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Objective: The Cross-Cultural Dementia (CCD) is a new screening tool to evaluate cognitive impairment based on a cross-cultural perspective to reduce the bias of education, and language and cultural differences. We aimed to evaluate the diagnostic properties of the CCD in Spaniards for the assessment of patients with Alzheimer's disease in mild cognitive impairment (AD-MCI) and mild dementia stages (AD-D) and patients with mild cognitive impairment associated with Parkinson's disease (PD-MCI)., Methods: Sixty participants with AD (50% MCI) and thirty with PD-MCI were enrolled. Each clinical group was compared against a healthy control group (HC) with the same number of participants and no significant differences in age, education, and sex. A comprehensive neuropsychological test battery and CCD were completed. Intergroup comparisons, ROC curves, and cut-off scores were calculated for the study of diagnostic properties., Results: Intergroup differences were found in accordance with the cognitive profile of each clinical condition. Memory measures (Objects test) were especially relevant for the classification between AD and HC. Memory and executive function scores (Sun-Moon and Dots tests) were useful in the case of PD-MCI and HC. Furthermore, CCD described differences in executive functions and speed scores comparing AD-MCI and PD-MCI. Correlations between standardized neuropsychological tests and CCD measures supported the convergent validity of the test., Conclusion: CCD showed good discrimination properties and cut-off scores for dementia and extended its application to a sample of prodromal stages of AD and PD with mild cognitive impairment., 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 © 2023 Delgado-Álvarez, Delgado-Alonso, Goudsmit, García-Ramos, Gil-Moreno, Valles-Salgado, Díez-Cirarda, Zamarrón-Cassinello, Matías-Guiu and Matias-Guiu.)

Background: Alexithymia, an inability to recognise one's emotions, has been associated with trauma-exposure and posttraumatic stress disorder (PTSD). Previous research suggests involvement of the oxytocin system, and socio-emotional neural processes. However, the paucity of neurobiological research on alexithymia, particularly in trauma-exposed populations, warrants further investigation. Objective: Explore associations between alexithymia, endogenous oxytocin levels, and socio-emotional brain function and morphometry in a trauma-exposed sample. Method: Dutch trauma-exposed police officers with ( n  = 38; 18 females) and without PTSD ( n  = 40; 20 females) were included. Alexithymia was assessed with the Toronto Alexithymia Scale (TAS-20). Endogenous salivary oxytocin was assessed during rest, using radioimmunoassay. Amygdala and insula reactivity to socio-emotional stimuli were assessed with functional MRI, amygdala and insula grey matter volume were derived using Freesurfer. Results: Alexithymia was higher in PTSD patients compared to trauma-exposed controls ( F (1,70) = 54.031, p  < .001). Within PTSD patients, alexithymia was positively associated with PTSD severity ( ρ (36) = 0.497, p  = .002). Alexithymia was not associated with childhood trauma exposure ( β  = 0.076, p  = .509), police work-related trauma exposure ( β  = -0.107, p  = .355), oxytocin levels ( β  = -0.164, p  = .161), insula ( β  = -0.170, p  = .158) or amygdala ( β  = -0.175, p  = .135) reactivity, or amygdala volume ( β  = 0.146, p  = .209). Insula volume was positively associated with alexithymia ( β  = 0.222, p  = .016), though not significant after multiple testing corrections. Bayesian analyses supported a lack of associations. Conclusions: No convincing neurobiological correlates of alexithymia were observed with any of the markers included in the current study. Yet, the current study confirmed high levels of alexithymia in PTSD patients, independent of trauma-exposure, substantiating alexithymia's relevance in the clinical phenotype of PTSD.

Introduction: Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations., Materials and Methods: This was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kg/m 2 (normal weight and reference), 25.0-29.9 kg/m 2 (overweight) or ≥30.0 kg/m 2 (obese). For survival analyses adjusted hazard ratios [aHR] were calculated using multivariate Cox regression analysis. Secondary outcomes were analyzed using multivariate logistic regression providing adjusted odd ratios [aOR]., Results: Overweight patients (n=174) had a significantly better OS (aHR=0.72, 95%-CI:0.59-0.89) and PFS (aHR=0.74, 95%-CI:0.61-0.90) compared to normal weight patients (n=268). OS nor PFS were different in obese (n=51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR=3.47, 95%-CI:1.75-6.90)., Conclusion: This study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kg/m 2 , and to verify calculated dosing of carboplatin for appropriateness., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Endotheliopathy following trauma is associated with poor outcome, but the underlying mechanisms are unknown. This study hypothesized that an increased extracellular vesicle (EV) concentration is associated with endotheliopathy after trauma and that red blood cell (RBC) transfusion could further enhance endotheliopathy. In this post hoc sub study of a multicentre observational trial, 75 trauma patients were stratified into three groups based on injury severity score or shock. In patient plasma obtained at hospital admission and after transfusion of four RBC transfusions, markers for endotheliopathy were measured and EVs were labelled with anti CD41 (platelet EVs), anti CD235a (red blood cell EVs), anti CD45 (leucocyte EVs), anti CD144 (endothelial EVs) or anti CD62e (activated endothelial EVs) and EV concentrations were measured with flow cytometry. Statistical analysis was performed by a Kruskall Wallis test with Bonferroni correction or Wilcoxon rank test for paired data. In patients with shock, syndecan-1 and von Willebrand Factor (vWF) were increased compared to patients without shock. Additionally, patients with shock had increased red blood cell EV and leucocyte EV concentrations compared to patients without shock. Endotheliopathy markers correlated with leucocyte EVs (ρ = 0.263, p = 0.023), but not with EVs derived from other cells. Injury severity score had no relation with EV release. RBC transfusion increased circulating red blood cell EVs but did not impact endotheliopathy. In conclusion, shock is (weakly) associated with EVs from leucocytes, suggesting an immune driven pathway mediated (at least in part) by shock., Competing Interests: The authors declare no conflict of interest.

Background: The presence of six or more rib fractures or a displaced rib fracture due to cardiopulmonary resuscitation (CPR) has been associated with longer hospital and intensive care unit (ICU) length of stay (LOS). Evidence on the effect of surgical stabilization of rib fractures (SSRF) following CPR is limited. This study aimed to evaluate outcomes after SSRF versus nonoperative management in patients with multiple rib fractures after CPR., Methods: An international, retrospective study was performed in patients who underwent SSRF or nonoperative management for multiple rib fractures following CPR between January 1, 2012, and July 31, 2020. Patients who underwent SSRF were matched to nonoperative controls by cardiac arrest location and cause, rib fracture pattern, and age. The primary outcome was ICU LOS., Results: Thirty-nine operatively treated patient were matched to 66 nonoperatively managed controls with comparable CPR-related characteristics. Patients who underwent SSRF more often had displaced rib fractures (n = 28 [72%] vs. n = 31 [47%]; p = 0.015) and a higher median number of displaced ribs (2 [P 25 -P 75 , 0-3] vs. 0 [P 25 -P 75 , 0-3]; p = 0.014). Surgical stabilization of rib fractures was performed at a median of 5 days (P 25 -P 75 , 3-8 days) after CPR. In the nonoperative group, a rib fixation specialist was consulted in 14 patients (21%). The ICU LOS was longer in the SSRF group (13 days [P 25 -P 75 , 9-23 days] vs. 9 days [P 25 -P 75 , 5-15 days]; p = 0.004). Mechanical ventilator-free days, hospital LOS, thoracic complications, and mortality were similar., Conclusion: Despite matching, those who underwent SSRF over nonoperative management for multiple rib fractures following CPR had more severe consequential chest wall injury and a longer ICU LOS. A benefit of SSRF on in-hospital outcomes could not be demonstrated. A low consultation rate for rib fixation in the nonoperative group indicates that the consideration to perform SSRF in this population might be associated with other nonradiographic or injury-related variables., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Many women experience giving birth as traumatic. Although women's subjective experiences of trauma are considered the most important, currently there is no clear inclusive definition of a traumatic birth to help guide practice, education, and research., Aim: To formulate a woman-centered, inclusive definition of a traumatic childbirth experience., Methods: After a rapid literature review, a five-step process was undertaken. First, a draft definition was created based on interdisciplinary experts' views. The definition was then discussed and reformulated with input from over 60 multidisciplinary clinicians and researchers during a perinatal mental health and birth trauma research meeting in Europe. A revised definition was then shared with consumer groups in eight countries to confirm its face validity and adjusted based on their feedback., Results: The stepwise process confirmed that a woman-centered and inclusive definition was important. The final definition was: "A traumatic childbirth experience refers to a woman's experience of interactions and/or events directly related to childbirth that caused overwhelming distressing emotions and reactions; leading to short and/ or long-term negative impacts on a woman's health and wellbeing.", Conclusions: This definition of a traumatic childbirth experience was developed through consultations with experts and consumer groups. The definition acknowledges that low-quality provider interactions and obstetric violence can traumatize individuals during childbirth. The women-centered and inclusive focus could help women to identify and validate their experiences of traumatic birth, offering benefits for practice, education, and research, as well as for policymaking and activism in the fields of perinatal mental health and respectful maternity care., (© 2022 The Authors. Birth published by Wiley Periodicals LLC.)

