METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important).
RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively).
CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.
OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD.
METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019).
RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT.
CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.
STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.
SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urine or plasma NGAL measured on clinical laboratory platforms.
SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.
DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by providing authors data specifications tailored to their studies and requesting standardized patient-level data analysis.
ANALYTICAL APPROACH: Individual-study-data meta-analysis utilized a bivariate time-to-event model for interval-censored data from which discriminative ability (area under the receiver operating characteristic curve (AUC)) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, as well as optimal sensitivity and specificity were also estimated. Models incorporated as confounders clinical setting and use versus non-use of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those studies for which the authors were unable to provide individual study data analyses.
RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 datasets for the individual-study-data meta-analysis with 837 AKI events, 304 severe AKI events, and 103 severe AKI-D events for analyses of urine NGAL and 705 AKI events, 271 severe AKI events, and 178 AKI-D events for analyses of plasma NGAL. Discriminative performance was similar in individual-study-data meta-analysis and literature-based meta-analysis. Individual-study-data meta-analysis AUCs for uNGAL were 0.75 (95% CI 0.73-0.76) and 0.80 (0.79-0.81) for severe AKI and AKI-D, respectively; for pNGAL, the corresponding values were 0.80 (0.79-0.81) and 0.86 (0.84-0.86). Cut-off-concentrations at 95% specificity for uNGAL were >580 ng/mL with 27% sensitivity for severe AKI and >589 ng/mL with 24% sensitivity for AKI-D. Corresponding cut-offs for pNGAL were >364 ng/mL with 44% sensitivity and >546 ng/mL with 26% sensitivity, respectively.
LIMITATIONS: Practice variability on initiation of acute dialysis. Imperfect harmonization of data across studies.
CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The reported cut-off concentrations in this study require prospective evaluation.