BEYOND THE BLUE: What Fellows Are Reading in Other Journals Fluid Protocol for Acute Respiratory Distress Syndrome, Catheter Thrombolysis for Intermediate Risk Pulmonary Embolism, and Steroids for Community-acquired Pneumonia Nandita Nadig, Sean Callahan, and Jean Paul Higuero Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina Recommended Reading from the Medical University of South Carolina Pulmonary and Critical Care Fellows; Nicholas J. Pastis, M.D., Program Director
Grissom CK, et al.; National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Fluid Management with a Simplified Conservative Protocol for the Acute Respiratory Distress Syndrome. Crit Care Med (1) Reviewed by Nandita Nadig
Numerous therapies have been evaluated in acute respiratory distress syndrome (ARDS), including the Fluid and Catheter Treatment Trial (FACTT), wherein patients were randomized and managed with either a FACTT Conservative fluid protocol or FACTT Liberal fluid protocol (2). Although there was no difference in 60-day mortality in the study, the conservative group had more ventilator-free days (VFD). Some critiques of this study were that the protocols were regimented and not generalizable in a real-life clinical setting. This current study tested the hypothesis that a simplified protocol for fluid management (FACTT Lite) is as effective as FACTT Conservative and better than FACTT Liberal with respect to fluid balances over 7 days, 60-day mortality, and VFD. This was a retrospective study of 503 subjects on FACTT Conservative, 497 on FACTT Liberal, and 1,124 subjects managed with FACTT Lite. The FACTT Lite provided three possible instructions determined by the central venous pressure and urine output: furosemide administration, fluid bolus, or no intervention, which was assessed every 4 hours for 7 days. The primary outcome was cumulative fluid balance over 7 days. Secondary outcomes included 60-day mortality, VFD, and incidence of acute renal failure. Results showed that cumulative fluid management with FACTT Lite resulted in a greater cumulative fluid balance by 2,054 ml than FACTT Conservative but a lower cumulative fluid balance by 5,074 ml than FACTT Liberal. After adjustment for age and APACHE III score, 60-day mortality was similar between the groups (P = 0.84). The FACTT Lite and FACTT Conservative had similar VFD (14, P = 0.61), and FACTT Lite had higher VFD than FACTT Liberal (14 vs. 12, P , 0.001).
In addition, after adjustment for fluid balance the acute renal failure prevalence was similar between the FACTT Lite and FACTT Conservative (56 vs. 58%, P = 0.60) but was much higher in the FACTT Liberal group (66 vs. 56%, P = 0.001). New-onset shock was lower in the FACTT Lite than in the FACTT Conservative (9 vs. 13%, P = 0.007) but similar to the FACTT Liberal (11%, P = 0.18). The study had several limitations, however. It is retrospective in nature. Of note, the FACTT Lite protocol was implemented after the original benefits noted in the prospectively designed FACCT studies involving conservative and liberal treatment groups. It excluded patients on chronic dialysis, leading to a large knowledge gap in these patients. The study also does not help us with fluid management during shock, which is a common occurrence in patients with ARDS (3). In summary, FACTT Lite can be used as a simplified and safe alternative to FACTT Conservative for the management of fluid balance in patients with ARDS. Clinicians using FACTT Lite should continue to do so in the future. n References 1. Grissom CK, Hirshberg EL, Dickerson JB, Brown SM, Lanspa MJ, Liu KD, Schoenfeld D, Tidswell M, Hite RD, Rock P, et al.; National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Fluid management with a simplified conservative protocol for the acute respiratory distress syndrome. Crit Care Med 2015;43:288–295. 2. Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006;354:2564–2575. 3. Chang DW, Huynh R, Sandoval E, Han N, Coil CJ, Spellberg BJ. Volume of fluids administered during resuscitation for severe sepsis and septic shock and the development of the acute respiratory distress syndrome. J Crit Care 2014;29:1011–1015.