Background: Methotrexate (MTX) is a systemic treatment for plaque-type psoriasis. At the time of approval, no dose-ranging studies were performed. Nowadays, a uniform dosing regimen is lacking. This might contribute to suboptimal treatment with the drug., Objective: To summarize the literature involving the MTX dosing regimens in psoriasis patients., Methods: In this SR, RCTs and documents with aggregated evidence (AgEv) on the MTX dosing regimen in psoriasis were summarized. All randomized controlled trials (RCTs) in which oral, subcutaneous or intramuscular MTX was used in patients with psoriasis and AgEv, were included. The MEDLINE, EMBASE and CENTRAL databases were searched up to June 20, 2022. This SR was registered in PROSPERO., Results: Thirty-nine RCTs had a high risk of bias. Test dosages were given in only 3 RCTs. In the RCTs, MTX was usually prescribed in a start dose of 7.5 mg/week ( n  = 13). MTX was mostly given in a start dose of 15 mg/week, in the AgEv ( n  = 5). One guideline recommended a test dose, in other aggregated evidence a test dose was not mentioned or even discouraged., Conclusions: There is a lack of high-quality evidence and available data for dosing MTX in psoriasis is heterogeneous.

Background: Previous studies on medication therapy management services, e.g. medication reconciliation and medication review, do not show consistent improvements in patient's health-related quality of life. However, these services can reduce adverse drug events., Aim: To evaluate the correlation between health-related quality of life and adverse events/adverse drug events reported by patients., Method: Older patients (≥ 65 years) with polypharmacy (≥ 5 medicines) admitted to orthopaedic or surgical wards were included. Patients were contacted post-discharge to evaluate patient-reported adverse events, health-related quality of life using the EuroQol questionnaire and self-perceived health status on a 5-point Likert scale. The outcomes were the correlation between health-related quality of life and the number of adverse events/adverse drug events, and potential predictors for these events. Spearman correlation and Poisson regression were used for data analysis., Results: 102 patients were included. The correlation between health-related quality of life and adverse events was weak but significant (Spearman correlation coefficient: - 0.328, p = 0.001). No correlation was found for adverse drug events (- 0.064, p = 0.521). Self-perceived health status was a predictor for adverse events, not for adverse drug events. Health-related quality of life was neither a predictor for adverse events, nor for adverse drug events., Conclusion: The correlation between the number of patient-reported adverse events, adverse drug events and health-related quality of life measured by the EuroQol was weak. There is a need for a questionnaire that includes the impact of medication use and is sensitive to outcomes that are affected by medication therapy management services., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Robot assisted laparoscopic abdominal wall surgery (RAWS) has seen a rapid adoption in recent years. The safe introduction of the robot platform in the treatment of abdominal wall hernias is important to safeguard the patient from harm during the learning curve. The scope of this paper is to describe the current European training curriculum in RAWS. Methods and Analysis: The pathway to competence in RAWS will depend on the robot platform, experience in other abdominal procedures (novice to expert) and experience in the abdominal wall repair techniques. An overview of the learning curve effect in the initial case series of several early adopters in RAWS was reviewed. In European centres, current training for surgeons wanting to adopt RAWS is managed by the specific technology-based training organized by the company providing the robot. It consists of four phases where phases I and II are preclinical, while phases III and IV focus on the introduction of the robotic platform into surgical practice. Conclusion: On behalf of the Robotic Surgery Task Force of the European Hernia Society (EHS) we believe that the EHS should play an important role in the clinical phases III and IV training. Courses organized in collaboration with the robot provider on relevant surgical anatomy of the abdominal wall and procedural steps in complex abdominal wall reconstruction like transversus abdominis release are essential. Whereas the robot provider should be responsible for the preclinical phases I and II to gain familiarity in the specific robot platform., Competing Interests: MV reports future participation in the Advisory Board of Medtronic. MS is a proctor for Intuitive Surgical. KB and BE report having received financial support for attending Intuitive courses. AdB received consulting fees from Medtronic, CMR surgical and BD Bard as well as speaker’s honoraria from Medtronic and BBraun. WR declares having received payment honoraria for lectures from Ricard Wolf Company. FM reports having received research grants from Medtronic, Intuitive Surgical and FEG Textiltechnik besides speakers’ honoraria from Medtronic, BD Bard, Intuitive Surgical and WL GORE, consultancy honoraria from Medtronic, CMR surgical and expert testimony from Sofradim. FM is proctor for Intuitive Surgical and participates in the Advisory Board of Medtronic. The remaining author declares 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 © 2022 Vierstraete, Simons, Borch, de Beaux, East, Reinpold, Stabilini and Muysoms.)

Since the advent of critical care in the twentieth century, the core elements that are the foundation for critical care systems, namely to care for critically ill and injured patients and to save lives, have evolved enormously. The past half-century has seen dramatic advancements in diagnostic, organ support, and treatment modalities in critical care, with further improvements now needed to achieve personalized critical care of the highest quality. For critical care to be even higher quality in the future, advancements in the following areas are key: the physical ICU space; the people that care for critically ill patients; the equipment and technologies; the information systems and data; and the research systems that impact critically ill patients and families. With acutely and critically ill patients and their families as the absolute focal point, advancements across these areas will hopefully transform care and outcomes over the coming years., (© 2022. The Author(s).)

Obesity is a global epidemic and people living with HIV (PLWH) are showing similar obesity trends to those in the general population. Obesity is manifested by several physiological features that can alter volume of distribution, elimination and metabolism of various medications including ART. Some drugs are increasingly prone to pharmacokinetic alteration during obesity depending on their physicochemical properties and clearance mechanism. These considerations raise concerns of hampered efficacy, development of resistance or increased toxicity of ART in PLWH. Here, we summarize available literature on the exposure and antiviral outcomes of currently available antiretroviral drugs in the context of obesity and provide a panel of recommendations for the clinical management and follow-up in this growing patient population., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Amid concerns about the decline of empathy during the clinical training of medical clerks, evidence that empathy improves patient outcomes suggests some potential for teaching empathy in ways that will affect the knowledge, attitude and behaviour of medical clerks. This potential alone cannot, however, guarantee the success of educational innovations to introduce empathy to the medical curriculum. This research aims to identify the barriers and facilitators of the implementation of a specific clinical initiative to enhance the empathy skills of clerks, namely the training of clerks to act as a 'MedGezel' or 'medical coach'., Method: We conducted an explorative qualitative study based on interview data collected and analyzed using reflexive thematic analysis and the readiness for change theory. We conducted semi-structured interviews with relevant stakeholders in this particular qualitative study. Thematic analysis was based on open and axial coding using ATLAS.ti 9, which facilitated the emergence of common themes of interest and meaning for the study., Results: A total of 13 relevant stakeholders participated as interviewees in our study. The data was collected from April to June 2021. Our analysis generated 6 main themes which can provide insights into why the implementation of the MedGezel educational innovation failed so far. The following themes emerged: the case for change: why change?; practical necessity; leadership; management and resources; staff culture; and alignment with the corporate strategy., Discussion: The implementation failure can be partially explained as resulting from the personal attitudes and choices of participants, who struggled to reconcile a vision that they liked with side effects that they feared. While participants repeatedly mentioned management and leadership issues, these organizational issues seemed less important as they could be easily resolved in practice. What was more important and fatal for the initiative was its lack of alignment with staff culture, despite its alignment with corporate strategy., Conclusion: This investigation into the barriers and facilitators influencing the implementation of the MedGezel program identified 6 explanatory themes, the most impactful one being staff culture., (© 2022. The Author(s).)

