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Persons with epilepsy and their caregivers understand the definition of ictal impairment of consciousness.

Marcinski Nascimento KJ et al. · ncbi_pmc
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Learn more: PMC Disclaimer | PMC Copyright Notice Epilepsia . 2026 Feb 18;67(4):e39–e45. doi: 10.1002/epi.70154 Search in PMC Search in PubMed View in NLM Catalog Add to search Persons with epilepsy and their caregivers understand the definition of ictal impairment of consciousness Kaley J Marcinski Nascimento Kaley J Marcinski Nascimento 1 Department of Pediatrics, Brooke Army Medical Center, San Antonio, Texas, USA Find articles by Kaley J Marcinski Nascimento 1 , Fábio A Nascimento Fábio A Nascimento 2 Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA Find articles by Fábio A Nascimento 2 , Torie Robinson Torie Robinson 3 Epilepsy Sparks, London, UK Find articles by Torie Robinson 3 , Birgit Frauscher Birgit Frauscher 4 Duke Comprehensive Epilepsy Center, Department of Neurology and Biomedical Engineering, Duke University, Durham, North Carolina, USA Find articles by Birgit Frauscher 4 , Eugen Trinka Eugen Trinka 5 Department of Neurology, Neurocritical Care, and Neurorehabilitation, Christian Doppler University Hospital, Center of Cognitive Neuroscience, Paracelsus Medical University, Salzburg, member of the European Reference Network EpiCARE, Salzburg, Austria 6 Neuroscience Institute, Christian Doppler University Hospital, Center of Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria 7 Karl Landsteiner Institute for Clinical Neuroscience, Salzburg, Austria Find articles by Eugen Trinka 5, 6, 7 , Sándor Beniczky Sándor Beniczky 8 Department of Clinical Neurophysiology, Danish Epilepsy Center, member of the European Reference Network EpiCARE, Dianalund, Denmark 9 Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark 10 Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark Find articles by Sándor Beniczky 8, 9, 10, ✉ Author information Article notes Copyright and License information 1 Department of Pediatrics, Brooke Army Medical Center, San Antonio, Texas, USA 2 Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA 3 Epilepsy Sparks, London, UK 4 Duke Comprehensive Epilepsy Center, Department of Neurology and Biomedical Engineering, Duke University, Durham, North Carolina, USA 5 Department of Neurology, Neurocritical Care, and Neurorehabilitation, Christian Doppler University Hospital, Center of Cognitive Neuroscience, Paracelsus Medical University, Salzburg, member of the European Reference Network EpiCARE, Salzburg, Austria 6 Neuroscience Institute, Christian Doppler University Hospital, Center of Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria 7 Karl Landsteiner Institute for Clinical Neuroscience, Salzburg, Austria 8 Department of Clinical Neurophysiology, Danish Epilepsy Center, member of the European Reference Network EpiCARE, Dianalund, Denmark 9 Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark 10 Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark * Correspondence , Sándor Beniczky, Visby Allé 5, 4293 Dianalund, Denmark. Email: [email protected] ✉ Corresponding author. Revised 2026 Jan 31; Received 2025 Dec 19; Accepted 2026 Feb 2; Issue date 2026 Apr. © 2026 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. PMC Copyright notice PMCID: PMC13075620  PMID: 41705916 Abstract The term consciousness has been reintroduced in the updated seizure classification. Concerns have been raised that "ictal impaired consciousness" may be misunderstood by persons with epilepsy (PWEs) and their caregivers, particularly that English‐speaking individuals might equate it with complete loss of consciousness. We conducted an online survey distributed via epilepsy organizations and social media to assess whether English‐speaking PWEs and caregivers could understand and apply a simple medical definition of consciousness: “In medical terms, consciousness means being able to remember things and respond to what is happening around you. During a seizure, consciousness is considered affected if the person cannot remember what happened and if they are unable to respond normally when people try to interact with them.” The survey was completed by 253 respondents (148 caregivers, 105 PWEs). Almost all participants (97%) found the definition clear, 