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Sepsis is a potentially life-threatening condition characterized by a deregulated body's response to infection causing injury to its own tissues and organs. Sepsis is the primary cause of death from infection. If not recognized and treated timely, it can evolve within minutes/hours to septic shock. Sepsis is associated with an acute deficiency of Vitamin C. Despite the proof-of-concept of the benefit of administering Vitamin C in patients with sepsis or septic shock, Vitamin C administration is not yet current practice. To investigate the potential benefit of early administration of high doses of Vitamin C in addition to standard of care in patients with sepsis or septic shock. This phase 3b multi-center trial is conducted in 8 hospitals throughout Belgium. In total 300 patients will be randomly assigned to one of two groups in a 1:1 allocation ratio. The intervention group will receive 1.5 g Vitamin C 4 times a day during 4 days, started within 6 hours after admission. The primary outcome is the average post-baseline patient SOFA score. This trial will determine whether the early administration of Vitamin C in patients with sepsis or septic shock can lead to a more rapid solution of shock and less deterioration from sepsis to septic shock, hereby reducing morbidity and mortality as well as the length of hospital stay in this patient population. The C-EASIE trial has been registered on the ClinicalTrials.gov website on 10 February 2021 with registration number NCT04747795. UZ Leuven (sponsor's reference S63213).

Background Sepsis and septic shock are associated with high mortality and morbidity despite adequate standard care. Vitamin C deficiency is a common, potentially reversible, contributor to morbidity and mortality in sepsis. Previous studies have shown mixed and conflicting results. Our study aimed to determine the potential benefit of early administration (within 6 h after admission) of vitamin C in patients with sepsis or septic shock. Methods This was a phase 3b prospective, multicenter, double-blinded, randomized placebo-controlled trial. Participants were enrolled in the Emergency Departments of 8 hospitals throughout Belgium. Patients were randomized to receive 1.5 g of vitamin C, or matching placebo, every 6 h for 4 days. The primary outcome was the average post-baseline patient Sequential Organ Failure Assessment (SOFA) score on day 2 to 5. Key secondary outcomes were the maximum SOFA score, 28-day mortality and length of ICU and hospital stay. Results A total of 300 patients were recruited between June 4th, 2021, and August 19th, 2023. 292 patients, of which 147 were assigned to the vitamin C and 145 to the placebo group, completed the trial and were included in the analysis. The primary outcome (vitamin C, 1.98; placebo, 2.19) was 8.7% lower in the vitamin C group, but not significantly (ratio 0.91, 95% CI 0.77 to 1.08, P  = 0.30). In a planned subgroup analysis, patients with a baseline SOFA score of 6 or above had a significant lower average post-baseline SOFA score in the vitamin C group (ratio 0.76, 95% CI 0.86 to 0.99, P  = 0.042). Findings were similar in the two groups regarding secondary outcomes and adverse events, except for a lower probability of being on renal replacement therapy in the vitamin C group of the per protocol analysis (ratio 0.28, 95% CI 0.078 to 1.0, P  = 0.05). Conclusions Early treatment with vitamin C did not result in a statistically significant reduction in organ dysfunction. Therefore, this study does not support the use of vitamin C in sepsis patients. Trial registration : ClinicalTrials.gov Identifier: NCT04747795 . Registered 4 February 2021. Key Points Question Does early treatment with vitamin C lead to a less severe disease course in patients with sepsis or septic shock? Findings In this randomized clinical trial that included 292 patients, treatment with intravenous vitamin C compared to placebo did not result in a lower average post-baseline patient Sequential Organ Failure Assessment (SOFA) score on day 2 to 5 (1.98 vs 2.19), except for a subgroup of patients with a baseline SOFA score of 6 or above. Meaning Early treatment with vitamin C did not result in a significant improvement of the disease course.

