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

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.

Paracetamol, non-steroidal anti-inflammatory drugs and glucocorticoids for postoperative pain: A protocol for a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Multimodal analgesia is the leading principle for managing postoperative pain. Recent guidelines recommend combinations of paracetamol and a non-steroidal anti-inflammatory drug (NSAID) for most surgeries. Glucocorticoids have been used for decades due to their potent anti-inflammatory and antipyretic properties. Subsequently, glucocorticoids may improve postoperative analgesia. We will perform a systematic review to assess benefits and harms of adding glucocorticoids to paracetamol and NSAIDs. We expect to uncover pros and cons of the addition of glucocorticoid to the basic standard regimen of paracetamol and NSAIDs for postoperative analgesia. METHOD: This protocol for a systematic review was written according to the The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search for trials in the following electronic databases: Medline, CENTRAL, CDSR and Embase. Two authors will independently screen trials for inclusion using Covidence, extract data and assess risk of bias using Cochrane's ROB 2 tool. We will analyse data using Review Manager and Trial Sequential Analysis. Meta-analysis will be performed according to the Cochrane guidelines and results will be validated according to the eight-step procedure suggested by Jakobsen et al We will present our primary findings in a 'summary of findings' table. We will evaluate the overall certainty of evidence using the GRADE approach. DISCUSSION: This review will aim to explore the combination of glucocorticoids together with paracetamol and NSAIDs for postoperative pain. We will attempt to provide reliable evidence regarding the role of glucocorticoids as part of a multimodal analgesic regimen in combination with paracetamol and NSAID.

Ketamine for post-operative pain treatment in spinal surgery. A protocol for a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Post-operative pain treatment with ketamine has been demonstrated to have post-operative opioid-sparing and anti-hyperalgesic effects. However, evidence regarding the beneficial and harmful effects and the optimal dose and timing of perioperative treatment with ketamine for patients undergoing spinal surgery is unclear. The objective of this systematic review is to assess the analgesic, serious and non-serious adverse effects of perioperative pain treatment with ketamine for patients undergoing spinal surgery. METHODS: This protocol for a systematic review is written according to The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search Embase, CENTRAL, PubMed, WHO's ICTRP, EU Clinical Trial Register and ClinicalTrials.gov to identify relevant randomised clinical trials. We will include all randomised clinical trials assessing perioperative ketamine treatment versus placebo or no intervention for patients undergoing spinal surgery. Two authors will independently screen trials for inclusion using Covidence, extract data and assess risk of bias using Cochrane's RoB tool. We will analyse data using Review Manager and Trial Sequential Analysis. Meta-analysis will be performed according to the Cochrane guidelines and results will be validated according to the eight-step procedure suggested by Jakobsen et al. We will present our primary findings in a 'summary of findings' table. We will evaluate the overall certainty of evidence using the GRADE approach. DISCUSSION: This systematic review will assess the beneficial and harmful effects of perioperative pain treatment with ketamine for patients undergoing spinal surgery and have the potential to inform best practice and advance research.

A systematic review of trial registry entries for randomized clinical trials investigating COVID-19 medical prevention and treatment.

AIM: To identify investigated interventions for COVID-19 prevention or treatment via trial registry entries on planned or ongoing randomised clinical trials. To assess these registry entries for recruitment status, planned trial size, blinding and reporting of mortality. METHODS: We identified trial registry entries systematically via the WHO International Clinical Trials Registry Platform and 33 trial registries up to June 23, 2020. We included relevant trial registry entries for randomized clinical trials investigating medical preventive, adjunct or supportive therapies and therapeutics for treatment of COVID-19. Studies with non-random and single-arm design were excluded. Trial registry entries were screened by two authors independently and data were systematically extracted. RESULTS: We included 1303 trial registry entries from 71 countries investigating 381 different single interventions. Blinding was planned in 47% of trials. Sample size was >200 participants in 40% of trials and a total of 611,364 participants were planned for inclusion. Mortality was listed as an outcome in 57% of trials. Recruitment was ongoing in 54% of trials and completed in 8%. Thirty-five percent were multicenter trials. The five most frequent investigational categories were immune modulating drugs (266 trials (20%)), unconventional medicine (167 trials (13%)), antimalarial drugs (118 trials (9%)), antiviral drugs (100 trials (8%)) and respiratory adjuncts (78 trials (6%)). The five most frequently tested uni-modal interventions were: chloroquine/hydroxychloroquine (113 trials with 199,841 participants); convalescent plasma (64 trials with 11,840 participants); stem cells (51 trials with 3,370 participants); tocilizumab (19 trials with 4,139 participants) and favipiravir (19 trials with 3,210 participants). CONCLUSION: An extraordinary number of randomized clinical trials investigating COVID-19 management have been initiated with a multitude of medical preventive, adjunctive and treatment modalities. Blinding will be used in only 47% of trials, which may have influence on future reported treatment effects. Fifty-seven percent of all trials will assess mortality as an outcome facilitating future meta-analyses.