Jørgensen Isabella Friis, Brunak Søren
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
NPJ Digit Med. 2021 Jan 29;4(1):12. doi: 10.1038/s41746-021-00382-y.
Diagnostic errors are common and can lead to harmful treatments. We present a data-driven, generic approach for identifying patients at risk of being mis- or overdiagnosed, here exemplified by chronic obstructive pulmonary disease (COPD). It has been estimated that 5-60% of all COPD cases are misdiagnosed. High-throughput methods are therefore needed in this domain. We have used a national patient registry, which contains hospital diagnoses for 6.9 million patients across the entire Danish population for 21 years and identified statistically significant disease trajectories for COPD patients. Using 284,154 patients diagnosed with COPD, we identified frequent disease trajectories comprising time-ordered comorbidities. Interestingly, as many as 42,459 patients did not present with these time-ordered, common comorbidities. Comparison of the individual disease history for each non-follower to the COPD trajectories, demonstrated that 9597 patients were unusual. Survival analysis showed that this group died significantly earlier than COPD patients following a trajectory. Out of the 9597 patients, we identified one subgroup comprising 2185 patients at risk of misdiagnosed COPD without the typical events of COPD patients. In all, 10% of these patients were diagnosed with lung cancer, and it seems likely that they are underdiagnosed for lung cancer as their laboratory test values and survival pattern are similar to such patients. Furthermore, only 4% had a lung function test to confirm the COPD diagnosis. Another subgroup with 2368 patients were found to be at risk of "classically" overdiagnosed COPD that survive >5.5 years after the COPD diagnosis, but without the typical complications of COPD.
诊断错误很常见，可能导致有害的治疗。我们提出了一种数据驱动的通用方法，用于识别有被误诊或过度诊断风险的患者，这里以慢性阻塞性肺疾病（COPD）为例。据估计，所有COPD病例中有5%-60%被误诊。因此，该领域需要高通量方法。我们使用了一个国家患者登记处，其中包含丹麦全体人口21年里690万患者的医院诊断信息，并确定了COPD患者具有统计学意义的疾病轨迹。利用284154例被诊断为COPD的患者，我们确定了包括按时间顺序排列的合并症在内的常见疾病轨迹。有趣的是，多达42459例患者没有出现这些按时间顺序排列的常见合并症。将每个非遵循者的个体疾病史与COPD轨迹进行比较，发现9597例患者情况异常。生存分析表明，这组患者的死亡时间明显早于遵循轨迹的COPD患者。在这9597例患者中，我们确定了一个亚组，包括2185例有被误诊为COPD风险的患者，他们没有COPD患者的典型症状。总体而言，这些患者中有10%被诊断为肺癌，而且由于他们的实验室检查值和生存模式与肺癌患者相似，他们似乎被漏诊了肺癌。此外，只有4%的患者进行了肺功能测试以确诊COPD。另一个有2368例患者的亚组被发现有“典型”过度诊断为COPD的风险，他们在COPD诊断后存活超过5.5年，但没有COPD的典型并发症。