90% reported they could apply it to their seizures, and 99% demonstrated comprehension by correctly interpreting an example question. No significant differences were observed between PWEs and caregivers, across education levels, or by seizure characteristics. These findings indicate that PWEs and caregivers can readily understand and apply the concept of ictal impairment of consciousness when given a concise, patient‐friendly definition. Keywords: classification, consciousness, epilepsy, seizure, terminology Key points. The 2025 ILAE seizure classification recognizes consciousness as a classifier. Consciousness is operationally defined by awareness (assessed through recall) and responsiveness (tested using verbal and motor tasks). Concerns have been raised that patients and caregivers may misinterpret impaired consciousness as implying complete loss of consciousness. We conducted an online survey to assess whether patients and caregivers could understand and apply the medical definition of consciousness. Our findings show that patients and caregivers can understand and apply the ILAE definition of consciousness. 1. INTRODUCTION In 2025, the International League Against Epilepsy (ILAE) updated the classification of epileptic seizures, 1 , 2 , 3 building upon the 2017 operational framework 4 , 5 and incorporating insights gained from real‐world implementation. 1 , 2 , 3 A key modification was replacing “awareness” with “consciousness” as the classifier for focal seizures and seizures of unknown origin. 1 , 2 , 3 The 2017 version proposed awareness as a surrogate marker for consciousness, operationally defined as the ability to recall events during the seizure. 4 , 5 The 2025 update reintroduced consciousness , a medical term widely used in neurology, operationally defined as the ability to recall (awareness) and respond (responsiveness evaluated using verbal and nonverbal/motor tasks). 1 , 2 , 3 There have been ongoing discussions regarding the real‐world applicability of the term consciousness, particularly within the epilepsy field. 1 , 2 , 3 Concerns have been raised that the operational definition of consciousness, inferred from recall and responsiveness, may be difficult for laypersons to understand, and that the term itself may be misunderstood by persons with epilepsy (PWEs) and their caregivers. Specifically, English‐speaking laypersons may equate ictal impaired consciousness with complete loss of consciousness, or “being unconscious,” often conceptualized as “lying flat on the floor.” The ability of PWEs and caregivers to understand the concept of ictal impairment of consciousness has therefore been questioned. We evaluated whether English‐speaking PWEs and their caregivers in the United States and internationally can understand, apply, and correctly put into practice a brief and simple (47 words) definition of consciousness based upon the 2025 ILAE classification. To do this, we surveyed respondents regarding the clarity of the provided definition of consciousness, the applicability of the definition to their seizure experiences, and their ability to correctly identify consciousness impairment when presented with an example in a case‐based comprehension question. 2. MATERIALS AND METHODS We conducted a cross‐sectional survey study among English‐speaking PWEs and their caregivers. Participants were recruited via national and state‐level epilepsy organizations in the United States and internationally through social media and Epilepsy Sparks (Supplementary Material S1 ). We used an online survey platform (SurveyMonkey) to record the input from the participants. All data were self‐reported. The US portion of the survey was conducted under an institutional review board (IRB)‐approved protocol from Washington University in St. Louis. The international portion of the survey was conducted under an IRB‐approved protocol from the Danish Epilepsy Center (EMN‐2025‐03515). Informed consent was obtained online from all participants prior to survey completion, and all responses were collected anonymously. Eligible participants included English‐speaking PWEs and their caregivers residing in the United States, Australia, Canada, Ireland, and the United Kingdom. Respondents were excluded if (1) they declined to participate in the study, after reading the informed consent; (b) they submitted an incomplete survey; (c) their first language was