{"paper_id":"2eb8d06b-44ce-45c1-a6f4-63118b3452e8","body_text":"Early physical rehabilitation dosage in the Intensive Care Unit predicts hospital outcomes after critical COVID-19 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Early physical rehabilitation dosage in the Intensive Care Unit predicts hospital outcomes after critical COVID-19 Kirby P. Mayer, Evan Haezebrouck, Lori M. Ginoza, Clarisa Martinez, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4319133/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Jul, 2024 Read the published version in Critical Care → Version 1 posted 9 You are reading this latest preprint version Abstract Objective : to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. Design: Retrospective practice analysis from March 5, 2020, to April 15, 2021. Setting: Intensive care units (ICU) at four medical institutions Patients: n = 3,780 adults with ICU admission and diagnosis of COVID-19 Interventions: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: 1) mortality; 2) discharge disposition; and 3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) “6-Clicks” (6-24, 24=greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). Measurements and Main Results: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m 2 and 46% (n=1739) required mechanical ventilation. For 2191 patients with complete data, rehabilitation dosage and AM-PAC at discharge were moderately, positively associated (Spearman’s rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R 2 = 0.68, p <0.001) demonstrates mechanical ventilation (β = -0.86, p = 0.001), average mobility score in first three sessions (β = 2.6, p <0.001) and physical rehabilitation dosage (β = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. Conclusions: Greater physical rehabilitation exposure early in the ICU is associated with physical function at hospital discharge. Phsyical rehabilitation early mobilization critical illness occupational therapy physical therapy COVID Figures Figure 1 Objectives Exercise and early mobility are key components of clinical practice guidelines for patients with critical illness, as defined in the Intensive Care Unit (ICU) Liberation bundle. 1 However, findings from multiple randomized ICU rehabilitation trials have been equivocal, demonstrating minimal impact on mortality and physical function. 2-4 A potential explanation for the lack of benefits is a non-specific exercise dose. Patients are routinely randomized to “one-size-fits-all” protocols leading to heterogeneity in the response to treatment. Dosage that accounts for the frequency and intensity of exercise is frequently overlooked or not addressed in critical care practice and research. The rehabilitation dosage delivered in large randomized controlled trials (RCTs) is rarely implemented in clinical practice 5,6 , and patients in the ICU seldomly receive a targeted or individualized dose of exercise. Patients with critical COVID-19 have not been studied to determine if dosage of exercise is related to outcomes. The COVID-19 pandemic may have unintentionally altered patterns in rehabilitation practice due to periods of isolation. 7 Thus, the primary objective of this study was to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. Design Retrospective practice analysis for patients hospitalized from March 5, 2020, to April 15, 2021. Setting ICUs at four academic medical institutions (University of Kentucky, Cleveland Clinic, University of Michigan, and University of Southern California) Patients 3,780 adults (≥ 18 years of age) admitted to ICU with primary diagnosis of COVID-19 Interventions We examined the relationship between ICU-based physical rehabilitation interventions and hospital-based outcomes. Outcomes included: 1) mortality; 2) discharge disposition; and 3) physical function at or near hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) “6-Clicks” Inpatient Mobility Short Form (6-24, 24=greater functional independence). 8 Physical rehabilitation parameters included time to first rehabilitation (physical [PT] or occupational [OT]) session in days, number of PT and OT sessions completed during hospital length of stay (LOS), frequency of PT and OT (# of session / hospital LOS), mobility status during first three and the last recorded (if more than 3 sessions) rehabilitation sessions. Mobility levels were quantified by the John Hopkins-Highest Level of Mobility (JH-HLM, 1-8, 1=lying in bed; 8=ambulating >250 feet). The physical rehabilitation dose was quantified in a novel method: the average JH-HLM score over the first three sessions (a surrogate measure of early intensity) was multiplied by rehabilitation frequency (PT + OT frequency). The novel dose provides information on delivery of ICU rehabilitation such that patients who achieve high mobility with daily frequency of rehabilitation receive the highest dosage, whereas patients with lower mobility levels and infrequent rehabilitation receive the lowest dose. Our method is based on our previous published studies demonstrating that the mobility levels obtained in the first 3 rehabilitation sessions predict, or at minimum, associate with patient-centered outcomes. 9,10 Measurements and Main Results Descriptive statistics were reported as mean ± SD, median [IQR], or n (%) as appropriate. A total of 3780 patients with COVID critical illness were included. Patients were stratified into groups according to discharge disposition (in-hospital death, subacute or long-term care facility, acute rehabilitation facility, home with services, or home independent). The change in mobility level during rehabilitation as measured by JH-HLM among discharge groups was compared using a two-way ANOVA. Dose of rehabilitation between discharge disposition groups was compared using Tukey’s multiple comparison test. Univariate analyses (Spearman’s correlation) were performed to assess associations between rehabilitation parameters and functional outcomes. Multivariate linear regression was performed to analyze the association between rehabilitation dose and discharge AM-PAC scores, which defined physical function among survivors, adjusting for pre-specified covariates including age, sex, body mass index (BMI), ICU length of stay, and receipt of mechanical ventilation. Patients demographics are described in Table 1. The cohort was a mean 64 ± 16 years old, 41% female and mean BMI of 32 ± 9 kg/m 2 . Mechanical ventilation was required in 46% (n=1739), and the median hospital LOS was 12 days (IQR 7-21). A total of 2200 (58%) and 1698 (45%) patients received at least one PT and OT session, respectively. The first rehabilitation session occurred 7.5 ± 8.0 days after ICU admission. Patients received PT at a frequency of 0.22 ± 0.14 days a week and OT at a frequency of 0.18 ± 0.11 days a week, equivalent to 2.8 rehabilitation sessions per week. Mobility levels on the JH-HLM scale generally increased from the first