Gastroschisis: Impact of Bedside Closure on Ventilator-Associated Outcomes

Aim In our practice, preformed silos are routine rather than reserved for difficult cases. We aimed to identify whether silo and bedside closure can minimize: general anesthetic (GA) exposure, need for intubation and ventilation, or days intubated for neonates with simple gastroschisis (SG). Methods After approval, patients were identified via the neonatal discharge log (April 2010 to April 2019). Data were collected by case-note review and analyzed with respect to GA, ventilation, and core outcomes. Results Of 104 patients (50 female, mean birth weight 2.43 kg, mean gestational age 36 + 2 weeks), 85 were SG and 19 complex. Silo application was initial management in 70 SG, 57 completed successful bedside closure (by day 4 of life—median). Fifteen SG had initial operative closure.Of the 70 SG managed with silo, 46 (66%) had no GA as neonates. Twelve required GA for line insertion. Thirteen patients with initial silo had closure in theater (7 opportunistic at time of GA for line). Nine required intubation and ventilation out-with the operating theater during neonatal management. Seven had already been intubated at delivery; 3 because of meconium aspiration.One-hundred percent of those treated with operative closure had GA, 1 patient subsequently required surgery for subglottic stenosis. Time to full feeds did not differ between groups. Conclusion Silo and bedside closure allow the majority of SG neonates to avoid GA or intubation in the neonatal period, without increased risk of complication. However, it is important that the nursing expertise required to manage these patients safely is not underestimated.

A Core Outcome Set for Trials in Glomerular Disease

Background and objectivesOutcomes reported in trials in adults with glomerular disease are often selected with minimal patient input, are heterogeneous, and may not be relevant for clinical decision making. The Standardized Outcomes in Nephrology–Glomerular Disease (SONG-GD) initiative aimed to establish a core outcome set to help ensure that outcomes of critical importance to patients, care partners, and clinicians are consistently reported.Design, setting, participants, and measurementsWe convened two 1.5-hour workshops in Melbourne, Australia, and Washington, DC, United States. Attendees were identified purposively with 50 patients/care partners and 88 health professionals from 19 countries; 51% were female. Patients and care partners were from the United States, Australia, and Canada, and had experience of a glomerular disease with systemic features (n=9), kidney-limited nephrotic disease (n=9), or other kidney-limited glomerular disease (n=8). Attendees reviewed the results of the SONG-GD Delphi survey and aims of the workshop and then discussed potential core outcomes and their implementation in trials among moderated breakout groups of eight to 12 people from diverse backgrounds. Transcripts of discussions were analyzed thematically.ResultsThree themes were identified that supported the proposed core outcomes: limiting disease progression, stability and control, and ensuring universal relevance (i.e., applicable across diverse populations and settings). The fourth theme, preparedness for implementation, included engaging with funders and regulators, establishing reliable and validated measures, and leveraging existing endorsements for patient-reported outcomes.ConclusionsWorkshop themes demonstrated support for kidney function, disease activity, death, life participation, and cardiovascular disease, and these were established as the core outcomes for trials in adults with glomerular disease. Future work is needed to establish the core measures for each domain, with funders and regulators central to the uptake of the core outcome set in trials.

A protocol for developing a core outcome set for ectopic pregnancy

Background Randomised controlled trials (RCTs) evaluating ectopic pregnancy have reported many different outcomes, which are themselves often defined and measured in distinct ways. This level of variation results in an inability to compare results of individual RCTs. The development of a core outcome set to ensure outcomes important to key stakeholders are collected consistently will guide future research in ectopic pregnancy. Study aim To develop and implement a core outcome set to guide future research in ectopic pregnancy. Methods and analysis We have established an international steering group of key stakeholders, including healthcare professionals, researchers, and individuals with lived experience of ectopic pregnancy. We will identify potential outcomes from ectopic pregnancy from a comprehensive literature review of published randomised controlled trials. We will then utilise a modified Delphi method to prioritise outcomes. Subsequently, key stakeholders will be invited to score potential core outcomes on a nine-point Likert scale, ranging from 1 (not important) to 9 (critical). Repeated reflection and rescoring should promote whole and individual stakeholder group convergence towards consensus ‘core’ outcomes. We will also establish standardised definitions and recommend high-quality measurements for individual core outcomes. Trial registration COMET 1492. Registered in November 2019.

1477The landscape of COVID-19 trials in Australia

Background The coronavirus disease 2019 (COVID-19) pandemic has seen a large number of clinical trials launched at unprecedented speed. We aimed to explore the landscape of COVID-19 trials in Australia, and to what extent Australian researchers have responded to global need for coordination and collaboration. Methods We systematically searched the Australian New Zealand Clinical Trials Registry (ANZCTR) and ClinicalTrials.gov from 1st January to 16th November 2020. We included all interventional studies addressing prevention, diagnosis or treatment of COVID-19, recruiting in Australia. We analysed the number and size of trials, additional recruitment countries, funding, trial purpose, study design, data sharing plans, and collection of COVID-19 core outcomes. Results We identified 56 COVID-19 trials, targeting 33,757 participants. They evaluated drugs (n = 34, 61%), vaccines (n = 10, 18%) or other interventions (n = 12, 21%), e.g. ventilators, digital health. Median target sample size was 150 (Q1-Q3=33-395). Only two trials utilised adaptive methods (Bayesian designs), and of the 34 COVID-19 treatment trials, only one included all core outcomes. Most (80%) indicated they were not planning to share data. Conclusions There has been impressive research scale-up and innovation in drug development and digital health, but fast-track procedures may have impacted scientific rigor and research prioritisation. Trials often lacked innovative study designs, were underpowered for clinical outcomes, collected limited core outcomes and did not intend to share data, precluding future evidence synthesis. Key messages The research response in Australia has been rapid, but better coordination is required. Infrastructure for innovation would support coordination of research efforts, and reduce research waste.

