The second Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT2) study was a randomized, controlled trial of rapid whole-genome sequencing (rWGS) or rapid whole-exome sequencing (rWES) in infants with diseases of unknown etiology in intensive care units (ICUs). Gravely ill infants were not randomized and received ultra-rapid whole-genome sequencing (urWGS). Herein we report results of clinician surveys of the clinical utility of rapid genomic sequencing (RGS). The primary end-point—clinician perception that RGS was useful— was met for 154 (77%) of 201 infants. Both positive and negative tests were rated as having clinical utility (42 of 45 [93%] and 112 of 156 [72%], respectively). Physicians reported that RGS changed clinical management in 57 (28%) infants, particularly in those receiving urWGS (p = 0.0001) and positive tests (p < 0.00001). Outcomes of 32 (15%) infants were perceived to be changed by RGS. Positive tests changed outcomes more frequently than negative tests (p < 0.00001). In logistic regression models, the likelihood that RGS was perceived as useful increased 6.7-fold when associated with changes in management (95% CI 1.8–43.3). Changes in management were 10.1-fold more likely when results were positive (95% CI 4.7–22.4) and turnaround time was shorter (odds ratio 0.92, 95% CI 0.85–0.99). RGS seldom led to clinician-perceived confusion or distress among families (6 of 207 [3%]). In summary, clinicians perceived high clinical utility and low likelihood of harm with first-tier RGS of infants in ICUs with diseases of unknown etiology. RGS was perceived as beneficial irrespective of whether results were positive or negative.

第二项新生儿基因组医学和公共卫生测序 (NSIGHT2) 研究是一项随机对照试验，对重症监护病房患有不明病因疾病的婴儿进行快速全基因组测序 (rWGS) 或快速全外显子组测序 (rWES)。重症监护室）。重症婴儿没有被随机分组​​并接受超快速全基因组测序（urWGS）。在此，我们报告临床医生对快速基因组测序 (RGS) 临床效用的调查结果。 201 名婴儿中有 154 名 (77%) 达到了主要终点——临床医生认为 RGS 有用。阳性和阴性测试均被评为具有临床实用性（分别为 45 项中的 42 项 [93%] 和 156 项中的 112 项 [72%]）。医生报告称，RGS 改变了 57 名 (28%) 婴儿的临床管理，特别是接受 urWGS (p = 0.0001) 和阳性检测 (p < 0.00001) 的婴儿。 32 名 (15%) 婴儿的结局被认为因 RGS 而改变。阳性测试比阴性测试更频繁地改变结果 (p < 0.00001)。在逻辑回归模型中，当与管理变化相关时，RGS 被认为有用的可能性增加了 6.7 倍（95% CI 1.8-43.3）。当结果为阳性（95% CI 4.7-22.4）且周转时间较短（比值比 0.92，95% CI 0.85-0.99）时，管理变化的可能性增加 10.1 倍。 RGS 很少导致临床医生感到家庭混乱或痛苦（207 名家庭中的 6 名[3%]）。总之，临床医生认为对 ICU 中患有未知病因疾病的婴儿进行一级 RGS 具有较高的临床实用性和较低的伤害可能性。无论结果是阳性还是阴性，RGS 都被认为是有益的。