not English; or (d) they experienced two or fewer seizures in their lifetime. Although two unprovoked seizures correspond to the diagnostic threshold for epilepsy diagnosis, 6 an inclusion criterion of three or more seizures was utilized to ensure sufficient experiential exposure to seizures by respondents. The survey (Supplementary [Link] , [Link] ) captured background data on the respondents, which consisted of demographic information including age, sex, race/ethnicity, and highest level of education. For United States‐based participants, insurance type was asked (private, public, both, or uninsured). A brief seizure history was collected including the duration of seizure diagnosis, total number of lifetime seizures, seizure frequency, seizure types, and the specialty of the provider managing their seizure care (epileptologist, neurologist, or primary care physician). Finally, the core assessment of the survey consisted of three questions to evaluate respondents´ understanding of the 2025 ILAE operational definition of consciousness. First, participants read a provided definition of the term consciousness—“In medical terms, consciousness means being able to remember things and respond to what is happening around you. During a seizure, consciousness is considered affected if the person cannot remember what happened or if they are unable to respond normally when people try to interact with them”—then asked if this definition was clear. Second, respondents were asked whether they felt they could apply this definition to their own seizures, or to the seizures of the person they cared for. Third, participants were presented with a practical application question: which of two statements regarding consciousness was correct: (1) “A person can have impaired consciousness without lying flat on the floor, if they are not responding normally or cannot remember what happened” or (2) “Impaired consciousness always means the person is lying flat on the floor.” Selection of the correct statement demonstrated comprehension of the distinction between consciousness as per the 2025 ILAE definition and the common misinterpretation of “consciousness” in which its impairment reflects “being unconscious” or “lying flat on the floor.” Statistical analysis was performed using Jamovi (version 2.0; The Jamovi Project). Descriptive statistics were used for respondent demographics and seizure characteristics, including counts and percentages for categorical variables and means with SDs or median with interquartile ranges for continuous variables. The responses to the three comprehension questions about consciousness are reported as counts and percentages for the definition being clear, for it being applicable to their seizures, and for ability to correctly identify impaired consciousness on the practice question. Comparisons between groups were made using Fisher exact or chi‐squared tests where appropriate. Statistical significance was defined as p < .05. 3. RESULTS There were 253 total respondents consisting of 203 respondents from the United States (Supplementary Material S4 ) and 50 from other countries (Australia [ n = 10], Canada [ n = 5], Ireland [ n = 3], and the United Kingdom [ n = 23]). Of the 253 total respondents, 148 (58%) were caregivers of a PWE, and 105 (42%) were PWEs (Table 1 ). Of the 148 caregivers, 126 (85%) were parents of a child with seizures, 13 (9%) were spouses or partners of a PWE, and nine (6%) were other family members or professional caregivers. Caregiver respondents averaged 47 (SD ±11) years of age, with the majority being female (88%) and White (90%). Regarding education, most caregivers completed a 4‐year degree or higher (69%). TABLE 1. Demographics of all respondents stratified by geography: US, international, and total cohorts. US International Total Total respondents 203 50 253 Caregiver of a person with seizures 130 (64%) 18 (36%) 148 (58%) Person with seizures 73 (36%) 32 (64%) 105 (42%) Caregiver of a person with epilepsy demographics Relationship to person with epilepsy Parent 109 (84%) 17 (94%) 126 (85%) Spouse or partner 13 (10%) 0 (0%) 13 (9%) Other 8 (6%) 1 (6%) 9 (6%) Age, years, average ± SD 46 ± 11 49 ± 10 47 ± 11 Sex Female 116 (89%) 14 (78%) 130 (88%) Male 14 (11%) 4 (22%) 18 (12%) Race White 115 (88%) 18 (100%) 133 (90%) Black 4 (3%) 0 (0%) 4 (3%) Hispanic/Latino 5 (4%) 0 (0%) 5 (3%) Other 6 (5%) 0 (0%) 6 (4%) Education Some high school/diploma or equivalent 23 (18%) 3 (17%) 26 (17.5%) Some college/2‐year degree 16 (12%) 4 (22%) 20 (13.5%) 4‐year degree or higher 91 (70%) 11 (56%) 102 (69%) Person with epilepsy demographics, as self‐reported or reported by caregiver Age, years, average ± SD 25 ± 16 34 ± 17 27 ± 17 Sex Female 120 (59%) 31 (62%) 151 (60%) Male 83 (41%) 19 (38%) 102 (40%) Race White 174 (86%) 45 (90%) 219 (87%) Black 7 (3%) 2 (4%) 9 (4%) Hispanic/Latino 6 (3%) 0 (0%) 6 (2%) Other 16 (8%) 3 (6%) 19 (8%) Education Some high school/diploma or equivalent 12 (16%) 2 (6%) 14 (13%) Some college/2‐year degree 24 (33%) 12 (38%) 36 (34%) 4‐year degree or higher 37 (51%) 18 (56%) 55 (52%) Insurance Private 97 (48%) Public or government 67 (33%) Both 35 (17%) Uninsured 4 (2%) Open in a new tab Among all 253 respondents, the PWEs, as reported by themselves or their caregivers, averaged 27 (±17) years of age, with the majority being female (60%) and White (87%). Of the PWEs who self‐reported ( n = 105), 52% completed a 4‐year degree or higher and 34% completed some college or 2‐year degree. Among US respondents, most PWEs had private insurance (48%), with 33% having public insurance and 17% having both private and public insurance. Regarding seizure history, the median duration since the first seizure was 12 years (range = 2–26), with 89% reporting more than 10 seizures since diagnosis, and 70% reporting seizures with impaired consciousness (Supplementary Material S4 ). Seizure frequency was reported as rare or infrequent by 48% of respondents, monthly by 19%, weekly by 13%, and daily or multiple daily seizures by 19%. Regarding seizure type characteristics, 178 respondents (70%) reported seizures with impaired consciousness, 68 (27%) reported seizures with preserved consciousness, 54 (21%) reported seizures with both, and 58 (23%) reported “passing out” but did not specify a level of consciousness (Supplementary Material S4 ). More than half of PWEs were managed by an epileptologist or epilepsy specialist (65%), whereas 32% were managed by a general neurologist and 3% by a general or primary care physician. Of all respondents, after reading the provided definition of the term consciousness , most respondents (96%) were able to understand the term (Table 2 ). The majority (91%) also felt as though they could apply the definition to their seizures or the seizures of the person they cared for. When quizzed about the definition and application of the term consciousness , 99% of respondents answered the question correctly. Furthermore, there were no statistically significant differences in the clarity, applicability, or comprehension performance between caregivers and PWEs ( p = .722, p = .241, p = .269; Table 2 ). Analysis of understanding by education level revealed no statically significant differences in comprehension of the consciousness definition regarding clarity ( p = .684), applicability ( p = .336), or performance on the practice question ( p = 1.00). Similarly, seizure characteristics including lifetime seizure burden, seizure frequency, reported consciousness level during seizures, and type of provider managing care were not significantly associated with differences in the clarity, applicability, or comprehension performance (Table 2 ). TABLE 2. All respondents' understanding of consciousness by demographics and seizure characteristics. Definition clear Definition applicable Practice question Yes No p Yes No p Correct Incorrect p Respondent Caregiver 144 4 .722 130 18 .241 a 145 3 .269 Person with epilepsy 101 4 97 8 105 0 Education Some high school/diploma 38 2 .684 37 3 .336 40 0 1.00 Some college/2‐year degree 54 2 47 9 55 1 4‐year degree or above 153 4 143 14 155 2 Number of lifetime seizures >10 seizures 217 7 1.00 203 21 .189 a 222 2 .307 3–10 seizures 28 1 24 5 28 1 Seizure frequency Daily/multiple daily 47 2 .956 43 6 .213 49 0 .518 Weekly 33 1 31 3 33 1 Monthly 47 1 47 1 48 0 Rare/infrequent 118 4 106 16 120 2 Reported consciousness during seizures Both 52 2 1.00 51 3 .612 54 0 1.00 Neither 58 2 53 7 59 1 Impaired 123 4 112 15 125 2 Preserved 12 0 11 1 12 0 Provider Epileptologist 160 5 .783 146 19 .497 164 1 .319 Neurologist 77 3 74 6 78 2 Primary Care 8 0 7 1 8 0 Open in a new tab Note : All respondents' understanding of the term consciousness by the clarity of the provided definition, applicability to their seizures or the seizures of the person they care for, and comprehension practice question by demographics and seizure characteristics. a Chi‐squared test. a Chi‐squared test. 4. DISCUSSION The purpose of this study was to address a specific concern arising from the 2025 ILAE seizure classification, which replaces awareness with consciousness as a classifier. 