Background: Drug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit., Methods: A multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group., Results: A total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039)., Conclusion: Emergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit., (© 2022. The Author(s).)

Background: Cocaine use is a well-established risk factor for acute coronary syndrome (ACS) although other recreational drugs (RD), are increasingly considered as potential cardiac risk factors. Compared to ACS without RD use, worse outcomes have been described for RD-associated ACS., Objective: The aim of this study was to explore the use of RD in a contemporary cohort of young ACS patients., Methods: Between June 2016 and October 2019, ACS patients aged 18-50 years, admitted to OLVG Hospital in Amsterdam, were retrospectively analysed. Medical chart review was performed to obtain patient and clinical characteristics, RD use, cardiac risk factors, outcome and follow up., Results: A total of 229 patients were included in the study. Recreational drug use prior to ACS was present in 24.9% of all patients, with cannabis (16.2%), cocaine (4.8%), or both (2.6%) most commonly observed. RD users were predominantly young men (87.7%) and had a significantly higher tobacco use compared to non-RD users (89.5% vs. 62.8%, P < 0.001), also after adjusting for age and sex. RD use was associated with larger myocardial infarctions with significantly higher CK-MB levels (104 ± 116 U/L vs 62 ± 96, P = 0.040) and poorer left ventricular function measured by echocardiography as compared to non-users (P = 0.007)., Conclusion: Recreational drug use was present in almost 25% of all young ACS patients evaluated for drug use and was associated with larger myocardial infarction resulting in poorer left ventricular function as compared to non-users. Additionally, RD-users were younger and were more often tobacco users, compared to non-users., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objectives: Despite the suspected higher prevalence of dementia in first generation ethnic minority populations, little is known about their pathway to geriatric diagnostic facilities. This study describes presenting symptoms, demographic and clinical characteristics of a large cohort of patients from ethnic minority populations at their first visit to a geriatric day clinic and compares them with those of native majority (Dutch) patients., Method: Retrospective case control study in an urban geriatric day clinic setting. Participants were 415 minority patients (cases) from 47 different countries and 428 native Dutch control patients. Measurements were demographic characteristics, cognitive screening results, informant questionnaires, neuropsychiatric and depressive symptoms and somatic comorbidity., Results: Ethnic minority patients presented with a different profile of psychiatric and somatic comorbidity. They were younger, had longer duration of symptoms and possibly presented somewhat later in the course of the dementia than the controls. Minority patients had more neuropsychiatric and depressive symptoms than native Dutch patients. They also had more often somatic comorbidities than controls, especially diabetes mellitus., Conclusions: Clinicians in geriatric diagnostic facilities should be aware of the younger age at presentation and the high prevalence of some specific risk factors for dementia in ethnic minority patients.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on healthcare systems. Most transcatheter aortic valve implantation (TAVI) centres have adopted different triage systems and procedural strategies to serve highest-risk patients first and to minimise the burden on hospital logistics and personnel. We therefore assessed the impact of the COVID-19 pandemic on patient selection, type of anaesthesia and outcomes after TAVI., Methods: We used data from the Netherlands Heart Registration to examine all patients who underwent TAVI between March 2020 and July 2020 (COVID cohort), and between March 2019 and July 2019 (pre-COVID cohort). We compared patient characteristics, procedural characteristics and clinical outcomes., Results: We examined 2131 patients who underwent TAVI (1020 patients in COVID cohort, 1111 patients in pre-COVID cohort). EuroSCORE II was comparable between cohorts (COVID 4.5 ± 4.0 vs pre-COVID 4.6 ± 4.2, p = 0.356). The number of TAVI procedures under general anaesthesia was lower in the COVID cohort (35.2% vs 46.5%, p < 0.001). Incidences of stroke (COVID 2.7% vs pre-COVID 1.7%, p = 0.134), major vascular complications (2.3% vs 3.4%, p = 0.170) and permanent pacemaker implantation (10.0% vs 9.4%, p = 0.634) did not differ between cohorts. Thirty-day and 150-day mortality were comparable (2.8% vs 2.2%, p = 0.359 and 5.2% vs 5.2%, p = 0.993, respectively)., Conclusions: During the COVID-19 pandemic, patient characteristics and outcomes after TAVI were not different than before the pandemic. This highlights the fact that TAVI procedures can be safely performed during the COVID-19 pandemic, without an increased risk of complications or mortality., (© 2022. The Author(s).)

Background: Several batteries have been developed for the cognitive assessment of people with multiple sclerosis (MS). However, all these tests have some limitations in general clinical practice and from a cross-cultural perspective. In this study, we aimed to validate a novel cognitive screening test, the Cross-Cultural Dementia screening test (CCD), in pwMS., Methods: Seventy-five participants with relapsing-remitting MS and 75 healthy controls were enrolled and completed a comprehensive neuropsychological battery and the CCD. Intergroup comparisons, effect sizes, and correlations with previously validated tests were calculated for a majority and a pilot study of a minority sample. ROC curves were estimated, and random forest classification models were developed., Results: There were statistically significant differences between cognitively impaired MS (MS-CI) group and healthy controls, and between MS-CI and non-cognitively impaired MS group in all subtests of CCD with medium to large effect sizes. Correlations with standardized neuropsychological tests were moderate to high, supporting concurrent validity. These results were replicated in the minority sample. The random forest models showed a very accurate classification using the CCD. This test showed good psychometric properties compared with SDMT., Conclusions: Our study validates the CCD for cognitive impairment screening in MS, showing advantages over other routinely used cognitive tests., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To evaluate 2 prognostic models for mortality after a fracture of the hip, the Nottingham Hip Fracture Score and Hip Fracture Estimator of Mortality Amsterdam and to compare their predictive performance to physician assessment of mortality risk in hip fracture patients., Design: Prospective cohort study., Setting: Two level-2 trauma centers located in the Netherlands., Patients: Two hundred forty-four patients admitted to the Emergency Departments of both hospitals with a fractured hip., Intervention: Data used in both prediction models were collected at the time of admission for each individual patient, as well as predictions of mortality by treating physicians., Main Outcome Measures: Predictive performances were evaluated for 30-day, 1-year, and 5-year mortality. Discrimination was assessed with the area under the curve (AUC); calibration with the Hosmer-Lemeshow goodness-of-fit test and calibration plots; clinical usefulness in terms of accuracy, sensitivity, and specificity., Results: Mortality was 7.4% after 30 days, 22.1% after 1 year, and 59.4% after 5 years. There were no statistically significant differences in discrimination between the prediction methods (AUC 0.73-0.80). The Nottingham Hip Fracture Score demonstrated underfitting for 30-day mortality and failed to identify the majority of high-risk patients (sensitivity 33%). The Hip fracture Estimator of Mortality Amsterdam showed systematic overestimation and overfitting. Physicians were able to identify most high-risk patients for 30-day mortality (sensitivity 78%) but with some overestimation. Both risk models demonstrated a lack of fit when used for 1-year and 5-year mortality predictions., Conclusions: In this study, prognostic models and physicians demonstrated similar discriminating abilities when predicting mortality in hip fracture patients. Although physicians overestimated mortality, they were better at identifying high-risk patients and at predicting long-term mortality., Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH., Methods and Findings: We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44-60] years, 85.5% male) and 440 controls (median age 43 [IQR 33-53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/μL (IQR 520-913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508-0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250-500 cells/μL (2.845, 95% CI 1.876-4.314, p < 0.001) or >500 cells/μL (2.936, 95% CI 1.961-4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286-0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients., Conclusions: After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required., Trial Registration: The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: All authors have completed the ICMJE disclosure form and declare no competing interests exist directly related to the submitted work Conflicts of interest outside the submitted work CR has received research grants from ViiV, Gilead, ZonMW, AIDSfonds, Erasmus MC, and Health~Holland and honorariums for advisory boards from Gilead and ViiV; WFWB declares reimbursement for participation of patient in trial by GSK to institution. DG and RDdV are supported by the Health~Holland grant EMCLHS20017 co-funded by the PPP Allowance made available by the Health~Holland, Top Sector Life Sciences & Health, to stimulate public–private partnerships. RDdV is listed as inventor of the fusion inhibitory lipopeptide [SARSHRC-PEG4]2-chol on a provisional patent application. VASHD has received research grants from ZonMw, Horizon 2020 – Marie Curie-Sklodowska, Takeda and payments for lectures and advisory boards from Takeda, CSL Behring, Pharming and GSK. KCES received honorariums for advisory boards from Gilead and ViiV. BJAR declares research grants from Gilead and MSD and honorary for advisory boards for Astra Zeneca, Roche, Gilead, F2G all outside the context of this work. RvM received consultancies fees paid to their institution from ViiV; Gilead; MSD, received research grants paid to their institution from ViiV; Gilead All other authors declare hat no competing interests exist.

