Investigating the Relationships Between Three Important Functional Tasks Early After Stroke: Movement Characteristics of Sit-To-Stand, Sit-To-Walk, and Walking.

Background: Walking, sit-to-stand (STS) and sit-to-walk (STW) are all considered important functional tasks in achieving independence after stroke. Despite knowledge that sensitive measurement of movement patterns is crucial to understanding neuromuscular restitution, there is surprisingly little information available about the detailed biomechanical characteristics of, and relationships between, walking, sit-to-stand and sit-to-walk, particularly in the important time window early after stroke. Hence, here, the study aimed to: Identify the biomechanical characteristics of and determine any differences in both movement fluidity (hesitation, coordination and smoothness) and duration of movement phases, between sit-to-stand (STS) and sit-to-walk (STW) in people early after stroke.Determine whether measures of movement fluidity (hesitation, coordination, and smoothness) and movement phases during sit-to-stand (STS) and/or sit-to-walk (STW) are correlated strongly to commonly used measures of walking speed and/or step length ratio in people early after stroke. Methods: This study consisted of secondary data analysis from the SWIFT Cast Trial. Specifically, we investigated movement fluidity using established assessments of smoothness, hesitation and coordination and the time duration for specific movement phases in a group of 48 people after stroke. Comparisons were made between STS and STW and relationships to walking measures were explored. Results: Participants spent significantly more time in the initial movement phase, flexion momentum, during STS [mean time (SD) 1.74 ±1.45 s] than they did during STW [mean time (SD) 1.13 ± 1.03 s]. STS was also completed more smoothly but with more hesitation and greater coordination than the task of STW. No strong relationships were found between movement fluidity or duration with walking speed or step length symmetry. Conclusions: Assessment of movement after stroke requires a range of functional tasks and no one task should predominate over another. Seemingly similar or overlapping tasks such as STS and STW create distinct biomechanical characteristics which can be identified using sensitive, objective measures of fluidity and movement phases but there are no strong relationships between the functional tasks of STS and STW with walking speed or with step-length symmetry

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The effect of physiotherapy treatment on functional mobility skills of elderly people with severe dementia

The predicted `epidemic of dementia', present lack of a cure, attitudinal changes towards institutionalisation and association of immobility with admission to long term care together highlight the need to research clinical claims that physiotherapy treatment improves mobility. Participants in this investigation were resident in hospital long term care (psychiatric). Mobility was measured by the Two Minute Walking Test and the assessment tool developed as part of this investigation. Biomechanical studies provided construct validity for the task analysis format which assessed ability from immobile (score 0) to walking four steps (score 18). Kappa coefficients for inter rater reliability ranged from 0.1, p&#60; 0.001 to 0.92, p&#60; 0.0001 with only three items being below 0.5. Thirty five people participated in a descriptive longitudinal study. Trends found suggested that natural improvements may be unlikely and that mobility was lower in the 17 participants who died during the year than those resident at the end of the study. In addition mobility may also be lower in the presence of abnormalities of muscle tone, posture and sitting balance but no differences were found in these neuromuscular features between those who died and those who survived. The response to physiotherapy treatment (functional mobility training, music and movement and body awareness) was examined by two studies. First sixteen people completed a randomised crossover study. In comparison with change of scores during the control phase the treatment phase showed a significant improvement (p&#61; 0.043). Secondly seven people completed all phases of an ABAB single case study. Six of these significantly improved mobility score when physiotherapy was introduced for the first time but maintenance of improvements was equivocal. Results suggest that poor sitting balance on initial assessment may be associated with deteriorating health (9 participants withdrew). The findings of this initial investigation suggest that physiotherapy treatment may improve mobility of elderly people with severe dementia. Therapeutic optimism is encouraged. Hypotheses for testing by controlled clinical trials have been generated.</p

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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