Stress and Multiple Sclerosis - Systematic review and meta-analysis of the association with disease onset, relapse risk and disability progression.

OBJECTIVE: This systematic review and meta-analysis address the evidence on the association of psychological stressors with onset of multiple sclerosis, inflammatory disease activity (relapses or new disease activity on magnetic resonance imaging, MRI) and disability progression. METHODS: PubMed was searched from 1946 to 15 July 2022. Studies and certain stressors were selected when they assessed stressors independent from stress elicited by the disease process itself. Risk of bias was assessed by the CASP Case Control Study Checklist and the CASP Cohort Study Checklist. Normal-Normal Hierarchical Model (NNHM) for random-effects meta-analysis was used in the Bayesian framework. RESULTS: 30 studies reporting data from 26 cohorts reporting on 24.781 cases could be identified. Ten studies addressed stressors and MS disease onset showing a weak to modest effect of psychological stressors. A meta-analysis of three studies investigating diagnosed stress disorders and MS risk showed a 1.87-fold (CI 1.061 to 3.429) increased MS risk. Stress and MS relapse risk were addressed in 19 heterogeneous studies. Meta-analyses from two independent cohorts investigating the same military threat of a population showed a threefold increased risk for relapses in association with war (relapse rate: 3.0, CI 1.56 to 5.81). In addition, two studies confirmed an association of stressful life events and MRI activity. Three studies of stressors and disease progression were included indicating some effect on disease progression. CONCLUSIONS: Taken together studies indicate a minor to modest impact of psychological stressors on disease onset, inflammatory activity and progression of MS. Possible case-selection bias and lack of confounder analysis were present in many studies.

Optic Nerve Sheath Viscoelastic Properties: Re-Examination of Biomechanical Behavior and Clinical Implications.

BACKGROUND: Meta-analyses show a variable relationship between optic nerve sheath diameter (ONSD) and the presence of raised intracranial pressure (ICP). Because optic nerve sheath (ONS) tissue can be deformed, it is possible that ONSD reflects not only the current ICP but also prior deforming biomechanical exposures. In this post hoc analysis of two published data sets, we characterize ONS Young's modulus (E, mechanical stress per unit of strain) and calculate threshold pressure for plastic deformation. METHODS: The authors of two previously published articles contributed primary data for these unique post hoc analyses. Human cadaveric ex vivo measurements of ONSD (n = 10) and luminal distending pressure (range 5 to 65 mm Hg) were used to calculate E and the threshold pressure for plastic deformation. Clinical in vivo measurements of ONSD and ICP during endotracheal tube suction from patients with traumatic brain injury (n = 15) were used to validate the ex vivo cadaveric findings. RESULTS: Ex vivo ONS estimate of E was 140 ± 1.3 mm Hg (mean ± standard error), with evidence of plastic deformation occurring with distending pressure at 45 mm Hg. Similar E (71 ± 10 mm Hg) was estimated in vivo with an average ICP of 34 ± 2 mm Hg. CONCLUSIONS: Ex vivo, ONS plastic deformation occurs at levels of pressure commonly seen in patients with raised ICP, leading to distortion of the ICP-ONSD relationship. This evidence of plastic deformation may illustrate why meta-analyses fail to identify a single threshold in ONSD associated with the presence of raised ICP. Future studies characterizing time-dependent viscous characteristics of the ONS will help determine the time course of ONS tissue biomechanical behavior.

Bone Char Mediated Dechlorination of Trichloroethylene by Green Rust.

Biochars function as electron transfer mediators and thus catalyze redox transformations of environmental pollutants. A previous study has shown that bone char (BC) has high catalytic activity for reduction of chlorinated ethylenes using layered Fe(II)-Fe(III) hydroxide (green rust) as reductant. In the present study, we studied the rate of trichloroethylene (TCE) reduction by green rust in the presence of BCs obtained at pyrolysis temperatures (PTs) from 450 to 1050 °C. The reactivity increased with PT, yielding a maximum pseudo-first-order rate constant (k) of 2.0 h-1 in the presence of BC pyrolyzed at 950 °C, while no reaction was seen for BC pyrolyzed at 450 °C. TCE sorption, specific surface area, extent of graphitization, carbon content, and aromaticity of the BCs also increased with PT. The electron-accepting capacity (EAC) of BC peaked at PT of 850 °C, and EAC was linearly correlated with the sum of concentrations of quinoid, quaternary N, and pyridine-N-oxide groups measured by XPS. Moreover, no TCE reduction was seen with graphene nanoparticles and graphitized carbon black, which have high degrees of graphitization but low EAC values. Further analyses showed that TCE reduction rates are well correlated with the EAC and the C/H ratio (proxy of electrical conductivity) of the BCs, strongly indicating that both electron-accepting functional groups and electron-conducting domains are crucial for the BC catalytic reactivity. The present study delineates conditions for designing redox-reactive biochars to be used for remediation of sites contaminated with chlorinated solvents.

