Supplementary Material for: Case fatality rates of subarachnoid hemorrhage are decreasing with substantial between-country variation: a systematic review of population-based studies between 1980 and 2020

Background: The declining prevalence of smoking and hypertension has been associated with the decrease of subarachnoid hemorrhage (SAH) incidence in the 21st century. Since these same risk factors are linked to SAH mortality, the case fatality rate (CFR) of SAH has potentially also decreased during recent decades. Thus, we conducted a systematic review to address SAH CFR changes over the last 40 years. Methods: We performed a systematic literature search in OVID Medline, Scopus and Cochrane Library databases. We focused on population-based studies published between 1980 and 2020 that had included both hospitalized and non-hospitalized SAH cases, and reported 1-month CFRs for at least two individual study periods for the same population. Finally, we used a linear regression analysis to estimate the annual CFR changes in each identified population, and pooled the regional changes for larger geographical and sex-specific analyses. Results: Of the 4562 initial publications, we included 22 studies (three of which reached a high-quality classification) consisting of 17 593 SAH patients from 16 different populations and 10 countries. Between 1980 and 2020, SAH CFR declined in all but two populations by an average of -1.5%/year. In the continent-based pooled geographical analyses, CFR decline was the most noticeable in North America (-2.4%/year) and Oceania (-2.2%/year). The decline was more moderate in Northern Europe (-0.8%/year) and Southern Europe (-0.7%/year). Overall, CFRs declined both in women (-1.9%/year) and in men (-1.2%/year). When comparing the first and second half of the study period, CFRs declined from 41% to 31%. Conclusion: Short-term SAH CFRs seem to have declined since 1980. Time trends of SAH CFRs can still be identified for only a few populations, and high-quality data is scarce. Whether the observed decline relates to changes in risk factors, treatment outcomes or diagnostics remains to be studied.

研究背景：21世纪以来，吸烟与高血压的患病率持续下降，与蛛网膜下腔出血（subarachnoid hemorrhage, SAH）的发病率降低存在关联。由于上述危险因素同样与SAH的病死率相关，近数十年来SAH的病例病死率（case fatality rate, CFR）或也有所下降。为此，本研究开展系统综述，以探究近40年间SAH病例病死率的变化趋势。
研究方法：我们在OVID Medline、Scopus及Cochrane Library数据库中进行了系统性文献检索。纳入1980年至2020年间发表的基于人群的研究，此类研究需同时纳入住院与非住院的SAH病例，且针对同一人群至少报告了两个独立研究时段的1个月病例病死率。最终，我们采用线性回归分析估算每个纳入人群的年度病例病死率变化，并针对更大范围的地域及性别分层分析，合并了各区域的变化趋势。
研究结果：初始检索共获得4562篇文献，最终纳入22项研究（其中3项为高质量研究），涵盖16个不同人群、10个国家的17593例SAH患者。1980年至2020年间，除2个人群外，其余所有人群的SAH病例病死率均呈下降趋势，年均降幅为1.5%。基于大洲的合并地域分析显示，北美（年均降幅2.4%）与大洋洲（年均降幅2.2%）的病例病死率下降最为显著；北欧（年均降幅0.8%）与南欧（年均降幅0.7%）的下降幅度则相对平缓。整体而言，女性（年均降幅1.9%）与男性（年均降幅1.2%）的病例病死率均有所下降。对比研究时段的前后两半期，病例病死率从41%降至31%。
研究结论：自1980年以来，SAH的短期病例病死率似乎呈下降趋势。但目前仅能在少数人群中识别出SAH病例病死率的时间变化趋势，且高质量数据较为匮乏。本次观察到的病死率下降是否与危险因素变化、治疗效果提升或诊断手段改进相关，仍有待进一步研究。