Lessons learned from the CONCOR-1 trial.

Faced with an evolving pandemic and a lack of clarity of the role of convalescent plasma for patients with COVID-19, the CONCOR-1 trial was launched. In 14 months the trial was designed, launched, completed, and submitted for publication. In total, 72 sites in three countries served by four blood suppliers randomised 940 patients. Many enablers facilitated the trial including: three study principal investigators to distribute the trial workload, diverse steering committee members, an international data safety monitoring committee, multiple statisticians and methodologists, virtual meeting platforms, REDCap data platform, pausing of non-COVID-19 trials, rapid approval pathways for institutional review boards and regulators, centralised institutional review boards in many locations, restriction of use of convalescent plasma to trial participants and the incredible dedication by research personnel. In future pandemics, we need to be prepared for rapid launch of trials. The protocols, consent forms, data collection tools, and procedures need to be in draft form ready for use at all times. We were well-prepared for blood shortages but should have anticipated the need to conduct trials with convalescent plasma. In this short article, we detail our lessons learned to inform researchers faced with the next pandemic pathogen.

A national survey of children's experiences and needs when attending Canadian pediatric emergency departments.

BACKGROUND: Optimizing a child's emergency department (ED) experience positively impacts their memories and future healthcare interactions. Our objectives were to describe children's perspectives of their needs and experiences during their ED visit and relate this to their understanding of their condition. METHODS: 514 children, aged 7-17 years, and their caregivers presenting to 10 Canadian pediatric EDs completed a descriptive cross-sectional survey from 2018-2020. RESULTS: Median child age was 12.0 years (IQR 9.0-14.0); 56.5% (290/513) were female. 78.8% (398/505) reported adequate privacy during healthcare conversations and 78.3% (395/504) during examination. 69.5% (348/501) understood their diagnosis, 89.4% (355/397) the rationale for performed tests, and 67.2% (338/503) their treatment plan. Children felt well taken care of by nurses (90.9%, 457/503) and doctors (90.8%, 444/489). Overall, 94.8% (475/501) of children were happy with their ED visit. Predictors of a child better understanding their diagnosis included doctors talking directly to them (OR 2.21 [1.15, 4.28]), having someone answer questions and worries (OR 2.51 [1.26, 5.01]), and older age (OR 1.08 [1.01, 1.16]). Direct communication with a doctor (OR 2.08 [1.09, 3.99]) was associated with children better understanding their treatment, while greater fear/ 'being scared' at baseline (OR 0.59 [0.39, 0.89]) or at discharge (OR 0.46 [0.22, 0.96]) had the opposite effect. INTERPRETATION: While almost all children felt well taken care of and were happy with their visit, close to 1/3 did not understand their diagnosis or its management. Children's reported satisfaction in the ED should not be equated with understanding of their medical condition. Further, caution should be employed in using caregiver satisfaction as a proxy for children's satisfaction with their ED visit, as caregiver satisfaction is highly linked to having their own needs being met.

Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial.

BACKGROUND: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection. METHODS: CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600). DISCUSSION: This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification. TRIAL REGISTRATION: Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.

Comparison of the psychometric properties of 3 pain scales used in the pediatric emergency department: Visual Analogue Scale, Faces Pain Scale-Revised, and Colour Analogue Scale.

Appropriate pain measurement relies on the use of valid, reliable tools. The aim of this study was to determine and compare the psychometric properties of 3 self-reported pain scales commonly used in the pediatric emergency department (ED). The inclusion criteria were children aged 6 to 17 years presenting to the ED with a musculoskeletal injury and self-reported pain scores ≥30 mm on the mechanical Visual Analogue Scale (VAS). Self-reported pain intensity was assessed using the mechanical VAS, Faces Pain Scale-Revised (FPS-R), and Colour Analogue Scale (CAS). Convergent validity was assessed by Pearson correlations and the Bland-Altman method; responsiveness to change was assessed using paired sample t tests and standardized mean responses; and reliability was estimated using relative and absolute indices. A total of 456 participants were included, with a mean age of 11.9 years ± 2.7 and a majority were boys (252/456, 55.3%). Correlations between each pair of scales were 0.78 (VAS/FPS-R), 0.92 (VAS/CAS), and 0.79 (CAS/FPS-R). Limits of agreement (95% confidence interval) were -3.77 to 2.33 (VAS/FPS-R), -1.74 to 1.75 (VAS/CAS), and -2.21 to 3.62 (CAS/FPS-R). Responsiveness to change was demonstrated by significant differences in mean pain scores among the scales (P < 0.0001). Intraclass correlation coefficient and coefficient of repeatability estimates suggested acceptable reliability for the 3 scales at, respectively, 0.79 and ±2.29 (VAS), 0.82 and ±2.07 (CAS), and 0.76 and ±2.82 (FPS-R). The scales demonstrated good psychometric properties for children with acute pain in the ED. The VAS and CAS showed a strong convergent validity, whereas FPS-R was not in agreement with the other scales.

Oral Analgesics Utilization for Children With Musculoskeletal Injury (OUCH Trial): An RCT.

BACKGROUND: Musculoskeletal injuries (MSK-Is) are a common and painful condition among children that remains poorly treated in the emergency department (ED). We aimed to test the efficacy of a combination of an anti-inflammatory drug with an opioid for pain management of MSK-I in children presenting to the ED. METHODS: In this randomized, double-blinded, placebo-controlled trial, we enrolled children between 6 and 17 years presenting to the ED with an MSK-I and a pain score >29 mm on the visual analog scale (VAS). Participants were randomly assigned to oral morphine (0.2 mg/kg) + ibuprofen (10 mg/kg) (morphine + ibuprofen) or morphine (0.2 mg/kg) + placebo of ibuprofen or ibuprofen (10 mg/kg) + placebo of morphine. Primary outcome was children with VAS pain score <30 mm at 60 minutes postmedication administration. RESULTS: A total of 501 participants were enrolled and 456 were included in primary analyses (morphine + ibuprofen = 177; morphine = 188; ibuprofen = 91). Only 29.9% (morphine + ibuprofen), 29.3% (morphine), and 33.0% (ibuprofen) of participants achieved the primary outcome (P = .81). Mean VAS pain reduction at 60 minutes were -18.7 (95% confidence interval [CI]: -21.9 to -16.6) (morphine + ibuprofen), -17.0 (95% CI: -20.0 to -13.9) (morphine), -18.6 (95% CI: -22.9 to -14.2) (ibuprofen) (P = .69). Children in the morphine + ibuprofen group (P < .001) and in the morphine group (P < .001) experienced more side effects than those in the ibuprofen group. No serious adverse event was reported. CONCLUSIONS: Combination of morphine with ibuprofen did not provide adequate pain relief for children with MSK-I in the ED. None of the study medication provided an optimal pain management because most of children did not reach a mild pain score (NCT02064894).