Twenty-four-hour fluid administration in emergency department patients with suspected infection: A multicenter, prospective, observational study.

BACKGROUND: To describe 24-hour fluid administration in emergency department (ED) patients with suspected infection. METHODS: A prospective, multicenter, observational study conducted in three Danish hospitals, January 20 to March 2, 2020. We included consecutive adult ED patients with suspected infection (drawing of blood culture and/or intravenous antibiotic administration within 6 hours of admission). Oral and intravenous fluids were registered for 24 hours. PRIMARY OUTCOME: 24-hour total fluid volume. We used linear regression to investigate patient and disease characteristics' effect on 24-hour fluids and to estimate the proportion of the variance in fluid administration explained by potential predictors. RESULTS: 734 patients had 24-hour fluids available: 387 patients had simple infection, 339 sepsis, eight septic shock. Mean total 24-hour fluid volumes were 3656 mL (standard deviation [SD]:1675), 3762 mL (SD: 1839), and 6080 mL (SD: 3978) for the groups, respectively. Fluid volumes varied markedly. Increasing age (mean difference [MD]: 60-79 years: -470 mL [95% CI: -789, -150], +80 years; -974 mL [95% CI: -1307, -640]), do-not-resuscitate orders (MD: -466 mL [95% CI: -797, -135]), and preexisting atrial fibrillation (MD: -367 mL [95% CI: -661, -72) were associated with less fluid. Systolic blood pressure < 100 mmHg (MD: 1182 mL [95% CI: 820, 1543]), mean arterial pressure < 65 mmHg (MD: 1317 mL [95% CI: 770, 1864]), lactate ≥ 2 mmol/L (MD: 655 mL [95% CI: 306, 1005]), heart rate > 120 min (MD: 566 [95% CI: 169, 962]), low (MD: 1963 mL [95% CI: 813, 3112]) and high temperature (MD: 489 mL [95% CI: 234, 742]), SOFA score > 5 (MD: 1005 mL [95% CI: 501, 510]), and new-onset atrial fibrillation (MD: 498 mL [95% CI: 30, 965]) were associated with more fluid. Clinical variables explained 37% of fluid variation among patients. CONCLUSIONS: Patients with simple infection and sepsis received equal fluid volumes. Fluid volumes varied markedly, a variation that was partly explained by clinical characteristics.

Improving quality of care in peptic ulcer bleeding: nationwide cohort study of 13,498 consecutive patients in the Danish Clinical Register of Emergency Surgery.

OBJECTIVES: The treatment of peptic ulcer bleeding (PUB) is complex, and mortality remains high. We present results from a nationwide initiative to monitor and improve the quality of care (QOC) in PUB. METHODS: All Danish hospitals treating PUB patients between 2004 and 2011 prospectively registered demographic, clinical, and prognostic data. QOC was evaluated using eight process and outcome indicators, including time to initial endoscopy, hemostasis obtainment, proportion undergoing surgery, rebleeding risks, and 30-day mortality. RESULTS: A total of 13,498 PUB patients (median age 74 years) were included, of which one-quarter were in-hospital bleeders. Preadmission use of anticoagulants, multiple coexisting diseases, and the American Society of Anesthesiologists scores increased between 2004 and 2011. Considerable improvements were observed for most QOC indicators over time. Endoscopic treatment was successful with primary hemostasis achieved in more patients (94% in 2010-2011 vs. 89% in 2004-2006, relative risk (RR) 1.06 (95% confidence intervals 1.04-1.08)), endoscopy delay for hemodynamically unstable patients decreased during this period (43% vs. 34% had endoscopy within 6 h, RR 1.33 (1.10-1.61)), and fewer patients underwent open surgery (4% vs. 6%, RR 0.72 (0.59-0.87)). After controlling for time changes in prognostic factors, rebleeding rates improved (13% vs. 18%, adjusted RR 0.77 (0.66-0.91)). Crude 30-day mortality was unchanged (11% vs. 11%), whereas adjusted mortality decreased nonsignificantly over time (adjusted RR 0.89 (0.78-1.00)). CONCLUSIONS: QOC in PUB has improved substantially in Denmark, but the 30-day mortality remains high. Future initiatives to improve outcomes may include earlier endoscopy, having fully trained endoscopists on call, and increased focus on managing coexisting disease.

Development and validation of a simulation-based assessment tool in colonoscopy.

BACKGROUND: Colonoscopy is difficult to learn. Virtual reality simulation training is helpful, but how and when novices should progress to patient-based training has yet to be established. To date, there is no assessment tool for credentialing novice endoscopists prior to clinical practice. The aim of this study was to develop such an assessment tool based on metrics provided by the simulator. The metrics used for the assessment tool should be able to discriminate between novices, intermediates, and experts and include essential checklist items for patient safety. METHODS: The validation process was conducted based on the Standards for Educational and Psychological Testing. An expert panel decided upon three essential checklist items for patient safety based on Lawshe's method: perforation, hazardous tension to the bowel wall, and cecal intubation. A power calculation was performed. In this study, the Simbionix GI Mentor II simulator was used. Metrics with discriminatory ability were identified with variance analysis and combined to form an aggregate score. Based on this score and the essential items, pass/fail standards were set and reliability was tested. RESULTS: Twenty-four participants (eight novices, eight intermediates, and eight expert endoscopists) performed two simulated colonoscopies. Four metrics with discriminatory ability were identified. The aggregate score ranged from 4.2 to 51.2 points. Novices had a mean score of 10.00 (SD 5.13), intermediates 24.63 (SD 7.91), and experts 30.72 (SD 11.98). The difference in score between novices and the other two groups was statistically significant (p<0.01). Although expert endoscopists had a higher score, the difference was not statistically significant (p=0.40). Reliability was good (Cronbach's alpha=0.86). A pass/fail score was defined at 17.1 points with correct completion of three essential checklist items, resulting in three experts and three intermediates failing and one novice passing the assessment. CONCLUSION: We established a valid and reliable assessment tool with a pass/fail standard on the simulator. We suggest using the assessment after simulation-based training before commencing work-based learning.

Publisher Correction: MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer.

Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clinical and archival material. We present MethCORR, an approach that allows uniform molecular characterization and classification of fresh-frozen and FFPE samples. MethCORR identifies genome-wide correlations between RNA expression and DNA methylation in fresh-frozen samples. This information is used to infer gene expression information in FFPE samples from their methylation profiles. MethCORR is here applied to methylation profiles from 877 fresh-frozen/FFPE samples and comparative analysis identifies the same two subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicts relapse-free survival (HR = 2.66, 95%CI [1.67-4.22], P value < 0.001 (log-rank test)) than UICC tumor, node, metastasis (TNM) staging and microsatellite instability status are identified and validated using DNA methylation-specific PCR. The MethCORR approach is general, and may be similarly successful for other cancer types.