A Silicate/Glycine Switch To Control the Reactivity of Layered Iron(II)-Iron(III) Hydroxides for Dechlorination of Carbon Tetrachloride.

Layered FeII-FeIII hydroxide chloride (chloride green rust, GRCl) has high reactivity toward reducible pollutants such as chlorinated solvents. However, this reactive solid is prone to dissolution, and hence loss of reactivity, during storage and handling. In this study, adsorption of silicate (Si) to GRCl was tested for its ability to minimize GRCl dissolution and to inhibit reduction of carbon tetrachloride (CT). Silicate adsorbed with high affinity to GRCl yielding a sorption maximum of 0.026 g of Si/g of GRCl. In the absence of Si, the pseudo-first-order rate constant for CT dehalogenation by GRCl was 2.1 h-1, demonstrating very high reactivity of GRCl but with substantial FeII dissolution up to 2.5 mM. When Si was adsorbed to GRCl, CT dehalogenation was blocked and FeII dissolution extent was reduced by a factor of 28. The addition of glycine (Gly) was tested for reactivation of the Si-blocked GRCl for CT dehalogenation. At 30 mM Gly, partial reactivation of the GRCl was observed with pseudo-first-order rate constant for CT reduction of 0.075 h-1. This blockage and reactivation of GRCl reactivity demonstrates that it is possible to design a switch for GRCl to control its stability and reactivity under anoxic conditions.

Amino Acid-Assisted Dehalogenation of Carbon Tetrachloride by Green Rust: Inhibition of Chloroform Production.

Layered FeII-FeIII hydroxides (green rusts, GRs) are promising reactants for reductive dechlorination of chlorinated solvents due to high reaction rates and the opportunity to inject reactive slurries of the compounds into contaminant plumes. However, it is necessary to develop strategies that reduce the formation of toxic byproducts such as chloroform (CF). In this study, carbon tetrachloride (CT) dehalogenation by the chloride form of GR (GRCl) was tested in the presence of glycine (GLY) and other selected amino acids. GLY, alanine (ALA), and serine (SER) all resulted in remarkable suppression of CF formation with only ∼10% of CF recovery while sarcosine (SAR) showed insignificant effects. For two nonamino acid buffers, TRIS had little effect while HEPES resulted in a 40 times lower rate constant compared to experiments in which no buffer was added. The FeII complexing properties of the amino acids and buffers caused variable extents of GRCl dissolution which was linearly correlated with CF suppression and dehalogenation rate. We hypothesize that the CF suppression seen for amino acids is caused by stabilization of carbene intermediates via the carbonyl group. Different effects on CF suppression and CT dehalogenation rate were expected because of the different structural and chemical properties of the amino acids.

UPLC-MS/MS determination of ptaquiloside and pterosin B in preserved natural water.

The naturally occurring carcinogen ptaquiloside and its degradation product pterosin B are found in water leaching from bracken stands. The objective of this work is to present a new sample preservation method and a fast UPLC-MS/MS method for quantification of ptaquiloside and pterosin B in environmental water samples, employing a novel internal standard. A faster, reliable, and efficient method was developed for isolation of high purity ptaquiloside and pterosin B from plant material for use as analytical standards, with purity verified by 1H-NMR. The chemical analysis was performed by cleanup and preconcentration of samples with solid phase extraction, before analyte quantification with UPLC-MS/MS. By including gradient elution and optimizing the liquid chromatography mobile phase buffer system, a total run cycle of 5 min was achieved, with method detection limits, including preconcentration, of 8 and 4 ng/L for ptaquiloside and pterosin B, respectively. The use of loganin as internal standard improved repeatability of the determination of both analytes, though it could not be employed for sample preparation. Buffering raw water samples in situ with ammonium acetate to pH ∼5.5 decisively increased sample integrity at realistic transportation and storing conditions prior to extraction. Groundwater samples collected in November 2015 at the shallow water table below a Danish bracken stand were preserved and analyzed using the above methods, and PTA concentrations of 3.8 ± 0.24 µg/L (±sd, n = 3) were found, much higher than previously reported. Graphical abstract Workflow overview of ptaquiloside determination.

