Factors associated with non‐response at health‐related quality of life follow‐up in a septic shock trial

Background ICU admission due to COVID‐19 may result in cognitive and physical impairment. We investigated the long‐term cognitive and physical status of Danish ICU patients with COVID‐19. Methods We included all patients with COVID‐19 admitted to Danish ICUs between March 10 and May 19, 2020. Patients were the contacted prospectively at 6 and 12 months for follow‐up. Our primary outcomes were cognitive function and frailty at 6 and 12 months after ICU admission, estimated by the Mini Montreal Cognitive Assessment, and the Clinical Frailty Scale. Secondary outcomes were 6‐ and 12‐month mortality, health‐related quality of life (HRQoL) assessed by EQ‐5D‐5L, functional status (Barthel activities of daily living and Lawton–Brody instrumental activities of daily living), and fatigue (Fatigue Assessment Scale). The study had no information on pre‐ICU admission status for the participants. Results A total of 326 patients were included. The 6‐ and 12‐month mortality was 37% and 38%, respectively. Among the 204 six‐month survivors, 105 (51%) participated in the 6‐month follow‐up; among the 202 twelve‐month survivors, 95 (47%) participated in the 12‐month follow‐up. At 6 months, cognitive scores indicated impairment for 26% (95% confidence interval [CI], 11.4–12.4) and at 12 months for 17% (95% CI, 12.0–12.8) of participants. Frailty was indicated in 20% (95% CI, 3.4–3.9) at 6 months, and for 18% (95% CI, 3.3–3.8) at 12 months. Fatigue was reported by 52% at 6 months, and by 47% at 12 months. For HRQoL, moderate, severe, or extreme health problems were reported by 28% at 6 months, and by 25% at 12 months. Conclusion Long‐term cognitive, functional impairment was found in up to one in four of patients surviving intensive care for COVID‐19. Fatigue was present in nearly half the survivors at both 6 and 12 months. However, pre‐ICU admission status of the patients was unknown.

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 57%

Long‐term cognitive and functional status in Danish ICU patients with COVID‐19

Weihe

Mortensen

Haase

et al. 2022

“…First, as expected, 11 the amounts of missing data were non‐negligible in both trial databases for HRQoL. This was handled using multiple imputations as specified in the protocol, 11 since missingness for HRQoL data is unlikely to be missing‐completely‐at‐random 38 . We assumed that missing data were missing‐at‐random and that missing data could be reasonably predicted from the other available data; 11 inherently, the missing‐at‐random assumption cannot be verified.…”

Section: Discussionmentioning

confidence: 99%

Association between days alive without life support/out of hospital and health‐related quality of life

Granholm

Schjørring

Jensen

et al. 2023

Background Trials in critically ill patients increasingly focus on days alive without life support (DAWOLS) or days alive out of hospital (DAOOH) and health‐related quality of life (HRQoL). DAWOLS and DAOOH convey more information than mortality and are simpler and faster to collect than HRQoL. However, whether these outcomes are associated with HRQoL is uncertain. We thus aimed to assess the associations between DAWOLS and DAOOH and long‐term HRQoL. Methods Secondary analysis of the COVID STEROID 2 trial including adults with COVID‐19 and severe hypoxaemia and the Handling Oxygenation Targets in the Intensive Care Unit (HOT‐ICU) trial including adult intensive care unit patients with acute hypoxaemic respiratory failure. Associations between DAWOLS and DAOOH at day 28 and 90 and long‐term HRQoL (after 6 or 12 months) using the EuroQol 5‐dimension 5‐level survey (EQ VAS and EQ‐5D‐5L index values) were assessed using flexible models and evaluated using measures of fit and prediction adequacy in both datasets (comprising internal performance and external validation), non‐parametric correlation coefficients and graphical presentations. Results We found no strong associations between DAWOLS or DAOOH and HRQoL in survivors at HRQoL‐follow‐up (615 and 1476 patients, respectively). There was substantial variability in outcomes, and predictions from the best fitted models were poor both internally and externally in the other trial dataset, which also showed inadequate calibration. Moderate associations were found when including non‐survivors, although predictions remained uncertain and calibration inadequate. Conclusion DAWOLS and DAOOH were poorly associated with HRQoL in adult survivors of severe or critical illness included in the COVID STEROID 2 and HOT‐ICU trials.

Section: Introductionmentioning

confidence: 99%

“…Loss-to-follow-up, and thereby missing data, may impact HRQoL results 7,8,13,14 and introduce attrition bias, as non-response may be associated with severity of illness and other patient characteristics. 7,8,13,14 Transparency in reporting and handling of missing data is therefore imperative for valid interpretation of trial results. 12,15,16 Complete case analysis, which disregards patients with missing data, has been reported as the most frequent approach for HRQoL outcomes, 17 however, excluding patients with missing data impacts the power and potentially the validity on the outcome if data are not missing completely at random.…”

Section: Introductionmentioning

confidence: 99%

Non‐response for health‐related quality of life outcomes in ICU patients: A systematic review of the reporting in randomised trials

Kjær

Madsen

Granholm

et al. 2023

Background: Health-related quality of life (HRQoL) is frequently assessed in randomised clinical trials (RCTs) in the intensive care unit (ICU), but data are limited regarding the proportions of patients without responses or not surviving to HRQoL follow-up and the handling of this. We aimed to describe the extent and pattern of missing HRQoL data in intensive care trials and describe how these data and deaths were handled statistically.Methods: We conducted a systematic review and meta-analysis following a published protocol. We searched PubMed, EMBASE, CINAHL and Cochrane Library for RCTs involving adult ICU patients reporting HRQoL as an outcome and excluded RCTs unobtainable in full text. We performed risk of bias assessment independently and in duplicate. Results:We included 196 outcomes from 88 RCTs published in the years 2002-2022; the numbers of patients alive and eligible to respond HRQoL were reported in 76% of trials. At follow-up, median 27% (interquartile range 14%-39%) of patients had died, and median 20% (9%-38%) of survivors did not respond across outcomes.Analyses of 80% of outcomes were restricted to complete cases only. The handling of non-survivors in analyses were reported for 46% of outcomes, with 26% of all outcomes reported as including non-survivors (using the value zero or the worst possible score). Conclusion:For HRQoL outcomes in ICU trials, we found that mortality at time of follow-up was high and non-response among survivors frequent. The reporting and statistical handling of these issues were insufficient, which may have biased results.