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基于层次化荟萃分析估算苯丙酮尿症患者血苯丙氨酸致智商损伤的概率。

Estimating the probability of IQ impairment from blood phenylalanine for phenylketonuria patients: a hierarchical meta-analysis.

机构信息

Department of Biostatistics, Vanderbilt University Medical Center, 1161 21st Ave South, S-2323 Medical Center North, Nashville, TN 37232-2158, USA.

出版信息

J Inherit Metab Dis. 2013 Sep;36(5):757-66. doi: 10.1007/s10545-012-9564-0. Epub 2012 Nov 30.

Abstract

Though the control of blood phenylalanine (Phe) levels is essential for minimizing impairment in individuals with phenylketonuria (PKU), the empirical basis for the selection of specific blood Phe levels as targets has not been evaluated. We evaluated the current evidence that particular Phe levels are optimal for minimizing or avoiding cognitive impairment in individuals with PKU. This work uses meta-estimates of blood Phe-IQ correlation to predict the probability of low IQ for a range of Phe levels. We believe this metric is easily interpretable by clinicians, and hence useful in making recommendations for Phe intake. The median baseline association of Phe with IQ was estimated to be negative, both in the context of historical (median = -0.026, 95 % BCI = [-0.040, -0.013]) and concurrent (-0.007, [-0.014, 0.000]) measurement of Phe relative to IQ. The estimated additive fixed effect of critical period Phe measurement was also nominally negative for historical measurement (-0.010, [-0.022, 0.003]) and positive for concurrent measurement (0.007, [-0.018, 0.035]). Probabilities corresponding to historical measures of blood Phe demonstrated an increasing chance of low IQ with increasing Phe, with a stronger association seen between blood Phe measured during the critical period than later. In contrast, concurrently-measured Phe was more weakly correlated with the probability of low IQ, though the correlation is still positive, irrespective of whether Phe was measured during the critical or non-critical period. This meta-analysis illustrates the utility of a Bayesian hierarchical approach for not only combining information from a set of candidate studies, but also for combining different types of data to estimate parameters of interest.

摘要

虽然控制血液苯丙氨酸(Phe)水平对于最大限度地减少苯丙酮尿症(PKU)患者的损害至关重要,但尚未评估选择特定血液 Phe 水平作为目标的经验依据。我们评估了目前的证据,即特定的 Phe 水平对于最小化或避免 PKU 患者的认知障碍是最佳的。这项工作使用血液 Phe-IQ 相关性的荟萃估计来预测一系列 Phe 水平下低智商的概率。我们认为,这种衡量标准易于临床医生解释,因此对于推荐 Phe 摄入量很有用。Phe 与 IQ 的中位数基线关联被估计为负相关,无论是在历史(中位数= -0.026,95% BCI = [-0.040,-0.013])还是同期(-0.007,[-0.014,0.000])测量的 Phe 相对于 IQ。对历史测量而言,关键时期 Phe 测量的估计加性固定效应也为负(-0.010,[-0.022,0.003]),而同期测量则为正(0.007,[-0.018,0.035])。与历史血液 Phe 测量值相对应的概率表明,随着 Phe 的增加,低智商的可能性增加,在关键时期测量的血液 Phe 与低智商之间的相关性更强。相比之下,同期测量的 Phe 与低智商的概率相关性较弱,但相关性仍然为正,无论 Phe 是在关键期还是非关键期测量的。这项荟萃分析说明了贝叶斯分层方法的实用性,不仅可以组合一组候选研究的信息,还可以组合不同类型的数据来估计感兴趣的参数。

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