Suspended particles only marginally reduce pyrethroid toxicity to the freshwater invertebrate Gammarus pulex (L.) during pulse exposure.

Current ecotoxicological research on particle-associated pyrethroids in freshwater systems focuses almost exclusively on sediment-exposure scenarios and sediment-dwelling macroinvertebrates. We studied how suspended particles influence acute effects of lambda-cyhalothrin and bifenthrin on the epibenthic freshwater amphipod Gammarus pulex (L.) using brief pulse exposures followed by a 144 h post exposure recovery phase. Humic acid (HA) and the clay mineral montmorillonite (MM) were used as model sorbents in environmentally realistic concentrations (5, 25 and 125 mg L(-1)). Mortality of G. pulex was recorded during the post exposure recovery phase and locomotor behavior was measured during exposure to lambda-cyhalothrin. We found that HA in concentrations ≥25 mg L(-1) adsorbed the majority of pyrethroids but only reduced mortality of G. pulex up to a factor of four compared to pyrethroid-only treatments. MM suspensions adsorbed a variable fraction of pyrethroids (10% for bifenthrin and 70% for lambda-cyhalothrin) but did not significantly change the concentration-response relationship compared to pure pyrethroid treatments. Behavioral responses and immobilisation rate of G. pulex were reduced in the presence of HA, whereas behavioral responses and immobilisation rate were increased in the presence of MM. This indicates that G. pulex was capable of sensing the bioavailable fraction of lambda-cyhalothrin. Our results imply that suspended particles reduce to only a limited extent the toxicity of pyrethroids to G. pulex and that passive uptake of pyrethroids can be significant even when pyrethroids are adsorbed to suspended particles.

Ptaquiloside in Irish Bracken Ferns and Receiving Waters, with Implications for Land Managers.

Ptaquiloside, along with other natural phytotoxins, is receiving increased attention from scientists and land use managers. There is an urgent need to increase empirical evidence to understand the scale of phytotoxin mobilisation and potential to enter into the environment. In this study the risk of ptaquiloside to drinking water was assessed by quantifying ptaquiloside in the receiving waters at three drinking water abstraction sites across Ireland and in bracken fronds surrounding the abstraction sites. We also investigated the impact of different management regimes (spraying, cutting and rolling) on ptaquiloside concentrations at plot-scale in six locations in Northern Ireland, UK. Ptaquiloside concentrations were determined using recent advances in the use of LC-MS for the detection and quantification of ptaquiloside. The results indicate that ptaquiloside is present in bracken stands surrounding drinking water abstractions in Ireland, and ptaquiloside concentrations were also observed in the receiving waters. Furthermore, spraying was found to be the most effective bracken management regime observed in terms of reducing ptaquiloside load. Increased awareness is vital on the implications of managing land with extensive bracken stands.

Land management of bracken needs to account for bracken carcinogens--a case study from Britain.

Bracken ferns are some of the most widespread ferns in the World causing immense problems for land managers, foresters and rangers. Bracken is suspected of causing cancer in Humans due to its content of the carcinogen ptaquiloside. Ingestion of bracken, or food and drinking water contaminated with ptaquiloside may be the cause. The aim of this study was to monitor the content of ptaquiloside in 20 bracken stands from Britain to obtain a better understanding of the ptaquiloside dynamics and to evaluate the environmental implications of using different cutting regimes in bracken management. The ptaquiloside content in fronds ranged between 50 and 5790 µg/g corresponding to a ptaquiloside load in the standing biomass of up to 590 mg/m(2) in mature fronds. Ptaquiloside was also found in the underground rhizome system (11-657 µg/g) and in decaying litter (0.1-5.8 µg/g). The amount of ptaquiloside present in bracken stands at any given time is difficult to predict and did not show any correlations with edaphic growth factors. The content of ptaquiloside turned out to be higher in fronds emerging after cutting compared to uncut fronds. Environmental risk assessment and bracken management must therefore be based on actual and site specific determinations of the ptaquiloside content. Care must be taken to avoid leaching from cut ferns to aquifers and other recipients and appropriate precautionary measures must be taken to protect staff from exposure to bracken dust.

