Alternative routine for reporting chiral amphetamine test results in assessment of attention-deficit/hyperactivity disorder medication: experiences from 2013 to 2023.

This study evaluated an alternative routine for reporting urinary chiral amphetamine results in assessment of attention-deficit/hyperactivity disorder (ADHD) treatment with amphetamine medications and for detecting side-use of illicit racemic amphetamine. Currently in Sweden, only enantiopure d-amphetamine-based ADHD medications (lisdexamphetamine dimesylate and dexamphetamine sulfate) are approved. It is therefore unsuitable to express the chiral result as the l/d-ratio, as before, because l-amphetamine should not be present provided treatment compliance. A new routine for LC-MS/MS chiral amphetamine testing was therefore introduced in 2020, whereby the relative proportion (%) of l-amphetamine and the total amphetamine and creatinine concentrations are reported. Evaluation of the new routine on 24,354 results from 2013 to 2023 revealed that it was useful to distinguish ADHD medication adherence from illicit drug use as the source for a positive test. The l-amphetamine proportion also reflected the enantiomeric content of the medications used. Overall, most results confirmed adherence to ADHD medication, as the l-amphetamine percentage was <1% in 76% of samples (2023) which is the recommended cutoff with enantiopure d-amphetamine medications. However, in all years, illicit drug use was indicated (>40% l-amphetamine) in 8.3%-14.5% of cases. In conclusion, this study demonstrated the clinical value and utility of a new routine for reporting urinary chiral amphetamine results to differentiate adherence to ADHD medication from illicit drug use. Unlike the l/d-amphetamine ratio, it considers differences in total amphetamine concentration and urine dilution, factors that can affect the interpretation.

Appearance of hexahydrocannabinols as recreational drugs and implications for cannabis drug testing - focus on HHC, HHC-P, HHC-O and HHC-H.

This study investigated the effects of hexahydrocannabinol (HHC) and other unclassified cannabinoids, which were recently introduced to the recreational drug market, on cannabis drug testing in urine and oral fluid samples. After the appearance of HHC in Sweden in 2022, the number of posts about HHC on an online drug discussion forum increased significantly in the spring of 2023, indicating increased interest and use. In parallel, the frequency of false positive screening tests for tetrahydrocannabinol (THC) in oral fluid, and for its carboxy metabolite (THC-COOH) in urine, rose from <2% to >10%. This suggested that HHC cross-reacted with the antibodies in the immunoassay screening, which was confirmed in spiking experiments with HHC, HHC-COOH, HHC acetate (HHC-O), hexahydrocannabihexol (HHC-H), hexahydrocannabiphorol (HHC-P), and THC-P. When HHC and HHC-P were classified as narcotics in Sweden on 11 July 2023, they disappeared from the online and street shops market and were replaced by other unregulated variants (e.g. HHC-O and THC-P). In urine samples submitted for routine cannabis drug testing, HHC-COOH concentrations up to 205 (mean 60, median 27) µg/L were observed. To conclude, cannabis drug testing cannot rely on results from immunoassay screening, as it cannot distinguish between different tetra- and hexahydrocannabinols, some being classified but others unregulated. The current trend for increased use of unregulated cannabinols will likely increase the proportion of positive cannabis screening results that need to be confirmed with mass spectrometric methods. However, the observed cross-reactivity also means a way to pick up use of new cannabinoids that otherwise risk going undetected.

Neural electrophysiological correlates of detection and identification awareness.

Humans have conscious experiences of the events in their environment. Previous research from electroencephalography (EEG) has shown visual awareness negativity (VAN) at about 200 ms to be a neural correlate of consciousness (NCC). However, when considering VAN as an NCC, it is important to explore which particular experiences are associated with VAN. Recent research proposes that VAN is an NCC of lower-level experiences (detection) rather than higher-level experiences (identification). However, previous results are mixed and have several limitations. In the present study, the stimulus was a ring with a Gabor patch tilting either left or right. On each trial, subjects rated their awareness on a three-level perceptual awareness scale that captured both detection (something vs. nothing) and identification (identification vs. something). Separate staircases were used to adjust stimulus opacity to the detection threshold and the identification threshold. Bayesian linear mixed models provided extreme evidence (BF10 = 131) that VAN was stronger at the detection threshold than at the identification threshold. Mean VAN decreased from [Formula: see text]2.12 microV [[Formula: see text]2.86, [Formula: see text]1.42] at detection to [Formula: see text]0.46 microV [[Formula: see text]0.79, [Formula: see text]0.11] at identification. These results strongly support the claim that VAN is an NCC of lower-level experiences of seeing something rather than of higher-level experiences of specific properties of the stimuli. Thus, results are consistent with recurrent processing theory in that phenomenal visual consciousness is reflected by VAN. Further, results emphasize that it is important to consider the level of experience when searching for NCC.

