Utility and limitations of patient-adjusted D-dimer cut-off levels for diagnosis of venous thromboembolism-A systematic review and meta-analysis.

PURPOSE: To systematically assess test performance of patient-adapted D-dimer cut-offs for the diagnosis of venous thromboembolism (VTE). METHODS: Systematic review and analysis of articles published in PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. Investigations assessing patient-adjusted D-dimer thresholds for the exclusion of VTE were included. A hierarchical summary receiver operating characteristic model was used to assess diagnostic accuracy. Risk of bias was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 score. RESULTS: A total of 68 studies involving 141,880 patients met the inclusion criteria. The standard cut-off revealed a sensitivity of 0.99 (95% confidence interval [CI] 0.98-0.99) and specificity of 0.23 (95% CI 0.16-0.31). Sensitivity was comparable to the standard cut-off for age-adjustment (0.97 [95% CI 0.96-0.98]) and YEARS algorithm (0.98 [95% CI 0.91-1.00]) but lower for pretest probability (PTP)-adjusted (0.95 [95% CI 0.89-0.98) and COVID-19-adapted thresholds (0.93 [95% CI 0.82-0.98]). Specificity was significantly higher across all adjustment strategies (age: 0.43 [95% CI 0.36-0.50]; PTP: 0.63 [95% CI 0.51-0.73]; YEARS algorithm: 0.65 [95% CI 0.39-0.84]; and COVID-19: 0.51 [95% CI 0.40-0.63]). The YEARS algorithm provided the best negative likelihood ratio (0.03 [95% CI 0.01-0.15]), followed by age-adjusted (both 0.07 [95% CI 0.05-0.09]), PTP (0.08 [95% CI 0.04-0.17), and COVID-19-adjusted thresholds (0.13 [95% CI 0.05-0.32]). CONCLUSIONS: This study indicates that adjustment of D-dimer thresholds to patient-specific factors is safe and embodies considerable potential for reduction of imaging. However, robustness, safety, and efficiency vary considerably among different adjustment strategies with a high degree of heterogeneity.

Early Rehabilitation Interventions and Physical Therapy in Adults Who Were Critically Ill With COVID-19 Pneumonia: A Retrospective Observational Study.

OBJECTIVE: The primary objective of this observational study was to analyze the time to the first edge-of-bed (EOB) mobilization in adults who were critically ill with severe versus non-severe COVID-19 pneumonia. Secondary objectives included the description of early rehabilitation interventions and physical therapy delivery. METHODS: All adults with laboratory-confirmed COVID-19 requiring intensive care unit admission for ≥72 hours were included and divided according to their lowest PaO2/FiO2 ratio into severe (≤100 mmHg) or non-severe (>100 mmHg) COVID-19 pneumonia. Early rehabilitation interventions consisted of in-bed activities, EOB or out-of-bed mobilizations, standing, and walking. The Kaplan-Meier estimate and logistic regression were used to investigate the primary outcome time-to-EOB and factors associated with delayed mobilization. RESULTS: Among the 168 patients included in the study (mean age = 63 y [SD = 12 y]; Sequential Organ Failure Assessment = 11 [interquartile range = 9-14]), 77 (46%) were classified as non-severe, and 91 (54%) were classified as severe COVID-19 pneumonia. Median time-to-EOB was 3.9 days (95% CI = 2.3-5.5) with significant differences between subgroups (non-severe = 2.5 days [95% CI = 1.8-3.5]; severe = 7.2 days [95% CI = 5.7-8.8]). Extracorporeal membrane oxygenation use and high Sequential Organ Failure Assessment scores (adjusted effect = 13.7 days [95% CI = 10.1-17.4] and 0.3 days [95% CI = 0.1-0.6]) were significantly associated with delayed EOB mobilization. Physical therapy started within a median of 1.0 days (95% CI = 0.9-1.2) without subgroup differences. CONCLUSION: This study shows that early rehabilitation and physical therapy within the recommended 72 hours during the COVID-19 pandemic could be maintained regardless of disease severity. In this cohort, the median time-to-EOB was fewer than 4 days, with disease severity and advanced organ support significantly delaying the time-to-EOB. IMPACT: Early rehabilitation in the intensive care unit could be sustained in adults who are critically ill with COVID-19 pneumonia and can be implemented with existing protocols. Screening based on the PaO2/FiO2 ratio might reveal patients at risk and increased need for physical therapy.