Reactions between ferric oxyhydroxide mineral coatings and a dimethoxyhydroquinone: A source of hydroxyl radicals.

Quinones are organic molecules that facilitate electron-transfer reactions in terrestrial environments. The reduced forms, hydroquinones, are powerful reductants that can trigger non-enzymatic radical-based decomposition of organic matter and contaminants by simultaneous reduction of iron and oxygen. Iron oxides often occur as coatings on other minerals, thus our study investigated the reactions between the ferric oxyhydroxide (FeO(OH)) surface coatings on gibbsite (Al(OH)3) and 2,6-dimethoxy-1,4-hydroquinone (2,6-DMHQ). The main aim was to investigate the oxidation of 2,6-DMHQ and the generation ∙OH in the presence of O2 at low Fe concentrations in a novel setup that allows local structural characterization. The heterogeneous redox reactions between 2,6-DMHQ and the FeO(OH) coatings were studied at pH 5.0 as a function of the amount of Fe present on the gibbsite surfaces, including the effect of aging of the FeO(OH) coatings. The results showed that reactions between 2,6-DMHQ and FeO(OH) coated gibbsite under ambient conditions can generate substantial amounts of ·OH, comparable with amounts generated on pure ferrihydrite surfaces. The ·OH is the product of two sequential reactions: hydroquinone oxidation by O2 and degradation of the formed H2O2. The calculated rate constant of the former reaction is the same regardless of amount of FeO(OH) coating suggesting a surface catalytic process where 2,6-DMHQ is oxidized by O2 resulting in formation of H2O2. Subsequently, the observed induction period, the low Fe2+ (aq) concentrations in solution and the dependency of FeO(OH) coating amount influencing ·OH formation suggest that the pathway for ∙OH is through H2O2 decomposition by the surface sites on the FeO(OH) coating. Overall, this study shows that co-existence of oxygen, FeO(OH) and organic reductants, possibly secreted by soil microorganisms, creates favorable conditions for generation of ·OH contributing to decomposition of organic matter and organic pollutants in soil environments.

Modeling the environmental fate of bracken toxin ptaquiloside: Production, release and transport in the rhizosphere.

Plants produce a diverse array of toxic compounds which may be released by precipitation, explaining their wide occurrence in surrounding soil and water. This study presents the first mechanistic model for describing the generation and environmental fate of a natural toxin, i.e. ptaquiloside (PTA), a carcinogenic phytotoxin produced by bracken fern (Pteridium aquilinum L. Kuhn). The newly adapted DAISY model was calibrated based on two-year monitoring performed in the period 2018-2019 in a Danish bracken population located in a forest glade. Several functions related to the fate of PTA were calibrated, covering processes from toxin generation in the canopy, wash off by precipitation and degradation in the soil. Model results show a good description of observed bracken biomass and PTA contents, supporting the assumption that toxin production can be explained by the production of new biomass. Model results show that only 4.4 % of the PTA produced in bracken is washed off by precipitation, from both canopy and litter. Model simulations showed that PTA degrades rapidly once in the soil, especially during summer due to the high soil temperatures. Leaching takes place in form of pulses directly connected to precipitation events, with maximum simulated concentrations up to 4.39 µg L-1 at 50 cm depth. Macropore transport is mainly responsible for the events with the highest PTA concentrations, contributing to 72 % of the total mass of PTA leached. Based on the results, we identify areas with high density of bracken, high precipitation during the summer and soils characterized by fast transport, as the most vulnerable to surface and groundwater pollution by phytotoxins.

The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

Optic disc edema in an astronaut after repeat long-duration space flight.

BACKGROUND: A number of ophthalmic findings including optic disc edema, globe flattening, and choroidal folds have been observed in several astronauts after long-duration space flights. The authors report the first astronaut with previously documented postflight ophthalmic abnormalities who developed new pathological changes after a repeat long-duration mission. METHODS: A case study of an astronaut with 2 long-duration (6 months) exposures to microgravity. Before and after his first long-duration space flight, he underwent complete eye examination, including fundus photography. Before and after his second flight, 9 years later, he underwent fundus photography, optical coherence tomography, ocular ultrasonography, and brain magnetic resonance imaging, as well as in-flight fundus photography and ultrasound. RESULTS: After his first long-duration mission, the astronaut was documented to have eye findings limited to unilateral choroidal folds and a single cotton wool spot. During a subsequent 6-month mission, he developed more widespread choroidal folds and new onset of optic disc edema in the same eye. CONCLUSION: Microgravity-induced anatomical changes that occurred during the first mission may have set the stage for recurrent or additional changes when the astronaut was subjected to physiological stress of repeat space flight.

