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A strategy for the optimisation of direct chiral separation of omeprazole and a metabolite, hydroxi-omeprazole, in reversed phase liquid chromatography is described. A factorial design was used, where mobile phase pH, concentration of a mobile phase modifier, ionic strength and column temperature were tested as the variables and enantioselective retention, column efficiency and asymmetry factor as the responses. The experimental results were evaluated with multivariate analyses, which demonstrated that the column temperature and content of mobile phase acetonitrile were by far the most important variables. The enantiomers of omeprazole and one of its metabolites were baseline resolved within 15 minutes. The optimised chromatographic system was used for a separation of the enantiomers of omeprazole and its main metabolite in a patient plasma sample. [ABSTRACT FROM AUTHOR]

Background: Healthcare organizations worldwide face persistent challenges relating to turnover and intention to leave the nursing profession among registered nurses. Factors contributing to their retention and well-being at work include high job satisfaction, professional competence, and self-efficacy. Few multicenter studies have investigated these factors in relation to work experience in a Nordic context. Therefore, this study aimed to investigate job satisfaction, professional competence, and self-efficacy among registered nurses., Methods: This multicenter cross-sectional study survey was part of a larger overarching Swedish-Norwegian project, and was conducted among registered nurses (n = 1137) in September 2021. The participants worked in a variety of health care units, e.g., hospital units, primary health care, and home care. Data was subjected to descriptive and comparative statistical analysis; chi-square test, one-way between-groups analysis of variance (ANOVA) and Kruskal-Wallis test., Results: The findings show that job satisfaction is reported as lowest in registered nurses with medium-term work experience as compared to newly qualified and long-term work-experienced registered nurses. Professional competence and self-efficacy are reported as higher among registered nurses with long-term work experience as compared to those with medium-term work experience and newly qualified registered nurses. However, the participants reported their professional competence as highest in relation to the same factor - "Value-based nursing care" - regardless of their work experience., Conclusions and Implications: This study underscores the need for continuous support and professional development for registered nurses throughout their careers. Proactive support for newly qualified nurses may improve job satisfaction as they progress to being registered nurses with medium-term work experience. Tailored interventions to address the distinct needs of both newly qualified and medium-term work-experienced registered nurses are crucial for nurturing a sustainable nursing workforce., (© 2024. The Author(s).)