1 , 2 , 3 Critics have suggested that PWEs and caregivers might misinterpret ictal impairment of consciousness as strictly implying complete loss of consciousness, especially in English‐speaking countries. We therefore surveyed English‐speaking PWEs and caregivers in the United States and other English‐speaking countries, using an online survey to assess whether they could understand and apply a brief, patient‐friendly definition of consciousness aligned with the updated ILAE terminology. Nearly all respondents found the definition clear and reported that they could apply it to real‐world seizures, and almost all correctly answered a case‐based comprehension question. Importantly, comprehension did not differ by role (PWE vs. caregiver), education level, or seizure characteristics. These findings should be interpreted in the context of long‐standing debate about how best to incorporate consciousness into seizure classification. The 2017 version proposed awareness as a surrogate for consciousness, focusing solely on recall. 4 , 5 However, consciousness is a central and clinically meaningful term, and it was argued that it should be retained, provided it is carefully defined and operationalized. 7 The 2025 update reflects this view, but concerns persisted that the term might confuse patients and families. Previous efforts to adapt terminology for lay audiences have focused on explanatory materials rather than empirically testing comprehension. 8 More broadly, studies of patients' and caregivers' views have concentrated on seizure control, treatment goals, and quality of life, rather than on seizure classification language itself. 9 Our results therefore fill a gap by showing that, when provided with a concise definition, PWEs and caregivers can easily understand and correctly apply the concept of ictal impairment of consciousness. First, as with all online survey studies, generalizability is an important limitation. Our sample was recruited via epilepsy organizations and social media, which may favor more engaged or health‐literate participants. Nonetheless, several features argue that the sample is reasonably representative. Respondents were drawn from a broad geographical catchment spanning multiple US states and four additional English‐speaking countries, with recruitment through a wide network of epilepsy organizations and online platforms. The cohort included both PWEs and caregivers and a wide range of educational attainment, seizure duration, lifetime seizure burden, seizure frequency, and seizure types, as well as patients cared for in primary, general neurology, and specialist epilepsy settings. Crucially, comprehension outcomes were highly consistent across these subgroups, with no significant differences by education, seizure characteristics, or provider type, which reduces concern that adequate understanding was confined to a narrow, highly selected subset. Second, the case‐based comprehension question (question #34 in Supplemental Material S2 , question #35 in Supplemental Material S3 ) was intentionally structured to include a single clearly correct statement to assess the misconception that impaired consciousness necessarily entails “being unconscious” or “lying flat on the floor.” However, in real‐world scenarios these distinctions are more nuanced. Third, our study exclusively included primary English‐speaking PWEs and caregivers; therefore, our findings are not generalizable to other patient populations whose primary language is not English. In conclusion, our study showed that English‐speaking PWEs and caregivers can understand and apply a simple operational definition of ictal impairment of consciousness, and their comprehension appears robust across demographic and clinical subgroups. Confusion surrounding “consciousness” appears to stem not predominantly from the terminology itself, but from suboptimal communication of its meaning. These findings suggest that, when clinicians and educational materials use clear, plain‐language explanations, adoption