BackgroundSepsis is a potentially life-threatening condition characterized by a deregulated body's response to infection causing injury to its own tissues and organs. Sepsis is the primary cause of death from infection. If not recognized and treated timely, it can evolve within minutes/hours to septic shock. Sepsis is associated with an acute deficiency of Vitamin C. Despite the proof-of-concept of the benefit of administering Vitamin C in patients with sepsis or septic shock, Vitamin C administration is not yet current practice.ObjectiveTo investigate the potential benefit of early administration of high doses of Vitamin C in addition to standard of care in patients with sepsis or septic shock.MethodsThis phase 3b multi-center trial is conducted in 8 hospitals throughout Belgium. In total 300 patients will be randomly assigned to one of two groups in a 1:1 allocation ratio. The intervention group will receive 1.5 g Vitamin C 4 times a day during 4 days, started within 6 hours after admission. The primary outcome is the average post-baseline patient SOFA score.ConclusionThis trial will determine whether the early administration of Vitamin C in patients with sepsis or septic shock can lead to a more rapid solution of shock and less deterioration from sepsis to septic shock, hereby reducing morbidity and mortality as well as the length of hospital stay in this patient population.Trial registrationThe C-EASIE trial has been registered on the ClinicalTrials.gov website on 10 February 2021 with registration number NCT04747795.Trial sponsorUZ Leuven (sponsor's reference S63213).

BACKGROUND Growing evidence indicates that improved nurse staffing in acute hospitals is associated with lower hospital mortality. Current research is limited to studies using hospital level data or without proper adjustment for confounders which makes the translation to practice difficult. METHOD In this observational study we analysed retrospectively the control group of a stepped wedge randomised controlled trial concerning 14 medical and 14 surgical wards in seven Belgian hospitals. All patients admitted to these wards during the control period were included in this study. Pregnant patients or children below 17 years of age were excluded. In all patients, we collected age, crude ward mortality, unexpected death, cardiac arrest with Cardiopulmonary Resuscitation (CPR), and unplanned admission to the Intensive Care Unit (ICU). A composite mortality measure was constructed including unexpected death and death up to 72 hours after cardiac arrest with CPR or unplanned ICU admission. Every four months we obtained, from 30 consecutive patient admissions across all wards, the Charlson comorbidity index. The amount of nursing hours per patient days (NHPPD) were calculated every day for 15 days, once every four months. Data were aggregated to the ward level resulting in 68 estimates across wards and time. Linear mixed models were used since they are most appropriate in case of clustered and repeated measures data. RESULTS The unexpected death rate was 1.80 per 1000 patients. Up to 0.76 per 1000 patients died after CPR and 0.62 per 1000 patients died after unplanned admission to the ICU. The mean composite mortality was 3.18 per 1000 patients. The mean NHPPD and proportion of nurse Bachelor hours were respectively 2.48 and 0.59. We found a negative association between the nursing hours per patient day and the composite mortality rate adjusted for possible confounders (B= -2.771, p=0.002). The proportion of nurse Bachelor hours was negatively correlated with the composite mortality rate in the same analysis (B= -8.845, p=0.023). Using the regression equation, we calculated theoretically optimal NHPPDs. CONCLUSIONS This study confirms the association between higher nurse staffing levels and lower patient mortality controlled for relevant confounders.

Background Growing evidence indicates that improved nurse staffing in acute hospitals is associated with lower hospital mortality. Current research is limited to studies using hospital level data or without proper adjustment for confounders which makes the translation to practice difficult. Method In this observational study we analysed retrospectively the control group of a stepped wedge randomised controlled trial concerning 14 medical and 14 surgical wards in seven Belgian hospitals. All patients admitted to these wards during the control period were included in this study. Pregnant patients or children below 17 years of age were excluded. In all patients, we collected age, crude ward mortality, unexpected death, cardiac arrest with Cardiopulmonary Resuscitation (CPR), and unplanned admission to the Intensive Care Unit (ICU). A composite mortality measure was constructed including unexpected death and death up to 72 h after cardiac arrest with CPR or unplanned ICU admission. Every 4 months we obtained, from 30 consecutive patient admissions across all wards, the Charlson comorbidity index. The amount of nursing hours per patient days (NHPPD) were calculated every day for 15 days, once every 4 months. Data were aggregated to the ward level resulting in 68 estimates across wards and time. Linear mixed models were used since they are most appropriate in case of clustered and repeated measures data. Results The unexpected death rate was 1.80 per 1000 patients. Up to 0.76 per 1000 patients died after CPR and 0.62 per 1000 patients died after unplanned admission to the ICU. The mean composite mortality was 3.18 per 1000 patients. The mean NHPPD and proportion of nurse Bachelor hours were respectively 2.48 and 0.59. We found a negative association between the nursing hours per patient day and the composite mortality rate adjusted for possible confounders (B = − 2.771, p  = 0.002). The proportion of nurse Bachelor hours was negatively correlated with the composite mortality rate in the same analysis (B = − 8.845, p  = 0.023). Using the regression equation, we calculated theoretically optimal NHPPDs. Conclusions This study confirms the association between higher nurse staffing levels and lower patient mortality controlled for relevant confounders.

