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Objective: To determine patients' perspectives on home monitoring at emergency department (ED) presentation and shortly after admission and compare these with their physicians' perspectives. Methods: Forty Dutch hospitals participated in this prospective flash mob study. Adult patients with acute medical conditions, treated by internal medicine specialties, presenting at the ED or admitted at the admission ward within the previous 24 h were included. The primary outcome was the proportion of patients who were able and willing to undergo home monitoring. Secondary outcomes included identifying barriers to home monitoring, patient's prerequisites, and assessing the agreement between the perspectives of patients and treating physicians. Results: On February 2, 2023, in total 665 patients [median age 69 (interquartile range: 55-78) years; 95.5% community dwelling; 29.3% Modified Early Warning Score ≥3; 29.5% clinical frailty score ≥5] were included. In total, 19.6% of ED patients were admitted and 26% of ward patients preferred home monitoring as continuation of care. Guaranteed readmission (87.8%), ability to contact the hospital 24/7 (77.3%), and a family caregiver at home (55.7%) were the most often reported prerequisites. Barriers for home monitoring were feeling too severely ill (78.8%) and inability to receive the required treatment at home (64.4%). The agreement between patients and physicians was fair (Cohens kappa coefficient 0.26). Conclusions: A substantial proportion of acutely ill patients stated that they were willing and able to be monitored at home. Guaranteed readmission, availability of a treatment team (24/7), and a home support system are needed for successful implementation of home monitoring in acute care.

Background: After 3 months of anticoagulation for venous thromboembolism (VTE), the decision needs to be made whether to stop anticoagulation or extend treatment indefinitely. The VTE-PREDICT calculator can be used to estimate individual risks of VTE recurrence and bleeding to guide this decision., Objectives: To evaluate the impact of predicted individual risks of recurrence and bleeding on clinicians' decisions on anticoagulation duration and to assess usefulness of the VTE-PREDICT calculator., Methods: A randomized controlled trial and within-subject study was conducted among clinicians treating VTE patients. The clinicians were asked to complete an online survey containing 6 fictional case vignettes. Group A proposed anticoagulant duration for each case without additional information first and subsequently after seeing calculator-predicted risks (within-subject analysis). Group B was directly provided with calculator risks and proposed treatment duration for each case vignette (for comparison with group A results in a randomized controlled trial analysis). Then, group B received questions on usefulness and credibility of the calculator., Results: Forty-five clinicians were assigned to group A and 48 to B. Overall, group A did not propose different anticoagulation durations than group B. However, individual clinicians in group A changed proposed duration in 35% of the cases after seeing the calculator risks. The calculator was considered useful and credible by most clinicians., Conclusion: Overall, use of the VTE-PREDICT calculator did not affect proposed anticoagulation duration. However, individual clinicians frequently changed their proposed duration after using the calculator, especially for patients with high bleeding risk., (© 2024 The Authors.)

Rapid discrimination between viral and bacterial infections in a point-of-care setting will improve clinical outcome. Expression of CD64 on neutrophils (neuCD64) increases during bacterial infections, whereas expression of CD169 on classical monocytes (cmCD169) increases during viral infections. The diagnostic value of automated point-of-care neuCD64 and cmCD169 analysis was assessed for detecting bacterial and viral infections at the emergency department. Additionally, their value as input for machine learning models was studied. A prospective observational cohort study in patients suspected of infection was performed at an emergency department. A fully automated point-of-care flow cytometer measured neuCD64, cmCD169, and additional leukocyte surface markers. Flow cytometry data were gated using the FlowSOM algorithm. Bacterial and viral infections were assessed in standardized clinical care. The sole and combined diagnostic value of the markers was investigated. Clustering based on unsupervised machine learning identified unique patient clusters. Eighty-six patients were included. Thirty-five had a bacterial infection, 30 had a viral infection, and 21 had no infection. neuCD64 was increased in bacterial infections (P < 0.001), with an area under the receiver operating characteristic curve (AUROC) of 0.73. cmCD169 was higher in virally infected patients (P < 0.001; AUROC 0.79). Multivariate analyses incorporating additional markers increased the AUROC for bacterial and viral infections to 0.86 and 0.93, respectively. The additional clustering identified 4 distinctive patient clusters based on infection type and outcome. Automated neuCD64 and cmCD169 determination can discriminate between bacterial and viral infections. These markers can be determined within 30 min, allowing fast infection diagnostics in the acute clinical setting., Competing Interests: Conflict of interest statement. Beckman Coulter Life Sciences (Miami, FL, USA) provided the AQUIOS “Load & Go” flow cytometer for this study but had no role in the design and execution of the study. All authors declare that the research was conducted without any commercial or financial relationships that could be interpreted as a potential conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Background: Virtual hospital-at-home care might be an alternative to standard hospital care for patients with infectious diseases. In this study, we explore the potential for virtual hospital-at-home care and a potential design for this population., Methods: This was a retrospective cohort study of internal medicine patients suspected of infectious diseases, admitted between 1 January and 31 December 2019. We collected information on delivered care during emergency department visits, the first 24 h, between 24 and 72 h, and after 72 h of admission. Care components that could be delivered at home were combined into care packages, and the potential number of eligible patients per package was described. The most feasible package was described in detail., Results: 763 patients were included, mostly referred for general internal medicine (35%), and the most common diagnosis was lower respiratory tract infection (27%). The most frequently administered care components were laboratory tests, non-oral medication, and intercollegiate consultation. With a combination of telemonitoring, video consultation, non-oral medication administration, laboratory tests, oxygen therapy, and radiological diagnostics, 48% of patients were eligible for hospital-at-home care, with 35% already eligible directly after emergency department visits., Conclusion: While the potential for virtual hospital-at-home care is high, it depends greatly on which care can be arranged.

Introduction: During the COVID-19 pandemic, hospital capacity was strained. Home-based care could relieve the hospital care system and improve patient well-being if safely organised.We designed an intervention embedded in a regional collaborative healthcare network for the home-based management of acutely ill COVID-19 patients requiring oxygen treatment. Here, we describe the design and pilot protocol for the evaluation of the feasibility of this complex intervention., Methods and Analysis: Following a participatory action research approach, the intervention was designed in four consecutive steps: (1) literature review and establishment of an expert panel; (2) concept design of essential intervention building blocks (acute medical care, acute nursing care, remote monitoring, equipment and technology, organisation and logistics); (3) safety assessments (prospective risk analysis and a simulation patient evaluation) and (4) description of the design of the pilot (feasibility) study aimed at including approximately 15-30 patients, sufficient for fine-tuning for a large-scale randomised intervention., Ethics and Dissemination: All patients will provide written, informed consent. The study was approved by the Medical Ethics Review Committee of the University Medical Center Utrecht, the Netherlands (protocol NL77421.041.21). The preparatory steps (1-4) needed to perform the pilot are executed and described in this paper. The findings of the pilot will be published in academic journals. If we consider the complex intervention feasible, we aim to continue with a large-scale randomised controlled study evaluating the clinical effectiveness, safety and implementation of the complex intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging testing in patients with clinically suspected pulmonary embolism (PE)., Aim: To externally validate the performance of 4PEPS in an independent cohort., Methods: In this post-hoc analysis of the prospective diagnostic management YEARS study, the primary outcome measures were discrimination, calibration, efficiency (proportion of imaging tests potentially avoided), and failure rate (venous thromboembolism (VTE) diagnosis at baseline or follow-up in patients with a negative 4PEPS algorithm). Multiple imputation was used for missing 4PEPS items. Based on 4PEPS, PE was considered ruled out in patients with a very low clinical pre-test probability (CPTP) without D-dimer testing, in patients with a low CPTP and D-dimer <1000 μg/L, and in patients with a moderate CPP and D-dimer below the age-adjusted threshold., Results: Of the 3465 patients, 474 (14 %) were diagnosed with VTE at baseline or during 3-month follow-up. Discriminatory performance of the 4PEPS items was good (area under ROC-curve, 0.82; 95%CI, 0.80-0.84) as was calibration. Based on 4PEPS, PE could be considered ruled out without imaging in 58 % (95%CI 57-60) of patients (efficiency), for an overall failure rate of 1.3 % (95%CI 0.86-1.9)., Conclusion: In this retrospective external validation, 4PEPS appeared to safely rule out PE with a high efficiency. Nevertheless, although not exceeding the failure rate margin by ISTH standards, the observed failure rate in our analysis appeared to be higher than in the original 4PEPS derivation and validation study. This highlights the importance of a prospective outcome study., Competing Interests: Declaration of competing interest MJHA Kruip received research support from Sobi, The Netherlands Organisation for Health Research and Development and The Dutch Thrombosis Association for research outside this study and speakers fee from BMS, Roche and Sobi, payment to institution. FA Klok has received research support from Bayer, BMS, BSCI, MSD, Leo Pharma, Actelion, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation and the Horizon Europe Program. The other authors have nothing to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Acute kidney injury (AKI) is defined as a sudden episode of kidney failure but is known to be under-recognized by healthcare professionals. The Kidney Disease Improving Global Outcome (KDIGO) guidelines have formulated criteria to facilitate AKI diagnosis by comparing changes in plasma creatinine measurements (PCr). To improve AKI awareness, we implemented these criteria as an electronic alert (e-alert), in our electronic health record (EHR) system., Methods: For every new PCr measurement measured in the University Medical Center Utrecht that triggered the e-alert, we provided the physician with actionable insights in the form of a memo, to improve or stabilize kidney function. Since e-alerts qualify for software as a medical device (SaMD), we designed, implemented and validated the e-alert according to the European Union In Vitro Diagnostic Regulation (IVDR)., Results: We evaluated the impact of the e-alert using pilot data six months before and after implementation. 2,053 e-alerts of 866 patients were triggered in the before implementation, and 1,970 e-alerts of 853 patients were triggered after implementation. We found improvements in AKI awareness as measured by (1) 2 days PCr follow up (56.6-65.8%, p-value: 0.003), and (2) stop of nephrotoxic medication within 7 days of the e-alert (59.2-63.2%, p-value: 0.002)., Conclusion: Here, we describe the design and implementation of the e-alert in line with the IVDR, leveraging a multi-disciplinary team consisting of physicians, clinical chemists, data managers and data scientists, and share our firsts results that indicate an improved awareness among treating physicians., (© 2023. The Author(s).)

Background: Continuous monitoring of vital signs is introduced at general hospital wards to detect patient deterioration. Interpretation and response currently rely on experience and expert opinion. This study aims to determine whether consensus exist among hospital professionals regarding the interpretation of vital signs of COVID-19 patients. In addition, we assessed the ability to recognise respiratory insufficiency and evaluated the interpretation process., Methods: We performed a mixed methods study including 24 hospital professionals (6 nurses, 6 junior physicians, 6 internal medicine specialists, 6 ICU nurses). Each participant was presented with 20 cases of COVID-19 patients, including 4 or 8 hours of continuously measured vital signs data. Participants estimated the patient's situation ('improving', 'stable', or 'deteriorating') and the possibility of developing respiratory insufficiency. Subsequently, a semi-structured interview was held focussing on the interpretation process. Consensus was assessed using Krippendorff's alpha. For the estimation of respiratory insufficiency, we calculated the mean positive/negative predictive value. Interviews were analysed using inductive thematic analysis., Results: We found no consensus regarding the patient's situation (α 0.41, 95%CI 0.29-0.52). The mean positive predictive value for respiratory insufficiency was high (0.91, 95%CI 0.86-0.97), but the negative predictive value was 0.66 (95%CI 0.44-0.88). In the interviews, two themes regarding the interpretation process emerged. "Interpretation of deviations" included the strategies participants use to determine stability, focused on finding deviations in data. "Inability to see the patient" entailed the need of hospital professionals to perform a patient evaluation when estimating a patient's situation., Conclusion: The interpretation of continuously measured vital signs by hospital professionals, and recognition of respiratory insufficiency using these data, is variable, which might be the result of different interpretation strategies, uncertainty regarding deviations, and not being able to see the patient. Protocols and training could help to uniform interpretation, but decision support systems might be necessary to find signs of deterioration that might otherwise go unnoticed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 van Goor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation., Methods and Results: Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48-0.71 (recurrence) and 0.61-0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% -19% for bleeding., Conclusion: The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making., Competing Interests: Conflict of Interest: Marc Carrier reports research funding from BMS, Leo Pharma, and Pfizer, and honoraria from Bayer, Sanofi, BMS, Leo Pharma, Servier and Pfizer. All fees are paid to his institution. Ander Cohen reports grants or contracts, consulting fees and payment or honoraria from Bayer AG, Daiichi Sankyo, BMS/Pfizer, and AstraZeneca. All fees were paid to his company. Alfredo Farjat was a full-time employee at Thrombosis Research Institute when he collaborated with this study. Akos Ference Pap is an employee of Bayer AG. Samuel Goldhaber reports grants or contracts from Bayer, Boston Scientific BTG EKOS, NHLBI, BMS, Janssen and Pfizer, consulting fees from Agile, Pfizer, Bayer, speaker fees from Lankenau Grand Rounds in Medicine, Bakken Symposium -University of Minnesota, The Brigham Board Review in Critical Care ‘Virtual Studio/Distance Learning’, New York Cardiovascular Symposium, Latin American Anticoagulation Series Conference, Jeresaty Symposium—Trinity Health of New England, Rutgers New Jersey Medical School Grand Rounds, SBACV Symposium—Brazil Society of Angiology and Vascular Medicine, Brigham-Sheba Collaboration on Thrombosis and Vascular Medicine and Philippine Society of Vascular Medicine Annual Convention. Michael Grosso is an employee of Daiichi Sankyo. Ajay Kakkar reports grants from Bayer AG, Sanofi SA, personal fees from Anthos Therapeutics, Bayer AG, Sanofi S.A. Karen Pieper reports consulting fees from Cryolife, J&J Pharmaceuticals, Artivion and Element Science. Gary Raskob reports consultancy fees or honoraria from AMAG Pharma, Anylam, Anthos Therapeutics, Bayer HealthCare Pharmaceuticals Inc., Bristol-Myers Squibb, Daiichi Sankyo Inc., Janssen Global Services LLC, Pfizer, and XaTrek; honoraria from BMS, Pfizer, Daiichi Sankyo; DSMB or advisory board membership from Anthos Therapetuics, Janssen, Bristol-Myers Squibb and Pfizer, leadership or fiduciary role in other board, society, committee or advocacy group of OU Health, stock or stock option ownership for AbbVie, Inc., Gilead Sciences Inc, GlaxoSmithKline, LLC., LLY, MRK, and Pfizer. Sam Schulman reports research grants, paid to his institution, from Octopharma, and consulting fees from Alexion, Bayer, Boehringer–Ingelheim, Sanofi, Daiichi Sankyo and Octopharma. Minggao Shi is an employee of Daiichi Sankyo. Phillip Wells reports grants and speaker fees from BMS/Pfizer, consulting fees from Anthos and speaker fees and consulting fees from Bayer Healthcare. All fees are paid to his institution. The other authors have nothing to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Since the beginning of the SARS-CoV-2 pandemic, studies have been reporting inconsistently on migration background as a risk factor for COVID-19 outcomes. The aim of this study was to evaluate the association between migration background and clinical outcomes with COVID-19 in the Netherlands., Methods: This cohort study included 2,229 adult COVID-19 patients admitted in two Dutch hospitals between February 27, 2020 and March 31, 2021. Odds ratios (ORs) for hospital admission, intensive care unit (ICU) admission and mortality with 95% confidence intervals (CIs) were calculated for non-Western (Moroccan, Turkish, Surinamese or other) persons as compared with Western persons in the general population of the province of Utrecht (the Netherlands) as source population. Furthermore, among hospitalized patients, Hazard ratios (HRs) with 95% CIs for in-hospital mortality and intensive care unit (ICU) admission were calculated using Cox proportional hazard analyses. Hazard ratios were adjusted for age, sex, body mass index, hypertension, Charlson Comorbidity Index, chronic corticosteroid use before admission, income, education and population density to investigate explanatory variables., Results: Of the 2,229 subjects, 1,707 were of Western origin and 522 were of non-Western origin. There were 313 in-hospital deaths and 503 ICU admissions. As compared with persons with a Western origin in the general population of the province of Utrecht, the ORs for non-Western persons was 1.8 (95% CI 1.7-2.0) for hospitalization, 2.1 (95% CI 1.7-2.5) for ICU admission and 1.3 (95% CI 1.0-1.7) for mortality. Among hospitalized patients, HR for ICU admission was 1.1 (95% CI 0.9-1.4) and 0.9 (95% CI 0.7-1.3) for mortality for non-Western hospitalized persons as compared with hospitalized patients of Western origin after adjustment., Conclusion: Non-Western persons, including Moroccan, Turkish and Surinamese subjects, had increased risks of hospital admission, ICU admission and COVID-19 related death on a population level. Among hospitalized COVID-19 patients, no association was found between migration background and ICU admission or mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ocak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Liquid fertilizers are widely used for fertilizing in- and outdoor vegetation. Despite the easy accessibility and widespread use, serious intoxications are rare. This case report describes a 61-year-old woman who was treated for life-threatening hyperkalemia, metabolic acidosis and ECG changes after intentional ingestion of liquid fertilizer. Our case shows that intake of liquid fertilizer, though infrequent, can cause serious, life threatening complications.

Accurate sepsis diagnosis is paramount for treatment decisions, especially at the emergency department (ED). To improve diagnosis, clinical decision support (CDS) tools are being developed with machine learning (ML) algorithms, using a wide range of variable groups. ML models can find patterns in Electronic Health Record (EHR) data that are unseen by the human eye. A prerequisite for a good model is the use of high-quality labels. Sepsis gold-standard labels are hard to define due to a lack of reliable diagnostic tools for sepsis at the ED. Therefore, standard clinical tools, such as clinical prediction scores (e.g. modified early warning score and quick sequential organ failure assessment), and claims-based methods (e.g. ICD-10) are used to generate suboptimal labels. As a consequence, models trained with these "silver" labels result in ill-trained models. In this study, we trained ML models for sepsis diagnosis at the ED with labels of 375 ED visits assigned by an endpoint adjudication committee (EAC) that consisted of 18 independent experts. Our objective was to evaluate which routinely measured variables show diagnostic value for sepsis. We performed univariate testing and trained multiple ML models with 95 routinely measured variables of three variable groups; demographic and vital, laboratory and advanced haematological variables. Apart from known diagnostic variables, we identified added diagnostic value for less conventional variables such as eosinophil count and platelet distribution width. In this explorative study, we show that the use of an EAC together with ML can identify new targets for future sepsis diagnosis research., (© 2022. The Author(s).)

Background: Care decision discussions are intended to align treatment with the patient's wishes, goals and values. To overcome the numerous barriers to such discussions, physicians as well as patients need tailored support. We evaluate the effect of a physicians' training and a conversation aid for patients about care decisions on patient and physician outcomes., Methods: At the internal medicine outpatient clinic of the University Medical Centre Utrecht, a 1:1 randomized, parallel-group study (patient conversation aid) was combined with a pre-post intervention (physicians' training) design. Primary outcome was patient satisfaction, secondary outcomes were patient-doctor relationship, shared-decision-making, doctor preparedness and patient appreciation of the conversation aid., Results: Between October 2018 and February 2020 11 physicians (36% residents, 73% female) and 185 patients (median age 58 years (interquartile range (IQR) 50-68), 60% male) participated. Only 28% of the patients reported a care decision discussion during the consultation. We found no effect of the interventions on patient satisfaction (effect sizes -0.14 (95% confidence interval (CI) -0.56-0.27) for conversation aid; 0.04 (95% CI -0.40-0.48) for physician's training), nor on the patient-doctor relationship or shared-decision-making. However, physicians felt more prepared to discuss care decisions after training (median 3 (IQR 1-4) vs 1 (IQR 0-3), p = 0.015). Patients assessed the conversation aid informative and gave an overall mark of median 7 (IQR 7-8)., Conclusions: First steps towards fruitful discussions about care decisions were made: patients considered the conversation aid informative and physicians felt better prepared to discuss care decisions after training. The low number of care decision conversations patients reported shows exactly how important it is to focus on interventions that facilitate these discussions, for both the patient and physician. Further work needs to be done to establish the best way to empower patients and physicians., Trial Registration: Dutch trial register, trial 6998 (NTR 7188), registered 04/05/2018, https://www.trialregister.nl/trial/6998 ., (© 2022. The Author(s).)

Background: Continuous monitoring of vital signs has the potential to assist in the recognition of deterioration of patients admitted to the general ward. However, methods to efficiently process and use continuously measured vital sign data remain unclear., Objective: The aim of this study was to explore methods to summarize continuously measured vital sign data and evaluate their association with respiratory insufficiency in COVID-19 patients at the general ward., Methods: In this retrospective cohort study, we included patients admitted to a designated COVID-19 cohort ward equipped with continuous vital sign monitoring. We collected continuously measured data of respiratory rate, heart rate, and oxygen saturation. For each patient, 7 metrics to summarize vital sign data were calculated: mean, slope, variance, occurrence of a threshold breach, number of episodes, total duration, and area above/under a threshold. These summary measures were calculated over timeframes of either 4 or 8 hours, with a pause between the last data point and the endpoint (the "lead") of 4, 2, 1, or 0 hours, and with 3 predefined thresholds per vital sign. The association between each of the summary measures and the occurrence of respiratory insufficiency was calculated using logistic regression analysis., Results: Of the 429 patients that were monitored, 334 were included for analysis. Of these, 66 (19.8%) patients developed respiratory insufficiency. Summarized continuously measured vital sign data in timeframes close to the endpoint showed stronger associations than data measured further in the past (ie, lead 0 vs 1, 2, or 4 hours), and summarized estimates over 4 hours of data had stronger associations than estimates taken over 8 hours of data. The mean was consistently strongly associated with respiratory insufficiency for the three vital signs: in a 4-hour timeframe without a lead, the standardized odds ratio for heart rate, respiratory rate, and oxygen saturation was 2.59 (99% CI 1.74-4.04), 5.05 (99% CI 2.87-10.03), and 3.16 (99% CI 1.78-6.26), respectively. The strength of associations of summary measures varied per vital sign, timeframe, and lead., Conclusions: The mean of a vital sign showed a relatively strong association with respiratory insufficiency for the majority of vital signs and timeframes. The type of vital sign, length of the timeframe, and length of the lead influenced the strength of associations. Highly associated summary measures and their combinations could be used in a clinical prediction score or algorithm for an automatic alarm system., (©Harriet M R van Goor, Lisette M Vernooij, Martine J M Breteler, Cor J Kalkman, Karin A H Kaasjager, Kim van Loon. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 23.11.2022.)

Objectives: To evaluate the prognostic value of the coefficient of variance of axial light loss of monocytes (cv-ALL of monocytes) for adverse clinical outcomes in patients suspected of infection in the emergency department (ED)., Methods: We performed an observational, retrospective monocenter study including all medical patients ≥18 years admitted to the ED between September 2016 and June 2019 with suspected infection. Adverse clinical outcomes included 30-day mortality and ICU/MCU admission <3 days after presentation. We determined the additional value of monocyte cv-ALL and compared to frequently used clinical prediction scores (SIRS, qSOFA, MEWS). Next, we developed a clinical model with routinely available parameters at the ED, including cv-ALL of monocytes., Results: A total of 3526 of patients were included. The OR for cv-ALL of monocytes alone was 2.21 (1.98-2.47) for 30-day mortality and 2.07 (1.86-2.29) for ICU/MCU admission <3 days after ED presentation. When cv-ALL of monocytes was combined with a clinical score, the prognostic accuracy increased significantly for all tested scores (SIRS, qSOFA, MEWS). The maximum AUC for a model with routinely available parameters at the ED was 0.81 to predict 30-day mortality and 0.81 for ICU/MCU admission., Conclusions: Cv-ALL of monocytes is a readily available biomarker that is useful as prognostic marker to predict 30-day mortality. Furthermore, it can be used to improve routine prediction of adverse clinical outcomes at the ED., Clinical Trial Registration: Registered in the Dutch Trial Register (NTR) und number 6916., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Vital signs follow circadian patterns in both healthy volunteers and critically ill patients, which seem to be influenced by disease severity in the latter. In this study we explored the existence of circadian patterns in heart rate, respiratory rate and skin temperature of hospitalized COVID-19 patients, and aimed to explore differences in circadian rhythm amplitude during patient deterioration., Methods: We performed a retrospective study of COVID-19 patients admitted to the general ward of a tertiary hospital between April 2020 and March 2021. Patients were continuously monitored using a wireless sensor and fingertip pulse oximeter. Data was divided into three cohorts: patients who recovered, patients who developed respiratory insufficiency and patients who died. For each cohort, a population mean cosinor model was fitted to detect rhythmicity. To assess changes in amplitude, a mixed-effect cosinor model was fitted., Results: A total of 429 patients were monitored. Rhythmicity was observed in heartrate for the recovery cohort (p<0.001), respiratory insufficiency cohort (p<0.001 and mortality cohort (p = 0.002). Respiratory rate showed rhythmicity in the recovery cohort (p<0.001), but not in the other cohorts (p = 0.18 and p = 0.51). Skin temperature also showed rhythmicity in the recovery cohort (p<0.001), but not in the other cohorts (p = 0.22 and p = 0.12). For respiratory insufficiency, only the amplitude of heart rate circadian pattern increased slightly the day before (1.2 (99%CI 0.16-2.2, p = 0.002)). In the mortality cohort, the amplitude of heart rate decreased (-1.5 (99%CI -2.6- -0.42, p<0.001)) and respiratory rate amplitude increased (0.72 (99%CI 0.27-1.3, p = 0.002) the days before death., Conclusion: A circadian rhythm is present in heart rate of COVID-19 patients admitted to the general ward. For respiratory rate and skin temperature, rhythmicity was only found in patients who recover, but not in patients developing respiratory insufficiency or death. We found no consistent changes in circadian rhythm amplitude accompanying patient deterioration., Competing Interests: The authors have declared that no competing interests exist.

Objective: Explore how often, when and how care decisions are discussed during consultations at an internal medicine outpatient clinic, and what we can learn from these observations., Methods: Qualitative analysis of 150 video-taped consultations. Consultations involving a discussion of care decisions were analyzed using conversation analysis., Results: 1) Only 21 of the 150 consultations involved a discussion of care decisions; 2) As there is no destined phase for the introduction of the topic of care decisions, the topic is most often introduced at the end of the phase 'treatment and course of the disease'; 3) A lot of interactional effort is needed to create common ground and make relevance clear with extensive justification. Hesitation markers, repairs and hypothetical talk show the precariousness of the topic., Conclusions: Three dilemma's need to be addressed: 1) a slot has to be created to introduce the topic of care decisions; 2) common ground has to be created, possibly over time; 3) the paradox of framing the topic as relevant 'in the future' but 'needs to be discussed now' needs to be attended to., Practice Implications: We recommend that physician training should address the three dilemmas. Future research should focus on how to do so., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Early recognition of sepsis is essential for improving outcomes and preventing complications such as organ failure, depression, and neurocognitive impairment. The emergency department (ED) plays a key role in the early identification of sepsis, but clinicians lack diagnostic tools. Potentially, biomarkers could be helpful in assisting clinicians in the ED, but no marker has yet been successfully implemented in daily practice with good clinical performance. Pancreatic stone protein (PSP) is a promising biomarker in the context of sepsis, but little is known about the diagnostic performance of PSP in the ED. We prospectively investigated the diagnostic value of PSP in such a population for patients suspected of infection. PSP was compared with currently used biomarkers, including white blood cell count (WBC) and C-reactive protein (CRP). Of the 156 patients included in this study, 74 (47.4%) were diagnosed with uncomplicated infection and 26 (16.7%) patients with sepsis, while 56 (35.9%) eventually had no infection. PSP was significantly higher for sepsis patients compared to patients with no sepsis. In multivariate regression, PSP was a significant predictor for sepsis, with an area under the curve (AUC) of 0.69. Positive and negative predictive values for this model were 100% and 84.4%, respectively. Altogether, these findings show that PSP, measured at the ED of a tertiary hospital, is associated with sepsis but lacks the diagnostic performance to be used as single marker.

The early recognition of acute kidney injury (AKI) is essential to improve outcomes and prevent complications such as chronic kidney disease, the need for renal-replacement therapy, and an increased length of hospital stay. Increasing evidence shows that inflammation plays an important role in the pathophysiology of AKI and mortality. Several inflammatory hematological ratios can be used to measure systemic inflammation. Therefore, the association between these ratios and outcomes (AKI and mortality) in patients suspected of having an infection at the emergency department was investigated. Data from the SPACE cohort were used. Cox regression was performed to investigate the association between seven hematological ratios and outcomes. A total of 1889 patients were included, of which 160 (8.5%) patients developed AKI and 102 (5.4%) died in <30 days. The Cox proportional-hazards model revealed that the neutrophil-to-lymphocyte ratio (NLR), segmented-neutrophil-to-monocyte ratio (SMR), and neutrophil-lymphocyte-platelet ratio (NLPR) are independently associated with AKI <30 days after emergency-department presentation. Additionally, the NLR, SMR and NLPR were associated with 30-day all-cause mortality. These findings are an important step forward for the early recognition of AKI. The use of these markers might enable emergency-department physicians to recognize and treat AKI in an early phase to potentially prevent complications.

Background: To ensure availability of hospital beds and improve COVID-19 patients' well-being during the ongoing pandemic, hospital care could be offered at home. Retrospective studies show promising results of deploying remote hospital care to reduce the number of days spent in the hospital, but the beneficial effect has yet to be established., Methods: We conducted a single centre, randomised trial from January to June 2021, including hospitalised COVID-19 patients who were in the recovery stage of the disease. Hospital care for the intervention group was transitioned to the patient's home, including oxygen therapy, medication and remote monitoring. The control group received in-hospital care as usual. The primary endpoint was the number of hospital-free days during the 30 days following randomisation. Secondary endpoints included health care consumption during the follow-up period and mortality., Results: A total of 62 patients were randomised (31 control, 31 intervention). The mean difference in hospital-free days was 1.7 (26.7 control vs. 28.4 intervention, 95% CI of difference -0.5 to 4.2, p = 0.112). In the intervention group, the index hospital length of stay was 1.6 days shorter (95% CI -2.4 to -0.8, p < 0.001), but the total duration of care under hospital responsibility was 4.1 days longer (95% CI 0.5 to 7.7, p = 0.028)., Conclusion: Remote hospital care for recovering COVID-19 patients is feasible. However, we could not demonstrate an increase in hospital-free days in the 30 days following randomisation. Optimising the intervention, timing, and identification of patients who will benefit most from remote hospital care could improve the impact of this intervention.

Objectives: The COVID-19 pandemic pressurised healthcare with increased shortage of care. This resulted in an increase of awareness for code status documentation (ie, whether limitations to specific life-sustaining treatments are in place), both in the medical field and in public media. However, it is unknown whether the increased awareness changed the prevalence and content of code status documentation for COVID-19 patients. We aim to describe differences in code status documentation between infectious patients before the pandemic and COVID-19 patients., Setting: University Medical Centre of Utrecht, a tertiary care teaching academic hospital in the Netherlands., Participants: A total of 1715 patients were included, 129 in the COVID-19 cohort (a cohort of COVID-19 patients, admitted from March 2020 to June 2020) and 1586 in the pre-COVID-19 cohort (a cohort of patients with (suspected) infections admitted between September 2016 to September 2018)., Primary and Secondary Outcome Measures: We described frequency of code status documentation, frequency of discussion of this code status with patient and/or family, and content of code status., Results: Frequencies of code status documentation (69.8% vs 72.7%, respectively) and discussion (75.6% vs 73.3%, respectively) were similar in both cohorts. More patients in the COVID-19 cohort than in the before COVID-19 cohort had any treatment limitation as opposed to full code (40% vs 25%). Within the treatment limitations, 'no intensive care admission' (81% vs 51%) and 'no intubation' (69% vs 40%) were more frequently documented in the COVID-19 cohort. A smaller difference was seen in 'other limitation' (17% vs 9%), while 'no resuscitation' (96% vs 92%) was comparable between both periods., Conclusion: We observed no difference in the frequency of code status documentation or discussion in COVID-19 patients opposed to a pre-COVID-19 cohort. However, treatment limitations were more prevalent in patients with COVID-19, especially 'no intubation' and 'no intensive care admission'., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors., Methods: Patients receiving checkpoint inhibitors between January 2013 and May 2020 at the University Medical Center Utrecht, the Netherlands, were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in serum creatinine of ≥1.5 times the baseline value, based on the Kidney Disease: Improving Global Outcomes criteria. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent renal dysfunction was diagnosed in AKI patients with a final serum creatinine measurement of >1.3 times the baseline value., Results: Among 676 patients receiving checkpoint inhibitors, the overall incidence of AKI was 14.2%. Baseline variables independently associated with AKI were a gynecologic malignancy, monotherapy with ipilimumab, and the use of a diuretic, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or proton pump inhibitor at baseline. AKI was checkpoint inhibitor-associated in one third of all patients with AKI. Checkpoint inhibitor-associated AKI was mostly low-grade, occurred a median of 15 weeks after checkpoint inhibitor initiation, and resulted in persistent renal dysfunction in approximately 40% of the patients. Patients with all-cause AKI had a twofold increased mortality risk, but checkpoint inhibitor-associated AKI was not associated with increased mortality., Conclusions: In this study, patients receiving checkpoint inhibitors frequently developed AKI due to various etiologies. AKI directly related to the effect of checkpoint inhibitor toxicity did not increase mortality. However, AKI not related to the effect of checkpoint inhibitor toxicity was associated with increased mortality., Competing Interests: The authors have declared that no competing interests exist.

Objectives: A high incidence of pulmonary embolism (PE) is reported in patients with critical coronavirus disease 2019 (COVID-19). Neutrophils may contribute to this through a process referred to as immunothrombosis. The aim of this study was to investigate the occurrence of neutrophil subpopulations in blood preceding the development of COVID-19 associated PE., Methods: We studied COVID-19 patients admitted to the ICU of our tertiary hospital between 19-03-2020 and 17-05-2020. Point-of-care fully automated flow cytometry was performed prior to ICU admission, measuring the neutrophil activation/maturation markers CD10, CD11b, CD16 and CD62L. Neutrophil receptor expression was compared between patients who did or did not develop PE (as diagnosed on CT angiography) during or after their ICU stay., Results: Among 25 eligible ICU patients, 22 subjects were included for analysis, of whom nine developed PE. The median (IQR) time between neutrophil phenotyping and PE occurrence was 9 (7-12) days. A significant increase in the immune-suppressive neutrophil phenotype CD16 bright /CD62L dim was observed on the day of ICU admission (P = 0.014) in patients developing PE compared to patients who did not., Conclusion: The increase in this neutrophil phenotype indicates that the increased number of CD16 bright /CD62L dim neutrophils might be used as prognostic marker to predict those patients that will develop PE in critical COVID-19 patients., (© 2021 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

A malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16, and CD62L) in the absence or presence of a formyl peptide (fNLF). Forty-five SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial ( n = 20) or other viral ( n = 10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSOM algorithm. Low blood eosinophil numbers (<100 cells/μL; p < 0.005) were found both in patients with COVID-19 and with other infectious diseases, albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11b bright population consisted of 5.4% (CI 95% = 3.8, 13.4) of total eosinophils. After activation, this population of CD11b bright cells comprised nearly half the population (42.21%, CI 95% = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11b bright cells before activation (7.6%, CI 95% = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11b bright fraction after activation (23.7%, CI 95% = 18.5, 27.6; p < 0.001). Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF. This might be caused by migration of fully functional cells to the tissue.

Dysnatremia-either hyponatremia or hypernatremia-is frequently encountered in the clinical practice and often poses a diagnostic and therapeutic challenge for physicians. Despite their frequent occurrence, disorders of the water and sodium balance in the human body have puzzled many physicians over the years and often remain elusive for those lacking experience in their interpretation and management. In this article, we derive a transparent governing equation that can be used by clinicians to describe how a change in relevant physiological parameters will affect the plasma sodium concentration. As opposed to many existing models, our model takes both input and output into account, and integrates osmolarity and tonicity. Our governing equation should be considered a means for clinicians to get a better qualitative understanding of the relationship between the plasma sodium concentration and the variables that influence it for a wide range of scenarios.

Background: Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and a high incidence of thrombotic event(s) (TE). Objectives: To study platelet reactivity in hospitalized COVID-19 patients and determine a possible association with the clinical outcomes thrombosis and all-cause mortality. Methods: Seventy nine hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality. Results: The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not develop a TE [median age of 55 vs. 70 years; adjusted odds ratio (AOR) = 0.96 per 1 year of age, 95% confidence interval (CI) 0.92-1.00; p = 0.041]. Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a thrombotic complication than patients that were not (18 vs. 54%; AOR = 0.19, 95% CI 0.04-0.84; p = 0.029). Conversely, having asthma strongly increased the risk on TE development (AOR = 6.2, 95% CI 1.15-33.7; p = 0.034). No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients ( n = 79) and COVID-19 negative hospitalized control patients ( n = 21), nor between COVID-19 positive survivors or non-survivors. However, patients showed decreased platelet reactivity in response to TRAP-6 following TE development. Conclusion: We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Clark, Jukema, Barendrecht, Spanjaard, Jorritsma, Smits, de Maat, Seinen, Verhoef, Parr, Sebastian, Koekman, van Wesel, van Goor, Spijkerman, Bongers, van der Vries, Nierkens, Boes, Koenderman, Kaasjager and Maas.)

Disorders of water and sodium homeostasis in the human body-or dysnatraemias-are frequently encountered in clinical practice, but their analysis is often complex and their management is often troublesome. For many clinicians, it remains challenging to correctly interpret all relevant biochemical parameters involved in the analysis of dysnatraemia, especially when a rapid 'bedside' evaluation is required to initiate treatment. By mathematically deriving the relationship between plasma osmolality and urine osmolality under physiological circumstances, we were able to propose a novel and clinically useful nomogram for the rapid evaluation of disorders of plasma osmolality. We believe that the presented osmolality nomogram could be a transparent and clinically useful tool for the quick evaluation of disorders of the water and sodium balance in patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Choosing Wisely aims to reduce low-value care to improve quality and lower costs. In the Netherlands, this campaign offers three recommendations for internal medicine applicable in emergency departments (EDs): (1) do not place an indwelling urinary catheter in non-critically ill patients who can void; (2) do not order plain abdominal radiographs in patients with acute abdominal pain; and (3) discuss whether treatment limitations are needed. This quality improvement project aims to increase the implementation of the recommendations by patient information leaflets., Methods: In a prospective before-after study, we collected data every other week during baseline and intervention periods (both 7 months) in two university medical centres. The primary outcomes were the adherence rates to the recommendations., Results: 805 patients visited the EDs for internal medicine, of whom 391 (48.6%) were hospitalised. Only 153 (19%) patients received the information leaflet. We found no change in implementation rates of the recommendations after the introduction of the patient information leaflet. In the baseline period, 28 patients received a urinary catheter, of whom 5 (17.9%) had no appropriate indication, compared with 4 (25.0%) of 16 patients in the intervention period (p=0.572). Unnecessary abdominal X-ray occurred once in the baseline period and not in the intervention period. Treatment limitations were not reported in 13 (6.5%) of 200 hospitalised patients in the baseline period, and in 17 (8.9%) of 191 patients in the intervention period (p=0.373)., Conclusions: Patient information leaflets did not increase the implementation of Choosing Wisely recommendations, which can be due to a high baseline rate and a poor dissemination of leaflets. Our ED seems not to be a practicable setting for dissemination of leaflets, since staff engagement was not possible due to high workload and shortage of qualified nursing staff in the Netherlands., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hypotonic hyponatremia. In our previous work, we have derived a novel model (Voets equation) that can be used by clinicians to predict the effect of crystalloid intravenous fluid therapy on the plasma sodium concentration in SIADH., Methods: In this retrospective chart review, the predictive accuracy of the Voets equation and the Adrogue-Madias equation for the plasma sodium response to crystalloid infusate was compared for fifteen plasma sodium response measurements (n = 15) in twelve SIADH patients. The medical records of these patients were accessed anonymously and none of the authors were their treating physicians. The Pearson correlation coefficient r and corresponding p-value were calculated for the predictions by the Voets model compared to the measured plasma sodium response and for the predictions by the Adrogue-Madias model compared to the measured plasma sodium response., Results and Conclusion: The presented results show that the Voets model (r = 0.94, p < 0.001) predicted the aforementioned plasma sodium response significantly more accurately than the Adrogue-Madias model (r = 0.49, p = 0.07) in SIADH patients and could therefore be a clinically useful addition to the existing prediction models., Competing Interests: The authors have declared that no competing interests exist.

Coronavirus disease 2019 (COVID-19) is a rapidly emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Critical COVID-19 is thought to be associated with a hyper-inflammatory process that can develop into acute respiratory distress syndrome, a critical disease normally mediated by dysfunctional neutrophils. This study tested the hypothesis whether the neutrophil compartment displays characteristics of hyperinflammation in COVID-19 patients. Therefore, a prospective study was performed on all patients with suspected COVID-19 presenting at the emergency room of a large academic hospital. Blood drawn within 2 d after hospital presentation was analyzed by point-of-care automated flow cytometry and compared with blood samples collected at later time points. COVID-19 patients did not exhibit neutrophilia or eosinopenia. Unexpectedly neutrophil activation markers (CD11b, CD16, CD10, and CD62L) did not differ between COVID-19-positive patients and COVID-19-negative patients diagnosed with other bacterial/viral infections, or between COVID-19 severity groups. In all patients, a decrease was found in the neutrophil maturation markers indicating an inflammation-induced left shift of the neutrophil compartment. In COVID-19 this was associated with disease severity., (©2020 Society for Leukocyte Biology.)

Background: To prevent bio-accumulation of low molecular weight heparins (LMWHs) in patients with decreased kidney function, dosage reduction and anti-Xa monitoring has been suggested. The aim of this study was to investigate the effect of pre-emptive dosage reduction of LMWH on anti-Xa levels. Furthermore, we investigated the association between anti-Xa levels and bleeding, thrombotic events and mortality., Methods: In this single center study, we followed 499 patients with decreased renal function in whom anti-Xa levels were measured. We observed how many patients had anti-Xa levels that fell within the reference range, with a standard protocol of a pre-emptive dosage reduction of LMWH (25% reduction in patients with an estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73m2 and a reduction of 50% in patients with an eGFR below the 30 ml/min/1.73m2). Furthermore, Cox proportional hazard analyses were used to estimate hazard ratios to investigate the association between anti-Xa levels and major bleeding, thrombotic events and mortality within three months of follow-up., Results: In a cohort of 499 patients (445 dalteparin and 54 nadroparin users), a pre-emptive dosage reduction of LMWH led to adequate levels of anti-Xa in only 19% of the patients (12% for the dalteparin users and 50% for nadroparin users). We did not find an association between anti-Xa levels and bleeding, thrombosis or mortality., Conclusion: Pre-emptive dosage reduction of LMWH leads to low anti-Xa levels in a large proportion, but this was not associated with bleeding, thrombosis or mortality., Competing Interests: The authors have declared that no competing interests exist.

Background: Poisoned patients are frequently admitted following Emergency Department (ED) presentation, while the necessity of such admissions is hardly investigated. We determined the proportion and characteristics of poisoned patients who were admitted, but in retrospect had an uneventful admission., Methods: For this observational cohort study, all patients presented to the ED of a Dutch University Hospital with various poisonings during a 1.5-year period (January 2015-July 2016) were included. The uneventfulness of admissions, defined as patients with a low Poisoning Severity Score (PSS) who received no treatment, was determined in retrospect., Results: We included 417 patients who visited the ED for poisoning. 247 Patients were admitted: 30% to a general ward, 58% to a MCU, and 12% to the ICU. The poisoning severity scores of the admitted patients were none to mild in 38%, moderate to severe in 59%, and fatal in 2%. Upon admission, 60% of the patients received treatment. In retrospect, 77% of the admitted patients had a moderate, severe or fatal poisoning and/or required treatment. However, 23% of the admitted patients had a mild poisoning and required no treatment. This group involved younger patients (median age of 23 versus 42 years) and a higher proportion of patients reporting exposure to only one substance (65% versus 51%)., Conclusions: The majority of poisoned patients presented to the ED was admitted, while in retrospect, a quarter of these admissions were uneventful. Predictive parameters should be sought to identify patients who can be sent home safely., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Purpose: To provide insight into the current use and results of ultrasound-facilitated catheter-directed thrombolysis (USAT) in patients with high-risk pulmonary embolism (PE)., Introduction: Systemic thrombolysis is an effective treatment for hemodynamically unstable, high-risk PE, but is associated with bleeding complications. USAT is thought to reduce bleeding and is therefore advocated in patients with high-risk PE and contraindications for systemic thrombolysis., Methods: We conducted a retrospective cohort study of all patients who underwent USAT for high-risk PE in the Netherlands from 2010 to 2017. Characteristics and outcomes were analyzed. Primary outcomes were major (including intracranial and fatal) bleeding and all-cause mortality after 1 month. Secondary outcomes were all-cause mortality and recurrent venous thromboembolism within 3 months., Results: 33 patients underwent USAT for high-risk PE. Major bleeding occurred in 12 patients (36%, 95% CI 22-53), including 1 intracranial and 3 fatal bleeding. All-cause mortality after 1 month was 48% (16/33, 95% CI 31-66). All-cause mortality after 3 months was 50% (16/32, 95% CI 34-66), recurrent venous thromboembolism occurred in 1 patient (1/32, 3%, 95% CI 1-16)., Conclusions: This study was the first to describe characteristics and outcomes after USAT in a study population of patients with high-risk PE only, an understudied population. Although USAT is considered a relatively safe treatment option, our results illustrate that at least caution is needed in critically ill patients with high-risk PE. Further research in patients with high-risk PE is warranted to guide patient selection.

Background: Morbidly obese patients are at increased risk to develop venous thromboembolism (VTE), especially after bariatric surgery. Adequate postoperative thrombosis prophylaxis is of utmost importance. It is assumed that morbidly obese patients need higher doses of low molecular weight heparin (LMWH) compared to normal-weight patients; however, current guidelines based on relative efficacy in obese populations are lacking., Objectives: First, we will evaluate the relationship between body weight descriptors and anti-Xa activity prospectively. Second, we will determine the dose-linearity of LMWH in morbidly obese patients., Setting: This study was performed in a general hospital specialized in bariatric surgery., Methods: Patients were scheduled for a Roux-en-Y gastric bypass with a total bodyweight (TBW) of ≥ 140 kg. Patients (n = 50, 64% female) received a daily postoperative dose of 5700 IU of nadroparin for 4 weeks. Anti-Xa activity was determined 4 h after the last nadroparin administration. To determine the dose linearity, anti-Xa was determined following a preoperative dose of 2850 IU nadroparin in another 50 patients (52%)., Results: TBW of the complete group was 148.5 ± 12.6 kg. Mean anti-Xa activity following 5700 IU nadroparin was 0.19 ± 0.07 IU/mL. Of all patients, 32% had anti-Xa levels below the prophylactic range. Anti-Xa activity inversely correlated with TBW (correlation coefficient - 0.410) and lean body weight (LBW; correlation coefficient - 0.447); 67% of patients with a LBW ≥ 80 kg had insufficient anti-Xa activity concentrations. No VTE events occurred., Conclusions: In morbidly obese patients, a postoperative dose of 5700 IU of nadroparin resulted in subprophylactic exposure in a significant proportion of patients. Especially in patients with LBW ≥ 80 kg, a higher dose may potentially be required to reach adequate prophylactic anti-Xa levels.

Background: Validated diagnostic algorithms in patients with suspected pulmonary embolism are often not used correctly or only benefit subgroups of patients, leading to overuse of computed tomography pulmonary angiography (CTPA). The YEARS clinical decision rule that incorporates differential D-dimer cutoff values at presentation, has been developed to be fast, to be compatible with clinical practice, and to reduce the number of CTPA investigations in all age groups. We aimed to prospectively evaluate this novel and simplified diagnostic algorithm for suspected acute pulmonary embolism., Methods: We did a prospective, multicentre, cohort study in 12 hospitals in the Netherlands, including consecutive patients with suspected pulmonary embolism between Oct 5, 2013, to July 9, 2015. Patients were managed by simultaneous assessment of the YEARS clinical decision rule, consisting of three items (clinical signs of deep vein thrombosis, haemoptysis, and whether pulmonary embolism is the most likely diagnosis), and D-dimer concentrations. In patients without YEARS items and D-dimer less than 1000 ng/mL, or in patients with one or more YEARS items and D-dimer less than 500 ng/mL, pulmonary embolism was considered excluded. All other patients had CTPA. The primary outcome was the number of independently adjudicated events of venous thromboembolism during 3 months of follow-up after pulmonary embolism was excluded, and the secondary outcome was the number of required CTPA compared with the Wells' diagnostic algorithm. For the primary outcome regarding the safety of the diagnostic strategy, we used a per-protocol approach. For the secondary outcome regarding the efficiency of the diagnostic strategy, we used an intention-to-diagnose approach. This trial is registered with the Netherlands Trial Registry, number NTR4193., Findings: 3616 consecutive patients with clinically suspected pulmonary embolism were screened, of whom 151 (4%) were excluded. The remaining 3465 patients were assessed of whom 456 (13%) were diagnosed with pulmonary embolism at baseline. Of the 2946 patients (85%) in whom pulmonary embolism was ruled out at baseline and remained untreated, 18 patients were diagnosed with symptomatic venous thromboembolism during 3-month follow-up (0·61%, 95% CI 0·36-0·96) of whom six had fatal pulmonary embolism (0·20%, 0·07-0·44). CTPA was not indicated in 1651 (48%) patients with the YEARS algorithm compared with 1174 (34%) patients, if Wells' rule and fixed D-dimer threshold of less than 500 ng/mL would have been applied, a difference of 14% (95% CI 12-16)., Interpretation: In our study pulmonary embolism was safely excluded by the YEARS diagnostic algorithm in patients with suspected pulmonary embolism. The main advantage of the YEARS algorithm in our patients is the absolute 14% decrease of CTPA examinations in all ages and across several relevant subgroups., Funding: This study was supported by unrestricted grants from the participating hospitals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Medication errors are a frequent problem in the accident and emergency (A&E) department., Case Description: A 17-year-old boy was referred to our A&E department with an anaphylactic reaction to peanuts. Because of various shortcomings in the care process in A&E, adrenaline was administered intravenously instead of intramuscularly, resulting in a broad complex tachycardia. We analysed these shortcomings using the 'Prevention and recovery information system for monitoring and analysis' (PRISMA) method., Conclusion: Medication errors are usually a result of shortcomings in non-technical skills, such as communication and situational awareness. Training these skills by applying the concept 'Crew resource management' may reduce medication errors and improve patient safety.