Systematic review on outcomes used in clinical research on autosomal recessive polycystic kidney disease—are patient-centered outcomes our blind spot?

Background Autosomal recessive polycystic kidney disease (ARPKD) is a rare severe hepatorenal disease. Survivors of pulmonary hypoplasia and patients with milder presentations often achieve long-term survival but frequently require kidney and/or liver transplantation. Objective To examine the use of clinical, surrogate and patient-centered outcomes in studies on ARPKD with special attention to core outcomes of the Standardized Outcomes in NephroloGy project for children with chronic kidney disease (SONG-Kids). Data sources and study eligibility criteria A systematic MEDLINE literature search identified 367 ARPKD studies published since 1990; however, of these 134 were excluded because they did not report any clinical outcomes (e.g. only histopathological, genetic, protein structure or radiological markers), 19 studies because they only included prenatal patients and 138 because they were case reports with ≤ 3 patients. Study appraisal Seventy-six eligible studies were examined for study type, size, intervention, and reported outcomes by organ system and type, including all SONG-kids tier 1–3 outcomes. Participants There were 3231 patient-reports of children and adults with ARPKD. Results The overwhelming majority of studies reported clinical and surrogate outcomes (75/76 (98%) and 73/76 (96%)), but only 11/76 (14%) examined patient-centered outcomes and only 2/76 (3%) used validated instruments to capture them. Of the SONG-Kids core outcomes, kidney function was reported almost universally (70/76 (92%), infection and survival in three quarters (57/76 (75%), 55/76 (72%)) and measures of life participation (including neurological impairment) only rarely and inconsistently (16/76 (21%)). Limitations Thirty studies (39%) were of low quality as they were either narrative case reports (n = 14, 18%) and/or patients with ARPKD were an indistinguishable subgroup (n = 18, 24%). Only 28 trials compared interventions, but none were randomized. Conclusions and implications Studies that reported clinical outcomes in ARPKD usually covered the core outcome domains of kidney function, infections, and survival, but measures of life participation and patient-centered outcomes are distinctly lacking and require more attention in future trials. Graphical abstract

Representation of published core outcome sets for research in regulatory guidance: protocol

Background: The COMET Initiative promotes the development and use of ‘core outcome sets’ (COS), agreed standardised sets of outcomes that should be measured and reported in all studies in a particular clinical condition. COS are determined by consensus amongst key stakeholders, including health professionals, policymakers and patients, ensuring that the priorities and expertise of these representatives inform the choice of the most important outcomes to measure for a given condition. There is increased recognition of the need to integrate COS across the healthcare system and with existing regulatory apparatus, to ensure that outcomes being recorded are those of key relevance to important stakeholders. The aim of this study is to assess the degree of concordance between outcomes recommended in COS for research and in guidance provided by two key regulators: US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Methods: COS for research published during 2015-2019 with patient involvement and covering drug or device interventions will be compared against relevant regulatory guidelines, matched by condition. Guidance documents matching in scope (relating to intervention and population) to a COS for research will be scrutinised to identify all suggested outcomes for comparison against the core outcomes in the corresponding COS. Discussion: This study will identify variation between outcomes suggested in FDA and EMA regulatory guidance relative to outcomes included in published COS for research, thus demonstrating the degree of representation of COS in regulatory guidance and vice versa. We will share the study findings (in particular, highlighting any lack of concordance between COS and regulatory guidance overall or for particular disease areas) and will invite feedback from FDA and EMA; we will seek to highlight where findings support the recommendations towards using well-developed COS or will make recommendations to COS developers on outcomes of importance to these key regulators.

Researchers’ perspectives on methodological challenges and outcomes selection in interventional studies targeting medication adherence in rheumatic diseases: an OMERACT-adherence study

Background Research on adherence interventions in rheumatology is limited by methodological issues, particularly heterogeneous outcomes. We aimed to describe researchers’ experiences with conducting interventional studies targeting medication adherence in rheumatology and their perspectives on establishing core outcomes. Methods Semi-structured interviews using audio conference were conducted with researchers who had conducted an adherence study of any design in the past 10 years. Data collection and thematic analysis were performed iteratively, until saturation. Results We interviewed 13 researchers, most of whom worked in academia and specialized in epidemiology and/or health services research. We identified three themes: 1) improving measurement of adherence (considering all phases of adherence, using appropriate and relevant measures, and establishing clinically meaningful thresholds); 2) challenges in designing and appraising adherence intervention studies (considering the confusion over a plethora of outcomes, difficulties with powering studies to demonstrate meaningful changes, and suboptimal descriptions of adherence interventions in published studies); and 3) advancing outcome assessment in adherence intervention studies (capturing rationale for developing a core domain set as well as recommendations and anticipated challenges by participants). Conclusions Uniquely gathering perspectives from international adherence researchers, our findings led to researcher-informed recommendations for improving adherence research including specifying the targeted adherence phase in designing interventions and studies and providing a glossary of terms to promote consistency in reporting. We also identified recommendations for developing a core domain set for interventional studies targeting medication adherence including involvement of patients, clinicians, and other stakeholders and methodological and practical considerations to establish rigor and support uptake.