Zhong Xiaomin, Ashiru-Oredope Diane, Pate Alexander, Martin Glen P, Sharma Anita, Dark Paul, Felton Tim, Lake Claire, MacKenna Brian, Mehrkar Amir, Bacon Sebastian C J, Massey Jon, Inglesby Peter, Goldacre Ben, Hand Kieran, Bladon Sian, Cunningham Neil, Gilham Ellie, Brown Colin S, Mirfenderesky Mariyam, Palin Victoria, van Staa Tjeerd Pieter
Centre for Health Informatics, School of Health Sciences, Faculty of Biology, Medicine, and Health, The University of Manchester, M13 9PL, UK.
Healthcare-Associated Infection (HCAI), Fungal, Antimicrobial Resistance (AMR), Antimicrobial Use (AMU) & Sepsis Division, United Kingdom Health Security Agency (UKHSA), London SW1P 3JR, UK.
EClinicalMedicine. 2023 Nov 23;66:102321. doi: 10.1016/j.eclinm.2023.102321. eCollection 2023 Dec.
Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality.
With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality.
The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77-1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35-3.73]), chronic liver disease (adjusted OR 3.08 [2.97-3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55-2.70], stage 5: adjusted OR 6.23 [5.81-6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods.
Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients.
The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.
脓毒症具有较高的发病率和死亡率，与社会经济差异及入院前临床病史密切相关。本研究旨在阐明在英国疫情期间，非新冠病毒相关脓毒症与健康不平等风险因素之间的关联，并次要关注它们与脓毒症30天死亡率的关联。
在英国国民医疗服务体系（NHS）英格兰地区的批准下，我们利用OpenSAFELY平台开展了一项队列研究和一项1:6匹配的病例对照研究。使用国际疾病分类第十版（ICD-10）编码从住院事件记录中识别脓毒症诊断。这包括了从2019年1月1日至2022年6月31日的2200万人群队列中的248,767例非新冠病毒脓毒症病例。使用多重剥夺指数得分衡量社会经济剥夺程度，该得分反映了收入、就业和教育等指标。与住院相关的脓毒症诊断分为社区获得性或医院获得性。根据年龄（逐步）、性别和日历月，将病例与无脓毒症诊断记录的对照进行匹配。对照的纳入标准主要基于无脓毒症诊断记录。通过条件逻辑回归模型评估潜在预测因素与发生非新冠病毒脓毒症几率之间的关联，多变量回归确定30天死亡率的比值比（OR）。
该研究纳入了224,361例（10.2%）非新冠病毒脓毒症病例和1,346,166例匹配对照。社会经济剥夺程度最高的五分位数人群发生非新冠病毒脓毒症的几率高于剥夺程度最低的五分位数人群（粗OR 1.80 [95% CI 1.77 - 1.83]）。其他风险因素（调整合并症后），如学习障碍（调整OR 3.53 [3.35 - 3.73]）、慢性肝病（调整OR 3.08 [2.97 - 3.19]）、慢性肾病（4期：调整OR 2.62 [2.55 - 2.70]，5期：调整OR 6.23 [5.81 - 6.69]）、癌症、神经系统疾病、免疫抑制状态也与发生非新冠病毒脓毒症有关。非新冠病毒脓毒症的发病率在新冠疫情期间下降，并在全国封锁解除后回升至疫情前水平（自2021年4月起）。在所有时间段内，社会经济剥夺程度最高的五分位数人群中，非新冠病毒脓毒症病例的30天死亡风险更高。
社会经济剥夺、合并症和学习障碍与在英国发生非新冠病毒相关脓毒症及30天死亡率增加有关。本研究强调需要改进脓毒症的预防措施，包括更精准地将抗菌药物用于高危患者。
英国卫生安全局、英国健康数据研究中心和英国国家卫生研究院。
