In the JournalsPerspective

Interventions for patients with pneumonia may be ineffective, lead to gastrointestinal bleeding

A variety of interventions that were deemed effective based on clinical trials were not useful for treating patients hospitalized with pneumonia and were associated with adverse events, according to a study published in JAMA Internal Medicine.

“In recent years, data from randomized clinical trials (RCTs) have emerged demonstrating improved patient and health-system outcomes in community-acquired pneumonia for several interventions,” Melanie Lloyd, MPhtySt, of the department of physiotherapy, Western Health, at the University of Melbourne in Australia, and colleagues wrote. “However, we observe a wide gap between evidence and actual clinical practice in which many of these interventions are poorly implemented or have not been incorporated into guidelines despite high-level supportive evidence (eg, corticosteroids). A reluctance to do so may reflect challenges in applying findings of RCT data to real-world settings because of concerns regarding the representativeness, generalizability, and external validity of existing clinical trial data.”

To evaluate the effectiveness of evidence-supported treatments when implemented under routine health care conditions, researchers conducted a double-blind, stepped-wedge, cluster-RCT at two tertiary hospitals between August 2016 and October 2017.

A total of 816 patients (mean age, 76 years) with community-acquired pneumonia were assigned to either the intervention group or the control group.

The intervention consisted of 50 mg of prednisolone acetate or equivalent for 7 days, a switch from parenteral to oral antibiotics, sitting out of bed for more than 20 minutes on the day of admission with daily progressive mobilization, routine screening for malnutrition and targeted nutritional therapy

The primary outcome of the study was hospital length of stay (LOS). Secondary outcomes included mortality, readmission and intervention-associated adverse events (specifically, gastrointestinal bleeding and hyperglycemia).

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A variety of interventions that were deemed effective based on clinical trials were not useful for treating patients hospitalized with pneumonia and were associated with adverse events.
Source: Adobe Stock

Researchers found that length of stay was similar between the two groups (LOS > 3 days for 30.8% in usual care vs. 34.6% in intervention; unadjusted geometric mean ratio = 0.95; 95% CI, 0.78-1.16).

Similarly, no significant differences were observed between usual care and intervention for mortality at 30 (10.4% vs. 11%) or 90 days (15.2% vs. 17.2%) or readmission.

As for adverse events, researchers found that 0.7% of the control group developed gastrointestinal bleeding compared with 2.2% of those receiving the intervention.

“This study underscores a groundswell of opinion arguing that interventions showing efficacy in RCTs should also undergo real-world evaluation prior to integration into clinical practice guidelines and pathways,” the researchers wrote. “Our novel implementation research design using a stepped-wedged RCT method provides a precedent and template for future evaluations that address this need. The risks and lack of effectiveness of the bundle of care demonstrated in this study strongly suggest that it is not useful as a means of improving the care of patients with community-acquired pneumonia.” – by Melissa J. Webb

Disclosures: Lloyd reports receiving personal fees from Australian Government Research Training Scheme and receiving grants from HCF Research Foundation. Please see the study for all other authors’ relevant financial disclosures.

 

A variety of interventions that were deemed effective based on clinical trials were not useful for treating patients hospitalized with pneumonia and were associated with adverse events, according to a study published in JAMA Internal Medicine.

“In recent years, data from randomized clinical trials (RCTs) have emerged demonstrating improved patient and health-system outcomes in community-acquired pneumonia for several interventions,” Melanie Lloyd, MPhtySt, of the department of physiotherapy, Western Health, at the University of Melbourne in Australia, and colleagues wrote. “However, we observe a wide gap between evidence and actual clinical practice in which many of these interventions are poorly implemented or have not been incorporated into guidelines despite high-level supportive evidence (eg, corticosteroids). A reluctance to do so may reflect challenges in applying findings of RCT data to real-world settings because of concerns regarding the representativeness, generalizability, and external validity of existing clinical trial data.”

To evaluate the effectiveness of evidence-supported treatments when implemented under routine health care conditions, researchers conducted a double-blind, stepped-wedge, cluster-RCT at two tertiary hospitals between August 2016 and October 2017.

A total of 816 patients (mean age, 76 years) with community-acquired pneumonia were assigned to either the intervention group or the control group.

