Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase 3 CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase 3 trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1:1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n= 103 without upfront PTR, n=101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (IQR 59-71). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% CI 16.0-22.2) compared to 20.1 months (95% CI 17.0-25.1) in the upfront PTR arm (p = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (p=0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSION: of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

[Prevalence and factors associated with benzodiazepine use in children and adult inpatients]. / Prevalentie van en factoren geassocieerd met benzodiazepinegebruik tijdens opname.

BACKGROUND: Given the growing focus on deprescribing, it is crucial to thoroughly evaluate our benzodiazepine prescribing practices considering the potential risks. AIM: To investigate the prevalence and predictors of benzodiazepine prescriptions during psychiatric hospitalization and as discharge medication. METHOD: This retrospective electronic patient file study included psychiatric admissions at the UMC Utrecht between 12/01/01 and 21/04/01. Descriptive statistics were used to evaluate prevalence of benzodiazepine prescriptions in youth and adults. Multivariate regression analyses were performed to predict factors associated with benzodiazepine prescriptions and dosage. RESULTS: In total, we analyzed data from 856 admissions of youth and 4002 admissions of adults. 36.0% of the youth were prescribed benzodiazepines during admission and 14.8% at discharge. Associated factors were age (OR: 1.38) and bipolar disorder (OR: 3.98). In adults, 69.7% were prescribed benzodiazepines during admission and 37.6% at discharge. Associated factors were length of hospital stay (OR: 1.01) and anxiety disorders (OR: 2.53). Male sex, age (resp. higher and lower), and a longer length of stay predicted benzodiazepine dosages for both youth (B = 3.48; 95% CI: 0.83-0.07) and adults (B = 2.17; 95% CI: -0.04-0.05). CONCLUSION: Benzodiazepines are frequently prescribed during inpatient stays and at discharge in youth and adults, offering opportunities for deprescribing.

Retina-arrestin specific CD8+ T cells are not implicated in HLA-A29-positive birdshot chorioretinitis.

BACKGROUND: HLA-A29-positive birdshot chorioretinitis (BCR) is an inflammatory eye disorder that is generally assumed to be caused by an autoimmune response to HLA-A29-presented peptides from retinal arrestin (SAG), yet the epitopes recognized by CD8+ T cells from patients remain to be identified. OBJECTIVES: The identification of natural ligands of SAG presented by HLA-A29. To quantify CD8+ T cells reactive to antigenic SAG peptides presented by HLA-A29 in patients and controls. METHODS: We performed mass-spectrometry based immunopeptidomics of HLA-A29 of antigen-presenting cell lines from patients engineered to express SAG. MHC-I Dextramer technology was utilised to determine expansion of antigen-specific CD8+ T cells reactive to SAG peptides in complex with HLA-A29 in a cohort of BCR patients, HLA-A29-positive controls, and HLA-A29-negative controls. RESULTS: We report on the naturally presented antigenic SAG peptides identified by sequencing the HLA-A29 immunopeptidome of antigen-presenting cells of patients. We show that the N-terminally extended SAG peptide precursors can be trimmed in vitro by the antigen-processing aminopeptidases ERAP1 and ERAP2. Unexpectedly, no enhanced antigen engagement by CD8+ T cells upon stimulation with SAG peptides was observed in patients or HLA-A29-positive controls. Multiplexed HLA-A29-peptide dextramer profiling of a case-control cohort revealed that CD8+ T cells specific for these SAG peptides were neither detectable in peripheral blood nor in eye biopsies of patients. CONCLUSIONS: Collectively, these findings demonstrate that SAG is not a CD8+ T cell autoantigen and sharply contrast the paradigm in the pathogenesis of BCR. Therefore, the mechanism by which HLA-A29 is associated with BCR does not involve SAG.

Acoustic speech markers for schizophrenia-spectrum disorders: a diagnostic and symptom-recognition tool.

