Appropriate use of blood cultures in the emergency department through machine learning (ABC): study protocol for a randomised controlled non-inferiority trial.

INTRODUCTION: The liberal use of blood cultures in emergency departments (EDs) leads to low yields and high numbers of false-positive results. False-positive, contaminated cultures are associated with prolonged hospital stays, increased antibiotic usage and even higher hospital mortality rates. This trial aims to investigate whether a recently developed and validated machine learning model for predicting blood culture outcomes can safely and effectively guide clinicians in withholding unnecessary blood culture analysis. METHODS AND ANALYSIS: A randomised controlled, non-inferiority trial comparing current practice with a machine learning-guided approach. The primary objective is to determine whether the machine learning based approach is non-inferior to standard practice based on 30-day mortality. Secondary outcomes include hospital length-of stay and hospital admission rates. Other outcomes include model performance and antibiotic usage. Participants will be recruited in the EDs of multiple hospitals in the Netherlands. A total of 7584 participants will be included. ETHICS AND DISSEMINATION: Possible participants will receive verbal information and a paper information brochure regarding the trial. They will be given at least 1 hour consideration time before providing informed consent. Research results will be published in peer-reviewed journals. This study has been approved by the Amsterdam University Medical Centers' local medical ethics review committee (No 22.0567). The study will be conducted in concordance with the principles of the Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act, General Data Privacy Regulation and Medical Device Regulation. TRIAL REGISTRATION NUMBER: NCT06163781.

Sex differences in pain catastrophizing and its relation to the transition from acute pain to chronic pain.

BACKGROUND AND IMPORTANCE: Differences exist between sexes in pain and pain-related outcomes, such as development of chronic pain. Previous studies suggested a higher risk for pain chronification in female patients. Furthermore, pain catastrophizing is an important risk factor for chronification of pain. However, it is unclear whether sex differences in catastrophic thinking could explain the sex differences in pain chronification. OBJECTIVES: The aim of this study was to examine sex differences in pain catastrophizing. Additionally, we investigated pain catastrophizing as a potential mediator of sex differences in the transition of acute to chronic pain. DESIGN, SETTINGS AND PARTICIPANTS: Adults visiting one of the 15 participating emergency departments in the Netherlands with acute pain-related complaints. Subjects had to meet inclusion criteria and complete questionnaires about their health and pain. OUTCOMES MEASURE AND ANALYSIS: The outcomes in this prospective cohort study were pain catastrophizing (short form pain catastrophizing) and pain chronification at 90 days (Numeric Rating Scale ≥ 1). Data was analysed using univariate and multivariable logistic regression models. Finally, stratified regression analyses were conducted to assess whether differences in pain catastrophizing accounted for observed differences in pain chronification between sexes. MAIN RESULTS: In total 1,906 patients were included. Females catastrophized pain significantly more than males (p < 0.001). Multiple regression analyses suggested that pain catastrophizing is associated with pain chronification in both sexes. CONCLUSIONS: This study reported differences between sexes in catastrophic cognitions in the development of chronic pain. This is possibly of clinical importance to identify high-risk patients and ensure an early intervention to prevent the transition from acute to chronic pain.

Merging of two level-1 trauma centers in Amsterdam: premerger demand in integrated acute trauma care.

