Childhood autoimmune hemolytic anemia: A scoping review.

BACKGROUND AND OBJECTIVE: Autoimmune hemolytic anemia (AIHA) is a rare but important cause of morbidity in pediatric hematology patients. Given its rarity, there is little high-quality evidence on which to base the investigation and management of pediatric AIHA. This scoping review aims to summarize the current evidence and highlight key gaps to inform future studies. METHODS: This review searched MEDLINE and the Cochrane CENTRAL Trials Register from 2000 to November 03, 2023. Experimental and observational studies reporting AIHA diagnostic criteria, laboratory workup, or treatment/management in populations with at least 20% of patients ≤18 years were included. RESULTS: Forty-three studies were included, with no randomized controlled trials identified. AIHA diagnostic criteria, diagnostic tests, and treatments were highly variable. First-line treatment approaches include corticosteroids, intravenous immunoglobulin, or both. Approaches to AIHA resistance to first-line therapy were widely variable between studies, but most commonly included rituximab and/or cyclosporine. CONCLUSIONS: We identify a heterogenous group of observational studies into this complex, immune-mediated disorder. Standardized definitions and classifications are needed to guide collaborative efforts needed to study this rare disease. The work done by the CEREVANCE group provides an important paradigm for future studies.

The response of Canada's clinical health research ecosystem to the COVID-19 pandemic.

BACKGROUND: The response of Canada's research community to the COVID-19 pandemic provides a unique opportunity to examine the country's clinical health research ecosystem. We sought to describe patterns of enrolment across Canadian Institutes of Health Research (CIHR)-funded studies on COVID-19. METHODS: We identified COVID-19 studies funded by the CIHR and that enrolled participants from Canadian acute care hospitals between January 2020 and April 2023. We collected information on study-and site-level variables from study leads, site investigators, and public domain sources. We described and evaluated factors associated with cumulative enrolment. RESULTS: We obtained information for 23 out of 26 (88%) eligible CIHR-funded studies (16 randomized controlled trials [RCTs] and 7 cohort studies). The 23 studies were managed by 12 Canadian and 3 international coordinating centres. Of 419 Canadian hospitals, 97 (23%) enrolled a total of 28 973 participants - 3876 in RCTs across 78 hospitals (median cumulative enrolment per hospital 30, interquartile range [IQR] 10-61), and 25 097 in cohort studies across 62 hospitals (median cumulative enrolment per hospital 158, IQR 6-348). Of 78 hospitals recruiting participants in RCTs, 13 (17%) enrolled 50% of all RCT participants, whereas 6 of 62 hospitals (9.7%) recruited 54% of participants in cohort studies. INTERPRETATION: A minority of Canadian hospitals enrolled the majority of participants in CIHR-funded studies on COVID-19. This analysis sheds light on the Canadian health research ecosystem and provides information for multiple key partners to consider ways to realize the full research potential of Canada's health systems.

Effectiveness of dexmedetomidine on patient-centred outcomes in surgical patients: a systematic review and Bayesian meta-analysis.

BACKGROUND: Dexmedetomidine is increasingly used for surgical patients requiring general anaesthesia. However, its effectiveness on patient-centred outcomes remains uncertain. Our main objective was to evaluate the patient-centred effectiveness of intraoperative dexmedetomidine for adult patients requiring surgery under general anaesthesia. METHODS: We conducted a systematic search of MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to October 2023. Randomised controlled trials (RCTs) comparing intraoperative use of dexmedetomidine with placebo, opioid, or usual care in adult patients requiring surgery under general anaesthesia were included. Study selection, data extraction, and risk of bias assessment were performed by two reviewers independently. We synthesised data using a random-effects Bayesian regression framework to derive effect estimates and the probability of a clinically important effect. For continuous outcomes, we pooled instruments with similar constructs using standardised mean differences (SMDs) and converted SMDs and credible intervals (CrIs) to their original scale when appropriate. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our primary outcome was quality of recovery after surgery. To guide interpretation on the original scale, the Quality of Recovery-15 (QoR-15) instrument was used (range 0-150 points, minimally important difference [MID] of 6 points). RESULTS: We identified 49,069 citations, from which 44 RCTs involving 5904 participants were eligible. Intraoperative dexmedetomidine administration was associated with improvement in postoperative QoR-15 (mean difference 9, 95% CrI 4-14, n=21 RCTs, moderate certainty of evidence). We found 99% probability of any benefit and 88% probability of achieving the MID. There was a reduction in chronic pain incidence (odds ratio [OR] 0.42, 95% CrI 0.19-0.79, n=7 RCTs, low certainty of evidence). There was also increased risk of clinically significant hypotension (OR 1.98, 95% CrI 0.84-3.92, posterior probability of harm 94%, n=8 RCTs) and clinically significant bradycardia (OR 1.74, 95% CrI 0.93-3.34, posterior probability of harm 95%, n=10 RCTs), with very low certainty of evidence for both. There was limited evidence to inform other secondary patient-centred outcomes. CONCLUSIONS: Compared with placebo or standard of care, intraoperative dexmedetomidine likely results in meaningful improvement in the quality of recovery and chronic pain after surgery. However, it might increase clinically important bradycardia and hypotension. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023439896).