of the revised terminology is unlikely to introduce misunderstanding at the patient and caregiver level. In practice, providers should consider incorporating such patient‐oriented explanations as a routine part of patient education. AUTHOR CONTRIBUTIONS Kaley J. Marcinski Nascimento: Drafting of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data. Fábio A. Nascimento: Revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data. Torie Robinson: Revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; interpretation of data. Birgit Frauscher: Revision of the manuscript for content, including medical writing for content; study concept or design; interpretation of data. Eugen Trinka: Revision of the manuscript for content, including medical writing for content; study concept or design; interpretation of data. Sándor Beniczky: Drafting and revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data. CONFLICT OF INTEREST STATEMENT E.T. and S.B. were cochairs of the ILAE Task Force on Seizure classification; S.B., E.T., B.F. are coauthors of the 2025 classification. 2 The remaining authors report no disclosures relevant to the article. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Supporting information Supplementary Material S1. EPI-67-e39-s002.pdf (89.5KB, pdf) Supplementary Material S2. EPI-67-e39-s001.pdf (64.7KB, pdf) Supplementary Material S3. EPI-67-e39-s003.pdf (66.7KB, pdf) Supplementary Material S4. EPI-67-e39-s004.pdf (86.5KB, pdf) ACKNOWLEDGMENTS We express our gratitude to the people with epilepsy and the caregivers who participated in this survey. Marcinski Nascimento KJ, Nascimento FA, Robinson T, Frauscher B, Trinka E, Beniczky S. Persons with epilepsy and their caregivers understand the definition of ictal impairment of consciousness. Epilepsia. 2026;67:e39–e45. 10.1002/epi.70154 Sándor Beniczky is the Member of the European Reference Network EpiCARE. DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. REFERENCES 1. Beniczky S, Trinka E, Wirrell E, Abdulla F, Al Baradie R, Alonso Vanegas M, et al. Updated classification of epileptic seizures: position paper of the international league against epilepsy. Epilepsia. 2025;66(6):1804–1823. 10.1111/epi.18338 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 2. Beniczky S, Trinka E, Wirrell E, Specchio N, Cendes F, Helen Cross J. Updating the ILAE seizure classification. Epilepsia. 2025;66(6):1824–1826. 10.1111/epi.18399 [ DOI ] [ PubMed ] [ Google Scholar ] 3. Beniczky S, Trinka E, Wirrell E, Singh MB, Blumenfeld H, Bogacz Fressola A, et al. A practical guide to the updated seizure classification 2025. Epileptic Disord. 2025;27:1087–1104. 10.1002/epd2.70110 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 4. Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the international league against epilepsy: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):522–530. 10.1111/epi.13670 [ DOI ] [ PubMed ] [ Google Scholar ] 5. Fisher RS, Cross JH, D'Souza C, French JA, Haut SR, Higurashi N, et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia. 2017;58(4):531–542. 10.1111/epi.13671 [ DOI ] [ PubMed ] [ Google Scholar ] 6. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475–482. 10.1111/epi.12550 [ DOI ] [ PubMed ] [ Google Scholar ] 7. Blumenfeld H, Meador KJ. Consciousness as a useful concept in epilepsy classification Epilepsia. Epilepsia. 2014;55(8):1145–1150. 10.1111/epi.12588 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 8. The 2014 Definition of Epilepsy: A perspective for patients and caregivers . https://www.ilae.org/guidelines/definition‐and‐classification/the‐2014‐definition‐of‐epilepsy‐a‐perspective‐for‐patients‐and‐caregivers?utm_source=chatgpt.com . Accessed December 6, 2025 9. Becker DA, Long L, Santilli N, Babrowicz J, Peck EY. Patient, caregiver, and healthcare professional perspectives on seizure control and treatment goals. Epilepsy Behav. 2021;117:107816. 10.1016/j.yebeh.2021.107816 [ DOI ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Supplementary Materials Supplementary Material S1. EPI-67-e39-s002.pdf (89.5KB, pdf) Supplementary Material S2. EPI-67-e39-s001.pdf (64.7KB, pdf) Supplementary Material S3. EPI-67-e39-s003.pdf (66.7KB, pdf) Supplementary Material S4. EPI-67-e39-s004.pdf (86.5KB, pdf) Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. 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