PURPOSE: Availability of adequate and appropriate trauma care is essential. A merger of two Dutch academic level-1 trauma centers is upcoming. However, in the literature, volume effects after a merger are inconclusive. This study aimed to examine the premerger demand for level-1 trauma care on integrated acute trauma care and evaluate the expected demand on the system. METHODS: A retrospective observational study was conducted between 1-1-2018 and 1-1-2019 in two level-1 trauma centers in the Amsterdam region using data derived from the local trauma registries and electronic patient records. All trauma patients presented at both centers' Emergency Departments (ED) were included. Patient- and injury characteristics and data concerning all prehospital and in-hospital-delivered trauma care were collected and compared. Pragmatically, the demand for trauma care in the post-merger setting was considered a sum of care demand for both centers. RESULTS: In total, 8277 trauma patients were presented at both EDs, 4996 (60.4%) at location A and 3281 (39.6%) at location B. Overall, 462 patients were considered severely injured patients (Injury Severity Score ≥ 16). In total, 702 emergency surgeries (< 24 h) were performed, and 442 patients were admitted to the ICU. The sum care demand of both centers resulted in a 167.4% increase in trauma patients and a 151.1% increase in severely injured patients. Moreover, on 96 occasions annually, two or more patients within the same hour would require advanced trauma resuscitation by a specialized team or emergency surgery. CONCLUSION: A merger of two Dutch level-1 trauma centers would, in this scenario, result in a more than 150% increase in the post-merger setting's demand for integrated acute trauma care.

The effect of a clock's presence on trauma resuscitation times in a Dutch level-1 trauma center: a pre-post cohort analysis.

PURPOSE: Interventions performed within the first hour after trauma increase survival rates. Literature showed that measuring times can optimize the trauma resuscitation process as time awareness potentially reduces acute care time. This study examined the effect of a digital clock placement on trauma resuscitation times in an academic level-1 trauma center. METHODS: A prospective observational pre-post cohort analysis was conducted for six months before and after implementing a visible clock in the trauma resuscitation room, indicating the time passed since starting the in-hospital resuscitation process. Trauma patients (age ≥ 16) presented during weekdays between 9.00 AM and 9.00 PM were included. Time until diagnostics (X-Ray, FAST, or CT scan), time until therapeutic intervention, and total resuscitation time were measured manually with a stopwatch by a researcher in the trauma resuscitation room. Patient characteristics and information regarding trauma- and injury type were collected. Times before and after clock implementation were compared. RESULTS: In total, 100 patients were included, 50 patients in each cohort. The median total resuscitation time (including CT scan) was 40.3 min (IQR 23.3) in the cohort without a clock compared to 44.3 (IQR 26.1) minutes in the cohort with a clock. The mean time until the first diagnostic and until the CT scan was 8.3 min (SD 3.1) and 25.5 min (SD 7.1) without a clock compared to 8.6 min (SD 6.5) and 26.6 min (SD 11.5) with a clock. Severely injured patients (Injury Severity Score (ISS) ≥ 16) showed a median resuscitation time in the cohort without a clock (n = 9) of 54.6 min (IQR 50.5) compared to 46.0 min (IQR 21.6) in the cohort with a clock (n = 8). CONCLUSION: This study found no significant reduction in trauma resuscitation time after clock placement. Nonetheless, the data represent a heterogeneous population, not excluding specific patient categories for whom literature has shown that a short time is essential, such as severely injured patients, might benefit from the presence of a trauma clock. Future research is recommended into resuscitation times of specific patient categories and practices to investigate time awareness.

Optimal use of procalcitonin to rule out bacteremia in patients with possible viral infections.

Objective: During the winter, many patients present with suspected infection that could be a viral or a bacterial (co)infection. The aim of this study is to investigate whether the optimal use of procalcitonin (PCT) is different in patients with and without proven viral infections for the purpose of excluding bacteremia. We hypothesize that when a viral infection is confirmed, this lowers the probability of bacteremia and, therefore, influences the appropriate cutoff of procalcitonin. Methods: This study was conducted in the emergency department of an academic medical center in The Netherlands in the winter seasons of 2019 and 2020. Adults (>18 years) with suspected infection, in whom a blood culture and a rapid polymerase chain reaction test for influenza was performed were included. Results: A total of 546 patients were included of whom 47 (8.6%) had a positive blood culture. PCT had an area under the curve of 0.85, 95% confidence interval (95% CI) 0.80-0.91, for prediction of bacteremia. In patients with a proven viral infection (N = 212) PCT < 0.5 µg/L had a sensitivity of 100% (95% CI 63.1-100) and specificity of 81.2% (95% CI 75.1-86.3) to exclude bacteremia. In patients without a viral infection, the procalcitonin cutoff point of < 0.25 µg/L showed a sensitivity of 87.2% (95% CI 72.6-95.7) and specificity of 64.1 % (95% CI 58.3-69.6). Conclusion: In patients with a viral infection, our findings suggest that a PCT concentration of <0.50 µg/L makes bacteremia unlikely. However, this finding needs to be confirmed in a larger population of patients with viral infections, especially because the rate of coinfection in our cohort was low.

