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Effectiveness of a Bundled Intervention Including Adjunctive Corticosteroids on Outcomes of Hospitalized Patients With Community-Acquired PneumoniaA Stepped-Wedge Randomized Clinical Trial

Educational Objective
To evaluate the effectiveness of a bundle of evidence-supported treatments under conditions of routine care in a representative population hospitalized for community-acquired pneumonia.
1 Credit CME
Key Points

Question  Does a bundle of evidence-supported treatments (including adjunctive corticosteroids) improve the outcomes of patients with community-acquired pneumonia under conditions of routine care?

Findings  In this stepped-wedge, cluster-randomized effectiveness trial of 816 patients hospitalized with community-acquired pneumonia, a bundled intervention aiming to optimize treatment with corticosteroids, early mobilization, early switch to oral antibiotics, and screening for malnutrition had no significant effect on length of hospital stay, readmissions, mortality, or other complications of community-acquired pneumonia and resulted in a higher incidence of gastrointestinal bleeding when compared with usual care.

Meaning  This process-of-care bundle failed to improve outcomes and may have increased risks of adverse events; it cannot be recommended for patients hospitalized with community-acquired pneumonia.

Abstract

Importance  Community-acquired pneumonia remains a leading cause of hospitalization, mortality, and health care costs worldwide. Randomized clinical trials support the use of adjunctive corticosteroids, early progressive mobilization, antibiotic switching rules, and dietary interventions in improving outcomes. However, it is uncertain whether implementing these interventions will translate into effectiveness under routine health care conditions.

Objective  To evaluate the effectiveness of a bundle of evidence-supported treatments under conditions of routine care in a representative population hospitalized for community-acquired pneumonia.

Design, Setting, and Participants  A double-blind, stepped-wedge, cluster-randomized clinical trial with 90-day follow-up was conducted between August 1, 2016, and October 29, 2017, in the general internal medicine service at 2 tertiary hospitals in Melbourne, Australia, among a consecutive sample of patients with community-acquired pneumonia. The primary analysis and preparation of results took place between May 14 and November 25, 2018.

Interventions  Treating clinical teams were advised to prescribe prednisolone acetate, 50 mg/d, for 7 days (in the absence of any contraindication) and de-escalate from parenteral to oral antibiotics according to standardized criteria. Algorithm-guided early mobilization and malnutrition screening and treatment were also implemented.

Main Outcomes and Measures  Hospital length of stay, mortality, readmission, and intervention-associated adverse events (eg, gastrointestinal bleeding and hyperglycemia).

Results  A total of 917 patients were screened, and 816 (351 women and 465 men; mean [SD] age, 76 [13] years) were included in the intention-to-treat analysis, with 401 patients receiving the intervention and 415 patients in the control group. An unadjusted geometric mean ratio of 0.95 (95% CI, 0.78-1.16) was observed for the difference in length of stay (days) between the intervention and control groups. Similarly, no significant differences were observed for the secondary outcomes of mortality and readmission, and the results remained unchanged after further adjustment for sex and age. The study reported higher proportions of gastrointestinal bleeding in the intervention group (9 [2.2%]) compared with the controls (3 [0.7%]), with an unadjusted estimated difference in mean proportions of 0.008 (95% CI, 0.005-0.010).

Conclusions and Relevance  This bundled intervention including adjunctive corticosteroids demonstrated no evidence of effectiveness and resulted in a higher incidence of gastrointestinal bleeding. Efficacy of individual interventions demonstrated in clinical trials may not necessarily translate into effectiveness when implemented in combination and may even result in net harm.

Trial Registration  ClinicalTrials.gov identifier: NCT02835040

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Article Information

Accepted for Publication: March 29, 2019.

Corresponding Author: Harin Karunajeewa, MBBS, PhD, General Internal Medicine Unit, Western Health, The University of Melbourne, Melbourne, Australia (harin.karunajeewa@wh.org.au).

Published Online: July 8, 2019. doi:10.1001/jamainternmed.2019.1438

Author Contributions: Ms Lloyd and Dr Karunajeewa had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Lloyd, Karahalios, Janus, Skinner, Haines, Shackell, Karunajeewa.

Acquisition, analysis, or interpretation of data: Lloyd, Karahalios, Janus, Skinner, Haines, De Silva, Lowe, Ko, Desmond, Karunajeewa.

Drafting of the manuscript: Lloyd, Janus, Skinner, Karunajeewa.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Lloyd, Karahalios, Haines, De Silva, Karunajeewa.

Obtained funding: Janus, Skinner, Haines, Karunajeewa.

Administrative, technical, or material support: Lloyd, Janus, Skinner, Lowe, Shackell, Ko, Desmond, Karunajeewa.

Supervision: Lloyd, Janus, Skinner, Karunajeewa.

Conflict of Interest Disclosures: Ms Lloyd reported personal fees from Australian Government Research Training Scheme during the conduct of the study. Ms Lloyd and Drs Janus, Skinner, Shackell, Ko, and Karunajeewa reported receiving grants from HCF Research Foundation during the conduct of the study. No other disclosures were reported.

Funding/Support: This study received funding from grant number EJWH2015163 from the HCF Research Foundation. Western Health, the University of Melbourne, and Monash University provided salary support to the investigators. Dr Karunajeewa was supported by an Australian National Health and Medical Research Council Career Development Fellowship. Ms Lloyd was supported by an Australian Government Research Training Scheme Scholarship.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Group Information: The members of the Improving Evidence-Based Treatment Gaps and Outcomes in Community-Acquired Pneumonia (IMPROVE-GAP) Implementation Team at Western Health are as follows: Monica Turczyniak, BPhysio, Department of Physiotherapy, Western Health, Melbourne; Kamya Kameshwar, MBBS, Department of General Internal Medicine, Western Health, Melbourne; Ben Stevenson, MBBS, Department of General Internal Medicine, Western Health, Melbourne; Parul Bali, MBBS, Department of General Internal Medicine, Western Health, Melbourne; Elena Gerstman, BPhysio, Department of Physiotherapy, Western Health, Melbourne; and Kirsty May, BPhysio (Hons), Department of Physiotherapy, Western Health, Melbourne.

Data Sharing Statement: See Supplement 3.

Additional Contributions: The Western Health Physiotherapy Team—Cassandra Raios, BPhysio, Melanie Paykel, DPT, Joshua Warren, Sarah Miller, DPT, Codey Lyon, BPhysio, Kate Ryan, BPhysio, Emily Simek, BPhysio, Diana Truong, MPhysio, and Rachel Whitford, DPT, Department of Physiotherapy, Western Health, Melbourne—delivered the early mobilization interventions. Anne-Maree Kelly, MBBS, Joseph Epstein Centre for Emergency Medicine Research at Western Health, Melbourne, May-Lea Ong, MD, Department of General Internal Medicine, Western Health, Melbourne; and Clarice Tang, DPT, Department of Physiotherapy, Western Health, Melbourne, provided advice on the development of the project. Vanessa Carter, MND, and Allison Lauder, MND, Department of Nutrition, Western Health, Melbourne; provided advice on the design of the nutrition intervention. Julie Simpson, PhD, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, provided advice regarding the statistical analysis plan. Ms Turczyniak, Mrs Gerstman, Ms May, Dr Kameshwar, Dr Bali, Dr Stevenson, Ms Raios, Mr Warren, Dr Paykel, Dr Miller, Ms Lyon, Ms Ryan, Ms Simek, Ms Truong, and Dr Whitford received compensation in the form of clinician salary support for delivery of the CAP Service interventions.

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