Abstract Objective To mitigate the burden of COVID-19 on the healthcare system, information on the prognosis of the disease is needed. The recently developed RISE UP score has very good discriminatory value with respect to short-term mortality in older patients in the emergency department (ED). It consists of six items: age, abnormal vital signs, albumin, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and bilirubin. We hypothesized that the RISE UP score could have discriminatory value with regard to 30-day mortality in ED patients with COVID-19. Setting Two EDs of the Zuyderland Medical Centre (MC), secondary care hospital in the Netherlands. Participants The study sample consisted of 642 adult ED patients diagnosed with COVID-19 between March 3 rd until May 25 th 2020. Inclusion criteria were: 1) admission to the hospital with symptoms suggestive of COVID-19, and 2) positive result of the polymerase chain reaction (PCR), or (very) high suspicion of COVID-19 according to the chest computed tomography (CT) scan. Outcome Primary outcome was 30-day mortality, secondary outcome was a composite of 30-day mortality and admission to intensive care unit (ICU). Results Within 30 days after presentation, 167 patients (26.0%) died and 102 patients (15.9%) were admitted to ICU. The RISE UP score showed good discriminatory value with respect to 30-day mortality (AUC 0.77, 95% CI 0.73-0.81), and to the composite outcome (AUC 0.72, 95% CI 0.68-0.76). Patients with RISE UP scores below 10% (121 patients) had favourable outcome (0% mortality and 5% ICU admissions). Patients with a RISE UP score above 30% (221 patients) were at high risk of adverse outcome (46.6% mortality and 19% ICU admissions). Conclusion The RISE UP score is an accurate prognostic model for adverse outcome in ED patients with COVID-19. It can be used to identify patients at risk of short-term adverse outcome, and may help guiding decision-making and allocating healthcare resources.
Objective To mitigate the burden of COVID-19 on the healthcare system, information on the prognosis of the disease is needed. The recently developed Risk Stratification in the Emergency Department in Acutely ill Older Patients (RISE UP) score has very good discriminatory value for short-term mortality in older patients in the emergency department (ED). It consists of six readily available items. We hypothesised that the RISE UP score could have discriminatory value for 30-day mortality in ED patients with COVID-19. Design Retrospective analysis. Setting Two EDs of the Zuyderland Medical Centre, secondary care hospital in the Netherlands. Participants The study sample consisted of 642 adult ED patients diagnosed with COVID-19 between 3 March and until 25 May 2020. Inclusion criteria were (1) admission to the hospital with symptoms suggestive of COVID-19 and (2) positive result of the PCR or (very) high suspicion of COVID-19 according to the chest CT scan. Outcome Primary outcome was 30-day mortality, secondary outcome was a composite of 30-day mortality and admission to intensive care unit (ICU). Results Within 30 days after presentation, 167 patients (26.0%) died and 102 patients (15.9%) were admitted to ICU. The RISE UP score showed good discriminatory value for 30-day mortality (area under the receiver operating characteristic curve (AUC) 0.77, 95% CI 0.73 to 0.81) and for the composite outcome (AUC 0.72, 95% CI 0.68 to 0.76). Patients with RISE UP scores below 10% (n=121) had favourable outcome (zero deaths and six ICU admissions), while those with scores above 30% (n=221) were at high risk of adverse outcome (46.6% mortality and 19.0% ICU admissions). Conclusion The RISE UP score is an accurate prognostic model for adverse outcome in ED patients with COVID-19. It can be used to identify patients at risk of short-term adverse outcome and may help guide decision-making and allocating healthcare resources.
The degree of hydrops in guinea pig ears that had undergone unilateral endolymphatic sac and duct obliteration was quantified. For 15 guinea pigs from a prior study, the correlation between the degree of hydrops and several electrophysiologic measures of the functional state of the cochlea was determined. A significant correlation between the degree of hydrops and a reduction in the low-frequency cochlear microphonic evoked by a 29-Hz tone was found. No correlation was found between the degree of hydrops and the magnitude of the summating potential evoked by 8-kHz probes. A weak correlation was found between the degree of hydrops and a reduction in the compound action potential evoked by 2-kHz probes. Possible differences in the way the endolymphatic duct obliteration exerts its effect on the different cochlear potentials are discussed.