Comparing lung ultrasound: extensive versus short in COVID-19 (CLUES): a multicentre, observational study at the emergency department.

BACKGROUND: Bedside lung ultrasound (LUS) is an affordable diagnostic tool that could contribute to identifying COVID-19 pneumonia. Different LUS protocols are currently used at the emergency department (ED) and there is a need to know their diagnostic accuracy. DESIGN: A multicentre, prospective, observational study, to compare the diagnostic accuracy of three commonly used LUS protocols in identifying COVID-19 pneumonia at the ED. SETTING/PATIENTS: Adult patients with suspected COVID-19 at the ED, in whom we prospectively performed 12-zone LUS and SARS-CoV-2 reverse transcription PCR. MEASUREMENTS: We assessed diagnostic accuracy for three different ultrasound protocols using both PCR and final diagnosis as a reference standard. RESULTS: Between 19 March 2020 and 4 May 2020, 202 patients were included. Sensitivity, specificity and negative predictive value compared with PCR for 12-zone LUS were 91.4% (95% CI 84.4 to 96.0), 83.5% (95% CI 74.6 to 90.3) and 90.0% (95% CI 82.7 to 94.4). For 8-zone and 6-zone protocols, these results were 79.7 (95% CI 69.9 to 87.6), 69.0% (95% CI 59.6 to 77.4) and 81.3% (95% CI 73.8 to 87.0) versus 89.9% (95% CI 81.7 to 95.3), 57.5% (95% CI 47.9 to 66.8) and 87.8% (95% CI 79.2 to 93.2). Negative likelihood ratios for 12, 8 and 6 zones were 0.1, 0.3 and 0.2, respectively. Compared with the final diagnosis specificity increased to 83.5% (95% CI 74.6 to 90.3), 78.4% (95% CI 68.8 to 86.1) and 65.0% (95% CI 54.6 to 74.4), respectively, while the negative likelihood ratios were 0.1, 0.2 and 0.16. CONCLUSION: Identifying COVID-19 pneumonia at the ED can be aided by bedside LUS. The more efficient 6-zone protocol is an excellent screening tool, while the 12-zone protocol is more specific and gives a general impression on lung involvement. TRIAL REGISTRATION NUMBER: NL8497.

Routine screening for pulmonary embolism in COVID-19 patients at the emergency department: impact of D-dimer testing followed by CTPA.

COVID-19 patients have increased risk of pulmonary embolism (PE), but symptoms of both conditions overlap. Because screening algorithms for PE in COVID-19 patients are currently lacking, PE might be underdiagnosed. We evaluated a screening algorithm in which all patients presenting to the ED with suspected or confirmed COVID-19 routinely undergo D-dimer testing, followed by CT pulmonary angiography (CTPA) if D-dimer is ≥ 1.00 mg/L. Consecutive adult patients presenting to the ED of two university hospitals in Amsterdam, The Netherlands, between 01-10-2020 and 31-12-2020, who had a final diagnosis of COVID-19, were retrospectively included. D-dimer and CTPA results were obtained. Of 541 patients with a final diagnosis of COVID-19 presenting to the ED, 25 (4.6%) were excluded because D-dimer was missing, and 71 (13.1%) because they used anticoagulation therapy. Of 445 included patients, 185 (41.6%; 95%CI 37.0-46.3) had a D-dimer ≥ 1.00 mg/L. CTPA was performed in 169 of them, which showed PE in 26 (15.4%; 95%CI 10.3-21.7), resulting in an overall detection rate of 5.8% (95%CI 3.9-8.4) in the complete study group. In patients with and without PE at CTPA, median D-dimer was 9.84 (IQR 3.90-29.38) and 1.64 (IQR 1.17-3.01), respectively (p < 0.001). PE prevalence increased with increasing D-dimer, ranging from 1.2% (95%CI 0.0-6.4) if D-dimer was 1.00-1.99 mg/L, to 48.6% (95%CI 31.4-66.0) if D-dimer was ≥ 5.00 mg/L. In conclusion, by applying this screening algorithm, PE was identified in a considerable proportion of COVID-19 patients. Prospective management studies should assess if this algorithm safely rules-out PE if D-dimer is < 1.00 mg/L.