This study analyses the contribution of system-related factors to maternal mortality in the low-resource setting of Mnazi Mmoja Hospital in Zanzibar, Tanzania. It is a retrospective cohort study including all maternal deaths (MD, n  = 139) and maternal near-misses (MNM, n  = 122) in Mnazi Mmoja Hospital with sufficient documentation during 2015 to 2018 (MD) and 2017 to 2018 (MNM). The number of admissions and surgical interventions per health care provider on the day of admission and the number of times vital signs were monitored per day were compared between MNM and MD cases using logistic regression. The mean number of times vital signs were monitored per day was associated with reduced odds of mortality (aOR 0.75, 95% CI 0.64-0.89), after adjustment for confounding factors such as severity of illness. The numbers of admissions or surgical procedures per health care provider were not associated with mortality. Concluding, the degree of monitoring of patients with life-threatening complications of pregnancy or childbirth is associated with the risk of mortality independent of the degree of severity. Preventing maternal mortality requires going beyond availability of essential interventions to tackle system-related factors that have a direct impact on the capacity to provide comprehensive care.Impact Statement What is already known on this subject? Root cause analyses of maternal deaths have identified many system-related factors, such as availability of health care providers, adequate training, and motivation to sustain high intensity monitoring (Madzimbamuto et al. 2014; Mahmood et al. 2018). What do the results of this study add? This is the first study to attempt to quantify the contribution of these system-related factors by comparing cases of maternal death with cases of maternal near-miss. We show that the degree of monitoring of patients with life-threatening complications is associated with the odds of mortality independent of the degree of severity. Even though this relation should not be regarded as causative, monitoring of vital signs can be seen as reflective of many system-related factors which hamper or facilitate comprehensive care. What are the implications of these findings for clinical practice and/or further research? This study helps increase general understanding of the factors leading to progression from severe disease to death in a high-volume low-income setting.

Background: Pediatric supracondylar humerus fractures (pSCHFs) may be challenging injuries to treat because of the potential residual deformity. There is debate regarding the technical aspects of adequate closed reduction and crossed Kirschner wire (K-wire) fixation., Purpose: Do surgeons have an agreement on the aspects of the fixation of pSCHFs?, Methods: Radiographs of 20 patients from a cohort of 154 patients with pSCHFs treated with closed reduction and crossed K-wire fixation were selected. Forty-four surgeons viewed the postoperative radiographs and diagnosed the presence or absence of technical flaws and made a recommendation for or against reoperation. An expert panel of three orthopedic and trauma surgeons provided a reference standard for technical factors. Furthermore, final outcome 2 years after trauma was assessed., Results: There was limited agreement on potential technical flaws (ICC 0.15-0.28), radiographic measures of alignment (ICC for anterior humeral line and Baumann angle of 0.37 and 0.23 respectively), the quality of postoperative reduction, position of the elbow in cast, and recommendation for repeat surgery (ICCs between 0.23 and 0.40). Sensitivity and specificity for these questions ranged from 0.59 to 0.90. There was no correlation between the voted quality of postoperative reduction and loss of reduction or final function., Conclusions: Surgeons have limited agreement on the quality of postoperative results in pSCHFs and the indication for reoperation. Reviewing postoperative radiographs may present a good learning opportunity and could help improve skills, but it is not a validated method for quality control and has to be seen in light of clinical outcome., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by elevated pulmonary arterial pressure and organized thrombi within pulmonary arteries. Riociguat is a soluble guanylate cyclase stimulator and is approved for patients with inoperable CTEPH or residual pulmonary hypertension after pulmonary endarterectomy (PEA). Previous work suggested that riociguat treatment is associated with an increased risk of bleeding, although the mechanism is unclear. The aim of this study is to assess how riociguat affects primary hemostasis by studying its effect on the interaction between platelets and endothelial cells derived from CTEPH patients. Pulmonary artery endothelial cells (PAECs) were isolated from thrombus-free regions of PEA material. Purified PAECs were cultured in flow chambers and were stimulated with 0.1 and 1 µM riociguat for 24 h before flow experiments. After stimulation with histamine, PAECs were exposed to platelets under shear stress. Platelet adhesion and expression of von Willebrand Factor (VWF) were evaluated to assess the role of riociguat in hemostasis. Under dynamic conditions, 0.1 and 1.0 µM of riociguat suppressed platelet adhesion on the surface of PAECs. Although riociguat did not affect intracellular expression and secretion of VWF, PAECs stimulated with riociguat produced fewer VWF strings than unstimulated PAECs. Flow cytometry suggested that decreased VWF string formation upon riociguat treatment may be associated with suppressed cell surface expression of P-selectin, a protein that stabilizes VWF anchoring on the endothelial surface. In conclusion, Riociguat inhibits VWF string elongation and platelet adhesion on the surface of CTEPH-PAECs, possibly by reduced P-selectin cell surface expression., Competing Interests: The authors declare no conflict of interest.This study was approved by the institutional Medical Ethical Review Board of the Amsterdam UMC, location VU University Medical Center, the Netherlands (METC Vumc, NL69167.029.19), and informed consent was obtained in accordance with the Declaration of Helsinki., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Objective: 4-Fluoroamphetamine (4-FA) is an amphetamine-type stimulant, with effects comparable to amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Severe 4-FA-related complications, such as cardiomyopathy, myocardial infarction, and cerebral hemorrhage, have been described. The aim of this study was to explore the cardiovascular symptoms and complications in 4-FA and compare them to MDMA and amphetamine in intoxicated patients who presented to the emergency department (ED)., Methods: Between November 2015 and March 2020, all self-reported 4-FA, MDMA, and amphetamine-intoxicated adult patients that presented at the ED of an inner-city hospital in Amsterdam, were retrospectively analyzed for cardiovascular symptoms, vital parameters, cardiovascular complications, interventions, admission rate, and Poisoning Severity Score (PSS)., Results: A total of 582 patients were included, of which 31 (5.3%) with 4-FA intoxication (10/31 mono-intoxications, 32.3%), 406 (69.8%) with MDMA (59/406 mono-intoxications, 14.5%), 100 (17.2%) with amphetamine (10/100 mono-intoxications, 10.0%), and 45 (7.7%) with a cross intoxication of these drugs. 4-FA mono-intoxicated patients experienced more headache (n = 8; 80.0%) compared to MDMA (n = 2; 3.3%; P < 0.001) and amphetamine mono-intoxicated patients (n = 0; 0.0%; P < 0.001) and their systolic blood pressure was higher (164 mm Hg ± 31 vs 139 mm Hg ± 19; P = 0.031 vs 135 mm Hg ± 22; P = 0.033, respectively). Severe 4-FA-related cardiovascular complications included Takotsubo cardiomyopathy (n = 1; 3.2%), subarachnoid hemorrhage (n = 1; 3.2%), and hypertensive urgency (n = 2; 6.5%)., Conclusions: 4-FA intoxication-related ED symptoms resemble MDMA and amphetamine complications, although patients presented more often with headache and hypertension. Severe 4-FA-related cardiovascular complications occurred in 40% of mono-intoxications., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA 2 LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy., (© 2022 Published by Elsevier Inc. on behalf of World Allergy Organization.)