Aerosol microparticles in exhaled breath carry non-volatile compounds from the deeper parts of the lung. When captured and analyzed, these aerosol microparticles constitute a non-invasive and readily available specimen for drugs of abuse testing. The present study aimed to evaluate a simple breath collection device in a clinical setting. The device divides a breath sample into three parallel "collectors" that can be individually analyzed. Urine was used as the reference specimen, and parallel specimens were collected from 99 patients undergoing methadone maintenance treatment. Methadone was used as the primary validation parameter. A sensitive multi-analyte method using tandem liquid chromatography - mass spectrometry was developed and validated as part of the project. The method was successfully validated for 36 analytes with a limit of detection of 1 pg/collector for most compounds. Based on the validation results tetrahydrocannabinol THC), cannabidiol (CBD), and lysergic acid diethylamide (LSD) are suitable for qualitative analysis, but all other analytes can be quantitively assessed by the method. Methadone was positive in urine in 97 cases and detected in exhaled breath in 98 cases. Median methadone concentration was 64 pg/collector. The methadone metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was detected in 90 % of the cases but below 10 pg/collector in most. Amphetamine was also present in the urine in 17 cases and in exhaled breath in 16 cases. Several other substances were detected in the exhaled breath and urine samples, but at a lower frequency. This study concluded that the device provides a specimen from exhaled breath, that is useful for drugs of abuse testing. The results show that high analytical sensitivity is needed to achieve good detectability and detection time after intake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Existing research has focused mostly on mentees' experiences of mentoring rather than mentors' experiences. Therefore, this study describes registered nurses' experiences of being a mentor for newly qualified nurses., Design: A qualitative interview study based on semistructured individual interviews. Interviews were analysed using qualitative content analysis., Participants and Setting: A purposive sample of experienced registered nurses (n=21) from healthcare units in northern Sweden and northern Norway. Inclusion criteria were to have been a mentor to at least one newly qualified nurse, hold permanent employment of 75%-100% as a registered nurse and to be able to communicate in Swedish or Norwegian., Results: Our study's findings suggest that being a mentor plays a crucial role in establishing safety in complex work environments. The main theme consists of three themes: feeling motivated in being a mentor; continuously developing the learning environment; and navigating obstacles and cultivating support., Conclusion: Being a mentor is a complicated role for registered nurses. The mentoring role is beneficial-ie, positive and rewarding-if facilitated sufficiently in the context of a structured organisation. This study brings a more profound understanding of and provides new insights into registered nurses' perspectives and needs regarding being a mentor and the study's findings make an important contribution to the field of nursing regarding the facilitation of mentoring., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Phosphatidylethanol (PEth) measurement in whole blood samples is established as a specific alcohol biomarker with clinical and forensic applications. Establishment of dried blood spots (DBSs) as a specimen for PEth determination offers several advantages and was the focus of this work. A liquid chromatography tandem mass spectrometry method using a 96-well format for sample preparation was developed and validated. PEth was extracted from DBSs by using isopropanol containing PEth-d5 as internal standard. The blood sampling used a commercial volumetric DBS device having a phosholipase D inhibitor incorporated to stop continuous PEth formation. The method quantified PEth in the range of 0.05-10 μmol/L, with a bias and imprecision of less than 15%. In a clinical study (n = 25) using fingerprick blood, the volumetric device offered more precise quantifications (CV 4.6%) compared with the Whatman 903 Protein Saver card device (CV 16.6%). In another clinical study (n = 48), the use of dried venous and capillary blood, and liquid venous blood was compared under real-life conditions with samples sent by postal service. The capillary and venous DBS samples gave identical results while the liquid blood gave slightly higher values. Calculation of elimination half-life (PEth 16:0/18:1) in 31 cases based on two consecutive samples with 2-9 days in between gave results (mean 6.2 days) that agree with literature but several cases with values over 10 days. In conclusion, this study demonstrates that volumetric DBS is a valid specimen for determination of PEth blood concentrations, offering several advantages., (© 2024 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

The prevalence of drug use among nightlife attendees needs to be accurately estimated to, for example, evaluate preventive interventions. This study tested the feasibility of using a breath-sampling device to estimate the prevalence of drug use among nightlife attendees. The study was conducted at five nightclubs and a large music festival in Stockholm, Sweden. Participants were invited to participate and microparticles in exhaled breath were sampled and analyzed for 47 compounds using a state-of-the-art analytic method that follows forensic standards. In addition, participants' breath alcohol concentration was measured and they were interviewed about demographics, drinking habits, and drug use. Of the people invited, 73.7% (n = 1223) agreed to participate, and breath samples were collected from 1204 participants. Breath sampling was fast and well-accepted by participants. 13 percent of participants tested positive for an illicit drug, but only 4.3% self-reported drug use during the last 48 h. The most common substances detected were cocaine, amphetamine, and MDMA. There was no agreement between self-reported and measured use of any drug. Breath sampling is a convenient method to test illicit drug use among a large number of participants at events, and can be used as an estimate of drug use prevalence., (© 2022. The Author(s).)

