Movahedi Mohammad, Costello Ruth, Lunt Mark, Pye Stephen Richard, Sergeant Jamie Christopher, Dixon William Gregory
Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Eur J Epidemiol. 2016 Oct;31(10):1045-1055. doi: 10.1007/s10654-016-0167-1. Epub 2016 Jun 2.
Previous studies of glucocorticoid (GC) therapy and mortality have had inconsistent results and have not considered possible perimortal bias-a type of protopathic bias where illness in the latter stages of life influences GC exposure, and might affect the observed relationship between GC use and death. This study aimed to investigate all-cause and cause-specific mortality in association with GC therapy in patients with rheumatoid arthritis (RA), and explore possible perimortal bias. A retrospective cohort study using the primary care electronic medical records. Oral GC exposure was identified from prescriptions. Mortality data were obtained from the UK Office for National Statistics. Multivariable Cox proportional hazards regression models assessed the association between GC use models and death. Several methods to explore perimortal bias were examined. The cohort included 16,762 patients. For ever GC use there was an adjusted hazard ratio for all-cause mortality of 1.97 (95 % CI 1.81-2.15). Current GC dose of below 5 mg per day (prednisolone equivalent dose) was not associated with an increased risk of death, but a dose-response association was seen for higher dose categories. The association between ever GC use and all-cause mortality was partly explained by perimortal bias. GC therapy was associated with an increased risk of mortality for all specific causes considered, albeit to a lesser extent for cardiovascular causes. GC use was associated with an increased risk of death in RA, at least partially explained by perimortal bias. Importantly, GC doses below 5 mg were not associated with an increased risk of death.
以往关于糖皮质激素(GC)治疗与死亡率的研究结果并不一致,且未考虑可能存在的濒死偏倚——一种原发病偏倚,即生命后期的疾病会影响GC暴露,并可能影响观察到的GC使用与死亡之间的关系。本研究旨在调查类风湿关节炎(RA)患者中与GC治疗相关的全因死亡率和特定病因死亡率,并探讨可能存在的濒死偏倚。一项利用基层医疗电子病历的回顾性队列研究。通过处方确定口服GC暴露情况。死亡率数据来自英国国家统计局。多变量Cox比例风险回归模型评估GC使用模型与死亡之间的关联。研究了几种探索濒死偏倚的方法。该队列包括16762名患者。对于曾经使用过GC的患者,全因死亡率的调整后风险比为1.97(95%可信区间1.81 - 2.15)。当前GC剂量低于每天5毫克(泼尼松等效剂量)与死亡风险增加无关,但在更高剂量类别中观察到剂量反应关联。曾经使用GC与全因死亡率之间的关联部分可由濒死偏倚解释。对于所有考虑的特定病因,GC治疗均与死亡风险增加相关,尽管心血管病因的关联程度较小。在RA中,GC使用与死亡风险增加相关,至少部分可由濒死偏倚解释。重要的是,低于5毫克的GC剂量与死亡风险增加无关。