Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations.

Importance
The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.


Objective
To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.


Design, Setting, and Participants
Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.


Interventions
Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).


Main Outcomes and Measures
The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.


Results
Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.


Conclusions and Relevance
Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

Acute respiratory distress syndrome (ARDS) is frequently associated with sepsis. ARDS and sepsis exhibit a common pathobiology, namely excessive inflammation. Corticosteroids are powerful anti-inflammatory agents that are routinely used in septic shock and in oxygen-dependent SARS-CoV-2 related acute respiratory failure. Recently, corticosteroids were found to reduce mortality in severe community-acquired pneumonia. Corticosteroids may therefore also have a role to play in the treatment of ARDS. This narrative review was undertaken following a PubMed search for English language reports published before January 2023 using the terms acute respiratory distress syndrome, sepsis and steroids. Additional reports were identified by examining the reference lists of selected articles and based on personnel knowledge of the authors of the field. High-quality research is needed to fully understand the role of corticosteroids in the treatment of ARDS and to determine the optimal timing, dosing and duration of treatment.

https://www.mdpi.com/2077-0383/12/9/3340/pdf?version=1683538563

Corticosteroids in ARDS.

The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5–24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (<60%), and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) number of symptoms of 5.7 ± 4.6, and 61.3% met the criteria for post-COVID syndrome at 1 year. During the follow-up, 46 patients were discharged, and 16 were transferred to other consultations. Other conditions, such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%), and lung cancer (1%) were identified. A high use of health care resources is observed in the first year. In conclusion, one-third of critically ill COVID-19 patients need to continue follow-up beyond 1 year, due to abnormalities on DLCO, chest CT, or persistent symptoms.

One Year Overview and Follow-Up in a Post-COVID Consultation of Critically Ill Patients

Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness.

Abstract Purpose Nystagmus is a disorder characterized by uncontrolled, rhythmic oscillations of the eyes. It often causes reduced visual function beyond reduced visual acuity alone. There is a paucity of literature regarding the public understanding of nystagmus, and there are no published data on the impact of the COVID-19 pandemic on people living with the condition. This study explores the self-reported impact of the COVID-19 pandemic on those with nystagmus, and examines both public understanding of how nystagmus affects people who have it and the perceptions of public understanding by those with the condition and their carers. Methods A qualitative questionnaire was designed following a stakeholder engagement process. This questionnaire was advertised via social media platforms and charity websites to achieve widespread recruitment. Data were collected between November and December 2020. Participants were divided into two groups based on their response to the question: “Do you, or anyone you know well, have nystagmus?”. Questions were posed to participants in a purpose-built, branching survey. The resulting data were analyzed using descriptive and inferential statistical methods. Results One thousand six hundred forty-five respondents were recruited, of which 849 (51.6%) answered “Yes” to the initial filtering question. Analysis showed that, broadly, public understanding of nystagmus differs from the perception of it by those with nystagmus and their carers, that the COVID-19 pandemic has had a significant impact on those with nystagmus, and that respondents who have met someone with nystagmus, even briefly, tend to have a greater understanding of the impact of the condition. Conclusion This study highlights the lack of public awareness regarding nystagmus and suggests opportunities to increase the awareness of nystagmus without the need for extensive knowledge of the condition. The COVID-19 pandemic has posed additional difficulties for those living with nystagmus, which is likely to be comparable among those with similar ocular disorders. 

/pdf/impact-of-the-covid-19-pandemic-on-individuals-with-1tf0aep7.pdf

Impact of the COVID-19 pandemic on individuals with nystagmus and an exploration of public assumptions about the condition: an electronic questionnaire study