Background: Critically ill COVID-19 patients are in a hypercoagulable state with increased risk of thrombotic complications. Rotational thromboelastometry (ROTEM) is a viscoelastic test with the potential to reflect COVID-19-associated hypercoagulability and may therefore be useful to predict thrombotic complications., Objective: To investigate the potential of ROTEM profiles to predict thrombotic complications in critically ill COVID-19 patients., Patients/methods: Retrospective multicenter cohort study in 113 adult patients with confirmed COVID-19 infection admitted to the intensive care unit (ICU) of two large teaching hospitals in the United States and in the Netherlands. ROTEM profiles of the EXTEM, INTEM, and FIBTEM tracings were measured within 72 h of ICU admission. Thrombotic complications encompass both arterial and venous thromboembolic complications, diagnosed with electrocardiogram, ultrasound, or computed tomography. ROTEM profiles were compared between patients with and without thrombosis. Univariable logistic regression followed by receiver operating characteristic (ROC) curves analysis was performed to identify ROTEM parameters associated with thrombosis., Results and Conclusions: Of 113 patients, 27 (23.9%) developed a thrombotic event. In the univariable analysis, EXTEM clot amplitude at 10 min (CA10) and EXTEM maximum clot formation (MCF) were associated with thrombosis with a p  < 0.2 ( p  = 0.07 and p  = 0.05, respectively). In ROC curve analysis, EXTEM CA10 had an area under the curve (AUC) of 0.58 (95% CI 0.47-0.70) and EXTEM MCF had an AUC of 0.60 (95% CI 0.49-0.71). Thereby, ROTEM profiles at ICU admission did not have the potential to differentiate between patients with a high and low risk for thrombotic complications., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: Adequate antibiotic dosing may improve outcomes in critically ill patients but is challenging due to altered and variable pharmacokinetics. To address this challenge, AutoKinetics was developed, a decision support system for bedside, real-time, data-driven and personalised antibiotic dosing. This study evaluates the feasibility, safety and efficacy of its clinical implementation., Methods: In this two-centre randomised clinical trial, critically ill patients with sepsis or septic shock were randomised to AutoKinetics dosing or standard dosing for four antibiotics: vancomycin, ciprofloxacin, meropenem, and ceftriaxone. Adult patients with a confirmed or suspected infection and either lactate > 2 mmol/L or vasopressor requirement were eligible for inclusion. The primary outcome was pharmacokinetic target attainment in the first 24 h after randomisation. Clinical endpoints included mortality, ICU length of stay and incidence of acute kidney injury., Results: After inclusion of 252 patients, the study was stopped early due to the COVID-19 pandemic. In the ciprofloxacin intervention group, the primary outcome was obtained in 69% compared to 3% in the control group (OR 62.5, CI 11.4-1173.78, p < 0.001). Furthermore, target attainment was faster (26 h, CI 18-42 h, p < 0.001) and better (65% increase, CI 49-84%, p < 0.001). For the other antibiotics, AutoKinetics dosing did not improve target attainment. Clinical endpoints were not significantly different. Importantly, higher dosing did not lead to increased mortality or renal failure., Conclusions: In critically ill patients, personalised dosing was feasible, safe and significantly improved target attainment for ciprofloxacin., Trial Registration: The trial was prospectively registered at Netherlands Trial Register (NTR), NL6501/NTR6689 on 25 August 2017 and at the European Clinical Trials Database (EudraCT), 2017-002478-37 on 6 November 2017., (© 2022. The Author(s).)

Purpose: Primary congenital glaucoma (PCG) is a form of childhood glaucoma caused by maldevelopment of the anterior chamber. Disease severity differs greatly amongst patients. Ultrasound biomicroscopy (UBM) is a non-invasive technique that can visualize the anterior segment in infants in vivo. The purpose of this narrative review is to make an overview of the UBM data in PCG and study the applicability of UBM in characterizing the disease., Methods: An online search was performed on PubMed in December 2020. After a critical appraisal of the included articles, study and patient characteristics were summarized. The UBM measurements of the anterior segment in PCG of the different studies were analysed., Results: Six studies were included in this review. All were cross-sectional prospective studies. A total of 221 PCG eyes were examined. PCG eyes showed a larger trabecular iris angle, decreased iris thickness, narrower or absent Schlemm's canal and an increased zonular length compared to controls. Abnormal tissue membrane covering the trabecular meshwork and abnormal insertion of the iris and ciliary process were frequently found. The success rate of glaucoma surgery depended on the severity of anterior segment malformations found with UBM., Conclusion: Malformations of the anterior segment in PCG can be demonstrated by UBM in vivo. This imaging can help to characterize disease severity and might support surgical treatment decisions., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objective: Anxiety, depression and greater pain intensity before total knee arthroplasty (TKA) may increase the probability of revision surgery for remaining symptoms even without clear pathology or technical issues. We aimed to assess whether preoperative anxiety/depression and pain intensity are associated with revision TKA for less clear indications., Methods: Less clear indications for revision were defined after a Delphi process in which consensus was reached among 59 orthopaedic knee experts. We performed a cox regression analyses on primary TKA patients registered in the Dutch Arthroplasty Registry (LROI) who completed the EuroQol 5D 3 L (EQ5D-3 L) anxiety/depression score to examine associations between preoperative anxiety/depression and pain (Numeric Rating Scale (NRS)) with TKA revision for less clear reasons. These analyses were adjusted for age, BMI, sex, smoking, ASA score, EQ5D-3 L thermometer and OKS score., Results: In total, 25.9% patients of the 56,233 included patients reported moderate or severe symptoms of anxiety/depression on the EQ5D-3 L anxiety/depression score. Of those, 615 revisions (45.5%) were performed for less clear reasons for revision (patellar pain, malalignment, instability, progression of osteoarthritis or arthrofibrosis). Not EQ5D-3 L anxiety/depression score, but higher NRS pain at rest and EQ5D-3 L pain score were associated with revision for less clear reason (HR: 1.058, 95% CI 1.019-1.099 & HR: 1.241, 95% CI 1.044-1.476, respectively)., Conclusion: Our findings suggest that pain intensity is a risk factor for TKA revision for a less clear reason. The finding that preoperative pain intensity was associated with reason for revision confirms a likely influence of subjective, personal factors on offer and acceptance of TKA revision. The association between anxiety/depression and reason for revision after TKA may also be found when including more specific outcome measures to assess anxiety/depression and we therefore hope to encourage further research on this topic with our study, ideally in a prospective setting., Study Design: Longitudinal Cohort Study Level III, Delphi Consensus., Competing Interests: Declaration of Competing Interest None. Each author certifies that he or she has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objectives: The primary aim was to predict upper airway collapse sites found in drug-induced sleep endoscopy (DISE) from demographic, anthropometric, clinical examination, sleep study, and snoring sound parameters in patients with obstructive sleep apnea (OSA). The secondary aim was to identify the above-mentioned parameters that are associated with complete concentric collapse of the soft palate., Methods: All patients with OSA who underwent DISE and simultaneous snoring sound recording were enrolled in this study. Demographic, anthropometric, clinical examination (viz., modified Mallampati classification and Friedman tonsil classification), and sleep study parameters were extracted from the polysomnography and DISE reports. Snoring sound parameters during DISE were calculated., Results: One hundred and nineteen patients with OSA (79.8% men; age = 48.1 ± 12.4 years) were included. Increased body mass index was found to be associated with higher probability of oropharyngeal collapse ( P < .01; odds ratio = 1.29). Patients with a high Friedman tonsil score were less likely to have tongue base collapse ( P < .01; odd ratio = 0.12) and epiglottic collapse ( P = .01; odds ratio = 0.20) than those with a low score. A longer duration of snoring events ( P = .05; odds ratio = 2.99) was associated with a higher probability of complete concentric collapse of the soft palate., Conclusions: Within the current patient profile and approach, given that only a limited number of predictors were identified, it does not seem feasible to predict upper airway collapse sites found in DISE from demographic, anthropometric, clinical examination, sleep study, and snoring sound parameters in patients with OSA., Citation: Huang Z, Bosschieter PFN, Aarab G, et al. Predicting upper airway collapse sites found in drug-induced sleep endoscopy from clinical data and snoring sounds in obstructive sleep apnea patients: a prospective clinical study. J Clin Sleep Med . 2022;18(9):2119-2131., (© 2022 American Academy of Sleep Medicine.)