Background/aim: Solar ultraviolet radiation (UVR) is a carcinogen and irradiation of the skin results in DNA damage. Cyclobutane pyrimidine dimers (CPDs), including thymidine dimers, are among the most frequent forms of DNA damage. When CPDs are formed, the nucleotide excision repair system is activated and CPDs are excreted in the urine. Here, we developed a mass spectrometry-based method to quantify thymidine dimers in the urine and tested the method on a small group of volunteers after whole-body UVR exposure., Patients and Methods: Years of research resulted in a method based on the "dilute-and-shoot" principle and ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry. The whole body of each of eight healthy volunteers was exposed to 1.5-2.0 standard erythema doses (SEDs) of UVR for 3 consecutive days. Morning urine was collected on Day 1 (before irradiation) and on the following 7-9 days. Prior to analysis, sample preparation consisted of a simple dilution. A tandem quadrupole mass spectrometer coupled to UPLC was used for quantitative analysis in the multiple reaction monitoring mode., Results: After 3 consecutive days of 1.5-2 SEDs, the highest level of thymidine dimer excretion occurred on Day 6 (0.7 ng/ml urine). Compared with baseline, significantly more thymidine dimers were excreted every day until Day 8 (p<0.016). Our method quantifies thymidine dimers that are excreted as dimers (i.e., not degraded further) after nucleotide excision repair., Conclusion: This is the first published mass spectrometry-based method for quantifying thymidine dimers in the urine after whole-body UVR exposure., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-affinity enrichment combined with liquid chromatography-mass spectrometry (LC-MS). This is a multiplexed strategy, based on targeted proteomics analysis and read-out by LC-MS, capable of precisely quantifying and confirming the presence of SARS-CoV-2 in phosphate-buffered saline (PBS) swab media from combined throat/nasopharynx/saliva samples. The results reveal that the levels of SARS-CoV-2 measured by LC-MS correlate well with their correspondingreal-time polymerase chain reaction (RT-PCR) read-out (r = 0.79). The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with a quantitative read-out of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 21 to 34. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% negative percent agreement (estimated specificity) and 95% positive percent agreement (estimated sensitivity) when analyzing clinical samples collected from asymptomatic individuals with a Ct within the limit of detection of the mass spectrometer (Ct ≤ 30). These results suggest that a scalable analytical method based on LC-MS has a place in future pandemic preparedness centers to complement current virus detection technologies., Competing Interests: AH, KT, MU, JA, LE, FE No competing interests declared, DF, TM, JV, RP, SF, SH, IB, AB, LC employed by Waters Corporation, MR, RY, MP, TP, LA employed by SISCAPA Assay Technologies, (© 2021, Hober et al.)

The kynurenine pathway of tryptophan degradation produces several neuroactive metabolites suggested to be involved in a wide variety of diseases and disorders, however, technical challenges in reliably detecting these metabolites hampers cross-comparisons. The main objective of this study was to develop an accurate, robust and precise bioanalytical method for simultaneous quantification of ten plasma kynurenine metabolites. As a secondary aim, we applied this method on blood samples taken from healthy subjects conducting 1 session of sprint interval exercise (SIE). It is well accepted that physical exercise is associated with health benefits and reduces risks of psychiatric illness, diabetes, cancer and cardiovascular disease, but also influences the peripheral and central concentrations of kynurenines. In line with this, we found that in healthy old adults ( n  = 10; mean age 64 years), levels of kynurenine increased 1 hour ( P  = .03) after SIE, while kynurenic acid (KYNA) concentrations were elevated after 24 hours ( P  = .02). In contrast, no significant changes after exercise were seen in young adults ( n  = 10; mean age 24 years). In conclusion, the described method performs well in reliably detecting all the analyzed metabolites in plasma samples. Furthermore, we also detected an age-dependent effect on the degree by which a single intense training session affects kynurenine metabolite levels., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Aim: Kynurenine metabolites are potential modulators of psychiatric disease. We aimed to develop a highly sensitive biochemical analysis of cerebrospinal fluid (CSF) tryptophan (TRP) metabolites, to investigate the stability of metabolites and to confirm our previous findings of aberrant CSF quinolinic acid (QUIN) and picolinic acid (PIC) in suicide attempters using this method. Methodology & results: Ten CSF TRP metabolites were analyzed with ultraperformance LC-MS/MS. The method showed small intra- and interassay variation. Metabolites were stable following freeze-thaw cycles. A decreased CSF PIC/QUIN ratio was found in suicide attempters. Conclusion: The feasibility of reliably determining CSF TRP metabolites were demonstrated, including separation of the two isomers PIC and nicotinic acid (NA) and the finding of a reduced PIC/QUIN ratio replicated in suicide attempters.

