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.

Plasma transfusion practices: A multicentre electronic audit.

BACKGROUND AND OBJECTIVES: Plasma is often transfused to patients with bleeding or requiring invasive procedures and with abnormal tests of coagulation. Chart audits find half of plasma transfusions unnecessary, resulting in avoidable complications and costs. This multicentre electronic audit was conducted to determine the proportion of plasma transfused without an indication and/or at a sub-therapeutic dose. METHODS: Data were extracted on adult inpatients in 2017 at five academic sites from the hospital electronic chart, laboratory information systems and the Canadian Institute for Health Information Discharge Abstract Database. Electronic criteria for plasma transfusion outside recommended indications were: (1) international normalized ratio (INR) < 1.5 with no to moderate bleeding; (2) INR ≥ 1.5, with no to mild bleeding and no planned procedures; and (3) no INR before or after plasma infusion. Sub-therapeutic dose was defined as ≤2 units transfused. RESULTS: In 1 year, 2590 patients received 6088 plasma transfusions encompassing 11,490 units of plasma occurred at the five sites. 77.7% of events were either outside indications or under-dosed. Of these, 34.8% of plasma orders had no indication identified, and 62% of these occurred in non-bleeding patients and no planned procedure with an isolated elevated INR. 70.7% of transfusions were under-dosed. Most plasma transfusions occurred in the intensive care unit or the operating room. Inter-hospital variability in peri-transfusion testing and dosing was observed. CONCLUSION: The majority of plasma transfusions are sub-optimal. Local hospital culture may be an important driver. Electronic audits, with definitions employed in this study, may be a practical alternative to costly chart audits.

A prospective multi-faceted interventional study of blood bank technologist screening of red blood cell transfusion orders: The START study.

BACKGROUND: Transfusion of red blood cells (RBC) is a common procedure, which when prescribed inappropriately can result in adverse patient outcomes. This study sought to determine the impact of a multi-faceted intervention on unnecessary RBC transfusions at hospitals with a baseline appropriateness below 90%. STUDY DESIGN AND METHODS: A prospective medical chart audit of RBC transfusions was conducted across 15 hospitals. For each site, 10 RBCs per month transfused to inpatients were audited for a 5-month pre- and 10-month post-intervention period, with each transfusion adjudicated for appropriateness based on pre-set criteria. Hospitals with appropriateness rates below 90% underwent a 3-month intervention which included: adoption of standardized RBC guidelines, staff education, and prospective transfusion order screening by blood bank technologists. Proportions of RBC transfusions adjudicated as appropriate and the total number of RBC units transfused per month in the pre- and post-intervention period were examined. RESULTS: Over the 15-month audit period, at the 13 hospital sites with a baseline appropriateness below 90%, 1950 patients were audited of which 81.2% were adjudicated as appropriate. Proportions of appropriateness and single-unit orders increased from 73.5% to 85% and 46.2% to 68.2%, respectively from pre- to post-intervention (P < .0001). Pre- and post-transfusion hemoglobin levels and the total number of RBCs transfused decreased from baseline (P < .05). The median pre-transfusion hemoglobin decreased from a baseline of 72.0 g/L to 69.0 g/L in the post-intervention period (P < .0001). RBC transfusions per acute inpatient days decreased significantly in intervention hospitals, but not in control hospitals (P < .001). The intervention had no impact on patient length of stay, need for intensive care support, or in-hospital mortality. CONCLUSION: This multifaceted intervention demonstrated a marked improvement in RBC transfusion appropriateness and reduced overall RBC utilization without impacts on patient safety.

Parents' Perceptions of the Acceptability of Evidence-Based Interventions to Support Transition From Neonatal to Rehabilitation Services.

BACKGROUND: Parents of children born preterm with a disability often experience profound psychological distress with transition from neonatal to rehabilitation services. Four interventions were found effective to support parents throughout this critical transition period whereby parental stress can threaten the child's development. PURPOSE: To examine parents' perceptions of the acceptability of four evidence-based interventions to support their transition. METHODS: A quantitative design using survey methods was employed with 24 parents with experience in transition to rehabilitation services. Each participant rated the acceptability of the interventions using the Treatment Perception and Preference scale. Descriptive statistics and repeated measures analysis of variance were used for data analysis. RESULTS: Mean overall acceptability scores differed across the four interventions (p = .042); the difference was of moderate size (η2 = .11). Parents perceived psychoeducation and narrative therapy as most acceptable, followed by website consultation with healthcare providers and parent support program, then parent self-help program. CONCLUSIONS: Psychoeducation and narrative therapy should be accessible to parents experiencing transition from neonatal to rehabilitation services.