( Received in original form February 18, 2015; accepted in final form March 30, 2015 ) Correspondence and requests for reprints should be addressed to Nicholas J. Pastis, M.D., Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 812, Charleston, SC 29425. E-mail: [email protected] Am J Respir Crit Care Med Vol 191, Iss 11, pp 1331–1333, Jun 1, 2015 Copyright © 2015 by the American Thoracic Society DOI: 10.1164/rccm.201502-0340RR Internet address: www.atsjournals.org
Beyond the Blue: What Fellows Are Reading in Other Journals
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BEYOND THE BLUE Kucher N, et al. Randomized, Controlled Trial of Ultrasound-assisted Catheter-directed Thrombolysis for Acute Intermediate-Risk Pulmonary Embolism. Circulation (4) Reviewed by Sean Callahan
Acute pulmonary embolism (PE) is a potential life-threatening diagnosis with outcomes varying based on severity and associated characteristics (5). Assessment of risk can be defined as low, intermediate, and high when taking into account hemodynamic stability and image or biomarker evidence of right ventricular (RV) dilatation or dysfunction (6). Treatment is less defined unless shock or impending death is clearly visible. Several studies attempt to rectify this, but clinical judgment generally prevails. Systemic thrombolysis in intermediate-risk PE remains controversial (7). The aim of this randomized, controlled trial was to determine whether ultrasound-assisted catheter-directed thrombolysis (USAT) was superior to standard anticoagulation alone, particularly in the reversal of RV dilatation in intermediate-risk patients. The primary endpoint was the difference in the RV/left ventricular (LV) ratio from baseline to 24 hours. Inclusion criteria were acute symptomatic PE confirmed by contrast-enhanced computed tomography with embolus located in at least one main or proximal lower lobe pulmonary artery and RV/LV ratio greater than or equal to 1 obtained from echocardiogram. Fifty-nine patients were randomized in openlabel fashion to receive USAT plus heparin (n = 30) or heparin alone (n = 29). Screening failure rate was 84%, with main reasons being small PE and RV/LV ratio less than 1. Baseline characteristics between groups were balanced, and all echocardiographic images were reviewed in a blinded fashion by a core laboratory. Participants in the USAT arm received either a unilateral or bilateral drug delivery device, and the maximum drug dose administered was either 10 mg or 20 mg, respectively. Use of USAT regimen reduced RV/LV ratio from 1.28 6 0.19 to 0.99 6 0.17 (P , 0.001) versus 1.20 6 0.14 to 1.17 6 0.20 (P = 0.31) in the heparin group. The mean difference in RV/LV between the two groups from baseline to 24 hours was 0.30 6 0.20 versus 0.03 6 0.16 (P , 0.001), in favor of the USAT group. Overall, there were no major bleeding complications and four minor bleeding episodes (three in USAT group). The most notable limitations of this study include its lack of focus on hard outcomes such as mortality, possible selection bias, and that data sets for additional echocardiographic analysis were incomplete because of poor quality of images. Localized delivery of thrombolytics with USAT may be promising, but further studies will need to focus on safety and long-term clinical outcomes such as morbidity and mortality. n References 4. Kucher N, Boekstegers P, Muller ¨ OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Muller ¨ R, Blessing E, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014;129:479–486.
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5. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999;353:1386–1389. 6. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, et al.; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011;123: 1788–1830. 7. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie` N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, et al.; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29: 2276–2315.
Blum CA, et al. Adjunct Prednisone Therapy for Patients with Community-acquired Pneumonia: A Multicentre, Double-Blind, Randomised, Placebo-controlled Trial. Lancet (8) Reviewed by Jean Paul Higuero
Community-acquired pneumonia (CAP) is a major cause of global morbidity and mortality. Major society guidelines focus on choice of empiric antibiotic therapy but do not make recommendations endorsing any adjuvant treatment (9, 10). A recent metaanalysis reported that adjunctive steroids in the treatment of CAP reduced hospital length of stay (LOS), but the authors acknowledged the significant limitations of the available data (11). This double-blind, multicenter, randomized, placebocontrolled trial tested whether adjunct therapy with steroids in patients with CAP within 24 hours of presentation would reduce time to clinical stability. The primary endpoint was defined as 24 hours or more of stable vital signs, mental status return to baseline before onset of CAP, ability for oral intake, and adequate oxygenation on room air. Secondary endpoints included time to hospital