BACKGROUND: Clinicians routinely use impressions of speech as an element of mental status examination. In schizophrenia-spectrum disorders, descriptions of speech are used to assess the severity of psychotic symptoms. In the current study, we assessed the diagnostic value of acoustic speech parameters in schizophrenia-spectrum disorders, as well as its value in recognizing positive and negative symptoms. METHODS: Speech was obtained from 142 patients with a schizophrenia-spectrum disorder and 142 matched controls during a semi-structured interview on neutral topics. Patients were categorized as having predominantly positive or negative symptoms using the Positive and Negative Syndrome Scale (PANSS). Acoustic parameters were extracted with OpenSMILE, employing the extended Geneva Acoustic Minimalistic Parameter Set, which includes standardized analyses of pitch (F0), speech quality and pauses. Speech parameters were fed into a random forest algorithm with leave-ten-out cross-validation to assess their value for a schizophrenia-spectrum diagnosis, and PANSS subtype recognition. RESULTS: The machine-learning speech classifier attained an accuracy of 86.2% in classifying patients with a schizophrenia-spectrum disorder and controls on speech parameters alone. Patients with predominantly positive v. negative symptoms could be classified with an accuracy of 74.2%. CONCLUSIONS: Our results show that automatically extracted speech parameters can be used to accurately classify patients with a schizophrenia-spectrum disorder and healthy controls, as well as differentiate between patients with predominantly positive v. negatives symptoms. Thus, the field of speech technology has provided a standardized, powerful tool that has high potential for clinical applications in diagnosis and differentiation, given its ease of comparison and replication across samples.

The power of effective study design in animal experimentation: Exploring the statistical and ethical implications of asking multiple questions of a data set.

One of the chief advantages of using highly standardised biological models including model organisms is that multiple variables can be precisely controlled so that the variable of interest is more easily studied. However, such an approach often obscures effects in sub-populations resulting from natural population heterogeneity. Efforts to expand our fundamental understanding of multiple sub-populations are in progress. However, such stratified or personalised approaches require fundamental modifications of our usual study designs that should be implemented in Brain, Behavior and Immunity (BBI) research going forward. Here we explore the statistical feasibility of asking multiple questions (including incorporating sex) within the same experimental cohort using statistical simulations of real data. We illustrate and discuss the large explosion in sample numbers necessary to detect effects with appropriate power for every additional question posed using the same data set. This exploration highlights the strong likelihood of type II errors (false negatives) for standard data and type I errors when dealing with complex genomic data, where studies are too under-powered to appropriately test these interactions. We show this power may differ for males and females in high throughput data sets such as RNA sequencing. We offer a rationale for the use of alternative experimental and statistical strategies based on interdisciplinary insights and discuss the real-world implications of increasing the complexities of our experimental designs, and the implications of not attempting to alter our experimental designs going forward.

[Do doctors speak a different language? The case of 'patient' without an article]. / Spreken artsen een andere taal? Het geval van 'patiënt' zonder lidwoord.

BACKGROUND: In medical speech and writing, the article before ‘patient’ is often omitted, while this would be ungrammatical in Standard Dutch. AIM: To investigate how and when the article is omitted in medical Dutch. METHOD: An online questionnaire was distributed among individuals with a medical background. RESULTS: 85 respondents participated in this study. The participants showed a strong preference to omit the definite article (‘the’) befor the word ‘patient’ and related words. This phenomenon seemed independent of the function of the word in the sentence, or of the sentence construction. However, the indefinite article (‘a’) was not omitted in the same situations. CONCLUSION: Doctors speak a different language, namely a variety of Standard Dutch in which the omission of the definite article befor ‘patient’ is preferred. We conclude that this phenomenon can be explained by recognizing ‘patient’ as a substitute for the name of the patient.

[Taal: een introductie]. / Taal: een introductie.

BACKGROUND: This special issue discusses the roles and functions of language in psychiatric practice from different perspectives. As an introduction, we discuss the phenomenon ‘language’ as an object of scientific investigation. AIM: To give a brief introduction to this theme issue. METHOD: After a terminological introduction and an outline of linguistics, we discuss some of the cognitive processes that enable humans to produce and interpret verbal utterances. RESULTS: The mental lexicon, the dictionary in our head, plays a central role in both language production and understanding. The starting point for language comprehension is recognizing basic form elements in the speech or sign stream (phonemes). Next, the perceiver must determine how words are related grammatically in order to deduce sentence meanings. We distinguish three successive steps in the production of language: conceptualizing, formulating and articulating. CONCLUSION: Production and understanding words and sentences rely on a complex interplay of cognitive processes. In communication, we use words and sentences to convey and recognize intentions. This requires close cooperation between interlocutors.

[Antipsychotic drugs for women: a narrative review and clinical guidelines]. / Antipsychotica voor vrouwen: overzicht van de literatuur en praktijkadviezen.

