1,721,290 research outputs found
Molnupiravir or nirmatrelvir–ritonavir plus usual care versus usual care alone in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
No full textBackground: molnupiravir and nirmatrelvir–ritonavir are oral antivirals that have shown efficacy in preventing disease progression in outpatients with COVID-19. We aimed to evaluate these treatments for patients hospitalised with COVID-19 pneumonia, for whom data on these antivirals are scarce.Methods: the RECOVERY trial is a randomised, controlled, open-label, adaptive platform trial testing treatments for COVID-19. In this study we report the molnupiravir and nirmatrelvir–ritonavir comparisons from the RECOVERY trial. In each comparison, participants aged 18 years and older were randomly allocated (1:1) to the relevant antiviral (5 days of molnupiravir 800 mg twice daily or 300 mg nirmatrelvir and 100 mg ritonavir twice daily) in addition to usual care, or to usual care alone. The molnupiravir comparison was conducted at 75 hospitals in the UK, two in Nepal, and two in Indonesia; the nirmatrelvir–ritonavir comparison was conducted at 32 hospitals in the UK. Participants could take part in both comparisons. The primary outcome was 28-day mortality, and secondary outcomes were time to discharge alive from hospital and progression to invasive ventilation or death. Analysis was by intention to treat. Both comparisons were stopped because of low recruitment. This study is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: from Jan 24, 2022, to May 24, 2023, 923 participants were recruited to the molnupiravir comparison (445 allocated to molnupiravir and 478 to usual care), and from March 31, 2022, to May 24, 2023, 137 participants were recruited to the nirmatrelvir–ritonavir comparison (68 allocated to nirmatrelvir–ritonavir and 69 to usual care). More than three-quarters of participants were vaccinated and had antispike antibodies at randomisation, and more than two-thirds were receiving other SARS-CoV-2 antivirals. In the molnupiravir comparison, 74 (17%) participants allocated to molnupiravir and 79 (17%) allocated to usual care died within 28 days (hazard ratio [HR] 0·93 [95% CI 0·68–1·28], p=0·66). In the nirmatrelvir–ritonavir comparison, 13 (19%) participants allocated to nirmatrelvir–ritonavir and 13 (19%) allocated to usual care died within 28 days (HR 1·02 [0·47–2·23], p=0·96). In neither comparison was there evidence of any difference in the duration of hospitalisation or the proportion of participants progressing to invasive ventilation or death. Interpretation: adding molnupiravir or nirmatrelvir–ritonavir to usual care was not associated with improvements in clinical outcomes. However, low recruitment meant a clinically meaningful benefit of treatment could not be ruled out, particularly for nirmatrelvir–ritonavir. Funding: UK Research and Innovation (UK Medical Research Council), the National Institute for Health and Care Research, and the Wellcome Trust.</p
Higher dose corticosteroids in hospitalised COVID-19 patients requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial
No full textBackground: low dose corticosteroids (e.g., 6 mg dexamethasone) have been shown to reduce mortality for hypoxic COVID-19 patients. We have previously reported that higher dose corticosteroids cause harm in patients with clinical hypoxia but not receiving ventilatory support (the combination of non-invasive mechanical ventilation, including high-flow nasal oxygen, continuous positive airway pressure and bilevel positive airway pressure ventilation, and invasive mechanical ventilation or extra-corporeal membrane oxygenation), but the balance of efficacy and safety in patients receiving ventilatory support is uncertain.Methods: this randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) assessed multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients receiving ventilatory support were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. Recruitment closed on 31 March 2024 when funding for the trial ended. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: between 25 May 2021 and 9 January 2024, 477 COVID-19 patients receiving ventilatory support were randomly allocated to receive usual care plus higher dose corticosteroids vs. usual care alone (of whom 99% received corticosteroids during the follow-up period). Of those randomised, 221 (46%) were in Asia, 245 (51%) in the UK and 11 (2%) in Africa. 143 (30%) had diabetes mellitus. Overall, 86 (35%) of 246 patients allocated to higher dose corticosteroids vs. 86 (37%) of 231 patients allocated to usual care died within 28 days (rate ratio [RR] 0.87; 95% CI 0.64–1.18; p = 0.37). There was no significant difference in the proportion of patients discharged from hospital alive within 28 days (128 [52%] in the higher dose corticosteroids group vs. 120 [52%] in the usual care group; RR 1.04, 0.81–1.33]; p = 0.78). Among those not on invasive mechanical ventilation at baseline, there was no clear reduction in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (76 [37%] of 206 vs. 93 [45%] of 205; RR 0.79 [95% CI 0.63–1.00]; p = 0.05). Interpretation: in patients hospitalised for COVID-19 receiving ventilatory support, we found no evidence that higher dose corticosteroids reduced the risk of death compared to usual care, which included low dose corticosteroids. Funding: UK Research and Innovation ( Medical Research Council) and National Institute for Health Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).</p
Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
No full textBackground
Aspirin has been proposed as a treatment for COVID-19 on the basis of its anti-thrombotic properties. We aimed to evaluate the efficacy and safety of aspirin in patients admitted to hospital with COVID-19.