AraC interacts with p75NTR transmembrane domain to induce cell death of mature neurons.

Cytosine arabinoside (AraC) is one of the main therapeutic treatments for several types of cancer, including acute myeloid leukaemia. However, after a high-dose AraC chemotherapy regime, patients develop severe neurotoxicity and cell death in the central nervous system leading to cerebellar ataxia, dysarthria, nystagmus, somnolence and drowsiness. AraC induces apoptosis in dividing cells. However, the mechanism by which it leads to neurite degeneration and cell death in mature neurons remains unclear. We hypothesise that the upregulation of the death receptor p75NTR is responsible for AraC-mediated neurodegeneration and cell death in leukaemia patients undergoing AraC treatment. To determine the role of AraC-p75NTR signalling in the cell death of mature neurons, we used mature cerebellar granule neurons' primary cultures from p75NTR knockout and p75NTRCys259 mice. Evaluation of neurite degeneration, cell death and p75NTR signalling was done by immunohistochemistry and immunoblotting. To assess the interaction between AraC and p75NTR, we performed cellular thermal shift and AraTM assays as well as Homo-FRET anisotropy imaging. We show that AraC induces neurite degeneration and programmed cell death of mature cerebellar granule neurons in a p75NTR-dependent manner. Mechanistically, Proline 252 and Cysteine 256 residues facilitate AraC interaction with the transmembrane domain of p75NTR resulting in uncoupling of p75NTR from the NFκB survival pathway. This, in turn, exacerbates the activation of the cell death/JNK pathway by recruitment of TRAF6 to p75NTR. Our findings identify p75NTR as a novel molecular target to develop treatments for counteract AraC-mediated cell death of mature neurons.

Auditory pseudoword rhyming effects in bilingual children reflect second language proficiency: An ERP study.

This study investigated second language (L2-English) phonological processing in 31 Spanish-English bilingual, 6- to 8-year-old schoolchildren in an event-related potential (ERP) auditory pseudoword rhyming paradigm. In addition, associations between ERP effects and L2 proficiency as measured by standardized tests of receptive language and receptive vocabulary were explored. We found a classic posterior ERP rhyming effect that was more widely distributed in children with higher L2 proficiency in group analyses and was larger for children with better L2 proficiency in correlation analyses. In contrast, the amplitude of an early (75-125 ms) auditory positivity was larger in children with lower L2 proficiency. This pattern suggests differential use of early and late auditory/phonological processing resources in the pseudoword rhyme task associated with L2 proficiency, which is consistent with the predictions of the lexical restructuring model in a bilingual context.

Brain responses to negated and affirmative meanings in the auditory modality.

Negation is frequently used in natural language, yet relatively little is known about its processing. More importantly, what is known regarding the neurophysiological processing of negation is mostly based on results of studies using written stimuli (the word-by-word paradigm). While the results of these studies have suggested processing costs in connection to negation (increased negativities in brain responses), it is difficult to know how this translates into processing of spoken language. We therefore developed an auditory paradigm based on a previous visual study investigating processing of affirmatives, sentential negation (not), and prefixal negation (un-). The findings of processing costs were replicated but differed in the details. Importantly, the pattern of ERP effects suggested less effortful processing for auditorily presented negated forms (restricted to increased anterior and posterior positivities) in comparison to visually presented negated forms. We suggest that the natural flow of spoken language reduces variability in processing and therefore results in clearer ERP patterns.

Semantic processing of verbal narratives compared to semantic processing of visual narratives: an ERP study of school-aged children.

