Article 1
Repurposed Antiviral Drugs for COVID-19 – Interim WHO Solidarity Trial Results. Pan H, Peto R, Henao-Restrepo AM, et al. NEJM. 2021 Feb 11;384(6):497-511.
In the early stages of the COVID-19 pandemic, prior to development of any vaccines, a number of initiatives were instituted around the globe to identify whether any existing retroviral therapies would be able to combat the SARS-Cov-2 virus. In February 2020, a WHO research forum identified four antiviral drugs that may have an effect on mortality from COVID-19: remdesevir, hydroxychloroquine, lopinavir, and interferon beta-1a. By March 2020, the WHO initiated a large, international, open-label, randomized trial to evaluate the effects of these drugs on in-hospital mortality. This was a massive effort involving hundreds of hospitals in dozens of countries – an unprecedented study. Given the emergent need of this study, all drugs were donated by various pharmaceutical companies: remdesevir was donated by Gilead Sciences, hydroxychloroquine by Mylan, lopinavir by AbbVie, Cipla, and Mylan, and interferon beta-1a by Merck (subcutaneous) and Faron Pharmaceuticals (intravenous).
In this study, inpatients infected with COVID-19 were randomly assigned one of the treatment drugs. The primary analysis for inpatient mortality was performed as an intention to treat, with pairwise comparisons between each drug and its control, defined by standard of care practice without administration of the drug. From March 22 to October 4, 2020, a total of 11,330 patients were entered in the trial from 405 hospitals in 30 countries. Only 0.6% had no follow up, leaving a total of 11,266 patient for the analysis. A total of 2750 patients were assigned to receive remdesevir, 954 to hydroxychloroquine, 1411 to lopinavir, 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. The majority of patients were younger than 70 years old, slightly more patients were male, and about 25% had diabetes. The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). The results of the study showed that no drug definitely reduced mortality, or reduced initiation of ventilation or hospitalization duration in the overall population or any of the subgroup analyses that were performed.
This study was an impressive initiative that had a significant effect on shaping the way patients infected with COVID-19 were managed across the globe. Although the results showed no effect of any drug, this allowed a change in management of COVID-19, thus reducing the unnecessary and wasteful use of these medications. While there has not been a cost analysis associated with this study, it clearly allowed for the shift in management away from their use and therefore massive production and utilization of these drugs, with the potential decrease in harm associated with their use.
Article 2
Key Components of ICU Recovery Programs: What did Patients Report Provided Benefit? McPeake J, Boehm LM, Hibbert E, et al. Crit Care Explor. 2020 Apr 29;2(4): e0088.
Despite the lack of randomized controlled evidence, a number of institutions have developed and initiated post-ICU clinics across the globe, recognizing the prolonged physical, psychological, and neurocognitive effects of prolonged stays in the ICU. Given this lack of data, it is unclear which factors are most important in creating effective ICU recovery programs. This study therefore conducted an international, qualitative study to understand the perspective of patients who did and did not attend ICU recovery programs to determine the most important components and how they should be organized.
The study included fourteen hospitals across the United States, United Kingdom, and Australia, interviewing 52 patients who attended an ICU recovery program and 14 who had not. Each of these sites were a part of the Society for Critical Care Medicine’s THRIVE program, which was developed in 2015 to bring together critical care clinicians to improve patient outcomes after critical illness. The authors then used content analysis to identify prevalent themes to understand what improved their outcomes. There were five processed identified by these patient interviews, which were directly linked to improved outcomes. 1) Continuity of care: treating ongoing physiologic problems and overseeing the entirety of care during the post-ICU phase of recovery. This was discussed in almost every interview. 2) Improving symptom status: the management, treatment, and prevention of the new and ongoing symptoms related to ICU recovery was felt to be fundamental to improving functional trajectories. Allowing patients to set their own goals was considered important for developing their own motivation and sense of self-efficacy to take back control of their own life. 3) Normalization and expectation management: patients perceived value in ICU recovery programs when they were able to understand what to expect next in the illness trajectory. This allowed them to shape to plans for recovery based on what was feasible. 4) Internal and external validation of progress: patients described value in recognizing their own individual progress and validating their feelings. In addition, returned visits to the ICU provided external validation of their progress in recovery. 5) Reducing feelings of guilt and helplessness: some patients felt helpless in relation to their symptoms and “new normal.” Centering interventions on adaptations to the challenges associated with recovery was seen as useful to reduce these feelings.
The limitations of this study were the small study population. In addition, the patients who did not attend post-ICU clinics were recruited to the study via pathways that still required some recognition that the patient needed help, such as online ICU chat rooms. Therefore, this may not accurately represent this patient population. However, given that the study was conducted in three separate countries, this provides an excellent framework for studies involving ICU recovery programs in the future. In addition, it identifies specific and reproducible modes of benefit as perceived by the patients themselves.
Article 3
Choosing Wisely for Critical Care: The Next Five. Zimmerman JJ, Harmon LA, Smithburger PL, et al. Crit Care Med. 2021 Mar 1;49(3):472-481.
In 2010, the American Board of Internal Medicine launched its “Choosing Wisely” campaign as a public health initiative to reduce wasteful interventions and encourage value-added, evidenced based care. Given that approximately 25% of total US healthcare spending is assessed as being waste, roughly translating to $800 billion per year, the ABIM was challenged with identifying interventions that were overused yet did not provide patient benefit. As a result, at least 70 medical societies formulated recommendations to reduce waste, including the Critical Care Societies Collaborative.
More recent data has indicated additional opportunities to align new evidence-based recommendations with how critical care has evolved. The Society of Critical Care Medicine therefore established a new taskforce to examine more recent articles in order to determine the Next Five “Choosing Wisely” recommendations. Phase 1 of the process to generate consensus involved individual literature reviews and generation of practice statements for group evaluation, with no limit on the number of practices brought forward for taskforce consideration. English language publications that examined critical care practices in relation to reducing cost or waste were evaluated. This generated thirteen separate and distinct recommendations. Phase 2 then narrowed the list of practices to eight using an importance ranking system reliant on the strength of evidence and potential impact on patient care. These eight recommendations were then sent out as an SCCM member survey to further decrease them to five. Phase 3 then included taskforce review of the survey recommendations and final rank scoring. The SCCM executive committee and council review was followed by submission to ABIM for final evaluation. The final Next Five “Choosing Wisely” statements are as follows, in ranking order:
1. Do not keep catheters, tubes, or drains in without a clear indication.
2. Do not delay mechanical ventilator weaning unless there is clinical evidence of need.
3. Do not give prolonged, broad spectrum antibiotic courses in the absence of ongoing culture data or symptoms.
4. Do not delay early mobility in ICU patients.
5. Do not provide care that does not align with the documented patient’s and family’s goals, values, and preferences for healthcare.
This article then provides the rationale behind each of these recommendations in detail, using up to date, high impact data. Given the high quality of the publications assessed, as well as the utilization of an extensive expert consensus process, these recommendations are highly robust and have great potential impact to improving patient outcomes in the ICU.