Construct validity of the family impact of assistive technology scale for augmentative and alternative communication.

The Family Impact of Assistive Technology Scale for Augmentative and Alternative Communication (FIATS-AAC) measures parent-reported functioning and factors that affect functioning in children who use AAC. The aim of the current study was to assess its construct validity. For the study, 47 parents of children with AAC needs completed the FIATS-AAC and two other parent-reported questionnaires: a child quality-of-life measure and a community participation measure. An interview was also conducted with a sub-set of six parents. The FIATS-AAC showed a significant correlation with the child quality-of-life measure, but no significant associations with the community participation measure. Interviews suggested some consistency between parents' perceptions of their child's communicative functioning after comparing their FIATS-AAC scores and interview responses. This study provides evidence for the emerging construct validity of the FIATS-AAC as a measure linked to psychosocial aspects of quality-of-life in children with AAC needs between the ages of 6- and 12-years.

Lean muscle volume of the thigh has a stronger relationship with muscle power than muscle strength in women with knee osteoarthritis.

BACKGROUND: Thigh lean muscle and intramuscular fat have been implicated in the impairment of physical function observed in people with knee osteoarthritis. We investigated the relationships of quadriceps and hamstrings intramuscular fat fraction and lean muscle volume with muscle power and strength, controlling for neuromuscular activation, and physical performance in women with knee OA. METHODS: Women (n=20) 55years or older with symptomatic, radiographic knee osteoarthritis underwent a 3.0T magnetic resonance imaging scan of the thigh of their most symptomatic knee. Axial fat-separated images were analyzed using software to quantify intramuscular fat and lean muscle volumes of the quadriceps and hamstrings. To quantify strength and power of the knee extensors and flexors, participants performed maximum voluntary isometric contraction and isotonic knee extensions and flexions, respectively. Electromyography of the quadriceps and hamstrings was measured. Participants also completed five physical performance tests. FINDINGS: Quadriceps and hamstrings lean muscle volumes were related to isotonic knee extensor (B=0.624; p=0.017) and flexor (B=1.518; p=0.032) power, but not knee extensor (B=0.001; p=0.615) or flexor (B=0.001; p=0.564) isometric strength. Intramuscular fat fractions were not related to isotonic knee extensor or flexor power, nor isometric strength. No relationships were found between intramuscular fat or lean muscle volume and physical performance. INTERPRETATION: Muscle power may be more sensitive than strength to lean muscle mass in women with knee osteoarthritis. Thigh lean muscle mass, but neither intramuscular nor intermuscular fat, is related to knee extensor and flexor power in women with knee osteoarthritis.

Sex disparities in systemic sclerosis-associated pulmonary arterial hypertension: a cohort study.

BACKGROUND: The impact of male sex as a determinant of health outcomes in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is controversial. The primary objective of this study was to evaluate the effect of sex on survival in patients with SSc-PAH. The secondary objectives were to evaluate the effect of sex on age of PAH diagnosis, time from SSc diagnosis to PAH diagnosis, and SSc disease manifestations. METHODS: Sex-based disparities were evaluated in a cohort of SSc-PAH patients with a primary outcome of time from PAH diagnosis to all-cause mortality. Secondary outcomes were differences in age of diagnosis, disease duration, and SSc manifestations. Survival differences were evaluated using Kaplan-Meier and Cox proportional hazard models. RESULTS: We identified 378 SSc-PAH (58 males, 320 females) patients, with a female:male ratio of 5.5:1. Males had a shorter mean ± standard deviation time from SSc diagnosis to PAH diagnosis (1.7 ± 14 versus 5.5 ± 14.2 years); shorter PAH duration (3.5 ± 3.1 versus 4.7 ± 4.2 years), increased frequency of renal crisis (19 % versus 8 %, relative risk (RR) 2.33, 95 %CI 1.22, 4.46), interstitial lung disease (67 % versus 48 %, RR 1.41, 95 %CI 1.14, 1.74), and diffuse subtype (40 % versus 22 %, RR 1.84, 95 %CI 1.26, 2.69). Males appeared to have decreased 1-, 2-, 3-, and 5-year survival (83.2 %, 68.7 %, 53.2 %, 45.6 %) compared to females (85.7 %, 75.7 %, 66.4 %, 57.4 %). However, there was no difference in mortality between sexes (HR 1.43 (95 %CI 0.97, 2.13). CONCLUSIONS: Sex disparities appear to exist in the frequency of PAH, time to PAH diagnosis, PAH disease duration and SSc disease burden. However, male sex does not independently impact SSc-PAH survival.