Degradation of chlorpyrifos in humid tropical soils.

The insecticide chlorpyrifos is extensively used in the humid tropics for insect control on crops and soils. Chlorpyrifos degradation and mineralization was studied under laboratory conditions to characterize the critical factors controlling the degradation and mineralization in three humid tropical soils from Malaysia. The degradation was fastest in moist soils (t1/2 53.3-77.0 days), compared to dry (t1/2 49.5-120 days) and wet soils (t1/2 63.0-124 days). Degradation increased markedly with temperature with activation energies of 29.0-76.5 kJ mol(-1). Abiotic degradation which is important for chlorpyrifos degradation in sub-soils containing less soil microbial populations resulted in t½ of 173-257 days. Higher chlorpyrifos dosages (5-fold) which are often applied in the tropics due to severe insects infestations caused degradation and mineralization rates to decrease by 2-fold. The mineralization rates were more sensitive to the chlorpyrifos application rates reflecting that degradation of metabolites is rate limiting and the toxic effects of some of the metabolites produced. Despite that chlorpyrifos is frequently used and often in larger amounts on tropical soils compared with temperate soils, higher temperature, moderate moisture and high activity of soil microorganisms will stimulate degradation and mineralization.

Nitrogen amended graphene catalyses fast reduction of vinyl chloride by nano zerovalent iron.

Vinyl chloride (VC) is a dominant carcinogenic residual in many aged chlorinated solvent plumes, and it remains a huge challenge to clean it up. Zerovalent iron (ZVI) is an effective reductant for many chlorinated compounds but shows low VC removal efficiency at field scale. Amendment of ZVI with a carbonaceous material may be used to both preconcentrate VC and facilitate redox reactions. In this study, nitrogen-doped graphene (NG) produced by a simple co-pyrolysis method using urea as nitrogen (N) source, was tested as a catalyst for VC reduction by nanoscale ZVI (nZVI). The extent of VC reduction to ethylene in the presence of 2 g/L of nZVI was less than 1% after 3 days, and barely improved with the addition of 4 g/L of graphene. In contrast, with amendment of nZVI with NG produced at pyrolysis temperature (PT) of 950 °C, the VC reduction extent increased more than 10-fold to 69%. The reactivity increased with NG PT increasing from 400 °C to an optimum at 950 °C, and it increased linearly with NG loadings. Interestingly, N dosage had little effect on reactivity if NG was produced at PT of 950 °C, while a positive correlation was observed for NG produced at PT of 600 °C. XPS and Raman analyses revealed that for NG produced at lower PT (<800 °C) mainly the content of pyridine-N-oxide (PNO) groups correlates with reactivity, while for NG produced at higher PT up to 950 °C, reactivity correlates mainly with N induced structural defects in graphene. The results of quenching and hydrogen yield experiments indicated that NG promote reduction of VC by storage of atomic hydrogen, thus increasing its availability for VC reduction, while likely also enabling electron transfer from nZVI to VC. Overall, these findings demonstrate effective chemical reduction of VC by a nZVI-NG composite, and they give insights into the effects of N doping on redox reactivity and hydrogen storage potential of carbonaceous materials.

Phosphorus doped cyanobacterial biochar catalyzes efficient persulfate oxidation of the antibiotic norfloxacin.

In this study, cyanobacterial biochars (CBs) enriched/doped with non-metallic elements were prepared by pyrolysis of biomass amended with different N, S, and P containing compounds. Their catalytic reactivity was tested for persulfate oxidation of the antibiotic norfloxacin (NOR). N and S doping failed to improve CB catalytic reactivity, while P doping increased reactivity 5 times compared with un-doped biochar. Biochars produced with organic phosphorus dopants showed the highest reactivity. Post-acid-washing improved catalytic reactivity. In particular, 950 ℃ acid-washed triphenyl-phosphate doped CB showed the largest degradation rate and reached 79% NOR mineralization in 2 h. Main attributes for P-doped CBs high reactivity were large specific surface areas (up to 655 m2/g), high adsorption, high C-P-O content, graphitic P and non-radical degradation pathway (electron transfer). This study demonstrates a new way to reuse waste biomass by producing efficient P-doped metal-free biochars and presents a basic framework for designing carbon-based catalysts for organic pollutant degradation.