Methods
In this randomised, controlled, open-label, platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. The trial took place at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150 mg aspirin once per day until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28 day mortality. All analyses were done by intention to treat. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).
Findings
Between Nov 1, 2020, and March 21, 2021, 14 892 (66%) of 22 560 patients enrolled into the RECOVERY trial were eligible to be randomly allocated to aspirin. 7351 patients were randomly allocated (1:1) to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) of 7351 patients allocated to aspirin and 1299 (17%) of 7541 patients allocated to usual care died within 28 days (rate ratio 0·96, 95% CI 0·89–1·04; p=0·35). Consistent results were seen in all prespecified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days, IQR 5 to >28, vs 9 days, IQR 5 to >28) and a higher proportion were discharged from hospital alive within 28 days (75% vs 74%; rate ratio 1·06, 95% CI 1·02–1·10; p=0·0062). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs 22%; risk ratio 0·96, 95% CI 0·90–1·03; p=0·23). Aspirin use was associated with a reduction in thrombotic events (4·6% vs 5·3%; absolute reduction 0·6%, SE 0·4%) and an increase in major bleeding events (1·6% vs 1·0%; absolute increase 0·6%, SE 0·2%).
Interpretation
In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28 day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days.
Funding
UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator
COVID-19 in children: current evidence and key questions
No full textPURPOSE OF REVIEW: SARS-CoV-2 infection in children has been less well characterized than in adults, primarily due to a significantly milder clinical phenotype meaning many cases have gone undocumented by health professionals or researchers. This review outlines the current evidence of the epidemiology of infection in children, the clinical manifestations of disease, the role of children in transmission of the virus and the recently described hyperinflammatory syndrome observed later during the first phase of the pandemic.RECENT FINDINGS: International seroprevalence studies have found younger children to have lower prevalence of antibodies to SARS-CoV-2, indicating they have not been infected as much as adults. This may be due to shielding by school closures, or by a reduced susceptibility to infection, as indicated by a significantly lower attack rate in children than adults in household contact tracing studies. The most well recognized symptoms in adults of cough, fever, anosmia and ageusia are less frequent in children, who may often present with mild and nonspecific symptoms, or with gastrointestinal symptoms alone. Risk factors for severe disease in children include chronic lung, cardiac or neurological disease, and malignancy. However, the absolute risk still appears very low for these cohorts. A new hyperinflammatory syndrome has emerged with an apparent immune cause.SUMMARY: Important questions remain unanswered regarding why children have mild disease compared with adults; how children of different ages contribute to asymptomatic community transmission of the virus; and the pathophysiology of and most appropriate investigation and treatment strategies for the novel hyperinflammatory syndrome.</p
Meningococcal infections
No full textBackgroundThe gram-negative diplococcus Neisseria meningitides is a major infectious cause of childhood death in developed countries. The mortality rate remains around 10%; however, in some specialist centers, it has decreased to less than 5%.1 Only meningitis is present in 30-50% of cases of invasive meningococcal disease, whereas 7-10% of cases have only features of septicemia, and 40% have meningitis with septicemia. The clinical difference between septicemia and meningitis is important because patients who present with shock are treated differently than patients who present primarily with increased intracranial pressure (ICP).<br/
Opportunities for paediatricians to do research with the National Institute for Health Research
No full textResearch is an essential part of the healthcare system and of the NHS. It benefits present and future patients, drives continual improvement in cost-effectiveness for the NHS and provides challenging but rewarding work for healthcare professionals. Whether pursuing an academic career or recruiting patients from clinical service, all clinicians should have the opportunity to be involved in research. The National Institute for Health Research is provides support, training, infrastructure and funding for undertaking research. In this review we will look at the different opportunities available in association with the National Institute for Health Research and how clinicians can access them at different stages of their caree
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