to last session (+0.93 ± 2.1). The mean JH-HLM score for all sessions was 4.6 ± 1.7; this suggests a likely ability to transfer from a bed to a chair but not stand for up to one minute. The mean dose of physical rehabilitation was 1.8 ± 1.3 units. Patients who died in the hospital (n = 994, 26%) were older, more likely to require mechanical ventilation, had longer durations of mechanical ventilation, and longer ICU LOS (Table 1) compared to patients who survived to hospital discharge. Compared to survivors, those who died in the hospital had an earlier start of rehabilitation, but had lower frequencies of rehabilitation, achieved lower levels of mobility, and received a lower dose of physical rehabilitation (Table 1). Stratified by discharge disposition, patients discharged to home had the highest dose of rehabilitation (F = 69, p <0.0001; Figure 1 ). For 2191 patients with complete data, mean AM-PAC scores at discharge were 15.6 ± 5.9; similar to the JH-HLM mean score, this suggests requiring a lot of help for bed-to-chair transfers. 11 Rehabilitation dose and AM-PAC at discharge were moderately, positively associated (Spearman’s rho [r] = 0.484, p < 0.001). Physical function at discharge as measured by AM-PAC was significantly associated with average mobility achieved in first 3 sessions (r = 0.799, p < 0.001), change in mobility from first to last session (r = 0.445, p < 0.001), and PT and OT frequency with physical function (r = 0.130, p < 0.001). Multivariate linear regression (model adjusted R 2 = 0.68, p <0.001) demonstrates mechanical ventilation (β = -0.86, p = 0.001), average mobility score in first three sessions (β = 2.6, p <0.001) and physical rehabilitation dosage (β = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. Conclusions Our expansive study, involving over 3700 critically ill patients with COVID-19 at four medical insitutions, underscores the pivotal role of physical rehabilitation exposure in the ICU, demonstrating a significant correlation with favorable hospital outcomes. This findings aligns with previous research highlighting the positive association between rehabilitation frequency and outcomes in COVID-19 patients, albeit not specifically focusing on those with critical illness. 12 Introducing a novel methodology, we measure rehabilitation dose by assessing both session frequency and a surrogate marker of intensity derived from achieved mobility levels during sessions. Although our approach lacks physiologic dosage markers such as vital signs, and duration of intensity, it introduces a groundbreaking method for quantifying ICU rehabilitation dose with a single unit. Adopting this approach may enable ICU rehabilitation programs to specifically delineate the intervention provided and anticipate patient benefit. In future, stratification and phenotypic analysis accounting for dose hold promise to guide interventions in clinical research settings. this approach may be useful for prescribing interventions in clinical research. Precision exercise, dose-reponse, and individual response heterogeneity are concepts in exercise dosing that are known to impact outcomes in older adults and diverse patient populations. 13-15 The intra-individual variations have also been recognized in critical care with ventilatory and pharmaceutical interventions. 16,17 To improve the ICU rehabilitation field, it is imperative that clinicians and researchers examine the dose-response. As clinicians, we must modify and adjust treatments based on patient- and clinical-related factors to enhance outcomes. Our work as well as other research demonstrates that older individuals and patients with chronic disease respond differently to exercise. 10,18 Thus, we strongly suggest that researchers and clinicians must begin to examine the response to targeted or individualized rehabilitation dose. Our study has several strengths including a large sample size from multiple academic medical centers with high functioning ICU rehabilitation programs. We also used real world data directly from each rehabilitation session provided to create our method. The study also has limitations. The retrospective study design limits our ability to draw definitive conclusions with regard to causation and is at risk of residual confounding, so our findings should be considered hypothesis-generating. Additionally, while we adjusted for receipt of MV and ICU length of stay, patients who survived may have had lower severity of illness and thus participated at higher levels of mobility with rehabilitation, regardless of the dose. Lastly, we could not account for duration of exercise intensity in our models; longer physiologic demands may produce additional benefits. In conclusion, we found that greater dose of rehabilitation during critical illness due to COVID-19 was associated with improved outcomes. Future studies should utilize personalized rehabilitation doses and identify the most optimal personalized dosage of rehabilitation in critically ill patients, including those with COVID-19. Declarations Ethics approval and consent to participate : Medical IRB with expedited review was approved at University of Kentucky (#47751, 9/27/2022). Informed consent was waived due to the study design and deidentifed nature of data. Data User and Transfer Agreements were approved for sharing of data between sites using REDCap platform with data integrity checks. Consent for publication : N/A Availability of data and materials : The datasets generated and/or analysed during the current study are not publicly available due ongoing analyses and secondary studies by the authors, but are available from the corresponding author on reasonable request. Competing interests : None Funding : Dr. Kirby Mayer was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health K23-AR079583 Authors' contributions Authors' contributions: All authors participated in conception of study, methodology and selection of variable for the database with regular meetings occurring in 2021 and 2022.KPM, EH, MFM, and JKJ performed initial data integrity, management, and statistical analyses. KPM drafted the manuscript and developed figures. All authors reviewed, edited, and provided final approval for the manuscript. Acknowledgements: the authors would like to acknowledge Joshua Veith, MD; Karna Sarin, MD; Eileen Bishop, DO; Heather Torbic, PharmD; Kathryn Bash, APRN, CNP; Maria Holztrager, APRN, PA; Jill O'Brien, PA-C; References Devlin JW, Skrobik Y, Gélinas C, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med 2018;46(9):e825-e873. (In eng). DOI: 10.1097/ccm.0000000000003299. Morris PE, Berry MJ, Files DC, et al. Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial. JAMA 2016;315(24):2694-702. DOI: 10.1001/jama.2016.7201. Moss M, Nordon-Craft A, Malone D, et al. A Randomized Trial of an Intensive Physical Therapy Program for Patients with Acute Respiratory Failure. American journal of respiratory and critical care medicine 2016;193(10):1101-10. (In eng). DOI: 10.1164/rccm.201505-1039OC. Tipping CJ, Harrold M, Holland A, Romero L, Nisbet T, Hodgson CL. The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review. Intensive Care Med 2017;43(2):171-183. (In eng). DOI: 10.1007/s00134-016-4612-0. Jolley SE, Moss M, Needham DM, et al. Point Prevalence Study of Mobilization Practices for Acute Respiratory Failure Patients in the United States. Crit Care Med 2017;45(2):205-215. (In eng). DOI: 10.1097/ccm.0000000000002058. Nydahl P, Ruhl AP, Bartoszek G, et al. Early mobilization of mechanically ventilated patients: a 1-day point-prevalence study in Germany. Crit Care Med 2014;42(5):1178-86. (In eng). DOI: 10.1097/ccm.0000000000000149. Myszenski A, Bello R, Melican C, Pfitzenmaier N. Patient Characteristics and Acute PT and OT Utilization During the Initial Surge of COVID-19: A Retrospective Observational Study. J Acute Care Phys Ther 2022;13(1):2-7. (In eng). DOI: 10.1097/jat.0000000000000163. Jette DU, Stilphen M, Ranganathan VK, Passek SD, Frost FS, Jette AM. Validity of the AM-PAC \"6-Clicks\" inpatient daily activity and basic mobility short forms. Physical therapy 2014;94(3):379-91. (In eng). DOI: 10.2522/ptj.20130199. Mayer KP, Pastva AM, Du G, et al. Mobility Levels With Physical Rehabilitation Delivered During and After Extracorporeal Membrane Oxygenation: A Marker of Illness Severity or an Indication of Recovery? Physical therapy 2022;102(3) (In eng). DOI: 10.1093/ptj/pzab301. Mayer KP, Silva S, Beaty A, et al. Relationship of Age And Mobility Levels During Physical Rehabilitation With Clinical Outcomes in Critical Illness. Arch Rehabil Res Clin Transl 2023;5(4):100305. (In eng). DOI: 10.1016/j.arrct.2023.100305. Jette AM, Tao W, Norweg A, Haley S. Interpreting rehabilitation outcome measurements. J Rehabil Med 2007;39(8):585-90. (In eng). DOI: 10.2340/16501977-0119. Johnson JK, Lapin B, Green K, Stilphen M. Frequency of Physical Therapist Intervention Is Associated With Mobility Status and Disposition at Hospital Discharge for Patients With COVID-19. Physical therapy 2021;101(1):pzaa181. DOI: 10.1093/ptj/pzaa181. Ross R, Goodpaster BH, Koch LG, et al. Precision exercise medicine: understanding exercise response variability. Br J Sports Med 2019;53(18):1141-1153. (In eng). DOI: 10.1136/bjsports-2018-100328. Sanders LMJ, Hortobágyi T, la Bastide-van Gemert S, van der Zee EA, van Heuvelen MJG. Dose-response relationship between exercise and cognitive function in older adults with and without cognitive impairment: A systematic review and meta-analysis. PloS one 2019;14(1):e0210036. (In eng). DOI: 10.1371/journal.pone.0210036. Herold F, Törpel A, Hamacher D, et al. Causes and Consequences of Interindividual Response Variability: A Call to Apply a More Rigorous Research Design in Acute Exercise-Cognition Studies. Front Physiol 2021;12:682891. (In eng). DOI: 10.3389/fphys.2021.682891. Buckel M, Maclean P, Knight JC, Lawler PR, Proudfoot AG. Extending the ‘host response’ paradigm from sepsis to cardiogenic shock: evidence, limitations and opportunities. Critical Care 2023;27(1):460. DOI: 10.1186/s13054-023-04752-8. Maslove DM, Tang B, Shankar-Hari M, et al. Redefining critical illness. Nature Medicine 2022;28(6):1141-1148. DOI: 10.1038/s41591-022-01843-x. Jones JRA, Karahalios A, Puthucheary ZA, et al. Responsiveness of Critically Ill Adults With Multimorbidity to Rehabilitation Interventions: A Patient-Level Meta-Analysis Using Individual Pooled Data From Four Randomized Trials*. Critical Care Medicine 2023;51(10):1373-1385. DOI: 10.1097/ccm.0000000000005936. Table Table 1: Demographic, clinical and rehabilitation parameters Parameter In-hospital Mortality (n = 994) Survivor (n = 2788) p-value Age, years, mean (SD) 70.8 ± 13 62. 2 ± 16 <0.001 Sex Female, n (%) Male, n (%) 411 (41) 583 (59) 1142 (41) 1644 (59) 0.687 Race White/Caucasian, n (%) Black/African American, n (%) Asian, n (%) Unknown/did not disclose, n (%) 660 (66) 258 (26) 6 (0.6) 70 (7) 1724 (62) 859 (31) 17 (0.6) 188 (7) 0.670 Ethnicity Hispanic, n (%) Non-Hispanic, n (%) Unknown, n (%) 75 (8) 901 (91) 18 (1) 194 (7) 2525 (91) 69 (2) 0.415 BMI (kg/m 2 ) 30.7 ± 8 32.4 ± 9 <0.001 Mechanical Ventilation, yes, n (%) 725 (73) 1013 (36) <0.001 Mechanical Ventilation duration days, mean (SD) 12.4 ± 13 14.2 ± 15.4 0.011 RASS, median [IQR] -1.4 ± 1.7 -0.6 ± 1.2 <0.001 PT, yes, n (%) 354 (35) 1846 (66) <0.001 OT, yes, n (%) 275 (34) 1423 (57) <0.001 Time to 1 st PT, days, mean (SD) 5.8 ± 7.8 7.8 ± 8.1 <0.001 Time to 1 st OT, days, mean (SD) 5.6 ± 6.9 7.8 ± 7.6 <0.001 Number of total PT sessions, mean (SD) 2.8 ± 5.7 4.6 ± 5.2 <0.001 Number of total OT sessions, mean (SD) 2.4 ± 3.4 3.1 ± 3.6 <0.001 PT Frequency days / week 0.16 ± 0.11 0.24 ± 0.14 <0.001 OT Frequency days / week 0.13 ± 0.10 0.18 ± 0.11 <0.001 AM-PAC at PT evaluation (6-24, 24 = greater functional independence) 12.3 ± 5.3 14.2 ± 5.8 <0.001 AM-PAC, last recorded (6-24, 24 = greater functional independence) 11.3 ± 5.1 16.4 ± 5.7 <0.001 AMPAC Change -0.9 ± 3.3 2.2 ± 4.3 <0.001 JHHLM- initial 3.9 ± 1.8 4.4 ± 1.8 <0.001 JHHLM-2 nd 3.5 ± 1.8 4.6 ± 1.9 <0.001 JHHLM-3 rd 3.5 ± 1.8 4.6 ± 1.9 <0.001 JHHLM-4 th 3.0 ± 1.4 4.9 ± 1.9 <0.001 JHHLM Change -0.8 ± 1.7 1.1 ± 2.0 <0.001 Rehabilitation Dosage (JHHLM average * Frequency) 0.97 ± 0.73 1.90 ± 1.4 <0.001 ICU LOS, days, median [IQR] 11.6 ± 12.5 8.3 ± 11.2 <0.001 Hospital LOS, days, median [IQR] 15.5 ± 13.6 16.6 ± 16.1 0.064 BMI = boody mass index; RASS = Richmond Agitation Sedation Scale; PT = physical therapy; OT = occupational therapy; AMPAC = Activity Measure-Post Acute Care (AM-PAC) “6-Clicks” Inpatient Mobility Short Form; JHHLM = the John Hopkins-Highest Level of Mobility; LOS = Length of stay; Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Jul, 2024 Read the published version in Critical Care → Version 1 posted Editorial decision: Revision requested 10 Jun, 2024 Reviews received at journal 10 Jun, 2024 Reviews received at journal 11 May, 2024 Reviewers agreed at journal 08 May, 2024 Reviewers agreed at journal 07 May, 2024 Reviewers invited by journal 07 May, 2024 Submission checks completed at journal 06 May, 2024 Editor assigned by journal 06 May, 2024 First submitted to journal 24 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-4319133\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Short Report\",\"associatedPublications\":[],\"authors\":[{\"id\":300084545,\"identity\":\"9b59382c-9ee9-4f64-93b1-592575d8d77b\",\"order_by\":0,\"name\":\"Kirby P. 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Pastva\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Duke University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Amy\",\"middleName\":\"M.