What Is Known and Objective: Many severe intoxications occur with substances with no specific antidote, which is why methods of extracorporeal elimination represent a particularly useful and even critical component in their management. The purpose of this review is to summarize the accumulating evidence and clinical results from the application of CytoSorb hemoadsorption therapy in patients with severe intoxications., Comment: The technology represents a promising technique with an increasing number of publications in a variety of severe intoxication scenarios suggesting that early intervention might provide rapid substance removal with subsequent overall clinical improvement., What Is New and Conclusion: Given the tremendous challenges in performing prospective, randomized trials in this field, the strong safety profile of the device and the high acuity of these life-threatening situations, CytoSorb should be considered as a therapeutic option in severe intoxications, particularly when direct antidotes are not available. However, further clinical data are desirable to provide precise recommendations., (© 2022 John Wiley & Sons Ltd.)

Background: Depression is associated with lower quality of life and increased risk of mortality. The prevalence of depression in chronic dialysis patients, as well as in patients with diabetes, is more than 20%. It is debated whether use of beta-blockers increases the risk of depression. Therefore, we examined in chronic dialysis patients with and without diabetes, the association between beta-blockers and depressive symptoms., Methods: Data were collected from the DIVERS-I study, a multicentre prospective cohort among chronic dialysis patients in the Netherlands. Depressive symptoms were assessed with the Beck Depression Inventory (BDI-II). We defined depressive symptoms as a BDI-II score ⩾16. The cross-sectional association at baseline between depressive symptoms and beta-blocker use in chronic dialysis patients, was studied by multivariable logistic regression adjusted for potential confounders., Results: We included 684 chronic dialysis patients, of whom 43% had diabetes mellitus, and 57% used a beta-blocker of which 97% were lipophilic. After multivariable adjustment, the OR (95% CI) for depressive symptoms in patients with compared to without diabetes was 1.41 (1.00-1.98), and in beta-blocker users compared to non-users 1.12 (0.80-1.56), respectively. Dialysis patients with diabetes and beta-blocker use compared to those without diabetes and not using beta-blockers had an OR of 1.73 (1.12-2.69) for depressive symptoms. The association was stronger in dialysis patients with diabetes and lipophilic beta-blocker use with an OR of 1.77 (1.14-2.74)., Conclusions: We found a possible association between lipophilic beta-blocker use and depressive symptoms in chronic dialysis patients with diabetes., Competing Interests: Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: The Dutch Working Party on Antibiotic Policy (SWAB) in collaboration with relevant professional societies, has updated their evidence-based guidelines on empiric antibacterial therapy of sepsis in adults., Methods: Our multidisciplinary guideline committee generated ten population, intervention, comparison, and outcome (PICO) questions relevant for adult patients with sepsis. For each question, a literature search was performed to obtain the best available evidence and assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The quality of evidence for clinically relevant outcomes was graded from high to very low. In structured consensus meetings, the committee formulated recommendations as strong or weak. When evidence could not be obtained, recommendations were provided based on expert opinion and experience (good practice statements)., Results: Fifty-five recommendations on the antibacterial therapy of sepsis were generated. Recommendations on empiric antibacterial therapy choices were differentiated for sepsis according to the source of infection, the potential causative pathogen and its resistance pattern. One important revision was the distinction between low, increased and high risk of infection with Enterobacterales resistant to third generation cephalosporins (3GRC-E) to guide the choice of empirical therapy. Other new topics included empirical antibacterial therapy in patients with a reported penicillin allergy and the role of pharmacokinetics and pharmacodynamics to guide dosing in sepsis. We also established recommendations on timing and duration of antibacterial treatment., Conclusions: Our multidisciplinary committee formulated evidence-based recommendations for the empiric antibacterial therapy of adults with sepsis in The Netherlands., (© 2022. The Author(s).)

Almost 30 years after the first endoscopic mitral valve repair, Minimally Invasive Mitral Valve Surgery (MIMVS) has become the standard at many institutions due to optimal clinical results and fast recovery. The question that arises is can already good results be further improved by an Institutional Risk Management Performance (IRMP) system in decreasing risks in minimally invasive mitral valve surgery (MIMVS)? As of yet, there are no reports on IRMP and learning systems in the literature. (2) Methods : We described and appraised our five-year single institutional experience with MIMVS in isolated valve surgery included in the Netherlands Heart Registry (NHR) and investigated root causes of high-impact complications. (3) Results : The 120-day and 12-month mortality were 1.1% and 1.9%, respectively, compared to the average of 4.3% and 5.3% reported in the NHR. The regurgitation rate was 1.4% compared to 5.2% nationwide. The few high-impact complications appeared not to be preventable. (4) Discussion : In MIMVS, freedom from major and minor complications is a strong indicator of an effective IRMP but remains concealed from physicians and patients, despite its relevance to shared decision making. Innovation adds to the complexity of MIMVS and challenges surgical competence. An IRMP system may detect and control new risks earlier. (5) Conclusion : An IRMP system contributes to an effective reduction of risks, pain and discomfort; provides relevant input for shared decision making; and warrants the safe introduction of new technology. Crossroads conclusions: investment in machine learning and AI for an effective IRMP system is recommended and the roles for commanding and operating surgeons should be considered.

Background: Weight-loss surgery is one of the recommended methods for treating obstructive sleep apnea (OSA) in obese patients. While weight reduction is critical to relieve symptoms of OSA, the biochemical factors involved in post-surgery improvement are still unknown. We aimed to explore the link between ANGPTL7 and OSA in patients with different OSA severity. Furthermore, we examined the effect of treating OSA with bariatric surgery on ANGPTL7 level., Methods: We quantified levels of circulating ANGPTL7 in fasting plasma and adipose tissue samples of 88 participants before and after bariatric surgery. Confocal microscopy analyses were also performed to assess the ANGPTL7 expression in subcutaneous white adipose tissue biopsies obtained from people with moderate-to-severe OSA compared to those with none or mild OSA. The study involved 57 individuals with none or mild OSA and 31 patients with moderate-to-severe OSA., Results: Levels of circulating ANGPTL7 were significantly higher in people with moderate-to-severe OSA (1440 ± 1310 pg/ml) compared to the none or mild OSA group (734 ± 904 pg/ml, p = 0.01). The increase in ANGPTL7 correlated significantly and positively with the apnea-hypopnea index (AHI, r = .226, p = .037), and AHI-supine (r = .266, p = .019) in participants with moderate-to-severe OSA. Multivariate logistic regression analysis demonstrated an association between ANGPTL7 and OSA severity (log 2 ANGPTL7; OR =1.24, p = 0.024). ANGPTL7 levels exhibited significant positive correlations with the levels of TG and oxLDL (p-value = 0.002 and 0.01 respectively). Bariatric surgery reduced the levels of both ANGPTL7 and AHI significantly., Conclusion: Here we report significantly increased levels of ANGPTL7 both in the circulation and in adipose tissue of patients with OSA, which concurred with increased inflammation and OSA severity. Levels of ANGPTL7 decreased significantly as OSA showed a significant improvement post-surgery supporting a potential role for ANGPTL7 in either OSA progression or a role in an OSA-related mechanism., Competing Interests: NV is a member of the Medical Advisory Board of NightBalance, consultant of Philips Healthcare, Inspire Medical Systems and Nyxoah. The remaining 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 © 2022 Leentjens, Alterki, Abu-Farha, Bosschieter, de Raaff, de Vries, Al Shawaf, Thanaraj, Al-Khairi, Cherian, Channanath, Kavalakatt, van Wagensveld, de Vries and Abubaker.)

Objective: Previous studies reported less prenatal healthcare consumption and more perinatal complications in women with a migrant background. Hence, we investigated in a country with free healthcare access whether women with a migrant background differed with respect to pregnancy complications, healthcare consumption and in terms of associations with psychological distress in comparison to native Dutch., Methods: We included 324 native Dutch and 303 women with a migrant background, who visited two hospitals in Amsterdam for antenatal care between 2014 and 2015. Participants completed the Edinburgh Postnatal Depression Scale, the Hospital Depression and Anxiety Scale, and sociodemographic questions. Complications and healthcare consumption during pregnancy were extracted from medical records. Regression analyses were used with adjustment for covariates., Results: Except for gestational diabetes [adjusted OR = 3.09; 95% CI = (1.51, 6.32)], no differences were found between groups in perinatal complications [OR = 1.15; 95% CI = (0.80, 1.64)], nor in healthcare consumption [OR = 0.87; 95% CI = (0.63, 1.19)]. Women with a migrant background reported more depressive symptoms [Cohen's d = 0.25; 95% CI = (0.10, 0.41)], even after adjustment for socio-economic factors. Psychological distress was associated with more hospital admissions during pregnancy. When experiencing depressive symptoms, women with a migrant background had an increased risk to be admitted [OR = 1.11; 95% CI = (1.01, 1.21)]., Conclusions for Practice: This cohort study found no differences in pregnancy-related complications, except for diabetes, nor different healthcare consumption, in women with a migrant background versus native Dutch, in a country with free health care access. However, women with a migrant background experienced more depressive symptoms, and when depressed their risk for hospital admission increased. Additional research is warranted to improve healthcare for this population., (© 2022. The Author(s).)