discharge, recurrence of pneumonia, readmission to hospital, intensive care unit admission, duration of antibiotic treatment, incidence of complications due to CAP, and all-cause mortality. Participants were randomized (1:1) to prednisone 50 mg daily for 7 days (n = 402) or placebo (n = 400). Baseline prognostic variables were balanced between groups, and follow up for the primary endpoint was complete. On the intention-to-treat analysis, time to clinical stability was reduced 1.4 days (3 d in the prednisone group vs. 4.4 d in the placebo group; hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.15–1.5). Among secondary endpoints, median time to hospital discharge was reduced by 1 day (6 d vs. 7 d; HR, 1.19; 95% CI, 1.04–1.38). There was no difference in mortality between treatment groups, but the study was not powered to detect this. The main adverse event was a significant increase of in-hospital hyperglycemia requiring new insulin treatment
American Journal of Respiratory and Critical Care Medicine Volume 191 Number 11 | June 1 2015
BEYOND THE BLUE (76 [19%] vs. 43 [11%] patients; HR, 1.96; 95% CI, 1.31–2.93). Limitations of this study include the small number of ICUadmitted patients and the choice of clinical stability as a primary outcome. This study also does not address the management of CAP in the ambulatory setting because it was limited to hospitalized patients. This is the largest study to date to test adjuvant steroids in the treatment of CAP and supports the prior published data showing benefit of their use without significant adverse events. A meta-analysis included in the supplementary appendix showed a significant reduction of LOS (mean difference, 21.3 d [95% CI, 21.92 to 20.67 d]) when the current results were added to the prior evidence. Although some questions remain, it appears to be time for an update to the current CAP guidelines, to include considering the use of adjuvant steroids for LOS reduction in hospitalized (non–intensive care unit) patients with CAP. n Author disclosures are available with the text of this article at www.atsjournals.org.
Beyond the Blue: What Fellows Are Reading in Other Journals
References 8. Blum CA, Nigro N, Briel M, Schuetz P, Ullmer E, Suter-Widmer I, Winzeler B, Bingisser R, Elsaesser H, Drozdov D, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebocontrolled trial. Lancet 2015;6736:1–8. 9. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, et al.; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27–S72. 10. Woodhead M, Blasi F, Ewig S, Garau J, Huchon G, Ieven M, Ortqvist A, Schaberg T, Torres A, van der Heijden G, et al.; Joint Taskforce of the European Respiratory Society and European Society for Clinical Microbiology and Infectious Diseases. Guidelines for the management of adult lower respiratory tract infections—full version. Clin Microbiol Infect 2011;17:E1–E59. 11. Shafiq M, Mansoor MS, Khan AA, Sohail MR, Murad MH. Adjuvant steroid therapy in community-acquired pneumonia: a systematic review and meta-analysis. J Hosp Med 2013;8:68–75.
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Grissom CK, et al.; National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Fluid Management with a Simplified Conservative Protocol for the Acute Respiratory Distress Syndrome. Crit Care Med (1) Reviewed by Nandita Nadig
Numerous therapies have been evaluated in acute respiratory distress syndrome (ARDS), including the Fluid and Catheter Treatment Trial (FACTT), wherein patients were randomized and managed with either a FACTT Conservative fluid protocol or FACTT Liberal fluid protocol (2). Although there was no difference in 60-day mortality in the study, the conservative group had more ventilator-free days (VFD). Some critiques of this study were that the protocols were regimented and not generalizable in a real-life clinical setting. This current study tested the hypothesis that a simplified protocol for fluid management (FACTT Lite) is as effective as FACTT Conservative and better than FACTT Liberal with respect to fluid balances over 7 days, 60-day mortality, and VFD. This was a retrospective study of 503 subjects on FACTT Conservative, 497 on FACTT Liberal, and 1,124 subjects managed with FACTT Lite. The FACTT Lite provided three possible instructions determined by the central venous pressure and urine output: furosemide administration, fluid bolus, or no intervention, which was assessed every 4 hours for 7 days. The primary outcome was cumulative fluid balance over 7 days. Secondary outcomes included 60-day mortality, VFD, and incidence of acute renal failure. Results showed that cumulative fluid management with FACTT Lite resulted in a greater cumulative fluid balance by 2,054 ml than FACTT Conservative but a lower cumulative fluid balance by 5,074 ml than FACTT Liberal. After adjustment for age and APACHE III score, 60-day mortality was similar between the groups (P = 0.84). The FACTT Lite and FACTT Conservative had similar VFD (14, P = 0.61), and FACTT Lite had higher VFD than FACTT Liberal (14 vs. 12, P , 0.001).