\",\"lastName\":\"Pastva\",\"suffix\":\"\"},{\"id\":300084574,\"identity\":\"2475e6ec-fb4d-45b7-abab-065504a65b5f\",\"order_by\":10,\"name\":\"Michelle Biehl\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Cleveland Clinic\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Michelle\",\"middleName\":\"\",\"lastName\":\"Biehl\",\"suffix\":\"\"},{\"id\":300084577,\"identity\":\"23380f62-e879-4510-9569-33f370f54eab\",\"order_by\":11,\"name\":\"Matthew F. Mart\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Vanderbilt University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Matthew\",\"middleName\":\"F.\",\"lastName\":\"Mart\",\"suffix\":\"\"},{\"id\":300084579,\"identity\":\"b745f6ac-7412-4277-bdf8-afe8a513cfa0\",\"order_by\":12,\"name\":\"Joshua K. Johnson\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Duke University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Joshua\",\"middleName\":\"K.\",\"lastName\":\"Johnson\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-04-24 15:05:11\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-4319133/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-4319133/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1186/s13054-024-05035-6\",\"type\":\"published\",\"date\":\"2024-07-18T15:57:17+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":56542814,\"identity\":\"160db8d1-b873-4269-9e44-704bf4aa6186\",\"added_by\":\"auto\",\"created_at\":\"2024-05-15 14:33:46\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":122336,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eDosage and change in mobility during physical rehabilitation grouped based on discharge disposition.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePanel A:\\u003c/strong\\u003e the change in mobility level measured by John Hopkins-Highest Level of Mobility (JH-HLM, 0-8) stratified by discharge disposition. Two-Way ANOVA demonstrated significant difference in JH-HLM scores based on group (F = 240.8, p \\u0026lt; 0.0001) and change over rehabilitation sessions (F = 11.13, p \\u0026lt;0.00) with interaction (F = 6.7 p\\u0026lt;0.0001). \\u003cstrong\\u003ePanel B\\u003c/strong\\u003e: the dosage of rehabilitation (JH-HLM average over four reported sessions multiplied by the frequency of rehabilitation) is significantly different based on discharge disposition (F = 69, p \\u0026lt;0.0001) with Tukey’s multiple comparison test revealing significant differences at the p\\u0026lt;0.0001 denoted with ****; P\\u0026lt;0.001 denoted with **, and * denoting p \\u0026lt;0.05.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4319133/v1/42d3a54a1aa706f4e615cbc3.jpg\"},{\"id\":61597355,\"identity\":\"4791cfe1-4d9e-44a3-9362-7b97e2860b01\",\"added_by\":\"auto\",\"created_at\":\"2024-08-01 17:33:03\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":788357,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4319133/v1/ecfaa1e1-188b-484e-84dd-fa222d1c44de.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Early physical rehabilitation dosage in the Intensive Care Unit predicts hospital outcomes after critical COVID-19\",\"fulltext\":[{\"header\":\"Objectives\",\"content\":\"\\u003cp\\u003eExercise and early mobility are key components of clinical practice guidelines for patients with critical illness, as defined in the Intensive Care Unit (ICU) Liberation bundle.\\u003csup\\u003e1\\u003c/sup\\u003e However, findings from multiple randomized ICU rehabilitation trials have been equivocal, demonstrating minimal impact on mortality and physical function.\\u003csup\\u003e2-4\\u003c/sup\\u003e A potential explanation for the lack of benefits is a non-specific exercise dose. Patients are routinely randomized to \\u0026ldquo;one-size-fits-all\\u0026rdquo; protocols leading to heterogeneity in the response to treatment. Dosage that accounts for the frequency and intensity of exercise is frequently overlooked or not addressed in critical care practice and research. The rehabilitation dosage delivered in large randomized controlled trials (RCTs) is rarely implemented in clinical practice\\u003csup\\u003e5,6\\u003c/sup\\u003e, and patients in the ICU seldomly receive a targeted or individualized dose of exercise. Patients with critical COVID-19 have not been studied to determine if dosage of exercise is related to outcomes. The COVID-19 pandemic may have unintentionally altered patterns in rehabilitation practice due to periods of isolation.\\u003csup\\u003e7\\u003c/sup\\u003e Thus, the primary objective of this study was to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"Design\",\"content\":\"\\u003cp\\u003eRetrospective\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003epractice analysis for patients hospitalized from March 5, 2020, to April 15, 2021.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"Setting\",\"content\":\"\\u003cp\\u003eICUs at four academic medical institutions (University of Kentucky, Cleveland Clinic, University of Michigan, and University of Southern California)\\u003c/p\\u003e\"},{\"header\":\"Patients\",\"content\":\"\\u003cp\\u003e3,780\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003eadults (\\u0026ge; 18 years of age) admitted to ICU with primary diagnosis of COVID-19\\u003c/p\\u003e\"},{\"header\":\"Interventions\",\"content\":\"\\u003cp\\u003eWe examined the relationship between ICU-based physical rehabilitation interventions and hospital-based outcomes. Outcomes included: 1) mortality; 2) discharge disposition; and 3) physical function at or near hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) \\u0026ldquo;6-Clicks\\u0026rdquo; Inpatient Mobility Short Form (6-24, 24=greater functional independence).\\u003csup\\u003e8\\u003c/sup\\u003e Physical rehabilitation parameters included time to first rehabilitation (physical [PT] or occupational [OT]) session in days, number of PT and OT sessions completed during hospital length of stay (LOS), frequency of PT and OT (# of session / hospital LOS), mobility status during first three and the last recorded (if more than 3 sessions) rehabilitation sessions. Mobility levels were quantified by the John Hopkins-Highest Level of Mobility (JH-HLM, 1-8, 1=lying in bed; 8=ambulating \\u0026gt;250 feet). The \\u0026nbsp;physical rehabilitation dose was quantified in a novel method: the average JH-HLM score over the first three sessions (a surrogate measure of early intensity) was multiplied by rehabilitation frequency (PT + OT frequency). The novel dose provides information on delivery of ICU rehabilitation such that patients who achieve high mobility with daily frequency of rehabilitation receive the highest dosage, whereas patients with lower mobility levels and infrequent rehabilitation receive the lowest dose. Our method is based on our previous published studies demonstrating that the mobility levels obtained in the first 3 rehabilitation sessions predict, or at minimum, associate with patient-centered outcomes.