Efficient dechlorination of carbon tetrachloride by hydrophobic green rust intercalated with dodecanoate anions.

The reductive dechlorination of carbon tetrachloride (CT) by Fe(II)-Fe(III) hydroxide (green rust) intercalated with dodecanoate, Fe(II)(4)Fe(III)(2)(OH)(12)(C(12)H(23)O(2))(2) · yH(2)O (designated GR(C12)), at pH ~ 8 and at room temperature was investigated. CT at concentration levels similar to those found in heavily contaminated groundwater close to polluted industrial sites (14-988 µM) was reduced mainly to the fully dechlorinated products carbon monoxide (CO, yields >54%) and formic acid (HCOOH, yields >6%). Minor formation of chloroform (CF), the only chlorinated degradation product, was also detected (yields <6.3%). Reactions carried out with excess GR followed pseudo first-order kinetics with respect to CT with rate constants ranging from 6.5 × 10(-2) to 0.47 h(-1). These rate constants are comparable to those measured for CT dechlorinations mediated by zerovalent iron. Reduction of the highest concentration of CT (1.4 mM) proceeds until 56% of the Fe(II) sites of GR(C12) was consumed. This reaction ceased after 10 h due to surface passivation of GR(C12).

Time course of optic nerve sheath dilation: In vitro response characteristics to controlled pressure elevations.

BACKGROUND: Optic nerve sheath (ONS) dilation indicates intracranial pressure elevation under clinical conditions but limited data exist with regard to the dynamics of sheath expansion. OBJECTIVE: To assess the time course of ONS widening and its stability under controlled pressure conditions in vitro. METHODS: Pre-defined pressure steps up to 65 mmHg were applied to the perineural space of ex-vivo human optic nerves (n = 16). Using ultrasound, the optic nerve sheath diameter (ONSD) was monitored over 500 s. Re-tests at low-pressure levels concluded each experimental series. RESULTS: In most cases, 50% of the total diameter-change were achieved within 50 s after pressure onset and 95% of the maximal diameter after 200 s. The diametric gains in each experiment were strongly correlated with the applied pressure levels (coefficient of variance 0,96) within preparations with variability of the transfer function across preparations. The time course of the dilation was found to follow an approximate natural logarithmic function (R2 = 0.93-0.99). The re-test condition revealed unchanged time course properties (5% significance level) despite starting regularly from a higher baseline-diameter after preceding exposures. CONCLUSIONS: ONS dilation commences rapidly after pressure exposure with a predictable time course over 3-4 min. Elasticity changes presumably affecting trabecular structures cause upward shifts of the optic nerve sheath pressure response. Clinically, ONSD shifts should be considered in serial measurements for increasing intracranial pressure monitoring, but relevant response delays are absent for lower or higher changes of intracranial pressure.

[Pitfalls in the diagnosis of delirium]. / Fallstricke in der Diagnostik des Delirs.

BACKGROUND: The diagnosis of delirium is challenging and requires precise definitions in both clinical routine and in studies. AIM: To point out various pitfalls in the clinical diagnosis of delirium and discuss solutions. METHODS: Review. RESULTS: Common problems include (a) clinical judgment of staff vs. the use of valid assessment tools, (b) different lists of criteria for delirium that may consider the symptoms of delirium differently and thus lead to inclusion or exclusion of patients, (c) different assessment tools that test the symptoms of delirium to different extents and thus have different accuracy, (d) patients with limited communication abilities, such as aphasia, where common tests often fail and alternative procedures may be more effective; (e) the decision whether to test delirium once, twice, three times, or more frequently in 24 h has consequences on the incidence and duration of delirium, (f) the end of delirium, often defined retrospectively as a delirium-free interval or prospectively as the time of transfer or occurrence of an exclusion criterion, can lead to considerable measurement inaccuracies. CONCLUSIONS: Although not all problems can be definitively answered, transparent definition, performance, and documentation of diagnostic procedures are recommended.