Purpose: There is growing evidence that patients with certain simple stable musculoskeletal injuries can be discharged directly from the Emergency Department (ED), without compromising patient outcome and experience. This study aims to review the literature on the effects of direct discharge (DD) of simple stable musculoskeletal injuries, regarding healthcare utilization, costs, patient outcome and experience., Methods: A systematic review was performed in Medline, Embase, CINAHL, Cochrane Library and Web of Science using PRISMA guidelines. Comparative and non-comparative studies on DD of simple stable musculoskeletal injuries from the ED in an adult/paediatric/mixed population were included if reporting ≥ 1 of: (1) logistic outcomes: DD rate (proportion of patients discharged directly); number of follow-up appointments; DD return rate; (2) costs; (3) patient outcomes/experiences: functional outcome; treatment satisfaction; adverse outcomes; other., Results: Twenty-six studies were included (92% conducted in the UK). Seven studies (27%) assessed functional outcome, nine (35%) treatment satisfaction, and ten (38%) adverse outcomes. A large proportion of studies defined DD eligibility criteria as injuries being minor/simple/stable, without further detail. ED DD rate was 26.7-59.5%. Mean number of follow-up appointments was 1.00-2.08 pre-DD, vs. 0.00-0.33 post-DD. Return rate was 0.0-19.4%. Costs per patient were reduced by €69-€210 (ranging from - 38.0 to - 96.6%) post-DD. Functional outcome and treatment satisfaction levels were 'equal' or 'better' (comparative studies), and 'high' (non-comparative studies), post-DD. Adverse outcomes were low and comparable., Conclusions: This systematic review supports the idea that DD of simple stable musculoskeletal injuries from the ED provides an opportunity to reduce healthcare utilization and costs without compromising patient outcomes/experiences. To improve comparability and facilitate implementation/external validation of DD, future studies should provide detailed DD eligibility criteria, and use a standard set of outcomes. Systematic review registration number: 120779, date of first registration: 12/02/2019., (© 2021. The Author(s).)

Introduction: Breast surgery has become less invasive without compromising survival and aimed at improving quality of life (QoL) in terms of satisfaction with cosmesis. Despite that, short-term patient-perceived aesthetic results after breast-conserving surgery (BCS) can still be displeasing. Long-term analysis regarding contentment with cosmesis are lacking and could be different, considering that over time, patients' priorities might change and a different thought-out judgment could be given. The goal of this study is to describe long-term results in QoL after BCS and to identify possible predictors for disappointing aesthetic results., Methods: In this retrospective cohort study, the long-term outcomes of QoL, patient-reported outcome measurements and aesthetic outcomes were investigated 4.5-10.8 years after BCS. In total, 104 patients received standardized questionnaires from the European Organisation of Research and Treatment of Cancer. The aesthetic results after BCS were evaluated subjectively through a diverse panel of healthcare observers. Objective assessment of the aesthetic results was done using the BCCT.core system of evaluating standardised breast photographs. Factors influencing aesthetic outcome were statistically analysed., Results: QoL was high in around 75% of the patients. Correlation between QoL and aesthetic outcomes was found according to Spearman's correlation (r = 0.262, p = 0.007). Significant factors negatively influencing patient reported aesthetic outcomes were sentinel node procedure (p = 0.016), axillary lymph node dissection (p = 0.004), chemotherapy (p = 0.001), and hormonal therapy (p = 0.001)., Conclusion: The majority of the patients have acceptable QoL after BCS during long-term follow-up. Unacceptable aesthetic outcomes after BCS are associated with lower QoL and are influenced by sentinel node procedure, axillary lymph node dissection, chemotherapy, and hormonal therapy., Competing Interests: Declaration of competing interest No declarations of interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Traumatic injuries of the shoulder or chest wall are commonly treated in the Emergency Department (ED). A complementary treatment is kinesiotaping, an elastic tape often used to treat musculoskeletal dysfunction and pain. However, the added pain-reducing effect of kinesiotape in comparison to standard conservative treatment is unknown. The aim of this study was to determine the effect of kinesiotaping on pain relief compared to standard treatment with pain medication and immobilization in patients with uncomplicated traumatic injury of the shoulder or chest wall in the ED., Method: A pilot randomized controlled trial (RCT) was conducted in the ED of a teaching hospital in the Netherlands from January 2021 until the end of March 2021. Patients diagnosed with uncomplicated isolated rib fractures, rib contusions, clavicle fracture, disruption of the AC joint and fracture of the proximal humerus were assigned to two treatment groups. The control group received the standard treatment with oral analgesics (acetaminophen q6h 1000 mg and NSAID (according to prescription) and if shoulder injury also a sling. The intervention group received kinesiotaping in addition to the same standard treatment. Pain intensity was measured with 0-10 Numeric Rating Scale (NRS) just before treatment (T1) and after 15 min (T2). On day 4 both groups were assessed with NRS in a follow up phone call (T3)., Results: A total of 251 patients presented with traumatic injury of the shoulder or chest wall in the study period, 85 patients were approached to participate and 2 of them were excluded. The remaining 83 were randomly allocated to kinesiotaping (n = 40) or control group (n = 43), 57 of them completed the study and had sufficient data for complete analysis In both groups, pain intensity after 15 min and 4 days significantly reduced compared with baseline. Regarding the reduction of pain intensity on day 4, kinesiotaping was significantly superior compared to the control group with a difference in pain reduction of 2.45 compared with 0.88 in control group (p = 0.018)., Conclusion: Compared to standard treatment alone, kinesiotaping combined with standard care appears to be more effective in terms of acute pain reduction in patients with uncomplicated traumatic injury of the shoulder or chest wall. Further research is recommended., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Viscoelastic hemostatic assays such as rotational thromboelastometry (ROTEM) are used to guide treatment of trauma induced coagulopathy. The authors hypothesized that ROTEM derangements reflect specific coagulation factor deficiencies after trauma., Methods: This was a secondary analysis of a prospective cohort study in six European trauma centers in patients presenting with full trauma team activation. Patients with dilutional coagulopathy and patients on anticoagulants were excluded. Blood was drawn on arrival for measurement of ROTEM, coagulation factor levels, and markers of fibrinolysis. ROTEM cutoff values to define hypocoagulability were as follows: EXTEM clotting time greater than 80 s, EXTEM clot amplitude at 5 min less than 40 mm, EXTEM lysis index at 30 min less than 85%, FIBTEM clot amplitude at 5 min less than 10 mm, and FIBTEM lysis index at 30 min less than 85%. Based on these values, patients were divided into seven deranged ROTEM profiles and compared to the reference group (ROTEM values within reference range). The primary endpoint was coagulation factors levels and fibrinolysis., Results: Of 1,828 patients, 732 (40%) had ROTEM derangements, most often consisting of a combined decrease in EXTEM and FIBTEM clot amplitude at 5 min, that was present in 217 (11.9%) patients. While an isolated EXTEM clotting time greater than 80 s had no impact on mortality, all other ROTEM derangements were associated with increased mortality. Also, coagulation factor levels in this group were similar to those of patients with a normal ROTEM. Of coagulation factors, a decrease was most apparent for fibrinogen (with a nadir of 0.78 g/l) and for factor V levels (with a nadir of 22.8%). In addition, increased fibrinolysis can be present when the lysis index at 30 min is normal but EXTEM and FIBTEM clot amplitude at 5 min is decreased., Conclusions: Coagulation factor levels and mortality in the group with an isolated clotting time prolongation are similar to those of patients with a normal ROTEM. Other ROTEM derangements are associated with mortality and reflect a depletion of fibrinogen and factor V. Increased fibrinolysis can be present when the lysis index after 30 min is normal., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Background: For patients on oral anticoagulants (OAC) undergoing percutaneous coronary intervention (PCI), European guidelines have recently changed their recommendations to dual antithrombotic therapy (DAT; P2Y 12 inhibitor and OAC) without aspirin., Aims: The prospective WOEST 2 registry was designed to obtain contemporary real-world data on antithrombotic regimens and related outcomes after PCI in patients with an indication for OAC., Methods: In this analysis, we compare DAT (P2Y 12 inhibitor and OAC) to triple antithrombotic therapy (TAT; aspirin, P2Y 12 inhibitor, and OAC) on thrombotic and bleeding outcomes after one year. Clinically relevant bleeding was defined as Bleeding Academic Research Consortium classification (BARC) grade 2, 3, or 5; major bleeding as BARC grade 3 or 5. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause mortality, myocardial infarction, stent thrombosis, ischaemic stroke, and transient ischaemic attack., Results: A total of 1,075 patients were included between 2014 and 2021. Patients used OAC for atrial fibrillation (93.6%) or mechanical heart valve prosthesis (4.7%). Non-vitamin K oral anticoagulants (NOAC) were prescribed in 53.1% and vitamin K antagonists in 46.9% of patients. At discharge, 60.9% received DAT, and 39.1% TAT. DAT was associated with less clinically relevant and similar major bleeding (16.8% vs 23.4%; p<0.01 and 7.6% vs 7.7%, not significant), compared to TAT. The difference in MACCE between the two groups was not statistically significant (12.4% vs 9.7%; p=0.17). Multivariable adjustment and propensity score matching confirmed these results., Conclusions: Dual antithrombotic therapy is associated with a substantially lower risk of clinically relevant bleeding without a statistically significant penalty in ischaemic events.