In addition, after adjustment for fluid balance the acute renal failure prevalence was similar between the FACTT Lite and FACTT Conservative (56 vs. 58%, P = 0.60) but was much higher in the FACTT Liberal group (66 vs. 56%, P = 0.001). New-onset shock was lower in the FACTT Lite than in the FACTT Conservative (9 vs. 13%, P = 0.007) but similar to the FACTT Liberal (11%, P = 0.18). The study had several limitations, however. It is retrospective in nature. Of note, the FACTT Lite protocol was implemented after the original benefits noted in the prospectively designed FACCT studies involving conservative and liberal treatment groups. It excluded patients on chronic dialysis, leading to a large knowledge gap in these patients. The study also does not help us with fluid management during shock, which is a common occurrence in patients with ARDS (3). In summary, FACTT Lite can be used as a simplified and safe alternative to FACTT Conservative for the management of fluid balance in patients with ARDS. Clinicians using FACTT Lite should continue to do so in the future. n References 1. Grissom CK, Hirshberg EL, Dickerson JB, Brown SM, Lanspa MJ, Liu KD, Schoenfeld D, Tidswell M, Hite RD, Rock P, et al.; National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Fluid management with a simplified conservative protocol for the acute respiratory distress syndrome. Crit Care Med 2015;43:288–295. 2. Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006;354:2564–2575. 3. Chang DW, Huynh R, Sandoval E, Han N, Coil CJ, Spellberg BJ. Volume of fluids administered during resuscitation for severe sepsis and septic shock and the development of the acute respiratory distress syndrome. J Crit Care 2014;29:1011–1015.
( Received in original form February 18, 2015; accepted in final form March 30, 2015 ) Correspondence and requests for reprints should be addressed to Nicholas J. Pastis, M.D., Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 812, Charleston, SC 29425. E-mail: [email protected] Am J Respir Crit Care Med Vol 191, Iss 11, pp 1331–1333, Jun 1, 2015 Copyright © 2015 by the American Thoracic Society DOI: 10.1164/rccm.201502-0340RR Internet address: www.atsjournals.org
Beyond the Blue: What Fellows Are Reading in Other Journals
1331
BEYOND THE BLUE Kucher N, et al. Randomized, Controlled Trial of Ultrasound-assisted Catheter-directed Thrombolysis for Acute Intermediate-Risk Pulmonary Embolism. Circulation (4) Reviewed by Sean Callahan
Acute pulmonary embolism (PE) is a potential life-threatening diagnosis with outcomes varying based on severity and associated characteristics (5). Assessment of risk can be defined as low, intermediate, and high when taking into account hemodynamic stability and image or biomarker evidence of right ventricular (RV) dilatation or dysfunction (6). Treatment is less defined unless shock or impending death is clearly visible. Several studies attempt to rectify this, but clinical judgment generally prevails. Systemic thrombolysis in intermediate-risk PE remains controversial (7). The aim of this randomized, controlled trial was to determine whether ultrasound-assisted catheter-directed thrombolysis (USAT) was superior to standard anticoagulation alone, particularly in the reversal of RV dilatation in intermediate-risk patients. The primary endpoint was the difference in the RV/left ventricular (LV) ratio from baseline to 24 hours. Inclusion criteria were acute symptomatic PE confirmed by contrast-enhanced computed tomography with embolus located in at least one main or proximal lower lobe pulmonary artery and RV/LV ratio greater than or equal to 1 obtained from echocardiogram. Fifty-nine patients were randomized in openlabel fashion to receive USAT plus heparin (n = 30) or heparin alone (n = 29). Screening failure rate was 84%, with main reasons being small PE and RV/LV ratio less than 1. Baseline characteristics between groups were balanced, and all echocardiographic images were reviewed in a blinded fashion by a core laboratory. Participants in the USAT arm received either a unilateral or bilateral drug delivery device, and the maximum drug dose administered was either 10 mg or 20 mg, respectively. Use of USAT regimen reduced RV/LV ratio from 1.28 6 0.19 to 0.99 6 0.17 (P , 0.001) versus 1.20 6 0.14 to 1.17 6 0.20 (P = 0.31) in the heparin group. The mean difference in RV/LV between the two groups from baseline to 24 hours was 0.30 6 0.20 versus 0.03 6 0.16 (P , 0.001), in favor of the USAT group. Overall, there were no major bleeding complications and four minor bleeding episodes (three in USAT group). The most notable limitations of this study include its lack of focus on hard outcomes such as mortality, possible selection bias, and that data sets for additional echocardiographic analysis were incomplete because of poor quality of images. Localized delivery of thrombolytics with USAT may be promising, but further studies will need to focus on safety and long-term clinical outcomes such as morbidity and mortality. n References 4. Kucher N, Boekstegers P, Muller ¨ OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Muller ¨ R, Blessing E, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014;129:479–486.