Psoriatic Arthritis Mutilans: Clinical and Radiographic Criteria. A Systematic Review.

OBJECTIVE: Research on psoriatic arthritis mutilans (PAM), the most severe form of psoriatic arthritis, is impeded by the lack of an accepted classification criteria. We performed a systematic review of the literature to identify and synthesize clinical and radiographic features associated with the definition of PAM. METHODS: A systematic literature search limited to human studies was conducted without language restriction. Abstracts were independently screened by 2 investigators and studies that reported information on patients with PAM were included. A standardized form was used to independently collect clinical and radiographic items defining PAM, patient's demographics, disease characteristics, and outcomes. RESULTS: There were 8570 citations searched to identify 112 articles for full review and 58 articles for data abstraction. We identified 8 definitions of PAM that were used in 283 subjects with a mean age ± SD at diagnosis of PsA of 33.9 ± 8.2 years. Disease manifestations (prevalence) included dactylitis (29-64%), enthesitis (29-32%), axial disease (14-27%), and nail lesions (47%). PAM definitions include 1 (n = 2 studies) or more (n = 14 studies) joints involving interphalangeal, metacarpophalangeal, or metatarsophalangeal joints. The most prevalent PAM clinical features were digital telescoping (34%), digital shortening (33%), and flail joints (22%). The most prevalent PAM radiographic items were bone resorption (41%), pencil-in-cup change (16%), total joint erosions (14%), ankylosis (21%), and subluxation (7%). CONCLUSION: We have identified 8 definitions of PAM, and synthesized the clinical and radiographic items that are important for the classification of PAM. We have established the groundwork for future development classification criteria for PAM.

Effectiveness of phosphodiesterase-5 inhibitor therapy for portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension is associated with significant morbidity and mortality. Phosphodiesterase-5 inhibitor therapy is efficacious in other causes of WHO group I pulmonary arterial hypertension. OBJECTIVE: To evaluate the efficacy and safety of phosphodiesterase-5 inhibitor therapy in patients with portopulmonary hypertension. METHODS: A single-centre retrospective cohort study that included patients with a diagnosis of portopulmonary hypertension was performed. The primary outcome was change in pulmonary vascular resistance after six months of phosphodiesterase-5 inhibitor therapy. A secondary evaluation investigated the effect on other hemodynamic measurements, 6 min walk distance, functional class, safety outcomes and survival. RESULTS: Of 1385 patients screened, 25 patients with portopulmonary hypertension were identified, of whom 20 received a phosphodiesterase-5 inhibitor. After six months, there was a significant decrease in pulmonary vascular resistance (-236 dyn • s • cm(-5) [95% CI -343 dyn • s • cm(-5) to -130 dyn • s • cm(-5)]; P<0.001), mean pulmonary artery pressure (-8.9 mmHg [95% CI -13.7 mmHg to -4.2 mmHg]; P=0.001) and an increase in Fick cardiac output (0.9 L/min [95% CI 0.1 L/min to 1.6 L/min]; P=0.02). There was no change in 6 min walk distance. The proportion of subjects with a WHO functional class III or IV was significantly reduced at six months compared with baseline (18% versus 61%; P=0.002). Safety outcomes did not reveal any adverse events. CONCLUSIONS: Phosphodiesterase-5 inhibitor therapy improved hemodynamics and functional class at six months in a cohort of patients with portopulmonary hypertension.