There is a misconception that pictures are easy to comprehend, which is problematic in pedagogical practices that include pictures. For example, if a child has difficulties with verbal narration to picture sequences, it may be interpreted as specific to spoken language even though the child may have additional difficulties with comprehension of visual narratives in the form of picture sequences. The purpose of the present study was therefore to increase our understanding of semantic processing in the pictorial domain in relation to semantic processing in the verbal domain, focusing on 9-13 years-old children with typical language development. To this end, we measured electrical brain responses (event related potentials, ERPs) in 17 children to (i) pictures (panels) that were predicted versus unpredicted in sequences of panels that conveyed visual narratives and (ii) words that were predicted versus unpredicted in sentences that conveyed verbal narratives. Results demonstrated similarities as there were no significant difference in the magnitude of the N400 effect across domains. The only difference between domains was the predicted difference in distribution, that is, a more posterior N400 effect in the verbal domain than in the pictorial domain. The study contributes to an increased understanding of the complexity of processing of visual narratives and its shared features with processing of verbal narratives, which should be considered in pedagogical practices.

First Language Matters: Event-Related Potentials Show Crosslinguistic Influence on the Processing of Placement Verb Semantics.

Second language (L2) learners experience challenges when word meanings differ across L1 and L2, and often display crosslinguistic influence (CLI) in speech production. In contrast, studies of online comprehension show more mixed results. Therefore, this study explored how L2 learners process fine-grained L2 verb semantics in the domain of caused motion (placement) and specifically the impact of having similar vs. non-similar semantics in the L1 and L2. Specifically, we examined English (20) and German (21) L2 learners of Swedish and native Swedish speakers (16) and their online neurophysiological processing and offline appropriateness ratings of three Swedish placement verbs obligatory for placement supported from below: sätta "set," ställa "stand," and lägga "lay." The learners' L1s differed from Swedish in that their placement verbs either shared or did not share semantic characteristics with the target language. English has a general placement verb put, whereas German has specific verbs similar but not identical to Swedish, stellen "set/stand" and legen "lay." Event-related potentials (ERPs) were recorded while participants watched still frames (images) of objects being placed on a table and listened to sentences describing the event with verbs that either matched the image or not. Participants also performed an offline appropriateness rating task. Both tasks suggested CLI. English learners' appropriateness ratings of atypical verb use differed from those of both native Swedish speakers' and German learners, with no difference in the latter pair. Similarly, German learners' ERP effects were more similar to those of the native Swedish speakers (increased lateral negativity to atypical verb use) than to those of the English learners (increased positivity to atypical verb use). The results of this explorative study thus suggest CLI both offline and online with similarity between L1 and L2 indicating more similar processing and judgments, in line with previous production findings, but in contrast to previous ERP work on semantic L2 processing.

Convergent dopamine and ALK4 signaling to PCBP1 controls FosB alternative splicing and cocaine behavioral sensitization.

ΔfosB is an alternatively spliced product of the FosB gene that is essential for dopamine-induced reward pathways and that acts as a master switch for addiction. However, the molecular mechanisms of its generation and regulation by dopamine signaling are unknown. Here, we report that dopamine D1 receptor signaling synergizes with the activin/ALK4/Smad3 pathway to potentiate the generation of ΔFosB mRNA in medium spiny neurons (MSNs) of the nucleus accumbens (NAc) via activation of the RNA-binding protein PCBP1, a regulator of mRNA splicing. Concurrent activation of PCBP1 and Smad3 by D1 and ALK4 signaling induced their interaction, nuclear translocation, and binding to sequences in exon-4 and intron-4 of FosB mRNA. Ablation of either ALK4 or PCBP1 in MSNs impaired ΔFosB mRNA induction and nuclear translocation of ΔFosB protein in response to repeated co-stimulation of D1 and ALK4 receptors. Finally, ALK4 is required in NAc MSNs of adult mice for behavioral sensitization to cocaine. These findings uncover an unexpected mechanism for ΔFosB generation and drug-induced sensitization through convergent dopamine and ALK4 signaling.

Native Word Order Processing Is Not Uniform: An ERP Study of Verb-Second Word Order.

Studies of native syntactic processing often target phrase structure violations that do not occur in natural production. In contrast, this study examines how variation in basic word order is processed, looking specifically at structures traditionally labelled as violations but that do occur naturally. We examined Swedish verb-second (V2) and verb-third (V3) word order processing in adult native Swedish speakers, manipulating sentence-initial adverbials (temporal idag 'today', spatial hemma 'at home' and sentential kanske 'maybe') in acceptability judgements, in simultaneously recorded event-related potentials (ERP) to visually presented sentences and in a written sentence completion task. An initial corpus study showed that the adverbials differ in frequency in fronted position (idag > kanske > hemma), and although all occur mainly with V2 word order, kanske occurs more frequently with V3 in natural production than both idag and hemma. The experimental results reflected these patterns such that V2 sentences were overall more frequently produced and were deemed more acceptable than V3 sentences. The ERP results consisted of a biphasic N400/P600 response to V3 word order that indicated effects of word retrieval and sentence reanalysis. We also found consistent effects of adverbials. As predicted, V3 was produced more frequently and judged as more acceptable in Kanske sentences than in sentences with the other two adverbials. The ERP analyses showed stronger effects for idag and hemma with V3, especially regarding the P600. The results suggest that the naturally occurring word order 'violation', V3 with kanske, is processed differently than V3 with other adverbials where the V2 norm is stronger. Moreover, these patterns are related to individuals' own production patterns. Overall, the results suggest a more varied native word order processing than previously reported.

