key: cord-0724318-p88lb6ev authors: Drenck, Nicolas; Grundtvig, Josefine; Christensen, Thomas; Iversen, Helle Klingenberg; Kruuse, Christina; Truelsen, Thomas; Wienecke, Troels; Christensen, Hanne title: Stroke admissions and revascularization treatments in Denmark during COVID‐19 date: 2021-10-03 journal: Acta Neurol Scand DOI: 10.1111/ane.13535 sha: d214e16edd4aa261506977f2da251ff77635c950 doc_id: 724318 cord_uid: p88lb6ev OBJECTIVE: The aim of this study was to assess the number of stroke‐related admissions and acute treatments during the first two waves of COVID‐19 and lockdowns in the Capital Region of Denmark and the Region of Zealand. MATERIALS & METHODS: The weekly numbers of admitted patients with stroke were retrieved from electronic patient records from January 2019 to February 2021 and analysed to reveal potential fluctuations in patient volumes during the pandemic. RESULTS: A total of 23,688 patients were included, of whom 2049 patients were treated with tissue‐type plasminogen activators (tPA) and 552 underwent endovascular thrombectomy (EVT). We found a transient decrease in the number of weekly admitted patients (pts/week) with all strokes (−9.8 pts/week, 95% CI: −19.4; −0.2, p = .046) and stroke mimics (−30.1 pts/week, 95% CI: −39.9; −20.3, p < .001) during the first lockdown compared to pre‐COVID‐19. The number of subarachnoid haemorrhage, intracerebral haemorrhage, and ischaemic stroke admissions showed insignificant declines. Analysing all COVID‐19 periods collectively revealed increased volumes of ischaemic stroke (+6.2 pts/week, 95% CI: +1.6; +10.7, p = .009) compared to pre‐COVID levels, while numbers of stroke mimics remained lower than pre‐COVID. Weekly tPA and EVT treatments remained constant throughout the study period. CONCLUSIONS: Our results are comparable with other studies in finding reductions in stroke‐related admissions early in the pandemic. This is the first study to report increased stroke volumes following the first wave of the pandemic. The mechanisms behind the observed drop and subsequent rise in strokes are unclear and warrant further investigation. In early 2020, an outbreak of the novel disease known as COVID-19 spread across the world, causing the World Health Organisation to characterise the outbreak as a pandemic on 11 March 2020. 1 Almost all countries have been affected by the pandemic, and in many places daily life was subject to strict restrictions. On Wednesday, 11 March 2020, the Danish government introduced what would become the first national lockdown effective from Friday, 13 March 2020. 2 From early on in the pandemic, reports of a distinct decline in the number of stroke-related admissions, ranging from 10% to 90%, emerged coming from the World Stroke Organization (WSO), with similar reports coming from the Danish Stroke Society. [3] [4] [5] [6] Stroke risk is largely determined by modifiable factors such as hypertension, physical inactivity, smoking, diet, and diabetes. No clear causal association between COVID-19 and the suspected drop in stroke-related admissions has been established. The objective of this study was to analyse the number of strokerelated admissions to hospital and the number of patients treated with tissue-type plasminogen activators (tPA) and endovascular thrombectomy (EVT) before and during the first two waves of the COVID-19 pandemic, by analysing data gathered from electronic patient records. We hypothesised that our data would remain consistent with the reported findings from around the world, showing a reduced number of stroke-related admissions and tPA and EVT treatments coinciding with the beginning of the pandemic. Data for the study were retrieved with the SlicerDicer tool in the electronic patient records system, Epic Sundhedsplatformen (Epic Systems Corporation, Verona, WI, United States of America, version November 2020), which is used by all public hospitals involved in the study. The study included data from the Capital Region of Denmark and the Region of Zealand, which cover an area with a population of 2.70 million. 7 All patients presenting with signs of stroke or TIA are evaluated to determine if further examination at a stroke centre is needed. At the stroke centre, targeted diagnostic work-up, including neuroimaging, is used to assess the patient's eligibility for intravenous tPA treatment and/or EVT, both of which are considered key treatment options to improve outcome after ischaemic stroke. 