\\u003csup\\u003e9,10\\u003c/sup\\u003e\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"Measurements and Main Results\",\"content\":\"\\u003cp\\u003eDescriptive statistics were reported as mean\\u003cstrong\\u003e\\u0026nbsp;\\u0026plusmn;\\u003c/strong\\u003e SD, median [IQR], or n (%) as appropriate. A total of 3780 patients with COVID critical illness were included. Patients were stratified into groups according to discharge disposition (in-hospital death, subacute or long-term care facility, acute rehabilitation facility, home with services, or home independent). The change in mobility level during rehabilitation as measured by JH-HLM among discharge groups was compared using a two-way ANOVA. Dose of rehabilitation between discharge disposition groups was compared using Tukey\\u0026rsquo;s multiple comparison test. Univariate analyses (Spearman\\u0026rsquo;s correlation) were performed to assess associations between rehabilitation parameters and functional outcomes. Multivariate linear regression was performed to analyze the association between rehabilitation dose and discharge AM-PAC scores, which defined physical function among survivors, adjusting for pre-specified covariates including age, sex, body mass index (BMI), ICU length of stay, and receipt of mechanical ventilation.\\u003c/p\\u003e\\n\\u003cp\\u003ePatients demographics are described in Table 1. The cohort was a mean 64 \\u0026plusmn; 16 years old, 41% female and mean BMI of 32 \\u0026plusmn; 9 kg/m\\u003csup\\u003e2\\u003c/sup\\u003e. Mechanical ventilation was required in 46% (n=1739), and the median hospital LOS was 12 days (IQR 7-21). A total of 2200 (58%) and 1698 (45%) patients received at least one PT and OT session, respectively. The first rehabilitation session occurred 7.5 \\u0026plusmn; 8.0 days after ICU admission. Patients received PT at a frequency of 0.22 \\u0026plusmn; 0.14 days a week and OT at a frequency of 0.18 \\u0026plusmn; 0.11 days a week, equivalent to 2.8 rehabilitation sessions per week. Mobility levels on the JH-HLM scale generally increased from the first to last session (+0.93 \\u0026plusmn; 2.1). The mean JH-HLM score for all sessions was 4.6 \\u0026plusmn; 1.7; this suggests a likely ability to transfer from a bed to a chair but not stand for up to one minute. The mean dose of physical rehabilitation was 1.8 \\u0026plusmn; 1.3 units.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003ePatients who died in the hospital (n = 994, 26%) were older, more likely to require mechanical ventilation, had longer durations of mechanical ventilation, and longer ICU LOS \\u003cstrong\\u003e(Table 1)\\u003c/strong\\u003e compared to patients who survived to hospital discharge. Compared to survivors, those who died in the hospital had an earlier start of rehabilitation, but had lower frequencies of rehabilitation, achieved lower levels of mobility, and received a lower dose of physical rehabilitation \\u003cstrong\\u003e(Table 1).\\u003c/strong\\u003e\\u0026nbsp; Stratified by discharge disposition, patients discharged to home had the highest dose of rehabilitation (F = 69, p \\u0026lt;0.0001;\\u0026nbsp;\\u003cstrong\\u003eFigure 1\\u003c/strong\\u003e).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eFor 2191 patients with complete data, mean AM-PAC scores at discharge were 15.6 \\u0026plusmn; 5.9; similar to the JH-HLM mean score, this suggests requiring a lot of help for bed-to-chair transfers.\\u003csup\\u003e11\\u003c/sup\\u003e Rehabilitation dose and AM-PAC at discharge were moderately, positively associated (Spearman\\u0026rsquo;s rho [r] = 0.484, p \\u0026lt; 0.001). \\u0026nbsp;Physical function at discharge as measured by AM-PAC was significantly associated with average mobility achieved in first 3 sessions (r = 0.799, p \\u0026lt; 0.001), change in mobility from first to last session (r = 0.445, p \\u0026lt; 0.001), and PT and OT frequency with physical function (r = 0.130, p \\u0026lt; 0.001). Multivariate linear regression (model adjusted R\\u003csup\\u003e2\\u003c/sup\\u003e= 0.68, p \\u0026lt;0.001) demonstrates mechanical ventilation (\\u0026beta; = -0.86, p = 0.001), average mobility score in first three sessions (\\u0026beta; = 2.6, p \\u0026lt;0.001) and physical rehabilitation dosage (\\u0026beta; = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS.\\u003c/p\\u003e\"},{\"header\":\"Conclusions\",\"content\":\"\\u003cp\\u003eOur expansive study, involving over 3700 critically ill patients with COVID-19 at four medical insitutions, underscores the pivotal role of physical rehabilitation exposure in the ICU, demonstrating a significant correlation with favorable hospital outcomes. This findings aligns with previous research highlighting the positive association between rehabilitation frequency and outcomes in COVID-19 patients, albeit not specifically focusing on those with critical illness.\\u003csup\\u003e12\\u003c/sup\\u003e Introducing a novel methodology, we measure rehabilitation dose by assessing both session frequency and a surrogate marker of intensity derived from achieved mobility levels during sessions. Although our approach lacks physiologic dosage markers such as vital signs, and duration of intensity, it introduces a groundbreaking method for quantifying ICU rehabilitation dose with a single unit. Adopting this approach may enable ICU rehabilitation programs to specifically delineate the intervention provided and anticipate patient benefit. In future, stratification and phenotypic analysis accounting for dose hold promise to guide interventions in clinical research settings. this approach may be useful for prescribing interventions in clinical research.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003ePrecision exercise, dose-reponse, and individual response heterogeneity are concepts in exercise dosing that are known to impact outcomes in older adults and diverse patient populations.\\u003csup\\u003e13-15\\u003c/sup\\u003e The intra-individual variations have also been recognized in critical care with ventilatory and pharmaceutical interventions.\\u003csup\\u003e16,17\\u003c/sup\\u003e To improve the ICU rehabilitation field, it is imperative that clinicians and researchers examine the dose-response. As clinicians, we must modify and adjust treatments based on patient- and clinical-related factors to enhance outcomes. Our work as well as other research demonstrates that older individuals and patients with chronic disease respond differently to exercise.\\u003csup\\u003e10,18\\u003c/sup\\u003e Thus, we strongly suggest that researchers and clinicians must begin to examine the response to targeted or individualized rehabilitation dose.