Background
In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.
Methods
This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and
ClinicalTrials.gov
(
NCT04381936
).
Findings
Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57%
vs
50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35%
vs
42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001).
Interpretation
In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.
Funding
UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Background
over 50% of older people in hospital are prescribed a pre-admission medicine that is potentially inappropriate; however, deprescribing by geriatricians and pharmacists is limited. This study aimed to characterise geriatricians’ and pharmacists’ barriers and enablers to deprescribing in hospital. It also intended to develop a framework of intervention components to facilitate implementation of hospital deprescribing.
Methods
fifty-four geriatricians and pharmacists representing four UK hospitals attended eight focus groups. We designed a topic guide to invite discussions about barriers and enablers to deprescribing. After thematic analysis, themes were mapped to the theoretical domains framework (TDF), enabling prioritisation of domains for behaviour change. We then identified evidence-based intervention components for changing behaviour within prioritised TDF domains.
Results
geriatricians and pharmacists described several deprescribing enablers in the hospital setting including alignment with their role and generalist knowledge, and routine patient monitoring. Five prioritised TDF domains represent the key barriers and enabler: patient and caregiver attachment to medication (social influence); perceptions that deprescribing is riskier than continuing to prescribe (beliefs about consequences); pharmacists’ working patterns limiting capacity to support deprescribing (environmental context and resources); deprescribing being a low hospital priority (goals) and incentives to deprescribe (reinforcement). Prioritised TDF domains aligned with 44 evidence-based intervention components to address the barriers and enabler to hospital deprescribing.
Conclusion
the behavioural determinants and their associated intervention components provide a hospital deprescribing implementation framework (hDIF). Intervention components should be selected from the hDIF to provide a theory and evidence-based intervention tailored to hospital contexts.
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