8 No alterations were made in existing stroke treatment pathways during the study period. For this study, we identified patients based on the following criteria: (1) aged 18 years or older; (2) admission to departments in- The study period covered 1 January 2019-28 February 2021. We December 2020, 'Lockdown 2', which lasted the remainder of the study period and covered 11 December 2020-28 February 2021. A series of eight search queries were developed to obtain the number of admitted patients from the departments involved in the study from SlicerDicer. Separate queries were made for the five prespecified DRG codes (DI60, DI61, DI63, DG459, and DR298) as well as one query containing both the intracerebral haemorrhage (DI61) and ischaemic stroke (DI63) codes, returning the number of 'all strokes'. Two queries contained both the code for ischaemic stroke (DI63) and an added criterion denoting either tPA (BOHA1) or EVT (KAAL11) respectively. In addition to the overall number of patients, the number of male and female patients was recorded separately, as well as the mean age of patients using the subgroups tool in SlicerDicer. Search results were returned for either 7 days intervals (DI61, DI63, all strokes (DI61 + DI63), DG459, DR298A, and tPA) or 1 month intervals (DI60 and EVT). In some cases, the date intervals were adjusted to accommodate the beginning and end of the study periods. All search criteria were linked to the same event (hospitalisation) and the diagnosis criterion was linked to the unique time point of diagnosis in order to minimise the risk of duplicates due to patient transfers between hospitals. The search query outline is illustrated in Figure 1 . To accommodate potential registration delays for the procedures, the final data extraction was performed at least 1 month after the last day of the study period. In Denmark, there is a national consensus among stroke physicians that patients with ischaemic stroke (DI63), who experience complete resolution of symptoms following tPA or EVT, should maintain their diagnosis, opposed to having it changed to TIA (DG459), as this is an expression of successful revascularization treatment and not a misdiagnosis. Therefore, the search queries for tPA and EVT patients were coupled only to the ischaemic stroke (DI63) DRG code. At all tPA and EVT capable centres included in this study, great efforts are made to ensure correct DRG coding. To analyse changes in patient numbers during the study period, the weekly mean number of admitted patients was calculated for each of the DRG codes in each of the time periods. Normality of data was F I G U R E 1 A diagram depicting the search query used for data collection in SlicerDicer. 1 Separate search queries were constructed for each individual diagnosis code (DI60, DI61, DI63, DG459, and DR298), as well as one containing both DRG codes DI61 and DI63. The Ethics Committee of the Capital Region of Denmark waives approval for registry-based studies on aggregated anonymised data (Section 14.2 of the Committee Act. 2; http://www.en.nvk.dk/). Our search queries returned a combined total of 23,688 patients across the five DRG codes. Of the total number of patients, 12, 238 were male, corresponding to 51.7%. Of the total number of patients, 2049 patients were treated with tPA of whom 1192 (58.2%) were male, and 552 patients were treated with EVT of whom 293 (53.1%) were male. Results are presented in more detail in Tables 1 and 2. TA B L E 1 Total number of patients, number and percentage of male patients and mean age of patients for each diagnosis and procedure The patient numbers for each of the diagnose codes during the study period are plotted as bar charts in Figure 2 A-H. When analysing patient numbers, we found that mean weekly pa- Our results also indicated lower patient numbers during Lockdown 1 for SAH (DI60), intracerebral haemorrhage (DI61), and ischaemic stroke (DI63); however, in all three cases, the differences failed to reach statistical significance (See Table 3 ). Results are presented in more detail in Table 3 . The comparison of the Intermission period with Lockdown 2 showed a significantly lower total number of patients with stroke mimics Table 3 . TA B L E 2 Mean number of weekly admitted patients and standard deviation (SD) for each part of the study period, including a combined 'All COVID' comprising data from the three COVID periods (Lockdown 1, Intermission and Lockdown 2) Pre The analysis of all pre-COVID versus All COVID data showed sig- Analysis of patient mean age for each of the diagnoses and the procedures showed slight but significant differences in mean age with patients being slightly younger during Lockdown 1 compared to pre-COVID for ischaemic stroke (DI63) (71.5 vs. 72.5, p = .038) and slightly older for stroke mimics (DR298A) (58.9 vs. 57.1, p = .022). Likewise, patients with TIA (DG459) were slightly older during Lockdown 2 than during Intermission (73.6 vs. 71.5, p = .002) (see Table 1 and Appendix 1, Table S1 ). This study found that weekly mean patient numbers for all stroke (DI61 + DI63) and stroke mimics (DR298A) were lower during Furthermore, a number of studies, which did not distinguish between stroke subtypes, report a reduced number of total stroke admissions. 3 Likewise, the number of patients treated with tPA or EVT remained unchanged. The unexpected finding of increased patient numbers with all stroke (DI61 + DI63) caused by a rise in numbers of ischaemic stroke (DI63) in the collective COVID-19 periods suggests that patient volumes did not only return to pre-COVID levels but also increased further following Lockdown 1. This is evident in Table 2 The previous studies found stroke volumes to remain low or return to pre-COVID levels within the first 2 months. 