Analytical and medico-legal problems linked to the presence of delta-8-tetrahydrocannabinol (delta-8-THC): Results from urine drug testing in Sweden.

During routine urine drug testing for cannabis use targeting delta-9-tetrahydrocannabinol carboxylic acid (delta-9-THC-COOH) at the Karolinska University Laboratory in Sweden, an unknown interfering peak was observed in the liquid-chromatographic-tandem mass-spectrometric (LC-MS/MS) confirmative analysis. The peak showed the same exact mass and most abundant fragments as delta-9-THC-COOH but a slightly shorter retention time, thereby not fulfilling all requirements for a positive identification. The analytical results suggested that it was a similar compound, and with access to reference material, it could be identified as the double bond isomer delta-8-THC-COOH. Delta-8-THC has recently become popular as a recreational drug, although its legality varies and is sometimes unclear. In Sweden, all THC isomers are classified substances. The slight difference in retention times was sufficient to distinguish the THC-COOH isomers in the routine LC-MS/MS method, but another LC method allowed better peak separation and individual quantification. At the Karolinska University Laboratory, delta-8-THC-COOH was first observed in April 2020, and the highest incidence was noted in June 2020 when it was present in 5.3% of all THC-COOH-positive samples. The incidence later decreased to today only occasional findings. Large differences in the relative presence of the isomers in the urine samples indicated different origin, for example, synthetically produced pure delta-8-THC, or mixtures of both THC isomers formed during combustion of cannabidiol (CBD). In conclusion, the appearance of delta-8-THC and other isomers on the recreational drug market risks causing analytical and medico-legal problems, due to confusion with delta-9-THC.

Adult medial habenula neurons require GDNF receptor GFRα1 for synaptic stability and function.

The medial habenula (mHb) is an understudied small brain nucleus linking forebrain and midbrain structures controlling anxiety and fear behaviors. The mechanisms that maintain the structural and functional integrity of mHb neurons and their synapses remain unknown. Using spatiotemporally controlled Cre-mediated recombination in adult mice, we found that the glial cell-derived neurotrophic factor receptor alpha 1 (GFRα1) is required in adult mHb neurons for synaptic stability and function. mHb neurons express some of the highest levels of GFRα1 in the mouse brain, and acute ablation of GFRα1 results in loss of septohabenular and habenulointerpeduncular glutamatergic synapses, with the remaining synapses displaying reduced numbers of presynaptic vesicles. Chemo- and optogenetic studies in mice lacking GFRα1 revealed impaired circuit connectivity, reduced AMPA receptor postsynaptic currents, and abnormally low rectification index (R.I.) of AMPARs, suggesting reduced Ca2+ permeability. Further biochemical and proximity ligation assay (PLA) studies defined the presence of GluA1/GluA2 (Ca2+ impermeable) as well as GluA1/GluA4 (Ca2+ permeable) AMPAR complexes in mHb neurons, as well as clear differences in the levels and association of AMPAR subunits with mHb neurons lacking GFRα1. Finally, acute loss of GFRα1 in adult mHb neurons reduced anxiety-like behavior and potentiated context-based fear responses, phenocopying the effects of lesions to septal projections to the mHb. These results uncover an unexpected function for GFRα1 in the maintenance and function of adult glutamatergic synapses and reveal a potential new mechanism for regulating synaptic plasticity in the septohabenulointerpeduncular pathway and attuning of anxiety and fear behaviors.

Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.

The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection. Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum. The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow. While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process. The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane. We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane. Our results indicate that for all the proteins tested, transmembranes (TMs) 1 and 3 integrate into the membrane, so that the protein assumes an overall topology of Ncyt-Ccyt. We also show that the segment predicted to be TM2 for each of the proteins likely does not reside in the membrane, but is translocated to the lumen.

