Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. 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. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Identifying a National Death Index Match

Data from the National Death Index (NDI) are frequently used to determine survival status in epidemiologic or clinical studies. On the basis of selected information submitted by the investigator, NDI returns a file containing a set of candidate matches. Although NDI deems some matches as perfect, multiple candidate matches may be available for other cases. Working across data from the Duke University site of the Established Populations for Epidemiologic Studies of the Elderly (EPESE), NDI, and the Social Security Death Index (SSDI), the authors found that, for this Established Populations for Epidemiologic Studies of the Elderly cohort of 1,896 cases born before 1922 and alive as of January 1, 1999, a match on Social Security number plus additional personal information (specific combinations of last name, first name, month of birth, day of birth) resulted in agreement between NDI and Social Security Death Index dates of death 94.7% of the time, while comparable agreement was found for only 12.3% of candidate decedents who did not have the required combination of information. Thus, an easy to apply algorithm facilitates accurate identification of NDI matches

Defining Care Needs in Older Adults With a Particular Set of Multiple Chronic Conditions: Coexisting Visual, Auditory and Cognitive Impairments

Background/Aims: Patients who have multiple chronic conditions (MCCs) represent a majority of older adults and have high health care needs. Considering the heterogeneity of MCC, one approach to identifying specific need gaps is to focus on common pairs or clusters of MCCs. Visual, auditory and cognitive impairments are common in old age, frequently coexist, and impact function. However, little is known about their combined association with patient-centered outcomes in older adults. Our objective was to assess the relationship of disability and self-reported health with various combinations of coexisting visual, auditory and/or cognitive impairments. Methods: We analyzed sample data from the North Carolina EPESE study (N=3,871; age 65–105 years), a population-based epidemiological study of community-dwelling seniors. Cognition was assessed by the Short Portable Mental Status Questionnaire, and visual and auditory status determined from self-reported information. Logistic regression characterized the cross-sectional associations of all combinations of visual, auditory and cognitive impairment with disability in activities of daily living (ADL), instrumental ADL (IADL) and poor self-reported health (SRH). Results: The prevalence of ADL disability was 9.9% (384 of 3,871), IADL disability 29.6% (1,146 of 3,871), and fair/poor SRH 46.6% (1,805 of 3,871). In adjusted analyses, compared to persons with no impairments, persons with all three impairments had increased odds of ADL disability (odds ratio [OR]: 4.99, 95% confidence interval [CI]: 2.95–8.44), IADL disability (OR: 10.39, 95% CI: 5.67–19.05) and low SRH (OR: 2.81, 95% CI: 1.64–4.82). The relationship between impairments and ADL disability exhibited a “step-wise” pattern (odds of disability increased as number of impairments increased), but IADL disability was particularly common in those with vision impairment, cognitive impairment, or the combination. While sensory impairments were associated with poor SRH, cognitive impairment was not unless both sensory impairments were present. Discussion: Older adults with coexistent sensory and cognitive impairments have high functional needs. People with combined vision and hearing loss are likely to perceive their health as poor, whereas cognitive impairment may confer some protection against illness perceptions. Persons with coexisting visual and cognitive impairments are especially likely to require assistance with IADLs (e.g. medication management, handling finances) and may benefit from targeted clinical services that help overcome those impairments

Association of Co-Existing Impairments in Cognition and Self-Rated Vision and Hearing With Health Outcomes in Older Adults

Objective: The objective of this study was to assess the relationship of disability (activities of daily living [ADL] and instrumental ADL [IADL]), self-rated health (SRH), and 6-year mortality with co-existing impairments in vision (self-rated), hearing (self-rated), and/or cognition (Short Portable Mental Status Questionnaire) in older adults. Method: The study sample comprised of 3,871 participants from the North Carolina Established Populations for Epidemiologic Studies of the Elderly study (NC EPESE). Results: Persons with all three impairments had increased odds of ADL/IADL disability and low SRH. Participants with combined visual and cognitive impairments had increased odds of mortality. Whereas sensory impairments were associated with poor SRH, cognitive impairment was not unless both sensory impairments were present. Conclusion: Co-existent sensory and cognitive impairments were associated with higher risk of impaired functional status. Self-rated auditory impairment alone was not associated with higher odds of death, but mortality was linked to visual and, particularly, cognitive impairment, alone or combined

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease