Plasma ESR1 mutations and outcome to first-line paclitaxel and bevacizumab in patients with advanced ER-positive/HER2-negative breast cancer.

BACKGROUND: ESR1 mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessed ESR1 mutations in circulating tumor DNA (ctDNA) for impact on outcome to taxane-based chemotherapy in advanced breast cancer patients. METHODS: ESR1 mutations were determined in archived plasma samples from patients treated with paclitaxel and bevacizumab (AT arm, N = 91) in the randomized phase II ATX study. Samples collected at baseline (n = 51) and at cycle 2 (n = 13, C2) were analyzed using a breast cancer next-generation sequencing panel. This study was powered to detect a benefit in progression-free survival (PFS) at six months for patients treated with paclitaxel/bevacizumab compared to historical trials with fulvestrant. PFS, overall survival (OS), and ctDNA dynamics were exploratory analyses. RESULTS: PFS at six months was 86% (18/21) in patients with an ESR1 mutation detected and 85% (23/27) in wildtype ESR1 patients. In our exploratory analysis, median progression-free survival (PFS) was 8.2 months [95% CI, 7.6-8.8] for ESR1 mutant patients versus 8.7 months [95% confidence interval (CI), 8.3-9.2] for ESR1 wildtype patients [p = 0.47]. The median overall survival (OS) was 20.7 months [95% CI, 6.6-33.7] for ESR1 mutant patients versus 28.1 months [95% confidence interval (CI), 19.3-36.9] for ESR1 wildtype patients [p = 0.27]. Patients with ≥ two ESR1 mutations had a significantly worse OS, but not PFS, compared to those who did not [p = 0.003]. Change in ctDNA level at C2 was not different between ESR1 and other mutations. CONCLUSIONS: Presence of ESR1 mutations in baseline ctDNA might not be associated with inferior PFS and OS in advanced breast cancer patients treated with paclitaxel/bevacizumab.

The effect of ICU-tailored drug-drug interaction alerts on medication prescribing and monitoring: protocol for a cluster randomized stepped-wedge trial.

BACKGROUND: Drug-drug interactions (DDIs) can cause patient harm. Between 46 and 90% of patients admitted to the Intensive Care Unit (ICU) are exposed to potential DDIs (pDDIs). This rate is twice as high as patients on general wards. Clinical decision support systems (CDSSs) have shown their potential to prevent pDDIs. However, the literature shows that there is considerable room for improvement of CDSSs, in particular by increasing the clinical relevance of the pDDI alerts they generate and thereby reducing alert fatigue. However, consensus on which pDDIs are clinically relevant in the ICU setting is lacking. The primary aim of this study is to evaluate the effect of alerts based on only clinically relevant interactions for the ICU setting on the prevention of pDDIs among Dutch ICUs. METHODS: To define the clinically relevant pDDIs, we will follow a rigorous two-step Delphi procedure in which a national expert panel will assess which pDDIs are perceived clinically relevant for the Dutch ICU setting. The intervention is the CDSS that generates alerts based on the clinically relevant pDDIs. The intervention will be evaluated in a stepped-wedge trial. A total of 12 Dutch adult ICUs using the same patient data management system, in which the CDSS will operate, were invited to participate in the trial. Of the 12 ICUs, 9 agreed to participate and will be enrolled in the trial. Our primary outcome measure is the incidence of clinically relevant pDDIs per 1000 medication administrations. DISCUSSION: This study will identify pDDIs relevant for the ICU setting. It will also enhance our understanding of the effectiveness of alerts confined to clinically relevant pDDIs. Both of these contributions can facilitate the successful implementation of CDSSs in the ICU and in other domains as well. TRIAL REGISTRATION: Nederlands Trial register Identifier: NL6762 . Registered November 26, 2018.

Carriage of antibiotic-resistant Gram-negative bacteria after discontinuation of selective decontamination of the digestive tract (SDD) or selective oropharyngeal decontamination (SOD).

BACKGROUND: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) reduce colonization with antibiotic-resistant Gram-negative bacteria (ARGNB), incidence of nosocomial infections and improve survival in ICU patients. The effect on bacterial gut colonization might be caused by growth suppression by antibiotics during SDD/SOD. We investigated intestinal colonization with ARGNB after discharge from ICU and discontinuation of SDD or SOD. METHODS: We performed a prospective, observational follow-up study in regular hospital wards of three teaching hospitals in the Netherlands in patients discharged from the ICU, who were participating in a cluster randomized trial comparing SDD with SOD. We determined rectal carriage with ARGNB at ICU discharge (time (T) = 0) and 3, 6 and 10 days after discharge. The primary endpoint was time to first colonization with ARGNB that was not present at T = 0. Bacteria that are intrinsically resistant to antibiotics were not included in the primary analysis, but were included in post-hoc analysis. RESULTS: Of 1370 patients screened for inclusion, 996 patients had samples at T = 0 (507 after SDD and 489 after SOD). At ICU discharge, the prevalence of intestinal carriage with any ARGNB was 22/507 (4.3%) after SDD and 87/489 (17.8%) after SOD (p < 0.0001): 426 (SDD) and 409 (SOD) patients had at least one follow-up sample for analysis. The hazard rate for acquiring carriage of ARGNB after discontinuation of SDD, compared to SOD, in the ICU was 0.61 (95% CI 0.40-0.91, p = 0.02), and cumulative risks of acquisition of at least one ARGNB until day 10 were 13% (SDD) and 18% (SOD). At day 10 after ICU discharge, the prevalence of intestinal carriage with ARGNB was 11.3% (26/230 patients) after SDD and 12.5% (28/224 patients) after SOD (p = 0.7). In post-hoc analysis of all ARGNB, including intrinsically resistant bacteria, colonization at ICU discharge was lower after SDD (4.9 vs. 22.3%, p < 0.0001), but acquisition rates after ICU discharge were similar in both groups. CONCLUSIONS: Intestinal carriage at ICU discharge and the acquisition rate of ARGNB after ICU discharge are lower after SDD than after SOD. The prevalence of intestinal carriage with ARGNB at 10 days after ICU discharge was comparable in both groups, suggesting rapid clearance of ARGNB from the gut after ICU discharge. TRIAL REGISTRATION: Netherlands Trial Registry, NTR3311 . Registered on 28 february 2012.

Dietary acid load, trabecular bone integrity, and mineral density in an ageing population: the Rotterdam study.

We studied the relation between a diet that is high in acid-forming nutrients (e.g. proteins) and low in base-forming nutrients (e.g. potassium) and bone structure. We showed a negative relation, which was more prominent if proteins were of animal rather than of vegetable origin and if intake of dietary fibre was high. INTRODUCTION: Studies on dietary acid load (DAL) and fractures have shown inconsistent results. Associations between DAL, bone mineral density (BMD) and trabecular bone integrity might play a role in these inconsistencies and might be influenced by renal function and dietary fibre intake. Therefore, our aim was to study (1) associations of DAL with BMD and with the trabecular bone score (TBS) and (2) the potential influence of renal function and dietary fibre in these associations. METHODS: Dutch individuals aged 45 years and over (n = 4672) participating in the prospective cohort of the Rotterdam study were included. Based on food frequency questionnaires, three indices of DAL were calculated: the net endogenous acid production (NEAP) and the ratios of vegetable or animal protein and potassium (VegPro/K and AnPro/K). Data on lumbar spinal TBS and BMD were derived from dual-energy X-ray absorptiometry measurements. RESULTS: Independent of confounders, NEAP and AnPro/K, but not VegPro/K, were associated with low TBS (standardized ß (95%) = -0.04 (-0.07, -0.01) and -0.08 (-0.11, -0.04)) but not with BMD. Associations of AnPro/K and VegPro/K with TBS were non-linear and differently shaped. Unfavourable associations between NEAP, BMD and TBS were mainly present in subgroups with high fibre intake. CONCLUSIONS: High NEAP was associated with low TBS. Associations of AnPro/K and VegPro/K and TBS were non-linear and differently shaped. No significant associations of DAL with BMD were observed, nor was there any significant interaction between DAL and renal function. Mainly in participants with high intake of dietary fibre, DAL might be detrimental to bone.

Metabolic phenotyping of human blood plasma: a powerful tool to discriminate between cancer types?

BACKGROUND: Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. However, up to now it is not clear whether different cancer types are characterized by a specific metabolite profile. Therefore, this study aims to evaluate whether the plasma metabolic phenotype allows to discriminate between lung and breast cancer. PATIENTS AND METHODS: The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 80 female breast cancer patients and 54 female lung cancer patients, all with an adenocarcinoma. The validity of the model was examined by permutation testing and by classifying an independent validation cohort of 60 female breast cancer patients and 81 male lung cancer patients, all with an adenocarcinoma. RESULTS: The model allows to classify 99% of the breast cancer patients and 93% of the lung cancer patients correctly with an area under the curve (AUC) of 0.96 and can be validated in the independent cohort with a sensitivity of 89%, a specificity of 82% and an AUC of 0.94. Decreased levels of sphingomyelin and phosphatidylcholine (phospholipids with choline head group) and phospholipids with short, unsaturated fatty acid chains next to increased levels of phospholipids with long, saturated fatty acid chains seem to indicate that cell membranes of lung tumors are more rigid and less sensitive to lipid peroxidation. The other discriminating metabolites are pointing to a more pronounced response of the body to the Warburg effect for lung cancer. CONCLUSION: Metabolic phenotyping of plasma allows to discriminate between lung and breast cancer, indicating that the metabolite profile reflects more than a general cancer marker. CLINICAL TRIAL REGISTRATION NUMBER: NCT02362776.

The effect of propofol on haemodynamics: cardiac output, venous return, mean systemic filling pressure, and vascular resistances.

BACKGROUND: Although arterial hypotension occurs frequently with propofol use in humans, its effects on intravascular volume and vascular capacitance are uncertain. We hypothesized that propofol decreases vascular capacitance and therefore decreases stressed volume. METHODS: Cardiac output (CO) was measured using Modelflow(®) in 17 adult subjects after upper abdominal surgery. Mean systemic filling pressure (MSFP) and vascular resistances were calculated using venous return curves constructed by measuring steady-state arterial and venous pressures and CO during inspiratory hold manoeuvres at increasing plateau pressures. Measurements were performed at three incremental levels of targeted blood propofol concentrations. RESULTS: Mean blood propofol concentrations for the three targeted levels were 3.0, 4.5, and 6.5 µg ml(-1). Mean arterial pressure, central venous pressure, MSFP, venous return pressure, Rv, systemic arterial resistance, and resistance of the systemic circulation decreased, stroke volume variation increased, and CO was not significantly different as propofol concentration increased. CONCLUSIONS: An increase in propofol concentration within the therapeutic range causes a decrease in vascular stressed volume without a change in CO. The absence of an effect of propofol on CO can be explained by the balance between the decrease in effective, or stressed, volume (as determined by MSFP), the decrease in resistance for venous return, and slightly improved heart function. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register: NTR2486.

Development and external validation of new ultrasound-based mathematical models for preoperative prediction of high-risk endometrial cancer.

OBJECTIVES: To develop and validate strategies, using new ultrasound-based mathematical models, for the prediction of high-risk endometrial cancer and compare them with strategies using previously developed models or the use of preoperative grading only. METHODS: Women with endometrial cancer were prospectively examined using two-dimensional (2D) and three-dimensional (3D) gray-scale and color Doppler ultrasound imaging. More than 25 ultrasound, demographic and histological variables were analyzed. Two logistic regression models were developed: one 'objective' model using mainly objective variables; and one 'subjective' model including subjective variables (i.e. subjective impression of myometrial and cervical invasion, preoperative grade and demographic variables). The following strategies were validated: a one-step strategy using only preoperative grading and two-step strategies using preoperative grading as the first step and one of the new models, subjective assessment or previously developed models as a second step. RESULTS: One-hundred and twenty-five patients were included in the development set and 211 were included in the validation set. The 'objective' model retained preoperative grade and minimal tumor-free myometrium as variables. The 'subjective' model retained preoperative grade and subjective assessment of myometrial invasion. On external validation, the performance of the new models was similar to that on the development set. Sensitivity for the two-step strategy with the 'objective' model was 78% (95% CI, 69-84%) at a cut-off of 0.50, 82% (95% CI, 74-88%) for the strategy with the 'subjective' model and 83% (95% CI, 75-88%) for that with subjective assessment. Specificity was 68% (95% CI, 58-77%), 72% (95% CI, 62-80%) and 71% (95% CI, 61-79%) respectively. The two-step strategies detected up to twice as many high-risk cases as preoperative grading only. The new models had a significantly higher sensitivity than did previously developed models, at the same specificity. CONCLUSION: Two-step strategies with 'new' ultrasound-based models predict high-risk endometrial cancers with good accuracy and do this better than do previously developed models.

Evaluation of the quality of the management of cancer of the corpus uteri--selection of relevant quality indicators and implementation in Belgium.

OBJECTIVE: Describe the methodology and selection of quality indicators (QI) to be implemented in the EFFECT (EFFectiveness of Endometrial Cancer Treatment) project. EFFECT aims to monitor the variability in Quality of Care (QoC) of uterine cancer in Belgium, to compare the effectiveness of different treatment strategies to improve the QoC and to check the internal validity of the QI to validate the impact of process indicators on outcome. METHODS: A QI list was retrieved from literature, recent guidelines and QI databases. The Belgian Healthcare Knowledge Center methodology was used for the selection process and involved an expert's panel rating the QI on 4 criteria. The resulting scores and further discussion resulted in a final QI list. An online EFFECT module was developed by the Belgian Cancer Registry including the list of variables required for measuring the QI. Three test phases were performed to evaluate the relevance, feasibility and understanding of the variables and to test the compatibility of the dataset. RESULTS: 138 QI were considered for further discussion and 82 QI were eligible for rating. Based on the rating scores and consensus among the expert's panel, 41 QI were considered measurable and relevant. Testing of the data collection enabled optimization of the content and the user-friendliness of the dataset and online module. CONCLUSIONS: This first Belgian initiative for monitoring the QoC of uterine cancer indicates that the previously used QI selection methodology is reproducible for uterine cancer. The QI list could be applied by other research groups for comparison.

Bloodstream infections in patients with or without cancer in a large community hospital.

PURPOSE: Cancer is associated with an increased risk of acquiring bloodstream infection (BSIs). Most knowledge on pathogens and outcome are derived from specialised cancer centres. We here sought to compare causative micro-organisms in BSIs in patients with or without cancer in a 600-bed teaching community hospital. METHODS: We analysed all positive blood cultures from adult patients between January 2005 and January 2011. RESULTS: A total of 4,918 episodes of BSI occurred in 2,891 patients, of whom 13.4% had a diagnosis of cancer (85.5% with a solid tumour). In both patient groups, Gram-positive isolates were more prevalent (58.7 and 61.4% in patients with and without cancer, respectively) than Gram-negative isolates (31.8 and 32.3%, respectively). Amongst Gram-positive organisms, coagulase-negative staphylococci, Staphylococcus aureus and enterococci were the most frequently isolated in both patient groups; in cancer patients, twice as many BSIs were caused by Enterococcus faecalis and E. faecium. Amongst Gram-negative organisms, Escherichia coli was the most common isolate; in cancer patients, twice as many BSIs were caused by Pseudomonas aeruginosa and Enterobacter cloacae. Yeasts were grown from 3.0% of blood cultures from cancer patients compared to 1.5% of cultures from non-cancer patients. Cancer patients had a 90-day mortality of 35.8% following BSI compared to 23.5% in patients without cancer. CONCLUSION: These data demonstrate distinct BSI pathogens and impaired outcomes in patients with cancer in the setting of a large community teaching hospital.

Consistency of nurses' daily predictions of survival in the intensive care.

In the Intensive Care Unit, clinicians are continuously faced with the difficult task of prognosis, but their predictions of patient survival status may not always be consistent. Specifically very little is known about consistency of predictions over time. The aim of this paper is to assess the consistency of nurses' daily predictions of survival in terms of inter-observer variance and variance of observers over time. We found a low consistency of these predictions between observers and over time, even though changes in the patients' condition are considered. Our findings have implications to the process of end-of-life decision-making, which pertains to withholding or withdrawing intensive care treatment.

ICONIC study-conservative versus conventional oxygenation targets in intensive care patients: study protocol for a randomized clinical trial.

BACKGROUND: Oxygen therapy is a widely used intervention in acutely ill patients in the intensive care unit (ICU). It is established that not only hypoxia, but also prolonged hyperoxia is associated with poor patient-centered outcomes. Nevertheless, a fundamental knowledge gap remains regarding optimal oxygenation for critically ill patients. In this randomized clinical trial, we aim to compare ventilation that uses conservative oxygenation targets with ventilation that uses conventional oxygen targets with respect to mortality in ICU patients. METHODS: The "ConservatIve versus CONventional oxygenation targets in Intensive Care patients" trial (ICONIC) is an investigator-initiated, international, multicenter, randomized clinical two-arm trial in ventilated adult ICU patients. The ICONIC trial will run in multiple ICUs in The Netherlands and Italy to enroll 1512 ventilated patients. ICU patients with an expected mechanical ventilation time of more than 24 h are randomized to a ventilation strategy that uses conservative (PaO2 55-80 mmHg (7.3-10.7 kPa)) or conventional (PaO2 110-150 mmHg (14.7-20 kPa)) oxygenation targets. The primary endpoint is 28-day mortality. Secondary endpoints are ventilator-free days at day 28, ICU mortality, in-hospital mortality, 90-day mortality, ICU- and hospital length of stay, ischemic events, quality of life, and patient opinion of research and consent in the emergency setting. DISCUSSION: The ICONIC trial is expected to provide evidence on the effects of conservative versus conventional oxygenation targets in the ICU population. This study may guide targeted oxygen therapy in the future. TRIAL REGISTRATION: Trialregister.nl NTR7376 . Registered on 20 July, 2018.

Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave.

INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study.

PURPOSE: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. MATERIALS & METHODS: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. RESULTS: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. CONCLUSIONS: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

Prospective external validation of the 'ovarian crescent sign' as a single ultrasound parameter to distinguish between benign and malignant adnexal pathology.

OBJECTIVE: To determine the sensitivity and specificity of the 'ovarian crescent sign' (OCS)-a rim of normal ovarian tissue seen adjacent to an ipsilateral adnexal mass-as a sonographic feature to discriminate between benign and malignant adnexal masses. METHODS: The patients included were a subgroup of patients participating in the International Ovarian Tumor Analysis (IOTA) Phase 2 study, which is an international multicenter study. The subgroup comprised 1938 patients, with an adnexal mass, recruited from 19 ultrasound centers in different countries. All patients were scanned using the same standardized ultrasound protocol. Information on more than 40 demographic and ultrasound variables were collected, but the evaluation of the OCS was optional. Only patients from centers that had evaluated the OCS in > or = 90% of their cases were included. The gold standard was the histological diagnosis of the adnexal mass. The ability of the OCS to discriminate between borderline or invasively malignant vs. benign adnexal masses, as well as between invasively malignant vs. other (benign and borderline) tumors, was determined and compared with the performance of subjective evaluation of ultrasound findings by the ultrasound examiner. RESULTS: The OCS was evaluated in 1377 adnexal masses from 12 centers, 938 (68%) masses being benign, 86 (6%) borderline, 305 (22%) primary invasive and 48 (3%) metastases. The OCS was present in 398 (42%) of 938 benign masses, in 14 (16%) of 86 borderline tumors, in 18 (6%) of 305 primary invasive tumors (one malignant struma ovarii, one uterine clear cell adenocarcinoma and 16 epithelial carcinomas, i.e. four Stage I and 12 Stage II-IV) and in two (4%) of 48 ovarian metastases. Hence, the sensitivity and specificity for absent OCS to identify a malignancy was 92% and 42%, respectively, and the positive and negative likelihood ratios (LR+ and LR-, respectively) were 1.60 and 0.18. Subjective impression performed significantly better than the OCS. Sensitivity and specificity were 90% and 92%, respectively, LR+ was 11.0 and LR- was 0.10. For discrimination between invasive vs. benign or borderline tumors, the sensitivity for absent OCS was 94%, the specificity was 40%, the LR+ was 1.58 and the LR- was 0.14. CONCLUSION: This study confirms previous reports that the presence of the OCS decreases the likelihood of invasive malignancy in adnexal masses. However it is a poor discriminator between benign and malignant adnexal masses.

Clinical and computed tomography characteristics of COVID-19 associated acute pulmonary embolism: A different phenotype of thrombotic disease?

INTRODUCTION: COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE). It is suggested that COVID-19 associated PE represents in situ immunothrombosis rather than venous thromboembolism, although the origin of thrombotic lesions in COVID-19 patients remains largely unknown. METHODS: In this study, we assessed the clinical and computed tomography (CT) characteristics of PE in 23 consecutive patients with COVID-19 pneumonia and compared these to those of 100 consecutive control patients diagnosed with acute PE before the COVID-19 outbreak. Specifically, RV/LV diameter ratio, pulmonary artery trunk diameter and total thrombus load (according to Qanadli score) were measured and compared. RESULTS: We observed that all thrombotic lesions in COVID-19 patients were found to be in lung parenchyma affected by COVID-19. Also, the thrombus load was lower in COVID-19 patients (Qanadli score -8%, 95% confidence interval [95%CI] -16 to -0.36%) as was the prevalence of the most proximal PE in the main/lobar pulmonary artery (17% versus 47%; -30%, 95%CI -44% to -8.2). Moreover, the mean RV/LV ratio (mean difference -0.23, 95%CI -0.39 to -0.07) and the prevalence of RV/LV ratio >1.0 (prevalence difference -23%, 95%CI -41 to -0.86%) were lower in the COVID-19 patients. CONCLUSION: Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19, fuelling the discussion on its pathophysiology.

Attitudes of Dutch intensive care unit clinicians towards oxygen therapy.

BACKGROUND: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands. METHODS: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios. RESULTS: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO2) of 85-90% as acceptable for 15 minutes, and a PaO2 7-10 kPa (53-75 mmHg) and SaO2 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO2) if SaO2 was 90-95% or PaO2 was 12 kPa (90 mmHg). CONCLUSION: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO2 targets in the lower physiological range and would adjust ventilation settings accordingly.

Ultrasound methods to distinguish between malignant and benign adnexal masses in the hands of examiners with different levels of experience.

OBJECTIVES: To determine the effect of an ultrasound training course on the performance of pattern recognition when used by less experienced examiners and to compare the performance of pattern recognition, a logistic regression model and a scoring system to estimate the risk of malignancy between examiners with different levels of experience. METHODS: Using ultrasound images of selected adnexal masses, two trainees classified the masses as benign or malignant by using pattern recognition both before and after they had attended a theoretical gynecological ultrasound course. They also classified the masses by using a logistic regression model and a scoring system, but only after they had attended the course. The performance of these three methods when they were used by the trainees was then compared with that when they were used by experts. RESULTS: One hundred and sixty-five adnexal masses were included, of which 42% were malignant (21% invasive tumors and 21% borderline tumors). The area under the receiver-operating characteristics curve of pattern recognition when used by the trainees was similar before and after they had attended the course. Training decreased sensitivity (84% vs. 70% for Trainee 1, P = 0.004; 70% vs. 61% for Trainee 2, P = 0.058) and increased specificity (77% vs. 92% for Trainee 1, P = 0.001; 89% vs. 95% for Trainee 2, P = 0.058). The performance of pattern recognition was poorer in the hands of the trainees than in the hands of the experts. The sensitivities of the logistic regression model were 70% and 54% for the trainees vs. 83% for an expert (P = 0.020 and < 0.001, respectively) and the specificities were 84% and 94% vs. 89% (P = 0.25 and 0.59, respectively). The sensitivities of the scoring system were 59% and 54% for the trainees vs. 75% for the expert (P = 0.002 and < 0.001, respectively), and the specificities were 90% and 93% vs. 85% (P = 0.103 and 0.008, respectively). CONCLUSION: Theoretical ultrasound teaching did not seem to improve the performance of pattern recognition in the hands of trainees. A logistic regression model and a scoring system to classify adnexal masses as benign or malignant perform less well when they were used by inexperienced examiners than when used by an expert. Before using a model or a scoring system, experience and/or proper training are likely to be of paramount importance if diagnostic performance is to be optimized.

[Behavioural changes during forensic psychiatric treatment: a multicenter study]. / Gedragsveranderingen tijdens tbs-behandeling: een multicenteronderzoek.

BACKGROUND: In forensic psychiatry it is essential that patients' risks of reoffending are assessed as reliably as possible. The risk assessment instrument hkt-30 assesses both static and dynamic risk factors. It is assumed that dynamic risk factors should change when a patient receives treatment. AIM: To find out whether dynamic risk factors changed during the course of forensic psychiatric treatment. METHOD: The hkt-30 was administered 984 times for forensic psychiatric patients in 3 different forensic psychiatric centres, in the period June 2003-November 2006. For 513 patients the instrument was administered at least once, for 313 this was done at least twice and for 158 patients for three years in succession. By subdividing the research group into 'new', 'old' and 'transferred' patients we were able to examine in which phase of treatment the largest changes in hkt-30 scores occurred. RESULTS: More than half the scores for dynamic risk factors, as well as the total score, declined significantly as treatment progressed, but the differences were small in absolute terms. The three subgroups of patients hardly differed from each other with regard to the degree of change. CONCLUSION: The scores for the risk factors, assumed in theory to be changeable, seemed to become lower as the treatment progressed. However, it is not yet certain whether these lower scores were in fact directly linked to a reduction on the risk of reoffending.

Difficult epidural placement in obese and non-obese pregnant women: a systematic review and meta-analysis.

INTRODUCTION: The increasing rates of obese pregnant women who receive epidural analgesia during delivery make it necessary to evaluate the rate of epidural failure and difficulties during epidural placement in these women. METHODS: PubMed, Embase, Medline and Google scholar were searched systematically until December 2017 for articles reporting epidural failure and/or difficulties in epidural placement in obese pregnant women and non-obese pregnant women. We excluded studies that used ultrasound during epidural placement. Outcomes were defined as first-pass success or multiple attempts. Quality assessment of the literature was performed in accordance with an adjusted Newland-Ottawa Scale. Two groups of women were defined (body mass index (BMI) ≥30 kg/m2 and BMI <30 kg/m2). Statistical analysis was performed using OpenMetaAnalyst software. RESULTS: Initially 221 articles were identified, of which we included eight in the systematic review and four in the meta-analyses. Five out of six studies reported an association between BMI and epidural failure and four out of five studies reported an association between BMI and difficult epidural placement or multiple attempts. The odds ratios (OR) for epidural failure were 1.82 [95% CI 1.23 to 2.68] and for multiple attempts 2.21 [95% CI 1.39 to 3.52], both of these ORs applying to obese pregnant women compared to non-obese pregnant women. CONCLUSION: The findings suggest that obesity in pregnant women increases the risk of epidural failure and difficult epidural placement during delivery at least two-fold, and that this risk increases with increasing BMI.