The purpose of the study is to determine the impact of a standardized nurse observation and escalation protocol on observation frequency, the measurement of vital signs, and the incidence of in-hospital mortality and resurgery. This is a preintervention and postintervention study by analysis of patient records for a 6-day postoperative period of all adult patients hospitalized in 4 hospital wards after surgery during a preintervention (November 2010 to March 2011; n = 2359) and postintervention (November 2011 to March 2012; n = 1888) period implementing a standardized nurse observation and escalation protocol including the Modified Early Warning Score. The mean patient observation frequency per nursing shift increased from 0.9076 (95% confidence interval [CI], 0.8921-0.9231) preintervention to 0.9940 (95% CI, 0.9708-1.0172; P < .001) postintervention and was lower in case of 6-day postoperative mortality (0.6686 [95% CI, 0.4984-0.8388] vs other patients 0.9475 [95% CI, 0.9340-0.9610]; P = .003) or resurgery (0.8402 [95% CI, 0.7894-0.8909] vs other patients 0.9564 [95% CI, 0.9378-0.9657]; P = .003). The mean number of vital signs measured per observation episode increased from a mean of 1.81 (95% CI, 1.79-1.83) preintervention to 2.45 (95% CI, 2.39-2.51; P < .001) postintervention. The relative risk reduction was 73.7% (95% CI, 22.8-91.0; P = .015) for 6-day postoperative in-hospital mortality and 30.9% (95% CI, 9.5-47.2; P = .007) for 6-day postoperative resurgery.

To support the COVID-19 pandemic response, many countries, including Belgium, implemented baseline genomic surveillance (BGS) programs aiming to early detect and characterize new SARS-CoV-2 variants. In parallel, Belgium maintained a sentinel network of six hospitals that samples patients with severe acute respiratory infections (SARI) and integrated SARS-CoV-2 detection within a broader range of respiratory pathogens. We evaluate the ability of the SARI surveillance to monitor general trends and early signals of viral genetic evolution of SARS-CoV-2 and compare it with the BGS as a reference model. Nine-hundred twenty-five SARS-CoV-2 positive samples from patients fulfilling the Belgian SARI definition between January 2020 and December 2022 were sequenced using the ARTIC Network amplicon tiling approach on a MinION platform. Weekly variant of concern (VOC) proportions and types were compared to those that were circulating between 2021 and 2022, using 96,251 sequences of the BGS. SARI surveillance allowed timely detection of the Omicron (BA.1, BA.2, BA.4, and BA.5) and Delta (B.1.617.2) VOCs, with no to 2 weeks delay according to the start of their epidemic growth in the Belgian population. First detection of VOCs B.1.351 and P.1 took longer, but these remained minor in Belgium. Omicron BA.3 was never detected in SARI surveillance. Timeliness could not be evaluated for B.1.1.7, being already major at the start of the study period. Genomic surveillance of SARS-CoV-2 using SARI sentinel surveillance has proven to accurately reflect VOCs detected in the population and provides a cost-effective solution for long-term genomic monitoring of circulating respiratory viruses.