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eOur study has several strengths including a large sample size from multiple academic medical centers with high functioning ICU rehabilitation programs. We also used real world data directly from each rehabilitation session provided to create our method. The study also has limitations. The retrospective study design limits our ability to draw definitive conclusions with regard to causation and is at risk of residual confounding, so our findings should be considered hypothesis-generating. Additionally, while we adjusted for receipt of MV and ICU length of stay, patients who survived may have had lower severity of illness and thus participated at higher levels of mobility with rehabilitation, regardless of the dose. Lastly, we could not account for duration of exercise intensity in our models; longer physiologic demands may produce additional benefits. In conclusion, we found that greater dose of rehabilitation during critical illness due to COVID-19 was associated with improved outcomes. Future studies should utilize personalized rehabilitation doses and identify the most optimal personalized dosage of rehabilitation in critically ill patients, including those with COVID-19.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e: \\u0026nbsp;Medical IRB with expedited review was approved at University of Kentucky (#47751, 9/27/2022). Informed consent was waived due to the study design and deidentifed nature of data. Data User and Transfer Agreements were approved for sharing of data between sites using REDCap platform with data integrity checks.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e: N/A\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials\\u003c/strong\\u003e: \\u0026nbsp;The datasets generated and/or analysed during the current study are not publicly available due ongoing analyses and secondary studies by the authors, but are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e: None\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e:\\u0026nbsp;Dr. Kirby Mayer was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health K23-AR079583\\u003c/p\\u003e\\n\\u003cp\\u003eAuthors' contributions\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors' contributions: \\u0026nbsp;\\u003c/strong\\u003eAll authors participated in conception of study, methodology and selection of variable for the database with regular meetings occurring in 2021 and 2022.KPM, EH, MFM, and JKJ performed initial data integrity, management, and statistical analyses. KPM drafted the manuscript and developed figures. All authors reviewed, edited, and provided final approval for the manuscript.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements: \\u0026nbsp;\\u003c/strong\\u003ethe authors would like to acknowledge Joshua Veith, MD; Karna Sarin, MD; Eileen Bishop, DO; Heather Torbic, PharmD; Kathryn Bash, APRN, CNP; Maria Holztrager, APRN, PA; Jill O'Brien, PA-C;\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eDevlin JW, Skrobik Y, G\\u0026eacute;linas C, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med 2018;46(9):e825-e873. (In eng). DOI: 10.1097/ccm.0000000000003299.\\u003c/li\\u003e\\n\\u003cli\\u003eMorris PE, Berry MJ, Files DC, et al. Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial. JAMA 2016;315(24):2694-702. DOI: 10.1001/jama.2016.7201.\\u003c/li\\u003e\\n\\u003cli\\u003eMoss M, Nordon-Craft A, Malone D, et al. A Randomized Trial of an Intensive Physical Therapy Program for Patients with Acute Respiratory Failure. American journal of respiratory and critical care medicine 2016;193(10):1101-10. (In eng). DOI: 10.1164/rccm.201505-1039OC.\\u003c/li\\u003e\\n\\u003cli\\u003eTipping CJ, Harrold M, Holland A, Romero L, Nisbet T, Hodgson CL. The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review. Intensive Care Med 2017;43(2):171-183. (In eng). DOI: 10.1007/s00134-016-4612-0.\\u003c/li\\u003e\\n\\u003cli\\u003eJolley SE, Moss M, Needham DM, et al. Point Prevalence Study of Mobilization Practices for Acute Respiratory Failure Patients in the United States. Crit Care Med 2017;45(2):205-215. (In eng). DOI: 10.1097/ccm.0000000000002058.\\u003c/li\\u003e\\n\\u003cli\\u003eNydahl P, Ruhl AP, Bartoszek G, et al. Early mobilization of mechanically ventilated patients: a 1-day point-prevalence study in Germany. Crit Care Med 2014;42(5):1178-86. (In eng). DOI: 10.1097/ccm.0000000000000149.\\u003c/li\\u003e\\n\\u003cli\\u003eMyszenski A, Bello R, Melican C, Pfitzenmaier N. Patient Characteristics and Acute PT and OT Utilization During the Initial Surge of COVID-19: A Retrospective Observational Study. J Acute Care Phys Ther 2022;13(1):2-7. (In eng). DOI: 10.1097/jat.0000000000000163.\\u003c/li\\u003e\\n\\u003cli\\u003eJette DU, Stilphen M, Ranganathan VK, Passek SD, Frost FS, Jette AM. Validity of the AM-PAC \\u0026quot;6-Clicks\\u0026quot; inpatient daily activity and basic mobility short forms. Physical therapy 2014;94(3):379-91. (In eng). DOI: 10.2522/ptj.20130199.\\u003c/li\\u003e\\n\\u003cli\\u003eMayer KP, Pastva AM, Du G, et al. 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DOI: 10.1093/ptj/pzaa181.\\u003c/li\\u003e\\n\\u003cli\\u003eRoss R, Goodpaster BH, Koch LG, et al. Precision exercise medicine: understanding exercise response variability. Br J Sports Med 2019;53(18):1141-1153. (In eng). DOI: 10.1136/bjsports-2018-100328.\\u003c/li\\u003e\\n\\u003cli\\u003eSanders LMJ, Hortob\\u0026aacute;gyi T, la Bastide-van Gemert S, van der Zee EA, van Heuvelen MJG. Dose-response relationship between exercise and cognitive function in older adults with and without cognitive impairment: A systematic review and meta-analysis. PloS one 2019;14(1):e0210036. (In eng). DOI: 10.1371/journal.pone.0210036.\\u003c/li\\u003e\\n\\u003cli\\u003eHerold F, T\\u0026ouml;rpel A, Hamacher D, et al. Causes and Consequences of Interindividual Response Variability: A Call to Apply a More Rigorous Research Design in Acute Exercise-Cognition Studies. Front Physiol 2021;12:682891. (In eng). DOI: 10.3389/fphys.2021.682891.\\u003c/li\\u003e\\n\\u003cli\\u003eBuckel M, Maclean P, Knight JC, Lawler PR, Proudfoot AG. Extending the \\u0026lsquo;host response\\u0026rsquo; paradigm from sepsis to cardiogenic shock: evidence, limitations and opportunities. Critical Care 2023;27(1):460. DOI: 10.1186/s13054-023-04752-8.\\u003c/li\\u003e\\n\\u003cli\\u003eMaslove DM, Tang B, Shankar-Hari M, et al. Redefining critical illness. Nature Medicine 2022;28(6):1141-1148. DOI: 10.1038/s41591-022-01843-x.\\u003c/li\\u003e\\n\\u003cli\\u003eJones JRA, Karahalios A, Puthucheary ZA, et al. Responsiveness of Critically Ill Adults With Multimorbidity to Rehabilitation Interventions: A Patient-Level Meta-Analysis Using Individual Pooled Data From Four Randomized Trials*. Critical Care Medicine 2023;51(10):1373-1385. DOI: 10.1097/ccm.0000000000005936.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Table\",\"content\":\"\\u003cp\\u003eTable 1: Demographic, clinical and rehabilitation parameters\\u0026nbsp;\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"714\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eParameter\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eIn-hospital Mortality\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e(n = 994)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSurvivor\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e(n = 2788)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep-value\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAge, years, mean (SD)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e70.8 \\u0026plusmn; 13\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e62. 