Assessing COVID-19 pneumonia-Clinical extension and risk with point-of-care ultrasound: A multicenter, prospective, observational study.

BACKGROUND: Assessing the extent of lung involvement is important for the triage and care of COVID-19 pneumonia. We sought to determine the utility of point-of-care ultrasound (POCUS) for characterizing lung involvement and, thereby, clinical risk determination in COVID-19 pneumonia. METHODS: This multicenter, prospective, observational study included patients with COVID-19 who received 12-zone lung ultrasound and chest computed tomography (CT) scanning in the emergency department (ED). We defined lung disease severity using the lung ultrasound score (LUS) and chest CT severity score (CTSS). We assessed the association between the LUS and poor outcome (ICU admission or 30-day all-cause mortality). We also assessed the association between the LUS and hospital length of stay. We examined the ability of the LUS to differentiate between disease severity groups. Lastly, we estimated the correlation between the LUS and CTSS and the interrater agreement for the LUS. We handled missing data by multiple imputation with chained equations and predictive mean matching. RESULTS: We included 114 patients treated between March 19, 2020, and May 4, 2020. An LUS ≥12 was associated with a poor outcome within 30 days (hazard ratio [HR], 5.59; 95% confidence interval [CI], 1.26-24.80; P = 0.02). Admission duration was shorter in patients with an LUS <12 (adjusted HR, 2.24; 95% CI, 1.47-3.40; P < 0.001). Mean LUS differed between disease severity groups: no admission, 6.3 (standard deviation [SD], 4.4); hospital/ward, 13.1 (SD, 6.4); and ICU, 18.0 (SD, 5.0). The LUS was able to discriminate between ED discharge and hospital admission excellently, with an area under the curve of 0.83 (95% CI, 0.75-0.91). Interrater agreement for the LUS was strong: κ = 0.88 (95% CI, 0.77-0.95). Correlation between the LUS and CTSS was strong: κ = 0.60 (95% CI, 0.48-0.71). CONCLUSIONS: We showed that baseline lung ultrasound - is associated with poor outcomes, admission duration, and disease severity. The LUS also correlates well with CTSS. Point-of-care lung ultrasound may aid the risk stratification and triage of patients with COVID-19 at the ED.

Chest CT in COVID-19 at the ED: Validation of the COVID-19 Reporting and Data System (CO-RADS) and CT Severity Score: A Prospective, Multicenter, Observational Study.

BACKGROUND: CT is thought to play a key role in coronavirus disease 2019 (COVID-19) diagnostic workup. The possibility of comparing data across different settings depends on the systematic and reproducible manner in which the scans are analyzed and reported. The COVID-19 Reporting and Data System (CO-RADS) and the corresponding CT severity score (CTSS) introduced by the Radiological Society of the Netherlands (NVvR) attempt to do so. However, this system has not been externally validated. RESEARCH QUESTION: We aimed to prospectively validate the CO-RADS as a COVID-19 diagnostic tool at the ED and to evaluate whether the CTSS is associated with prognosis. STUDY DESIGN AND METHODS: We conducted a prospective, observational study in two tertiary centers in The Netherlands, between March 19 and May 28, 2020. We consecutively included 741 adult patients at the ED with suspected COVID-19, who received a chest CT and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR (PCR). Diagnostic accuracy measures were calculated for CO-RADS, using PCR as reference. Logistic regression was performed for CTSS in relation to hospital admission, ICU admission, and 30-day mortality. RESULTS: Seven hundred forty-one patients were included. We found an area under the curve (AUC) of 0.91 (CI, 0.89-0.94) for CO-RADS using PCR as reference. The optimal CO-RADS cutoff was 4, with a sensitivity of 89.4% (CI, 84.7-93.0) and specificity of 87.2% (CI, 83.9-89.9). We found a significant association between CTSS and hospital admission, ICU admission, and 30-day mortality; adjusted ORs per point increase in CTSS were 1.19 (CI, 1.09-1.28), 1.23 (1.15-1.32), 1.14 (1.07-1.22), respectively. Intraclass correlation coefficients for CO-RADS and CTSS were 0.94 (0.91-0.96) and 0.82 (0.70-0.90). INTERPRETATION: Our findings support the use of CO-RADS and CTSS in triage, diagnosis, and management decisions for patients presenting with possible COVID-19 at the ED.

Diagnosing COVID-19 pneumonia in a pandemic setting: Lung Ultrasound versus CT (LUVCT) - a multicentre, prospective, observational study.

BACKGROUND: In this coronavirus disease 2019 (COVID-19) pandemic, fast and accurate testing is needed to profile patients at the emergency department (ED) and efficiently allocate resources. Chest imaging has been considered in COVID-19 workup, but evidence on lung ultrasound (LUS) is sparse. We therefore aimed to assess and compare the diagnostic accuracy of LUS and computed tomography (CT) in suspected COVID-19 patients. METHODS: This multicentre, prospective, observational study included adult patients with suspected COVID-19 referred to internal medicine at the ED. We calculated diagnostic accuracy measures for LUS and CT using both PCR and multidisciplinary team (MDT) diagnosis as reference. We also assessed agreement between LUS and CT, and between sonographers. RESULTS: One hundred and eighty-seven patients were recruited between March 19 and May 4, 2020. Area under the receiver operating characteristic (AUROC) was 0.81 (95% CI 0.75-0.88) for LUS and 0.89 (95% CI 0.84-0.94) for CT. Sensitivity and specificity for LUS were 91.9% (95% CI 84.0-96.7) and 71.0% (95% CI 61.1-79.6), respectively, versus 88.4% (95% CI 79.7-94.3) and 82.0% (95% CI 73.1-89.0) for CT. Negative likelihood ratio was 0.1 (95% CI 0.06-0.24) for LUS and 0.14 (95% CI 0.08-0.3) for CT. No patient with a false negative LUS required supplemental oxygen or admission. LUS specificity increased to 80% (95% CI 69.9-87.9) compared to MDT diagnosis, with an AUROC of 0.85 (95% CI 0.79-0.91). Agreement between LUS and CT was 0.65. Interobserver agreement for LUS was good: 0.89 (95% CI 0.83-0.93). CONCLUSION: LUS and CT have comparable diagnostic accuracy for COVID-19 pneumonia. LUS can safely exclude clinically relevant COVID-19 pneumonia and may aid COVID-19 diagnosis in high prevalence situations.

[A woman with a palpable abnormality in the breast]. / Een vrouw met een palpabele afwijking in de borst.

Mondor's disease is a rare benign condition characterized by thrombophlebitis of superficial veins of the chest and the breast. Typically, there is a spontaneous onset of tenderness and redness due to a cord-like induration on the lateral thoracic wall. It is a self-limiting disease that should be distinguished from breast cancer. In general, the combination of clinical symptoms and mammography confirms the diagnosis.