Impact of Legal Guardian Absence on Research Enrollment in the PICU.

OBJECTIVES: To identify the frequency of which a legal guardian is at the bedside of children admitted to the PICU that are eligible for research studies. DESIGN: A prospective, observational study. SETTING: Three tertiary Canadian PICUs. PATIENTS: Two hundred one patients were admitted to the PICU between September 2021 and March 2023 (site 1), from March 2019 to March 2020 and March 2022 to March 2023 (site 2), and from March 2019 to March 2020 and July 2020 to November 2021 (site 3). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At each center, the duration of consent encounters was recorded for patients eligible for research by documenting the length of each attempt (min). The frequency of parental presence at bedside and the ability for a guardian to make a decision were also recorded. Thirty-five percent of patients eligible for research did not have a legal guardian at the bedside on the first attempted consent encounter. Twenty-three percent of approached patients were not enrolled due to an inability for a consent decision to be made by the child's legal guardian or an inability to contact the guardian before discharge. CONCLUSIONS: The absence of legal guardians in the PICU poses a barrier to the enrollment of critically ill children in pertinent research studies and suggests that a model of deferred consent or implied consent would aid in the future of critical care research.

Reporting of social determinants of health in randomized controlled trials conducted in the pediatric intensive care unit.

Introduction: The influence of social determinants of health (SDOH) on access to care and outcomes for critically ill children remains an understudied area with a paucity of high-quality data. Recent publications have highlighted the importance of incorporating SDOH considerations into research but the frequency with which this occurs in pediatric intensive care unit (PICU) research is unclear. Our objective was to determine the frequency and categories of SDOH variables reported and how these variables were defined in published PICU randomized controlled trials (RCTs). Methods: We searched Medline, Embase, Lilacs, and Central from inception to Dec 2022. Inclusion criteria were randomized controlled trials of any intervention on children or their families in a PICU. Data related to study demographics and nine WHO SDOH categories were extracted, and descriptive statistics and qualitative data generated. Results: 586 unique RCTs were included. Studies had a median sample size of 60 patients (IQR 40-106) with 73.0% of studies including ≤100 patients and 41.1% including ≤50 patients. A total of 181 (181/586, 30.9%) studies reported ≥1 SDOH variable of which 163 (163/586, 27.8%) reported them by randomization group. The most frequently reported categories were food insecurity (100/586, 17.1%) and social inclusion and non-discrimination (73/586, 12.5%). Twenty-five of 57 studies (43.9%) investigating feeding or nutrition and 11 of 82 (13.4%) assessing mechanical ventilation reported baseline nutritional assessments. Forty-one studies investigated interventions in children with asthma or bronchiolitis of which six reported on smoking in the home (6/41, 14.6%). Discussion: Reporting of relevant SDOH variables occurs infrequently in PICU RCTs. In addition, when available, categorizations and definitions of SDOH vary considerably between studies. Standardization of SDOH variable collection along with consistent minimal reporting requirements for PICU RCT publications is needed.

The Diversity of Research Participants in Randomized Controlled Trials and Observational Studies Conducted by the Canadian Critical Care Trials Group.