Background: Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options., Methods and Design: The Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects-and their putative determinants-are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine., Discussion: This study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol., Clinical Trial Registration: EudraCT 2014-003385-24., (Copyright © 2022 Henstra, Feenstra, Kok, Spaans, van Exel, Dols, Oudega, Vergouwen, van der Loo, Bet, Loer, Eikelenboom, Sienaert, Lambrichts, Bouckaert, Bosmans, van der Velde, Beekman, Stek and Rhebergen.)

Background: Recent reports indicate that the prevalence of food allergy is increasing, but accurate estimates remain a challenge due to cross-reactivity and limited use of precise diagnostic methods. Molecular allergy diagnostics, in which sensitization to individual molecular allergens is measured, is emerging as a promising tool for evaluation of sensitization profiles. In this systematic review, we summarized estimates of prevalence of sensitization to molecular food allergens in the general population in Europe., Methods: Following a protocol prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; reference CRD42021266657), we searched seven databases with no restrictions on publication date or language. Two reviewers independently screened the literature, extracted data, and appraised the risk of bias in the included studies. The findings were synthesized narratively., Results: From 4776 de-duplicated records, five studies, with low to moderate overall risk of bias, were included. Forty-six molecular allergens from 18 foods were investigated. Overall, the prevalence of sensitization was low, particularly for major allergens, and non-existent for 10 molecular allergens (0% [95% CI 0-0.8]). The highest prevalence was seen for PR-10 proteins, such as Cor a 1.04 (13.6% [95% CI 10.9-16.9])., Conclusions: Available data, primarily from North-western Europe, indicate that sensitization to molecular food allergens is overall low. The highest estimates were found for cross-reactive PR-10 proteins. There were not enough studies to discern regional differences or perform meta-analysis, highlighting the need for more population-representative studies in order to elucidate patterns of sensitization to molecular food allergens in Europe., Competing Interests: Carina Venter reports: grants (Reckitt Benckiser, Food Allergy Research and Education, and National Peanut Board) and personal fees (Reckitt Benckiser, Nestle Nutrition Institute, Danone, Abbott Nutrition, Else Nutrition, Sifter, and Before Brands). Ronald van Ree reports: consultancies (HAL Allergy BV, Citeq BV, Angany Inc., Reacta Healthcare Ltd., Mission MightyMe, and AB Enzymes), speaker's fees (HAL Allergy BV, ThermoFisher Scientific, and ALK), and stock options (Angany Inc.). Margitta Worm reports: grants and personal fees (Stallergens, HAL Allergie, Bencard Allergie, Allergopharma, ALK‐Abello, Mylan Germany, Actelion Pharmaceuticals Deutschland, Biotest, AbbVie Deutschland, Lilly Deutschland Aimmune, DBV Technologies SA, Regeneron Pharmaceuticals, Sanofi Aventis, Leo Pharma, Novartis, and Viatris) outside of the submitted work and being past WAO co‐chair of the anaphylaxis committee and past chair of the food allergy interest group of EAACI. Berber Vlieg‐Boerstra reports: personal fees (Marfo Food Group, Nestlé, and Nutricia) and grants (Nutricia). Antonella Muraro reports: grants and speaker's fees (Aimmune), speaker's fees (DVB Technologies SA, Viatris [Mylan], ALK, and Nestlé), and being member of the Executive Committee of GA2LEN and past president of EAACI. Graham Roberts reports grants (Asthma UK and National Institutes of Health Research). Bright Nwaru reports unrestricted grants and personal fees from DBV Technologies and AstraZeneca, respectively. The other authors report no conflicting interests related to this work. The funder played no role in the content and decision to submit this manuscript., (© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Objective: To evaluate the number of medical conditions detected by periodic health evaluations (PHEs) in elite athletes, and their consequences for management and medical clearance., Design: Retrospective design., Participants: Elite athletes of various sports in a high-performance program in The Netherlands, in the period between 2009 and 2020., Interventions: The PHEs consisted of a questionnaire, general and musculoskeletal physical examination, laboratory blood test, electrocardiogram, pulmonary function testing, and (cardiopulmonary) exercise test., Main Outcome Measures: We extracted and analyzed the medical conditions that led to advice, clinical follow-up, further diagnostic investigation or treatment, and the medical clearance status of the athlete (clearance, temporarily no clearance, or permanently no clearance)., Results: We included 721 PHEs of 451 elite athletes. We found 1389 medical conditions that led to advice (n = 923, 66%), clinical follow-up (n = 124, 9%), further diagnostic investigation (n = 190, 14%), treatment (n = 132, 10%), or sports restriction (n = 20, 1%). Only 20 cases (3%) led to temporarily no medical clearance. After further investigation or treatment, no permanent sports restriction was imposed on any of the athletes., Conclusions: We found a high number of medical conditions detected with a PHE in elite athletes. However, the vast majority of detected conditions were mild, with consequences limited to preventive advice and follow-up. The yield of PHE to detect (potentially) severe pathological conditions seems low. Clinical relevance of PHE in elite athletes and potential future health benefits remain unclear., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

To directly compare and describe the differences between juvenile idiopathic arthritis (JIA) patients and pediatric controls regarding features of the synovial and tenosynovial membrane on contrast-enhanced magnetic resonance imaging (MRI) of the wrist. T1-weighted contrast-enhanced MRI scans of 25 JIA patients with clinically active wrist arthritis and 25 children without a history of joint complaints nor any clinical signs of joint inflammation were evaluated by two readers blinded to clinical data. The synovium was scored at five anatomical sites based on thickening of the synovium (0-3 scale) and synovial enhancement (0-2 scale). Thickening and/or enhancement of the tenosynovium was scored at four anatomical sites using a 0-3 scale. Significantly higher scores for synovial thickening (median 4 vs. 1, p < 0.001) and synovial enhancement (median 4 vs. 1, p < 0.001) are found in the wrist of JIA patients as compared to controls. JIA patients experienced the highest synovial scores at the mid-/inter-carpal, 2nd -5th carpometacarpal, and radiocarpal joints. No significant difference in tenosynovial scores is found between both groups (median 0 vs. 0, p = 0.220). This study highlights the higher synovial thickening/enhancement scores on contrast-enhanced MRI of the wrist in JIA patients compared to pediatric controls. Tenosynovial thickening and/or enhancement was rarely present in both groups. In JIA patients, synovial thickening and enhancement were particularly present at three anatomical sites. These results substantially support rheumatologists and radiologists when navigating through MRI of the wrist in search for JIA disease activity., (© 2021. The Author(s).)