The intervention consisted of 50 mg of prednisolone acetate or equivalent for 7 days, a switch from parenteral to oral antibiotics, sitting out of bed for more than 20 minutes on the day of admission with daily progressive mobilization, routine screening for malnutrition and targeted nutritional therapy

The primary outcome of the study was hospital length of stay (LOS). Secondary outcomes included mortality, readmission and intervention-associated adverse events (specifically, gastrointestinal bleeding and hyperglycemia).

#
A variety of interventions that were deemed effective based on clinical trials were not useful for treating patients hospitalized with pneumonia and were associated with adverse events.
Source: Adobe Stock

Researchers found that length of stay was similar between the two groups (LOS > 3 days for 30.8% in usual care vs. 34.6% in intervention; unadjusted geometric mean ratio = 0.95; 95% CI, 0.78-1.16).

Similarly, no significant differences were observed between usual care and intervention for mortality at 30 (10.4% vs. 11%) or 90 days (15.2% vs. 17.2%) or readmission.

As for adverse events, researchers found that 0.7% of the control group developed gastrointestinal bleeding compared with 2.2% of those receiving the intervention.

“This study underscores a groundswell of opinion arguing that interventions showing efficacy in RCTs should also undergo real-world evaluation prior to integration into clinical practice guidelines and pathways,” the researchers wrote. “Our novel implementation research design using a stepped-wedged RCT method provides a precedent and template for future evaluations that address this need. The risks and lack of effectiveness of the bundle of care demonstrated in this study strongly suggest that it is not useful as a means of improving the care of patients with community-acquired pneumonia.” – by Melissa J. Webb

Disclosures: Lloyd reports receiving personal fees from Australian Government Research Training Scheme and receiving grants from HCF Research Foundation. Please see the study for all other authors’ relevant financial disclosures.

 

    Perspective

    Multiple studies and meta-analyses have investigated the impact of corticosteroid use in community-acquired pneumonia (CAP). Most notably, many meta-analyses (most recently, Stern et al, 2017) have shown a decrease in mortality in patients with severe CAP who have been treated with corticosteroids. However, the impact of corticosteroids on patients who are less severely ill has been less clear. In this paper, Lloyd et al investigate the real-world outcomes of the application of a pneumonia bundle, which included early mobilization, early switch to oral antibiotics, screening for malnutrition, and 50 mg of prednisolone (or equivalent) for 7 days. Their investigated outcomes include a primary outcome of length of stay, and secondary outcomes of mortality, decompensation, readmissions and intervention-related side effects. They found no difference in length of stay or mortality, but did report a significant increase in GI bleeding in the intention-to-treat group (3 out of 415 vs. 9 out of 401). Of note, however, major GI bleeding was minimal; only one patient in the control group and three patients in the intention-to-treat group required transfusion.

    Previous studies have likewise demonstrated that mortality benefit has been confined to patients with severe pneumonia — this study was not powered to do a subgroup analysis. This is also not the first study to call into question whether steroids may cause harm; Briel at al (2018) suggested that patients treated with steroids may be at increased risk of CAP-related readmissions. No other studies have shown an increased risk of GI bleeding in patients with CAP treated with steroids.

    While this study should not discourage the use of steroids in severe pneumonia, the study does highlight that further investigation is necessary to determine whether there is a subpopulation of less severely ill patients who benefit from steroids with reduced risk of side effects. In the meantime, clinicians should be aware of the exclusion criteria of these studies and balance the benefits and risks when using steroids to treat patients who do not have severe CAP.

    Briel M, et al. Corticosteroids in patients hospitalized for community-acquired pneumonia: systematic review and individual patient data metaanalysis. Clinical Infectious Diseases. 2018;doi:10.1093/cid/cix801.

    Stern A, et al. Corticosteroids for pneumonia. Cochrane Database of Systematic Reviews. 2017;doi:10.1002/14651858.CD007720.pub3.

    • Joanna M. Bonsall, MD, PhD, SFHM
    • Chief of Hospital Medicine
      Grady Memorial Hospital
      Clinical Co-Director of MD/PhD Program
      Associate Professor of Medicine
      Emory University School of Medicine

    Disclosures: Bonsall reports no relevant financial disclosures.