17, 18 This study is currently the most extensive in terms of study period, and also the first to report increased volumes of ischaemic stroke (DI63) and all stroke (DI61 + DI63) following the first wave of the pandemic. The scope of this study did not include data on stroke severity. Consequently, we cannot draw final conclusions as to whether the observed transient decline during Lockdown 1 and subsequent rise in stroke admissions comprise mild and severe stroke presentations equally. A large American study reported a decrease in the total volume of stroke patients during the pandemic with an increased proportion of more severe strokes, indicating that the decrease in total volume was brought on mainly by a decrease in mild stroke presentations. 19 In contrast, other studies have not identified differences in stroke severity during the pandemic. 14, 20 Since tPA and EVT rates were not found to fluctuate in this study, it may be hypothesized that the changes in stroke volumes were due to mild stroke presentations. However, the size of the study population may have also limited our analyses' ability to detect differences in revascularization treatments, and it is possible that an analysis based on a larger cohort would have been able to detect smaller fluctuations in tPA and EVT volumes if present. The finding of constant tPA and EVT rates is similar to that of some studies, 15, 16 while others report reductions in patients receiving tPA and/or EVT. 12, 14, 20 The ability to maintain treatment activity might in part have been determined by the regional severity of the pandemic and availability of resources for COVID-19 management. Reports from Italy and France have described how the most severely affected regions have had to drastically reorganize stroke treatment pathways. In the Italian region of Lombardy, a large number of stroke centres were converted into COVID-19 centres to cope with COVID patient loads early on in the pandemic. 21, 22 In contrast, Denmark has been affected relatively mildly by the COVID pandemic resulting in relatively few alterations in existing stroke treatment pathways. We might therefore find tPA and EVT to remain stable because the stroke centres in our study have had adequate resources to uphold their usual treatment activity. The cause of the reduced stroke volumes reported globally remains unknown. Similar reductions have been reported for patients presenting with acute myocardial infarction, extremely premature birth rates, and overall emergency department visits, suggesting that the phenomenon is not unique to stroke. [23] [24] [25] There is no reason to assume that COVID-19 itself reduces the risk of thromboembolic diseases such as ischaemic stroke or TIA. On the contrary, studies have found increased stroke risk related to respiratory infections, 26-28 and one study found higher rates of cerebrovascular events in patients with increasing severity of COVID-19 infection. 29 We retrieved data from the electronic patient records system, Having a continuous study period could potentially make our analysis sensitive to seasonal variations in stroke numbers. The role of seasonal variations in stroke has been investigated, and while some studies failed to show significant variations, 33 others have found stroke numbers to peak in winter and spring, and be low during summer, which was supported by a meta-analysis that found evidence of numbers peaking in winter and decreasing during the summer. [34] [35] [36] However, in this study, a pre-COVID baseline level of patient numbers was used that covered all seasons, thereby minimising the risk of confounding by seasonal variations. In this study, a transient reduction in weekly patient numbers was found with all stroke (DI61 + DI63) and stroke mimics (DR298A) during the first lockdown. The results indicate that the same might be the case for SAH (DI60), intracerebral haemorrhage (DI61), and ischaemic stroke (DI63). The cause of this decline remains unknown but might be founded in apprehension to seek medical assistance due to fear of exposure to the virus in the hospital, or failure to recognize stroke symptoms amid social distancing practices. In contrast, the number of TIAs (DG459) and patients treated with tPA and EVT remained constant throughout the entire study period. This study also found increased numbers of patients with ischaemic stroke (DI63) and all stroke (DI61 + DI63) in the time following the first lockdown (i.e., the first wave of the pandemic). Such an increase has not previously been reported and no studies have so far included data from such a long time period following the first lockdown. The causality between COVID-19 and the post-lockdown increase in stroke is unknown but may relate to an under-detection of strokes and subsequent lack of preventive measures during the first lockdown. This study underlines the need for a robust organization of stroke care facilitating access to care also when the healthcare system is under pressure. The authors would like to extend their gratitude to Philip Hywel Thompson, MD, for his assistance in linguistic revision of the manuscript. The authors declare that they have no conflicts of interest. The peer review history for this article is available at https://publo ns.com/publo n/10.1111/ane.13535. 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