The purpose of this work was to develop and evaluate a fast, robust and specific UPLC-MS/MS screening platform for the determination and quantification of a variety of commonly used drugs of abuse in urine, i.e. a high-throughput quantitative analysis. Substances in the drug classes opioids, central nervous system stimulants and benzodiazepines and related agents were included in addition to cannabis and pregabalin, a total of 35 different analytes. Based on the concentrations and the physico-chemical properties of the substances, three UPLC-MS/MS methods were developed in parallel. Prior to analysis, sample preparation consisted of two different simple dilutions with 60 and 100 μL urine, respectively, using a Tecan Freedom Evo pipetting robot platform. A Waters Xevo TQ-S tandem quadrupole mass spectrometer coupled to a Waters I-class UPLC was used for quantitative analysis of one quantitative and one qualifying MRM transition for each analyte, except for tramadol for which the metabolite O-desmethyl-tramadol was included in the MRM method to confirm tramadol identity. Deuterated analogs were included as internal standards. The between-assay relative standard deviations varied from 2% to 11% and the limits of quantification were in the range 1-200 ng/mL for the various analytes. After development and initial testing, the method has been successfully implemented and routinely used at our hospital for quantitative screening of drugs of abuse in more than 35,000 urinary samples., (Copyright © 2013 Elsevier B.V. All rights reserved.)

An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for detection of 23 benzodiazepines and related compounds in whole blood was developed and validated. The method is used for screening and quantitation of benzodiazepines in whole blood received from autopsy cases and living persons. The detected compounds were alprazolam, bromazepam, brotizolam, chlordiazepoxide, demoxepam, clobazam, clonazepam, 7-aminoclonazepam, diazepam, nordiazepam, estazolam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, lormetazepam, midazolam, nitrazepam, 7-aminonitrazepam, oxazepam, temazepam, triazolam, zaleplon, and zopiclone. Whole blood from drug-free volunteers was used for all experiments. Blood samples (0.200 g) were extracted with ethyl acetate at pH 9. Target drugs were quantified using a Waters ACQUITY UPLC system coupled to a Waters Quattro Premier XE triple quadrupole in positive electrospray ionization, multiple reaction monitoring mode. The use of deuterated internal standards for most compounds verified that the accuracy of the method was not influenced by matrix effects. Extraction recoveries were 73-108% for all analytes. Lower limits of quantification ranged from 0.002 to 0.005 mg/kg. Long-term imprecision (CV%) ranged from 6.0 to 18.7%. We present a fully validated UPLC-MS-MS method for 23 benzodiazepines in whole blood with a run-time of only 5 min and using only 0.200 g of whole blood.

From 1.1.1986-31.12.1987 we treated 78 fractures of the femoral neck with two Hansson nails in the Department of Orthopedic Surgery in the County Hospital in Roskilde. All cases were evaluated after two years. Fifteen patients had died (19.2%). Seventeen patients had had a secondary operation (21.8%). Secondary total hip replacement was performed in 19.2% of the patients, all of whom had primarily had a displaced fracture. There was one incident of deep infection, otherwise the rate of complications was low. The duration of the osteosynthesis operation was short and patients were discharged early from hospital. After two years, 31 patients were reexamined radiologically and clinically. The results were satisfactory in all cases. The method of osteosynthesis is recommended as a simple procedure with good results.

Functional and angiographic follow-up was performed in 61 patients 3.9 months (range 2-8 months) and 3.7 years (range 2-8 years) after successful transluminal coronary angioplasty. The mean degree of stenosis prior to angioplasty was 78.7% and after the procedure, 36%. After 3.9 months there was a slight increase to 39% because of 12 recurrences. In three of these patients a second angioplasty was performed; nine were continued on medical treatment because of sustained clinical benefit. After 3.7 years, the mean degree of stenosis was 29%. No patient with persistent vessel patency after 3.9 months showed an increase of the dilated stenosis of more than 15% after 3.7 years. Prior to angioplasty, 41 patients (75%) had one-vessel disease; 19 (18%) two- and 4 (7%) three-vessel disease. 2-8 years after successful angioplasty, 48% of patients showed no stenosis of greater than or equal to 50% narrowing. Progression of coronary artery disease was found in 29/61 patients at the late follow-up. Of these 29 patients, 11 underwent another angioplasty because of a new stenosis in another vessel or segment; 18 were treated medically. There was no need for bypass surgery. It is concluded that a sustained success 3.9 months after angioplasty predicts excellent long-term vessel patency.