BACKGROUND: It has long been thought that women with a schizophrenia spectrum disorder have a more favorable course than men. However, this is not the case, even though they become ill later in life and are less likely to have comorbid drug abuse. Guidelines for prescribing antipsychotics are based on research with mostly male participants, and by following these guidelines we are doing our female patients a disservice. Gender and sex differences lead to differences in preferences, pharmacokinetics and pharmacodynamics. AIM: Providing an overview of antipsychotics for women with a schizophrenia spectrum disorder and discuss the consequences for practice. METHOD: A clinically oriented study of the literature. RESULTS: Women reach higher plasma levels than men when they receive the same dose of antipsychotic drugs (except for lurasidone and quetiapine). The effect of antipsychotics is also greater in women, because estrogens increase the brain’s dopamine sensitivity. This leads to higher risks of side effects. Clinical guidelines differ for women at different stages of life because estrogens greatly contribute to the sex differences seen in the efficacy and tolerability of antipsychotics. CONCLUSION: Clinicians should be aware that women should be treated differently with antipsychotics than men.

[Recognizing depression through computational language analysis]. / Herkennen van depressie met computationele taalanalyse.

BACKGROUND: Currently, clinical practice lacks a usable biomarker for the detection and differentiation of depression. Such a biomarker may be found in speech, from which important information can be distilled using automated speech analysis. AIM: To provide an overview of the fast-developing field of automated speech analysis for depression. METHOD: We summarize the current literature on speech features in depression. RESULTS: Current computational models can detect depression with high accuracy, rendering them applicable for diagnostic tools based on automatic speech analysis. Such tools are developing at a fast rate. CONCLUSION: Some challenges are still in the way of clinical implementation. For example, results differ largely between studies due to much variation in methodology. Furthermore, privacy and ethical issues need to be addressed before tools can be used.

[Automated speech analysis can distinguish frontotemporal dementia from depression: a pilot study]. / Geautomatiseerde spraakanalyse bij onderscheiden van frontotemporale dementie en depressie.

BACKGROUND: Differentiating the behavioural variant of frontotemporal dementia from a depression is challenging. Recent development of automated speech analyses might add to diagnostic. AIM: To investigate the value of automated speech analyses in differentiating bvFTD from a depressive disorder. METHOD: A semistructured interview was recorded in 15 patients with bvFTD, 15 patients with a depressive disorder and 15 healthy controls, which was transcribed and analysed. Acoustic and semantic values were extracted and classified using machine learning. RESULTS: Acoustic values showed an 80% accuracy for differentiating bvFTD from depressive disorder and semantic values showed an 70.8% accuracy. CONCLUSION: Acoustic as well as semantic values show significant differences between bvFTD and depressive disorder. In automated speech analyses researches should consider privacy matters as well as possible confounders like age, sex and ethnicity. This study should be repeated in a larger population.

Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study.

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (ß = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Negative content in auditory verbal hallucinations: a natural language processing approach.

INTRODUCTION: Negative content of auditory verbal hallucinations (AVH) is a strong predictor of distress and impairment. This paper quantifies emotional voice-content in order to explore both subjective (i.e. perceived) and objectively (i.e. linguistic sentiment) measured negativity and investigates associations with distress. METHODS: Clinical and non-clinical participants with frequent AVH (n = 40) repeated and recorded their AVH verbatim directly upon hearing. The AVH were analyzed for emotional valence using Pattern, a rule-based sentiment analyzer for Dutch. The AVH of the clinical individuals were compared to those of non-clinical voice-hearers on emotional valence and associated with experienced distress. RESULTS: The mean objective valence of AVH in patients was significantly more negative than those of non-clinical voice-hearers. In the clinical individuals a larger proportion of the voice-utterances was negative (34.7% versus 18.4%) in objective valence. The linguistic valence of the AVH showed a significant, strong association with the perceived negativity, amount of distress and disruption of life, but not with the intensity of distress. CONCLUSIONS: Our results indicate that AVH of patients have a more negative linguistic content than those of non-clinical voice-hearers, which is associated with the experienced distress. Thus, patients not only perceive their voices as more negative, objective analyses confirm this.

[Improving care for women with schizophrenia-spectrum disorders]. / Vrouwen met schizofreniespectrum-stoornissen verdienen betere zorg.