ALK4 coordinates extracellular and intrinsic signals to regulate development of cortical somatostatin interneurons.

Although the role of transcription factors in fate specification of cortical interneurons is well established, how these interact with extracellular signals to regulate interneuron development is poorly understood. Here we show that the activin receptor ALK4 is a key regulator of the specification of somatostatin interneurons. Mice lacking ALK4 in GABAergic neurons of the medial ganglionic eminence (MGE) showed marked deficits in distinct subpopulations of somatostatin interneurons from early postnatal stages of cortical development. Specific losses were observed among distinct subtypes of somatostatin+/Reelin+ double-positive cells, including Hpse+ layer IV cells targeting parvalbumin+ interneurons, leading to quantitative alterations in the inhibitory circuitry of this layer. Activin-mediated ALK4 signaling in MGE cells induced interaction of Smad2 with SATB1, a transcription factor critical for somatostatin interneuron development, and promoted SATB1 nuclear translocation and repositioning within the somatostatin gene promoter. These results indicate that intrinsic transcriptional programs interact with extracellular signals present in the environment of MGE cells to regulate cortical interneuron specification.

Correction: MAG induces apoptosis in cerebellar granule neurons through p75NTR demarcating granule layer/white matter boundary.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

MAG induces apoptosis in cerebellar granule neurons through p75NTR demarcating granule layer/white matter boundary.

MAG (Myelin-associated glycoprotein) is a type I transmembrane glycoprotein expressed by Schwann cells and oligodendrocytes, that has been implicated in the control of axonal growth in many neuronal populations including cerebellar granule neurons (CGNs). However, it is unclear whether MAG has other functions in central nervous system, in particular, in cerebellar development and patterning. We find that MAG expression in the cerebellum is compartmentalised resulting in increased MAG protein levels in the cerebellar white matter. MAG induces apoptosis in developing CGNs through p75NTR signalling. Deletion of p75NTR in vivo reduced the number of apoptotic neurons in cerebellar white matter during development leading to reduction in the size of white matter in the adulthood. Furthermore, we show that MAG impairs CGNs neurite outgrowth as consequence of MAG-induced apoptosis in CGNs. Mechanistically, we find that MAG/NgR1-induced cell death is dependent of p75NTR-mediated activation of JNK/cell death signalling pathway. Together, these findings identify the mechanisms by which MAG induces CGNs apoptotic activity, a crucial event that facilitates cerebellar layer refinement during development.

Development of parallel reaction monitoring assays for cerebrospinal fluid proteins associated with Alzheimer's disease.

Detailed knowledge of protein changes in cerebrospinal fluid (CSF) across healthy and diseased individuals would provide a better understanding of the onset and progression of neurodegenerative disorders. In this study, we selected 20 brain-enriched proteins previously identified in CSF by antibody suspension bead arrays (SBA) to be potentially biomarkers for Alzheimer's disease (AD) and verified these using an orthogonal approach. We examined the same set of 94 CSF samples from patients affected by AD (including preclinical and prodromal), mild cognitive impairment (MCI), non-AD dementia and healthy individuals, which had previously been analyzed by SBA. Twenty-eight parallel reaction monitoring (PRM) assays were developed and 13 of them could be validated for protein quantification. Antibody profiles were verified by PRM. For seven proteins, the antibody profiles were highly correlated with the PRM results (r > 0.7) and GAP43, VCAM1 and PSAP were identified as potential markers of preclinical AD. In conclusion, we demonstrate the usefulness of targeted mass spectrometry as a tool for the orthogonal verification of antibody profiling data, suggesting that these complementary methods can be successfully applied for comprehensive exploration of CSF protein levels in neurodegenerative disorders.

Anterior and posterior erp rhyming effects in 3- to 5-year-old children.

During early literacy skills development, rhyming is an important indicator of the phonological precursors required for reading. To determine if neural signatures of rhyming are apparent in early childhood, we recorded event-related potentials (ERPs) from 3- to 5-year-old, preliterate children (N = 62) in an auditory prime-target nonword rhyming paradigm (e.g., bly-gry, blane-vox). Overall, nonrhyming targets elicited a larger negativity (N450) than rhyming targets over posterior regions. In contrast, rhyming targets elicited a larger negativity than nonrhyming targets over fronto-lateral sites. The amplitude of the two rhyming effects was correlated, such that a larger posterior effect occurred with a smaller anterior effect. To determine whether these neural signatures of rhyming related to phonological awareness, we divided the children into two groups based on phonological awareness scores while controlling for age and socioeconomic status. The posterior rhyming effect was stronger and more widely distributed in the group with better phonological awareness, whereas differences between groups for the anterior effect were small and not significant. This pattern of results suggests that the rhyme processes indexed by the anterior effect are developmental precursors to those indexed by the posterior effect. Overall, these findings demonstrate early establishment of distributed neurocognitive networks for rhyme processing.