RATIONALE: Women, older individuals, and racial and ethnic minority groups are often underrepresented in research studies. OBJECTIVES: We evaluated the demographics and diversity of participants enrolled in randomized trials (RCTs) and observational studies published by investigators in association with the Canadian Critical Care Trials Group (CCCTG). METHODS: Quantitative content analysis of peer reviewed RCTs and observational studies from December 1994 to December 2022. For each publication, we extracted participant demographic variables, including sex/gender, age, race or ethnicity, sexual orientation, pregnancy status, language proficiency, income/financial status, housing, education, disability, and geography. RESULTS: 120 publications (28 RCTs, 92 observational studies) enrolled 211,144 participants. Most (107/120, 89.2%) were multicenter studies, and 70% (84/120) were conducted exclusively in Canadian centers; 77.5% (93/120) studies enrolled adult participants, and 19.2% (23/120) enrolled pediatric participants. All studies reported participant mean or median age, 118 (98.3%) reported binary sex or gender, and 9 (7.5%) reported race or ethnicity. No justification was provided in 35 studies which listed pregnancy as an exclusion. There was infrequent reporting of housing (N=4), employment (N=2), income (N=2), and education (N=1). No studies reported language proficiency, sexual orientation, disability or geography of participants. Of the studies reporting gender, women/girls comprised 42.3% participants (range 8.9 to 67.7%). Within 9 studies reporting race or ethnicity of 2950 participants, 59.7% were white, 8% South Asian, 7% Indigenous, 3% Asian, 1% Black, 14% unknown, and 6% 'Other'. CONCLUSIONS: Research publications from the CCCTG infrequently report important participant demographics, and diversity of research participants is disproportionate compared to Canadian societal demographics.

Measuring continuing medical education conference impact and attendee experience: a scoping review.

Objectives: The aim was to comprehensively identify published research evaluating continuing medical education conferences, to search for validated tools and perform a content analysis to identify the relevant domains for conference evaluation. Methods: We used scoping review methodology and searched MEDLINE® for relevant English or French literature published between 2008 and 2022 (last search June 3, 2022). Original research (including randomized controlled trials, non-randomized studies, cohort, mixed-methods, qualitative studies, and editorial pieces) where investigators described impact, experience, or motivations related to conference attendance were eligible. Citations were assessed in triplicate, and data extracted in duplicate. Results: Eighty-three studies were included, 69 (83%) of which were surveys or interview based, with the majority conducted at the end of or following conference conclusion. Of the 74 tools identified, only one was validated and was narrowly focused on a specific conference component. A total of 620 items were extracted and categorized into 4 a priori suggested domains (engagement-networking, education-learning, impact, scholarship), and an additional 4 identified through content analysis (value-satisfaction, logistics, equity-diversity-inclusivity, career influences). Time trends were evident, including the absence of items related to equity-diversity-inclusivity prior to 2019, and a focus on logistics, particularly technology and virtual conferences, since 2020. Conclusions: This study identified 8 major domains relevant for continuing medical education conference evaluation. This work is of immediate value to individuals and organizations seeking to either design or evaluate a conference and represents a critical step in the development of a standardized tool for conference evaluation.

Core socioDemographic data variables in ICU Trials (CoDe-IT): a protocol for generating core data variables using a Delphi consensus process.

INTRODUCTION: Sociodemographic variables influence health outcomes, either directly (ie, gender identity) or indirectly (eg, structural/systemic racism based on ethnoracial group). Identification of how sociodemographic variables can impact the health of critically ill adults is important to guide care and research design for this population. However, despite the growing recognition of the importance of collecting sociodemographic measures that influence health outcomes, insufficient and inconsistent data collection of sociodemographic variables persists in critical care studies. We aim to develop a set of core data variables (CoDaV) for social determinants of health specific to studies involving critically ill adults. METHODS AND ANALYSIS: We will conduct a scoping review to generate a list of possible sociodemographic measures to be used for round 1 of the modified Delphi processes. We will engage relevant knowledge users (previous intensive care unit patients and family members, critical care researchers, critical care clinicians and research co-ordinators) to participate in the modified Delphi consensus survey to identify the CoDaV. A final consensus meeting will be held with knowledge user representatives to discuss the final CoDaV, how each sociodemographic variable will be collected (eg, level of granularity) and how to disseminate the CoDaV for use in critical care studies. ETHICS AND DISSEMINATION: The University of Calgary conjoint health research ethics board has approved this study protocol (REB22-1648).

