Adapting Patient and Public Involvement processes in response to the Covid-19 pandemic.

BACKGROUND: The COVID-19 pandemic brought rapid and major changes to research, and those wishing to carry out Patient and Public Involvement (PPI) activities faced challenges, such as restrictions on movement and contact, illness, bereavement and risks to potential participants. Some researchers moved PPI to online settings during this time but remote consultations raise, as well as address, a number of challenges. It is important to learn from PPI undertaken in this period as face-to-face consultation may no longer be the dominant method for PPI. METHODS: UK stay-at-home measures announced in March 2020 necessitated immediate revisions to the intended face-to-face methods of PPI consultation for the ESORT Study, which evaluated emergency surgery for patients with common acute conditions. PPI plans and methods were modified to all components being online. We describe and reflect on: initial plans and adaptation; recruitment; training and preparation; implementation, contextualisation and interpretation. Through first-hand accounts we show how the PPI processes were developed, experienced and viewed by different partners in the process. DISCUSSION AND CONCLUSIONS: While concerns have been expressed about the possible limiting effects of forgoing face-to-face contact with PPI partners, we found important benefits from the altered dynamic of the online PPI environment. There were increased opportunities for participation which might encourage the involvement of a broader demographic, and unexpected benefits in that the online platform seemed to have a 'democratising' effect on the meetings, to the benefit of the PPI processes and outcomes. Other studies may however find that their particular research context raises particular challenges for the use of online methods, especially in relation to representation and inclusion, as new barriers to participation may be raised. It is important that methodological challenges are addressed, and researchers provide detailed examples of novel methods for discussion and empirical study. PATIENT AND PUBLIC CONTRIBUTION: We report a process which involved people with lived experience of emergency conditions and members of the public. A patient member was involved in the design and implementation, and two patients with lived experience contributed to the manuscript.

Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE: In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

Cost-effectiveness of alternative minimum recall intervals between whole blood donations.

BACKGROUND: The INTERVAL trial showed shorter inter-donation intervals could safely increase the frequency of whole-blood donation. We extended the INTERVAL trial to consider the relative cost-effectiveness of reduced inter-donation intervals. METHODS: Our within-trial cost-effectiveness analysis (CEA) used data from 44,863 whole-blood donors randomly assigned to 12, 10 or 8 week (males), and 16, 14 or 12 week inter-donation intervals (females). The CEA analysed the number of whole-blood donations, deferrals including low- haemoglobin deferrals, and donors' health-related quality of life (QoL) to report costs and cost-effectiveness over two years. FINDINGS: The mean number of blood donation visits over two years was higher for the reduced interval strategies, for males (7.76, 6.60 and 5.68 average donations in the 8-, 10- and 12- week arms) and for females (5.10, 4.60 and 4.01 donations in the 12-, 14- and 16- week arms). For males, the average rate of deferral for low haemoglobin per session attended, was 5.71% (8- week arm), 3.73% (10- week), and 2.55% (12- week), and for females the rates were: 7.92% (12-week), 6.63% (14- week), and 5.05% (16- week). Donors' QoL was similar across strategies, although self-reported symptoms were increased with shorter donation intervals. The shorter interval strategies increased average cost, with incremental cost-effectiveness ratios of £9.51 (95% CI 9.33 to 9.69) per additional whole-blood donation for the 8- versus 12- week interval for males, and £10.17 (95% CI 9.80 to 10.54) for the 12- versus 16- week interval arm for females. CONCLUSIONS: Over two years, reducing the minimum donation interval could provide additional units of whole-blood at a small additional cost, including for those donor subgroups whose blood type is in relatively high demand. However, the significance of self-reported symptoms needs to be investigated further before these policies are expanded.

Impact of the first wave of COVID-19 on outcomes following emergency admissions for common acute surgical conditions: analysis of a national database in England.

BACKGROUND: This study assessed the impact of the first COVID-19 wave in England on outcomes for acute appendicitis, gallstone disease, intestinal obstruction, diverticular disease, and abdominal wall hernia. METHODS: Emergency surgical admissions for patients aged 18 years and older to 124 NHS Trust hospitals between January and June in 2019 and 2020 were extracted from Hospital Episode Statistics. The risk of 90-day mortality after admission during weeks 11-19 in 2020 (national lockdown) and 2019 (pre-COVID-19) was estimated using multilevel logistic regression with case-mix adjustment. The primary outcome was all-cause mortality at 90 days. RESULTS: There were 12 231 emergency admissions and 564 deaths within 90 days during weeks 11-19 in 2020, compared with 18 428 admissions and 542 deaths in the same interval in 2019. Overall, 90-day mortality was higher in 2020 versus 2019, with an adjusted OR of 1.95 (95 per cent c.i. 0.78 to 4.89) for appendicitis, 2.66 (1.81 to 3.92) for gallstone disease, 1.99 (1.44 to 2.74) for diverticular disease, 1.70 (1.13 to 2.55) for hernia, and 1.22 (1.01 to 1.47) for intestinal obstruction. After emergency surgery, 90-day mortality was higher in 2020 versus 2019 for gallstone disease (OR 3.37, 1.26 to 9.02), diverticular disease (OR 2.35, 1.16 to 4.73), and hernia (OR 2.34, 1.23 to 4.45). For intestinal obstruction, the corresponding OR was 0.91 (0.59 to 1.41). For admissions not leading to emergency surgery, mortality was higher in 2020 versus 2019 for gallstone disease (OR 2.55, 1.67 to 3.88), diverticular disease (1.90, 1.32 to 2.73), and intestinal obstruction (OR 1.30, 1.06 to 1.60). CONCLUSION: Emergency admission was reduced during the first lockdown in England and this was associated with higher 90-day mortality.

Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.

BACKGROUND: COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England. METHODS: We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region. FINDINGS: Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories. INTERPRETATION: Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination. FUNDING: Medical Research Council.

Factors associated with COVID-19-related death using OpenSAFELY.

Coronavirus disease 2019 (COVID-19) has rapidly affected mortality worldwide1. There is unprecedented urgency to understand who is most at risk of severe outcomes, and this requires new approaches for the timely analysis of large datasets. Working on behalf of NHS England, we created OpenSAFELY-a secure health analytics platform that covers 40% of all patients in England and holds patient data within the existing data centre of a major vendor of primary care electronic health records. Here we used OpenSAFELY to examine factors associated with COVID-19-related death. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59 (95% confidence interval 1.53-1.65)); greater age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people of white ethnicity, Black and South Asian people were at higher risk, even after adjustment for other factors (HR 1.48 (1.29-1.69) and 1.45 (1.32-1.58), respectively). We have quantified a range of clinical factors associated with COVID-19-related death in one of the largest cohort studies on this topic so far. More patient records are rapidly being added to OpenSAFELY, we will update and extend our results regularly.