from indeterminate pulmonary nodules ranges from 6% to 60%, which is a large range.

The shape of the nodule provides additional information, Dr. Massion said. Triangular shape abutting a fissure and central calcification are generally indicators of benign disease and typically do not require follow-up. Alternatively, solid, noncalcified spiculated nodules have a high likelihood of being cancer. Part solid nodules are "very worrisome," he said. "These are most likely to contain malignancy. Nonsolid lesions, also called ground-glass opacities, are troublesome and difficult to assess. They represent about a 20% probability of disease."

The rate of growth of small nodules over time "is probably one of the best imaging markers, [but] for small nodules such as those 5 mm in diameter, the volumetric analysis has a large coefficient of variance," he said.

Prediction models are important to the evaluation of lung nodules, yet even with existing tools "we’re wrong about 30% of the time," he said. The best three prediction models come from studies of patients at the Mayo Clinic (Arch. Intern. Med. 1997;157:849-55) and the Veterans Affairs department (Chest 2007;131:383-88), and from patients enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (N. Engl. J. Med. 2013;368:728-36). These prediction models are now recommended for use on nodules greater than 8 mm in diameter in the ACCP 2013 guidelines for evaluation of lung nodules (Chest 2013;143[5 Suppl]:e93S-120S).

"We have no models for never-smokers, which is a huge problem in the community at the moment."

Dr. Massion predicted that serum biomarkers might "come to the rescue" for deciding which patients with indeterminate pulmonary nodules might need to go for a biopsy or resection and which can be carefully watched over time.

In a separate study of 62 lung nodules that integrated clinical, imaging, and protein biomarker findings, clinical information alone resulted in about 50% sensitivity for predicting disease, "which is not great," said Dr. Massion, who was the principal investigator (Cancer Epidemiol. Biomarkers Prev. 2012;21:786-92). The addition of CT imaging increased the area under the curve to about 61%. Adding biomarkers in the blood raised the bar to about 69%.

"It’s not a panacea, but we show a trend toward improvement of classification of these nodules, which is where I think this field is going – integrating information from the clinic, imaging, and the discriminatory power of biomarkers."

Dr. Massion said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com