Improving imputation quality in Samoans through the integration of population-specific sequences into existing reference panels.

Genotype imputation is fundamental to association studies, and yet even gold standard panels like TOPMed are limited in the populations for which they yield good imputation. Specifically, Pacific Islanders are poorly represented in extant panels. To address this, we constructed an imputation reference panel using 1,285 Samoan individuals with whole-genome sequencing, combined with 1000 Genomes (1000G) samples, to create a reference panel that better represents Pacific Islander, specifically Samoan, genetic variation. We compared this panel to 1000G and TOPMed panels based on imputed variants using genotyping array data for 1,834 Samoan participants who were not part of the panels. The 1000G + 1285 Samoan panel yielded up to 2.25-2.76 times more well-imputed (r 2 ≥ 0.80) variants than TOPMed and 1000G. There was improved imputation accuracy across the minor allele frequency (MAF) spectrum, although it was more pronounced for variants with 0.01 ≤ MAF ≤ 0.05. Imputation accuracy (r 2 ) was greater for population-specific variants (high fixation index, F ST ) and those from larger haplotypes (high LD score). The gain in imputation accuracy over TOPMed was largest for small haplotypes (low LD score), reflecting the Samoan panel's ability to capture population-specific variation not well tagged by other panels. We also augmented the 1000G reference panel with varying numbers of Samoan samples and found that panels with 48 or more Samoans included outperformed TOPMed for all variants with MAF ≥ 0.001. This study identifies variants with improved imputation using population-specific reference panels and provides a framework for constructing other population-specific reference panels.

Measuring Performance on the ABCDEF Bundle During Interprofessional Rounds via a Nurse-Based Assessment Tool.

BACKGROUND: Nurse-led rounding checklists are a common strategy for facilitating evidence-based practice in the intensive care unit (ICU). To streamline checklist workflow, some ICUs have the nurse or another individual listen to the conversation and customize the checklist for each patient. Such customizations assume that individuals can reliably assess whether checklist items have been addressed. OBJECTIVE: To evaluate whether 1 critical care nurse can reliably assess checklist items on rounds. METHODS: Two nurses performed in-person observation of multidisciplinary ICU rounds. Using a standardized paper-based assessment tool, each nurse indicated whether 17 items related to the ABCDEF bundle were discussed during rounds. For each item, generalizability coefficients were used as a measure of reliability, with a single-rater value of 0.70 or greater considered sufficient to support its assessment by 1 nurse. RESULTS: The nurse observers assessed 118 patient discussions across 15 observation days. For 11 of 17 items (65%), the generalizability coefficient for a single rater met or exceeded the 0.70 threshold. The generalizability coefficients (95% CIs) of a single rater for key items were as follows: pain, 0.86 (0.74-0.97); delirium score, 0.74 (0.64-0.83); agitation score, 0.72 (0.33-1.00); spontaneous awakening trial, 0.67 (0.49-0.83); spontaneous breathing trial, 0.80 (0.70-0.89); mobility, 0.79 (0.69-0.87); and family (future/past) engagement, 0.82 (0.73-0.90). CONCLUSION: Using a paper-based assessment tool, a single trained critical care nurse can reliably assess the discussion of elements of the ABCDEF bundle during multidisciplinary rounds.