Background   Women with a schizophrenia-spectrum disorder (SSD) have a better clinical profile than men at the start of their illness but lose this advantage within the first few years of living with SSD. There are benefits to be gained across different areas in the care currently offered to women with psychosis. Aim   To describe point of improvement in the care for women with SSD. Method   Review or relevant literature. Results   An important point for improvement is the early detection of female-specific signs of a first episode of psychosis, to shorten the duration of untreated psychosis, with prompt access to early intervention services. Special attention should be paid to sexual health, and to any history of childhood trauma. Antipsychotics clearly require dosing and prescription tailored to the female body, considering hormonal life phases such as menopause. Switching to prolactin-sparing medications can benefit both mental and somatic health. Finally, hormone replacement therapy should be considered for postmenopausal women. Conclusion   By providing female-specific care, women with SSD can live up to their full potential.

[Tapering of psychotropic drugs: current practice and needs of patients and their relatives]. / Deprescriptie van psychofarmaca; praktijk en behoeften van patiënten en naasten.

BACKGROUND: The prevalence of mental illness has remained stable in recent decades, yet the use of psychotropic drugs has increased. This trend suggests that psychotropic drugs are being prescribed with an unnecessary frequency. Internationally, there is growing attention for deprescribing. AIM: To investigate what experiences and needs patients and their loved ones/relatives have with regard to deprescribing of psychotropics. METHOD: An online questionnaire was distributed among members of the MIND mental health care panel, which consists of (former) patients with a psychiatric disorder and their loved ones. RESULTS: A total of 564 respondents took part in this survey. Most patients have phased out/stopped their psychotropic drugs (83.8%). This was usually done at the initiative of the patient (66.7%), in consultation with the practitioner (72.9%). The practitioner only took the initiative to deprescribe in 15.1% of the cases. In 68.6% tapering was not discussed at the start of psychotropic drug use. Patients did not experience willingness from practitioners in deprescribing, and would like to discuss deprescribing more often (79.5%). CONCLUSION: There is an undeniable demand among patients and near ones for more emphasis on deprescribing of psychotropic drugs. We advise to include this topic in the shared decision making process.

Vector-apodizing phase plate coronagraph: design, current performance, and future development [Invited].

Over the last decade, the vector-apodizing phase plate (vAPP) coronagraph has been developed from concept to on-sky application in many high-contrast imaging systems on 8 m class telescopes. The vAPP is a geometric-phase patterned coronagraph that is inherently broadband, and its manufacturing is enabled only by direct-write technology for liquid-crystal patterns. The vAPP generates two coronagraphic point spread functions (PSFs) that cancel starlight on opposite sides of the PSF and have opposite circular polarization states. The efficiency, that is, the amount of light in these PSFs, depends on the retardance offset from a half-wave of the liquid-crystal retarder. Using different liquid-crystal recipes to tune the retardance, different vAPPs operate with high efficiencies (${\gt}96\%$) in the visible and thermal infrared (0.55 µm to 5 µm). Since 2015, seven vAPPs have been installed in a total of six different instruments, including Magellan/MagAO, Magellan/MagAO-X, Subaru/SCExAO, and LBT/LMIRcam. Using two integral field spectrographs installed on the latter two instruments, these vAPPs can provide low-resolution spectra (${\rm{R}} \sim 30$) between 1 µm and 5 µm. We review the design process, development, commissioning, on-sky performance, and first scientific results of all commissioned vAPPs. We report on the lessons learned and conclude with perspectives for future developments and applications.

Substitution among milk and yogurt products and the risk of incident type 2 diabetes in the EPIC-NL cohort.

BACKGROUND: Higher dairy consumption has been associated with lower type 2 diabetes (T2D) risk, whereas dairy product subtypes appear to differ in their T2D risk association. We investigated whether replacing one type of milk or yogurt product with another is associated with T2D incidence. METHODS: Participants of the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort (n = 35 982) were included in the present study. Information on milk and yogurt consumption at baseline was obtained by a validated food frequency questionnaire. T2D cases were identified by self-report or linkage to the hospital discharge registry, and validated by consulting the general practitioner. Multivariable Cox proportional hazard models were used to estimate associations. RESULTS: During a mean of 15 years of follow-up, 1467 indecent T2D cases were validated. Median total milk and yogurt intake was 1.5 servings (25th percentile to 75th percentile: 0.8-2.4). After adjustment for demographic and cardiovascular risk factors, replacement of one serving (200 g) of whole-fat milk [hazard ratio (HR) = 0.93, 95% confidence interval (CI) = 0.60-1.44], buttermilk (HR = 0.88, 95% CI = 0.58-1.34), skimmed milk (HR = 0.87, 95% CI = 0.57-1.32) or skimmed fermented milk (HR = 0.99, 95% CI = 0.63-1.54) with whole-fat yogurt was not associated with T2D risk. Substitutions among other milk and yogurt products were also not associated with T2D risk. Sensitivity analysis investigating T2D risk halfway follow-up suggested a lower risk for substitutions with whole-fat yogurt. CONCLUSIONS: No evidence was found for the association between substitutions among milk and yogurt products and the risk of incident T2D, although we cannot exclude possible attenuation of results as a result of dietary changes over time. This analysis should be repeated in a population with a wider consumption range of whole-fat yogurt.

Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults.

PURPOSE: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. METHODS: A total of 255,170 participants aged 25-70 years were recruited in ten European countries (1992-2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC-MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. RESULTS: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. CONCLUSION: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

Ongoing transcatheter aortic valve implantation (TAVI) practice amidst a global COVID-19 crisis: nurse-led analgesia for transfemoral TAVI.

The current coronavirus disease 2019 (COVID-19) crisis has led to a relative unavailability of anaesthesiological support for non-acute cardiac care. Currently, transfemoral transcatheter aortic valve implantation (TF-TAVI) is predominantly performed as an elective catheterisation laboratory (cath lab) procedure. Hence, the performance of TAVI could come to a halt amidst the COVID-19 crisis. Our study population comprised 90 patients treated with TF-TAVI, with local analgesia performed by our dedicated cath lab nurses. The patients had a mean age of 80 ± 5 years and 59% were male, with a predicted surgical risk of 2.2 ± 0.9/3.1 ± 2.4% (Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM] score/EuroSCORE II), depicting a contemporary, lower-risk population. The composite endpoint of device success (Valve Academic Research Consortium [VARC]-2) was reached in all patients. No patients showed more than mild paravalvular leakage (3/90, 3.3%). Overall, intravenous medication was sparsely used during the procedure, with 48 of the 90 (53%) patients receiving no unplanned intravenous medication. There was neither procedural nor in-hospital mortality. The performance of TF-TAVI using local analgesia only, managed by a dedicated nurse instead of an anaesthesiologist, was shown to be feasible and safe in a selected group of patients. This strategy may (temporarily) eliminate the need for an anaesthesiologist to be present in the cath lab and enables ongoing TAVI treatment amidst the global COVID-19 crisis.

[Burnout and work stress]. / Burn-out en werkdruk bij tandartsen.

Work stress and burnout among Dutch dentists have been studied in the past; since then, however, considerable changes have taken place in practicing dentistry. The aim of this study was to investigate whether these changes are reflected in reported burnout and stress. Also, the study sought to investigate whether burnout could be associated with making mistakes during treatment or being confronted with a formal complaint. 500 Dutch dentists were randomly selected for an online survey, 105 of whom responded (21%); 50.5% male and 49.5% female. Higher mean scores on emotional exhaustion (EE) and personal accomplishment (PA) were reported, compared to previous results, and to reference scores from the burnout measuring manual, and lower mean scores on depersonalisation (DP) compared to reference scores. No gender differences were found for burnout. Women reported more work stress on Patient Contacts and Considerations about work. The 36 to 45-year-old age group reported higher mean scores on burnout and work stress. Having been confronted with patient complaints was associated with higher scores on DP, while worrying about making mistakes was associated with higher scores on EE and DP. Burnout is a relevant topic for dentists, which appears to be most prominent at middle age. Recognising, and knowing how to deal with, demanding aspects of work is a crucial means to prevent burnout.

[Three estimations of the outflow of orthodontists from the field]. / Drie schattingen van de uitstroom van orthodontisten uit het vak.

The outflow of orthodontists through retirement is an important factor in the estimation of the required training capacity for this group of professionals. From 2002 through 2018, studies of the professional activity and retirement plans of orthodontists age 55 and older have been conducted fairly frequently, the most recent one dating from 2018. Based on the findings of these surveys, 3 estimations were obtained of the outflow through retirement. These were based on answers in earlier editions, the answers of their contemporaries and on the basis of the legal retirement age in the Netherlands. The number of active orthodontists in 2018 age 55 or older is estimated respectively to be 117, 116 and 102; according to all estimations, they will have retired in 2030. The estimations predict, respectively 56, 57 and 30 orthodontists will retire before 2023. According to 2 of the estimations, the outflow of orthodontists from the field will exceed the inflow from the universities in the coming years. The present training capacity in the Netherlands is not sufficient to compensate for the outflow of the first 2 estimations.