We report a 74-year-old patient who developed an acute aortic syndrome (AAS) with intramural haematoma (IMH) during treatment with nintedanib, a tyrosine kinase inhibitor. As we suspected a role for nintedanib, this was immediately interrupted. Four months later, a computed tomographic angiography (CTA) showed significant regression of the IMH. Therefore, we state that, when patients use nintedanib and develop acute chest or back pain, diagnostic work-up for AAS should be considered. Furthermore, other risk factors for AAS, such as hypertension, genetic diseases and comedication should be taken into account when prescription of medication of this class is considered.
We aim to evaluate the clinical pharmacokinetics of a single dose interleukin-6 (IL-6) antibody tocilizumab (TCZ) in methylprednisolone (MP)-treated COVID-19 patients with cytokine storm syndrome (CSS).
To compare survival of individuals with coronavirus disease 2019 (COVID-19) treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine. We analysed data of COVID-19 patients treated in nine hospitals in the Netherlands. Inclusion dates ranged from 27 February to 15 May 2020, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated patients with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox regression with adjustment for age, sex and covariates based on premorbid health, disease severity and the use of steroids for adult respiratory distress syndrome, including dexamethasone. Among 1949 individuals, 21-day mortality was 21.5% in 1596 patients treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 15.0% in 353 patients treated in hospitals that did not. In the adjusted Cox regression models this difference disappeared, with an adjusted hazard ratio of 1.09 (95% CI 0.81-1.47). When stratified by treatment actually received in individual patients, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95% CI 1.24-2.02) in the full model. After adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in hospitalised patients with COVID-19.
Initial antibiotic treatment of severe infections can lead to clinical deterioration due to sudden endotoxin release and concomitant exaggerated inflammatory response. Antibiotic-induced morphological changes may contribute to this phenomenon. High-dose ceftazidime, which inhibits penicillin-binding protein (PBP)-1 in Gram-negative bacteria, causes quick bacteriolysis and low endotoxin release. Low-dose ceftazidime leads to PBP-3 inhibition, which causes bacterial filament formation, associated with high endotoxin releases. PBP-2-specific antibiotics induce spheroplasts, again associated with low endotoxin release. We hypothesized that antibiotic type, concentration and regimen influence bacterial morphology, endotoxin levels and inflammatory response.Neutropenic mice with Escherichia coli or Pseudomonas aeruginosa sepsis were treated with ceftazidime or meropenem 10-320 mg/kg as an intravenous bolus or as continuous tail vein infusions of 0.1 mL/h. Four hours later, bacterial counts, morphology, plasma endotoxin, pro-inflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)] and antibiotic concentrations were measured.Continuous infusion of 80 mg/kg ceftazidime was the lowest dose preventing filaments in E. coli infections. Bolus treatment resulted in filament formation, irrespective of the dose. During continuous treatment, IL-6 and TNF-alpha concentrations were higher compared with bolus treatment and controls for both antibiotics and both strains. A clear relationship between cfu counts in muscle and circulating IL-6 was shown (r=- 0.579, P=0.007), suggesting that plasma IL-6 is a valuable indicator of bacterial killing at the infection site.Our findings show that not PBP affinity but the method of antibiotic administration is crucial during initial treatment of severe infections.
The emergency department (ED) is a hectic place, where many critically ill patients are treated. For residents working in the ED, this environment may be demanding. The aim of this study was to investigate the [1] cognitive load experienced by residents working in the ED, and [2] differences in cognitive load during the day. In this multicentre, prospective study in three EDs in the Netherlands, the experienced cognitive load was graded by residents on three scales, agreed upon during Delphi meetings: the complexity (low-high: 1-3), mental effort (low-high: 1-9) and comfortability scale (low-high: 0-100%). We applied the scores per decision, 1-hour and 2-hour intervals, patient and shift. We observed 14 residents and analysed 74 1-hour and 45 2-hour intervals, 79 patients, 24 shifts and 592 separate decisions. The experienced cognitive load per decision was low. In contrast, the cognitive load was higher per 2-hour interval (mental effort: median 4.0 (IQR 4.0) and comfortability 80% (IQR 20)) and per shift (mental effort: median 5.5 (IQR 4.0) and comfortability 80% (IQR 20). Complexity was low for all measurements. Mental effort rose from 17h onwards higher values, whereas a decrease in comfortability was seen from 21h onwards. From 17h onwards, residents working in the ED experienced rather high mental effort and reported feeling not optimally comfortable when making decisions. The mental effort was highest between 21-23h. This was found when cognitive load was measured per 2-hour interval and per shift, but not per decision. This study may provide an insights to optimise cognitive load by reorganisation of the ED.