Barriers, Solutions, and Opportunities for Adapting Critical Care Clinical Trials in the COVID-19 Pandemic.

Importance: The COVID-19 pandemic created unprecedented challenges for clinical trials worldwide, threatening premature closure and trial integrity. Every phase of research operations was affected, often requiring modifications to protocol design and implementation. Objectives: To identify the barriers, solutions, and opportunities associated with continuing critical care trials that were interrupted during the pandemic, and to generate suggestions for future trials. Design, Setting, and Participants: This mixed-methods study performed an explanatory sequential analysis involving a self-administered electronic survey and focus groups of principal investigators (PIs) and project coordinators (PCs) conducting adult and pediatric individual-patient randomized trials of the Canadian Critical Care Trials Group during the COVID-19 pandemic. Eligible trials were actively enrolling patients on March 11, 2020. Data were analyzed between September 2023 and January 2024. Main Outcomes and Measures: Importance ratings of barriers to trial conduct and completion, solutions employed, opportunities arising, and suggested strategies for future trials. Quantitative data examining barriers were analyzed using descriptive statistics. Data addressing solutions, opportunities, and suggestions were analyzed by qualitative content analysis. Integration involved triangulation of data sources and perspectives about 13 trials, synthesized by an interprofessional team incorporating reflexivity and member-checking. Results: A total of 13 trials run by 29 PIs and PCs (100% participation rate) were included. The highest-rated barriers (on a 5-point scale) to ongoing conduct during the pandemic were decisions to pause all clinical research (mean [SD] score, 4.7 [0.8]), focus on COVID-19 studies (mean [SD] score, 4.6 [0.8]), and restricted family presence in hospitals (mean [SD] score, 4.1 [0.8]). Suggestions to enable trial progress and completion included providing scientific leadership, implementing technology for communication and data management, facilitating the informed consent process, adapting the protocol as necessary, fostering site engagement, initiating new sites, streamlining ethics and contract review, and designing nested studies. The pandemic necessitated new funding opportunities to sustain trial enrollment. It increased public awareness of critical illness and the importance of randomized trial evidence. Conclusions and Relevance: While underscoring the vital role of research in society and drawing the scientific community together with a common purpose, the pandemic signaled the need for innovation to ensure the rigor and completion of ongoing trials. Lessons learned to optimize research procedures will help to ensure a vibrant clinical trials enterprise in the future.

"We Aren't Meant to Go Through the Hardest Parts of Our Lives Alone": Family Experience With Restricted PICU Presence During the COVID-19 Pandemic.

CONTEXT: PICUs across Canada restricted family presence (RFP) in response to the COVID-19 pandemic from allowing two or more family members to often only one family member at the bedside. The objective of this study was to describe the experiences and impact of RFP on families of critically ill children to inform future policy and practice. HYPOTHESIS: RFP policies negatively impacted families of PICU patients and caused moral distress. METHODS AND MODELS: National, cross-sectional, online, self-administered survey. Family members of children admitted to a Canadian PICU between March 2020 and February 2021 were invited to complete the survey. RFP-attributable distress was measured with a modified distress thermometer (0-10). Closed-ended questions were reported with descriptive statistics and multivariable linear regression assessed factors associated with RFP-attributable distress. Open-ended questions were analyzed using inductive content analysis. RESULTS: Of 250 respondents who experienced RFP, 124 (49.6%) were restricted to one family member at the bedside. The median amount of distress that families attributed to RFP policies was 6 (range: 0-10). Families described isolation, removal of supports, and perception of trauma related to RFP. Most families (183, 73.2%) felt that policies were enforced in a way that made them feel valued by PICU clinicians, which was associated with less RFP-attributable distress. Differential impact was seen where families with lower household income indicated higher RFP-attributable distress score (2.35; 95% CI, 0.53-4.17; p = 0.03). Most respondents suggested that future policies should allow at least two family members at the bedside. INTERPRETATIONS AND CONCLUSIONS: Families of children admitted to PICUs during the COVID-19 pandemic described increased distress, trauma, and removal of supports due to RFP policies. Vulnerable families showed an increased odds of higher distress. Healthcare professionals played an important role in mitigating distress. Allowance of at least two family members at the bedside should be considered for future policy.