Thermal evolution of the crystal structure of proton conducting BaCe0.8Y0.2O3-δ from high-resolution neutron diffraction in dry and humid atmosphere.

The crystal structure of the proton conducting perovskite BaCe(0.8)Y(0.2)O(3-δ) (BCY20) has been studied via high-resolution in situ neutron diffraction performed in controlled dry and humid (heavy water) oxygen flow. Two phase transitions, cubic Pm3[combining macron]m→R3[combining macron]c (775 °C)→Imma (250 °C) were observed on cooling from 1000 °C in dry O(2). A significant shift of the phase stability fields was observed on cooling in wet oxygen (pD(2)O ≈ 0.2 atm) with the R3[combining macron]c structure stabilised at 900 °C, and the R3[combining macron]c→Imma transition occurring at 675 °C. On cooling below 400 °C a monoclinic, I2/m, phase started to appear. The structural dependence on hydration level is primarily due to the de-stabilisation of the correlated, octahedra tilts as a consequence of structural relaxation around the oxygen vacancies present in the non-hydrated phase. The tendency of hydrated BaCe(0.8)Y(0.2)O(3-δ) to show octahedral tilting is also found to be enhanced, indicating that the deuteronic (protonic) defects influence the crystal structure, possibly via hydrogen bonding. Stabilisation of the monoclinic I2/m phase is attributed to the structural effect of deuterons that is inferred to increase on cooling as deuterons localise to a greater extent. Changing from wet oxidising (O(2) + D2O(g)) to wet reducing (5% H2 in Ar + D2O(g)) atmosphere did not influence the structure or the phase stability, indicating that Ce(4+) was not reduced under the present conditions. Based on the observed cell volume expansion protonic defects are present in the material at 900 °C at a D(2)O partial pressure of ∼0.2 atm. The origin of the chemical expansion is explained by the effective size of the oxygen vacancy being significantly smaller than the [OD] defect. Rietveld analysis has been used to locate possible sites for the deuterons in the high temperature, R3[combining macron]c and Imma, phases that are most relevant for proton transport.

Assessment of the breath alcohol concentration in emergency care patients with different level of consciousness.

BACKGROUND: Many patients seeking emergency care are under the influence of alcohol, which in many cases implies a differential diagnostic problem. For this reason early objective alcohol screening is of importance not to falsely assign the medical condition to intake of alcohol and thus secure a correct medical assessment. OBJECTIVE: At two emergency departments, demonstrate the feasibility of accurate breath alcohol testing in emergency patients with different levels of cooperation. METHOD: Assessment of the correlation and ratio between the venous blood alcohol concentration (BAC) and the breath alcohol concentration (BrAC) measured in adult emergency care patients. The BrAC was measured with a breathalyzer prototype based on infrared spectroscopy, which uses the partial pressure of carbon dioxide (pCO2) in the exhaled air as a quality indicator. RESULT: Eighty-eight patients enrolled (mean 45 years, 53 men, 35 women) performed 201 breath tests in total. For 51% of the patients intoxication from alcohol or tablets was considered to be the main reason for seeking medical care. Twenty-seven percent of the patients were found to have a BAC of <0.04 mg/g. With use of a common conversion factor of 2100:1 between BAC and BrAC an increased agreement with BAC was found when the level of pCO2 was used to estimate the end-expiratory BrAC (underestimation of 6%, r = 0.94), as compared to the BrAC measured in the expired breath (underestimation of 26%, r = 0.94). Performance of a forced or a non-forced expiration was not found to have a significant effect (p = 0.09) on the bias between the BAC and the BrAC estimated with use of the level of CO2. A variation corresponding to a BAC of 0.3 mg/g was found between two sequential breath tests, which is not considered to be of clinical significance. CONCLUSION: With use of the expired pCO2 as a quality marker the BrAC can be reliably assessed in emergency care patients regardless of their cooperation, and type and length of the expiration.