Rationale The outcomes of survivors of critical illness due to coronavirus disease (COVID-19) compared with non–COVID-19 are yet to be established. Objectives We aimed to investigate new disability at 6 months in mechanically ventilated patients admitted to Australian ICUs with COVID-19 compared with non–COVID-19. Methods We included critically ill patients with COVID-19 and non–COVID-19 from two prospective observational studies. Patients were eligible if they were adult (age ⩾ 18 yr) and received ⩾24 hours of mechanical ventilation. In addition, patients with COVID-19 were eligible with a positive laboratory PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Measurements and Main Results Demographic, intervention, and hospital outcome data were obtained from electronic medical records. Survivors were contacted by telephone for functional outcomes with trained outcome assessors using the World Health Organization Disability Assessment Schedule 2.0. Between March 6, 2020, and April 21, 2021, 120 critically ill patients with COVID-19, and between August 2017 and January 2019, 199 critically ill patients without COVID-19, fulfilled the inclusion criteria. Patients with COVID-19 were older (median [interquartile range], 62 [55–71] vs. 58 [44–69] yr; P = 0.019) with a lower Acute Physiology and Chronic Health Evaluation II score (17 [13–20] vs. 19 [15–23]; P = 0.011). Although duration of ventilation was longer in patients with COVID-19 than in those without COVID-19 (12 [5–19] vs. 4.8 [2.3–8.8] d; P < 0.001), 180-day mortality was similar between the groups (39/120 [32.5%] vs. 70/199 [35.2%]; P = 0.715). The incidence of death or new disability at 180 days was similar (58/93 [62.4%] vs. 99/150 [66/0%]; P = 0.583). Conclusions At 6 months, there was no difference in new disability for patients requiring mechanical ventilation for acute respiratory failure due to COVID-19 compared with non–COVID-19. Clinical trial registered with www.clinicaltrials.gov (NCT04401254).

https://doi.org/10.1164/rccm.202110-2335oc

Comparison of 6-Month Outcomes of Survivors of COVID-19 versus Non–COVID-19 Critical Illness

OBJECTIVE
Hip fractures are common and significantly impact mobility and physical function. Measurement of patient progress post hip fracture in the acute hospital setting is important to monitor early recovery and outcomes. The objective of this systematic review was to assess the measurement properties (reliability, validity, responsiveness), interpretability, and clinical utility of instruments used to measure mobility and physical function in patients with hip fracture in the acute hospital setting.


METHODS
Three databases (MEDLINE, Embase, and CINAHL) were searched. Studies reporting direct clinician assessment instruments to measure mobility or physical function in patients with hip fracture were included. Data were extracted by 2 reviewers and the quality of each study was determined using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias checklist.


RESULTS
Sixty-eight studies were included with 19 measurement instruments identified. The most frequently used instruments were the Timed "Up & Go" Test (TUG) (19 studies), Barthel Index (BI) (18 studies), Cumulated Ambulation Score (CAS) (18 studies), and Functional Independence Measure (FIM) (14 studies). All 4 of these instruments demonstrated good predictive validity (clinical outcomes and mortality) and responsiveness over time (effect sizes 0.63-2.79). The BI and CAS also had good reliability (ICC >0.70). Floor effects were demonstrated for the TUG, CAS and FIM (16%-60% of patients). The TUG, CAS and BI all had good clinical utility.


CONCLUSION
Depending on the context (use by treating clinicians, research, benchmarking) 1 or a combination of the BI, CAS, and TUG provide robust measurement of mobility and physical function for patients with hip fracture in the acute hospital setting.


IMPACT
This study identified 3 instruments suitable for measuring mobility and physical function in hospitalised patients following hip fracture. This provides clinicians with tools to measure patient progress and benchmark across sites to improve patient outcomes.

Measurement of Mobility and Physical Function in Patients Who Are Hospitalized With Hip Fracture: A Systematic Review of Instruments and Their Measurement Properties.

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Papers

Impact of the COVID-19 pandemic on individuals with nystagmus and an exploration of public assumptions about the condition: an electronic questionnaire study

Comparison of 6-Month Outcomes of Survivors of COVID-19 versus Non–COVID-19 Critical Illness

Measurement of Mobility and Physical Function in Patients Who Are Hospitalized With Hip Fracture: A Systematic Review of Instruments and Their Measurement Properties.