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5. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999;353:1386–1389. 6. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, et al.; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011;123: 1788–1830. 7. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie` N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, et al.; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29: 2276–2315.
Blum CA, et al. Adjunct Prednisone Therapy for Patients with Community-acquired Pneumonia: A Multicentre, Double-Blind, Randomised, Placebo-controlled Trial. Lancet (8) Reviewed by Jean Paul Higuero
Community-acquired pneumonia (CAP) is a major cause of global morbidity and mortality. Major society guidelines focus on choice of empiric antibiotic therapy but do not make recommendations endorsing any adjuvant treatment (9, 10). A recent metaanalysis reported that adjunctive steroids in the treatment of CAP reduced hospital length of stay (LOS), but the authors acknowledged the significant limitations of the available data (11). This double-blind, multicenter, randomized, placebocontrolled trial tested whether adjunct therapy with steroids in patients with CAP within 24 hours of presentation would reduce time to clinical stability. The primary endpoint was defined as 24 hours or more of stable vital signs, mental status return to baseline before onset of CAP, ability for oral intake, and adequate oxygenation on room air. Secondary endpoints included time to hospital discharge, recurrence of pneumonia, readmission to hospital, intensive care unit admission, duration of antibiotic treatment, incidence of complications due to CAP, and all-cause mortality. Participants were randomized (1:1) to prednisone 50 mg daily for 7 days (n = 402) or placebo (n = 400). Baseline prognostic variables were balanced between groups, and follow up for the primary endpoint was complete. On the intention-to-treat analysis, time to clinical stability was reduced 1.4 days (3 d in the prednisone group vs. 4.4 d in the placebo group; hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.15–1.5). Among secondary endpoints, median time to hospital discharge was reduced by 1 day (6 d vs. 7 d; HR, 1.19; 95% CI, 1.04–1.38). There was no difference in mortality between treatment groups, but the study was not powered to detect this. The main adverse event was a significant increase of in-hospital hyperglycemia requiring new insulin treatment
American Journal of Respiratory and Critical Care Medicine Volume 191 Number 11 | June 1 2015
BEYOND THE BLUE (76 [19%] vs. 43 [11%] patients; HR, 1.96; 95% CI, 1.31–2.93). Limitations of this study include the small number of ICUadmitted patients and the choice of clinical stability as a primary outcome. This study also does not address the management of CAP in the ambulatory setting because it was limited to hospitalized patients. This is the largest study to date to test adjuvant steroids in the treatment of CAP and supports the prior published data showing benefit of their use without significant adverse events. A meta-analysis included in the supplementary appendix showed a significant reduction of LOS (mean difference, 21.3 d [95% CI, 21.92 to 20.67 d]) when the current results were added to the prior evidence. Although some questions remain, it appears to be time for an update to the current CAP guidelines, to include considering the use of adjuvant steroids for LOS reduction in hospitalized (non–intensive care unit) patients with CAP. n Author disclosures are available with the text of this article at www.atsjournals.org.
Beyond the Blue: What Fellows Are Reading in Other Journals
References 8. Blum CA, Nigro N, Briel M, Schuetz P, Ullmer E, Suter-Widmer I, Winzeler B, Bingisser R, Elsaesser H, Drozdov D, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebocontrolled trial. Lancet 2015;6736:1–8. 9. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, et al.; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27–S72. 10. Woodhead M, Blasi F, Ewig S, Garau J, Huchon G, Ieven M, Ortqvist A, Schaberg T, Torres A, van der Heijden G, et al.; Joint Taskforce of the European Respiratory Society and European Society for Clinical Microbiology and Infectious Diseases. Guidelines for the management of adult lower respiratory tract infections—full version. Clin Microbiol Infect 2011;17:E1–E59. 11. Shafiq M, Mansoor MS, Khan AA, Sohail MR, Murad MH. Adjuvant steroid therapy in community-acquired pneumonia: a systematic review and meta-analysis. J Hosp Med 2013;8:68–75.
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