Nonuniform attenuation correction in brain SPECT can be done routinely by means of additional gamma transmission CT (TCT) measurements, using different commercially available line-source isotopes, 201Tl, 153Gd, and 99mTc are among the most commonly used isotopes, depending on practical and cost-effectiveness issues. We have measured additional radiation burden from static uncollimated brain SPECT transmission sources for these isotopes. The influence of the transmission isotope on brain quantification was also measured and compared with uniform attenuation correction for phantom and human data. Full iterative transmission and emission reconstruction were compared with filtered backprojection techniques. Rod sources with 201Tl, 153Gd, and 99mTc were used on a triple-head gamma camera. Dosimetry was performed using LiF TLD-100 pellets and an anthropomorphic RANDO phantom. Effective dose equivalents were calculated on the basis of measured and extrapolated absorbed doses. For brain activity measurements, a Hoffman phantom was used. Images were corrected for scatter (triple-energy window) and were reconstructed by Chang attenuation correction and filtered backprojection as well as full iterative reconstruction (ordered-subsets expectation maximization [OSEM]). To study the effect of inhomogeneous bone attenuation, realistic measurements were performed on 10 young, healthy volunteers with 153Gd TCT. After stereotactic image realignment, a volume-of-interest analysis normalized to total counts was performed. Brain SPECT-TCT using 201Tl, 153Gd, and 99mTc produced total effective dose-rate equivalents of 50.3 +/- 11.2, 32.0 +/- 2.7, and 71.1 +/- 7.1 microSv/GBq x h, respectively, representing dose equivalents of 18.6, 11.9, and 26.3 microSv for a typical 20-min brain SPECT scan at maximal used source strength. Standardized quantification resulted in insignificant differences between the isotopes and methods (Chang versus OSEM) used for nonuniform correction. Iterative reconstruction enhanced image contrast and provided more accurate gray-to-white matter ratios. Between nonuniform and uniform attenuation with an optimized attenuation coefficient, slight central discrepancies were found for volunteer studies. Significantly lower intersubject variation was found for nonuniform corrected values in infratentorial and posterior brain regions. Brain transmission scanning using 201Tl, 153Gd, or 99mTc results in limited effective radiation dose equivalents compared with the typical radiation burden. Relative brain perfusion quantification is not significantly different for the various nonuniform TCT isotopes. Iterative reconstruction improves gray-to-white contrasts but has no significant influence on brain perfusion semiquantification. Nonuniform attenuation correction decreases intersubject variability in the posterior brain regions that were compared, which may lead to improved sensitivity toward clinical applications.

Nonuniform attenuation correction in brain SPECT can be done routinely by means of additional gamma transmission CT (TCT) measurements, using different commercially available line-source isotopes, 201Tl, 153Gd, and 99mTc are among the most commonly used isotopes, depending on practical and cost-effectiveness issues. We have measured additional radiation burden from static uncollimated brain SPECT transmission sources for these isotopes. The influence of the transmission isotope on brain quantification was also measured and compared with uniform attenuation correction for phantom and human data. Full iterative transmission and emission reconstruction were compared with filtered backprojection techniques. Rod sources with 201Tl, 153Gd, and 99mTc were used on a triple-head gamma camera. Dosimetry was performed using LiF TLD-100 pellets and an anthropomorphic RANDO phantom. Effective dose equivalents were calculated on the basis of measured and extrapolated absorbed doses. For brain activity measurements, a Hoffman phantom was used. Images were corrected for scatter (triple-energy window) and were reconstructed by Chang attenuation correction and filtered backprojection as well as full iterative reconstruction (ordered-subsets expectation maximization [OSEM]). To study the effect of inhomogeneous bone attenuation, realistic measurements were performed on 10 young, healthy volunteers with 153Gd TCT. After stereotactic image realignment, a volume-of-interest analysis normalized to total counts was performed. Brain SPECT-TCT using 201Tl, 153Gd, and 99mTc produced total effective dose-rate equivalents of 50.3 +/- 11.2, 32.0 +/- 2.7, and 71.1 +/- 7.1 microSv/GBq x h, respectively, representing dose equivalents of 18.6, 11.9, and 26.3 microSv for a typical 20-min brain SPECT scan at maximal used source strength. Standardized quantification resulted in insignificant differences between the isotopes and methods (Chang versus OSEM) used for nonuniform correction. Iterative reconstruction enhanced image contrast and provided more accurate gray-to-white matter ratios. Between nonuniform and uniform attenuation with an optimized attenuation coefficient, slight central discrepancies were found for volunteer studies. Significantly lower intersubject variation was found for nonuniform corrected values in infratentorial and posterior brain regions. Brain transmission scanning using 201Tl, 153Gd, or 99mTc results in limited effective radiation dose equivalents compared with the typical radiation burden. Relative brain perfusion quantification is not significantly different for the various nonuniform TCT isotopes. Iterative reconstruction improves gray-to-white contrasts but has no significant influence on brain perfusion semiquantification. Nonuniform attenuation correction decreases intersubject variability in the posterior brain regions that were compared, which may lead to improved sensitivity toward clinical applications.