2 \\u0026plusmn; 16\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSex\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cul\\u003e\\n \\u003cli\\u003e\\u003cstrong\\u003eFemale, n (%)\\u003c/strong\\u003e\\u003c/li\\u003e\\n \\u003cli\\u003e\\u003cstrong\\u003eMale, n (%)\\u003c/strong\\u003e\\u003c/li\\u003e\\n \\u003c/ul\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003e411 (41)\\u003c/p\\u003e\\n \\u003cp\\u003e583 (59)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003e1142 (41)\\u003c/p\\u003e\\n \\u003cp\\u003e1644 (59)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e0.687\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eRace\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cul\\u003e\\n \\u003cli\\u003e\\u003cstrong\\u003eWhite/Caucasian, n (%)\\u003c/strong\\u003e\\u003c/li\\u003e\\n \\u003cli\\u003e\\u003cstrong\\u003eBlack/African American, n (%)\\u003c/strong\\u003e\\u003c/li\\u003e\\n \\u003cli\\u003e\\u003cstrong\\u003eAsian, n (%)\\u003c/strong\\u003e\\u003c/li\\u003e\\n \\u003cli\\u003e\\u003cstrong\\u003eUnknown/did not disclose, n (%)\\u003c/strong\\u003e\\u003c/li\\u003e\\n \\u003c/ul\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003e660 (66)\\u003c/p\\u003e\\n \\u003cp\\u003e258 (26)\\u003c/p\\u003e\\n \\u003cp\\u003e6 (0.6)\\u003c/p\\u003e\\n \\u003cp\\u003e70 (7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003e1724 (62)\\u003c/p\\u003e\\n \\u003cp\\u003e859 (31)\\u003c/p\\u003e\\n \\u003cp\\u003e17 (0.6)\\u003c/p\\u003e\\n \\u003cp\\u003e188 (7)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e0.670\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eEthnicity\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cul\\u003e\\n \\u003cli\\u003e\\u003cstrong\\u003eHispanic, n (%)\\u003c/strong\\u003e\\u003c/li\\u003e\\n \\u003cli\\u003e\\u003cstrong\\u003eNon-Hispanic, n (%)\\u003c/strong\\u003e\\u003c/li\\u003e\\n \\u003cli\\u003e\\u003cstrong\\u003eUnknown, n (%)\\u003c/strong\\u003e\\u003c/li\\u003e\\n \\u003c/ul\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003e75 (8)\\u003c/p\\u003e\\n \\u003cp\\u003e901 (91)\\u003c/p\\u003e\\n \\u003cp\\u003e18 (1)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003e194 (7)\\u003c/p\\u003e\\n \\u003cp\\u003e2525 (91)\\u003c/p\\u003e\\n \\u003cp\\u003e69 (2)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e0.415\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBMI (kg/m\\u003csup\\u003e2\\u003c/sup\\u003e)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e30.7 \\u0026plusmn; 8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e32.4 \\u0026plusmn; 9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMechanical Ventilation, yes, n (%)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e725 (73)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e1013 (36)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMechanical Ventilation duration days, mean (SD)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e12.4 \\u0026plusmn; 13\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e14.2 \\u0026plusmn; 15.4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e0.011\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eRASS, median [IQR]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e-1.4 \\u0026plusmn; 1.7\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e-0.6 \\u0026plusmn; 1.2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePT, yes, n (%)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e354 (35)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e1846 (66)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eOT, yes, n (%)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e275 (34)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e1423 (57)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTime to 1\\u003csup\\u003est\\u003c/sup\\u003e PT, days, mean (SD)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e5.8 \\u0026plusmn; 7.8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e7.8 \\u0026plusmn; 8.1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTime to 1\\u003csup\\u003est\\u003c/sup\\u003e OT, days, mean (SD)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e5.6 \\u0026plusmn; 6.9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e7.8 \\u0026plusmn; 7.6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNumber of total PT sessions, mean (SD)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e2.8 \\u0026plusmn; 5.7\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e4.6 \\u0026plusmn; 5.2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eNumber of total OT sessions, mean (SD)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e2.4 \\u0026plusmn; 3.4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e3.1 \\u0026plusmn; 3.6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePT Frequency days / week\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e0.16 \\u0026plusmn; 0.11\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e0.24 \\u0026plusmn; 0.14\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eOT Frequency days / week\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e0.13 \\u0026plusmn; 0.10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e0.18 \\u0026plusmn; 0.11\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAM-PAC at PT evaluation\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e(6-24, 24 = greater functional independence)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e12.3 \\u0026plusmn; 5.3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e14.2 \\u0026plusmn; 5.8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAM-PAC, last recorded\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e(6-24, 24 = greater functional independence)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e11.3 \\u0026plusmn; 5.1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e16.4 \\u0026plusmn; 5.7\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAMPAC Change\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e-0.9 \\u0026plusmn; 3.3\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e2.2 \\u0026plusmn; 4.3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp; \\u0026nbsp; \\u0026nbsp; JHHLM- initial\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e3.9 \\u0026plusmn; 1.8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e4.4 \\u0026plusmn; 1.8\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp; 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1.9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp; \\u0026nbsp; \\u0026nbsp; JHHLM-4\\u003csup\\u003eth\\u003c/sup\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e3.0 \\u0026plusmn; 1.4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e4.9 \\u0026plusmn; 1.9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp; \\u0026nbsp; \\u0026nbsp; JHHLM Change\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e-0.8 \\u0026plusmn; 1.7 \\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e1.1 \\u0026plusmn; 2.0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eRehabilitation Dosage (JHHLM average * Frequency)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e0.97 \\u0026plusmn; 0.73\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e1.90 \\u0026plusmn; 1.4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eICU LOS, days, median [IQR]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e11.6 \\u0026plusmn; 12.5\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e8.3 \\u0026plusmn; 11.2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e\\u0026lt;0.001\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"52.94117647058823%\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eHospital LOS, days, median [IQR]\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"21.008403361344538%\\\"\\u003e\\n \\u003cp\\u003e15.5 \\u0026plusmn; 13.6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"15.126050420168067%\\\"\\u003e\\n \\u003cp\\u003e16.6 \\u0026plusmn; 16.1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd width=\\\"10.92436974789916%\\\"\\u003e\\n \\u003cp\\u003e0.064\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd width=\\\"100%\\\" colspan=\\\"4\\\"\\u003e\\n \\u003cp\\u003eBMI = boody mass index; RASS = Richmond Agitation Sedation Scale; PT = physical therapy; OT = occupational therapy; AMPAC = Activity Measure-Post Acute Care (AM-PAC) \\u0026ldquo;6-Clicks\\u0026rdquo; Inpatient Mobility Short Form; JHHLM = \\u0026nbsp; \\u0026nbsp; the John Hopkins-Highest Level of Mobility; LOS = Length of stay;\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"critical-care\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"cric\",\"sideBox\":\"Learn more about [Critical Care](http://ccforum.biomedcentral.com/)\",\"snPcode\":\"13054\",\"submissionUrl\":\"https://submission.nature.com/new-submission/13054/3\",\"title\":\"Critical Care\",\"twitterHandle\":\"@Crit_Care\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC/SO AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Phsyical rehabilitation, early mobilization, critical illness, occupational therapy, physical therapy, COVID\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4319133/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4319133/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eObjective\\u003c/strong\\u003e: to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDesign: \\u003c/strong\\u003eRetrospective\\u003cstrong\\u003e \\u003c/strong\\u003epractice\\u003cstrong\\u003e \\u003c/strong\\u003eanalysis from March 5, 2020, to April 15, 2021.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eSetting: \\u003c/strong\\u003eIntensive care units (ICU) at four medical institutions\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePatients: \\u003c/strong\\u003en =\\u003cstrong\\u003e \\u003c/strong\\u003e3,780\\u003cstrong\\u003e \\u003c/strong\\u003eadults with ICU admission and diagnosis of COVID-19\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eInterventions: \\u003c/strong\\u003eWe measured the physical rehabilitation treatment delivered in ICU and patient outcomes: 1) mortality; 2) discharge disposition; and 3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) “6-Clicks” (6-24, 24=greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMeasurements and Main Results: \\u003c/strong\\u003eThe cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m\\u003csup\\u003e2\\u003c/sup\\u003e and 46% (n=1739) required mechanical ventilation. For 2191 patients with complete data, rehabilitation dosage and AM-PAC at discharge were moderately, positively associated (Spearman’s rho [r] = 0.484, p \\u0026lt; 0.001). Multivariate linear regression (model adjusted R\\u003csup\\u003e2\\u003c/sup\\u003e= 0.68, p \\u0026lt;0.001) demonstrates mechanical ventilation (β = -0.86, p = 0.001), average mobility score in first three sessions (β = 2.6, p \\u0026lt;0.001) and physical rehabilitation dosage (β = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions: \\u003c/strong\\u003eGreater physical rehabilitation exposure early in the ICU is associated with physical function at hospital discharge.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Early physical rehabilitation dosage in the Intensive Care Unit predicts hospital outcomes after critical COVID-19\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-05-15 14:33:41\",\"doi\":\"10.21203/rs.3.rs-4319133/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2024-06-10T14:23:53+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2024-06-10T09:15:20+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2024-05-11T08:30:06+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"128091822473206155566557634698227906961\",\"date\":\"2024-05-08T08:43:43+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"40956334666867143479652239028067014736\",\"date\":\"2024-05-07T19:22:53+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2024-05-07T10:46:03+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2024-05-06T09:38:42+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2024-05-06T09:38:42+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Critical Care\",\"date\":\"2024-04-24T15:01:56+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"critical-care\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"cric\",\"sideBox\":\"Learn more about [Critical Care](http://ccforum.biomedcentral.com/)\",\"snPcode\":\"13054\",\"submissionUrl\":\"https://submission.nature.com/new-submission/13054/3\",\"title\":\"Critical Care\",\"twitterHandle\":\"@Crit_Care\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC/SO AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"220a29e9-efe1-426a-ba02-bd12e6835b03\",\"owner\":[],\"postedDate\":\"May 15th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-08-01T17:20:14+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-4319133\",\"link\":\"https://doi.org/10.1186/s13054-024-05035-6\",\"journal\":{\"identity\":\"critical-care\",\"isVorOnly\":false,\"title\":\"Critical Care\"},\"publishedOn\":\"2024-07-18 15:57:17\",\"publishedOnDateReadable\":\"July 18th, 2024\"},\"versionCreatedAt\":\"2024-05-15 14:33:41\",\"video\":\"\",\"vorDoi\":\"10.1186/s13054-024-05035-6\",\"vorDoiUrl\":\"https://doi.org/10.1186/s13054-024-05035-6\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4319133\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4319133\",\"identity\":\"rs-4319133\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}