The profiles of polar metabolites were significantly dependent on the type of the sample, while lipid profiles were similar in serum and different types of plasma. Extended storage of plasma at room temperature resulted in degradation of lipids already after 1 day. Serum clotting at room temperature generally resulted in higher metabolite concentration compared with serum clotting on ice.

A sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been developed and validated for the quantification of buprenorphine, fentanyl and lysergic acid diethylamide (LSD) in whole blood. Sample preparation was performed by liquid-liquid extraction (LLE) with methyl tert-butyl ether. UPLC-MS-MS analysis was performed with a mobile phase consisting of ammonium formate (pH 10.2) and methanol. Positive electrospray ionization MS-MS detection was performed with two multiple reaction monitoring transitions for each of the analytes and the deuterium labeled internal standards. Limit of detection values of buprenorphine, fentanyl and LSD were 0.28, 0.044 and 0.0097 ng/mL and limit of quantification values were 0.94, 0.14 and 0.036 ng/mL, respectively. Most phospholipids were removed during LLE. No or only minor matrix effects were observed. The method has been routinely used at the Norwegian Institute of Public Health since September 2011 for qualitative and quantitative detections of buprenorphine, fentanyl and/or LSD in more than 400 whole blood samples with two replicates per sample.

Aims Valid measures to identify harmful alcohol use are important. Alcohol Use Disorders Identification Test (AUDIT) is a validated questionnaire used to self-report harmful drinking in several cultures and settings. Phosphatidylethanol 16:0/18:1 (PEth) is a direct alcohol biomarker measuring alcohol consumption levels. The aim of this study was to investigate how PEth levels correlate with AUDIT-QF and weekly grams of alcohol consumed among patients in two urban hospitals. In addition, we wanted to investigate the predictive value of PEth in identifying harmful alcohol use as defined by AUDIT-QF and weekly grams of alcohol cutoffs. Methods A cross-sectional study comprising acute medically ill patients with measurable PEth levels (≥0.030 μM) admitted to two urban hospitals in Oslo, Norway (N = 931) and Moscow, Russia (N = 953) was conducted using PEth concentrations in whole blood, sociodemographic data and AUDIT-QF questionnaires. Results PEth levels from patients with measurable PEth were found to be positively correlated with AUDIT-QF scores, with PEth cutpoints of 0.128 μM (Oslo) and 0.270 μM (Moscow) providing optimal discrimination for harmful alcohol use defined by AUDIT-QF (the difference between cities probably reflecting different national drinking patterns in QF). When converting AUDIT-QF into weekly grams of alcohol consumed, the predictive value of PEth improved, with optimal PEth cutpoints of 0.327 (Oslo) and 0.396 (Moscow) μM discriminating between harmful and non-harmful alcohol use as defined in grams (≥350 grams/week). Conclusions By using PEth levels and converting AUDIT-QF into weekly grams of alcohol it was possible to get an improved rapid and sensitive determination of harmful alcohol use among hospitalized patients.

Objective: To study the association between self-reported road traffic crashes (RTCs) and recent use of alcohol, medicinal and illicit drug use and self-reported speeding the previous two years. Methods: During the period from April 2016 to April 2017, drivers of cars, vans, motorcycles and mopeds were stopped in a Norwegian roadside survey performed in collaboration with the police. Participation was voluntary and anonymous. The drivers were asked to deliver an oral fluid sample (mixed saliva), which was analyzed for alcohol and 39 illicit and medicinal drugs and metabolites. In addition, data on age, sex, and self-reported speeding tickets and RTCs during the previous two years were collected. Results: A total of 5031 participants were included in the study, and 4.9% tested positive for the use of one or more illicit or medicinal drug or alcohol. We found a significant, positive association between the use of cannabis and RTC involvement (OR=1.93, 95% CI=1.05-3.57, p=0.035) and also between previous speeding tickets and RTC involvement (OR=1.39, 95% CI=1.08-1.80, p=0.012). In addition, older age groups were found to have a significant, negative association with RTC involvement, with ORs equal to or less than 0.49, when using age group 16-24 as reference. Conclusion: Speeding, as an indicator of risk behavior, and the use of cannabis was associated with previous RTC involvement, while increasing age was significantly associated with lower risk. This is consistent with previous studies on RTCs.

AimsMutations in the cardiac myosin-binding protein C gene (MYBPC3) are the most common genetic cause of hypertrophic cardiomyopathy (HCM) worldwide. The molecular mechanisms leading to HCM are poorly understood. We investigated the metabolic profiles of mutation carriers with the HCM-causing MYBPC3-Q1061X mutation with and without left ventricular hypertrophy (LVH) and non-affected relatives, and the association of the metabolome to the echocardiographic parameters.Methods and Results34 hypertrophic subjects carrying the MYBPC3-Q1061X mutation, 19 non-hypertrophic mutation carriers and 20 relatives with neither mutation nor hypertrophy were examined using comprehensive echocardiography. Plasma was analyzed for molecular lipids and polar metabolites using two metabolomics platforms. Concentrations of branched chain amino acids, triglycerides and ether phospholipids were increased in mutation carriers with hypertrophy as compared to controls and non-hypertrophic mutation carriers, and correlated with echocardiographic LVH and signs of diastolic and systolic dysfunction in subjects with the MYBPC3-Q1061X mutation.ConclusionsOur study implicates the potential role of branched chain amino acids, triglycerides and ether phospholipids in HCM, as well as suggests an association of these metabolites with remodeling and dysfunction of the left ventricle.

ObjectivesThe use of psychoactive prescription medication is increasing in the general population. This is a cause for concern, particularly among the elderly, where physiological changes related to senescence increase the risk for adverse effects. While previous studies regarding psychoactive substance use have generally been population based, we sought to determine the frequency of such use among acutely hospitalised patients.SettingTwo emergency departments (EDs), one in Oslo and one in Moscow, admitting patients to Departments of Internal Medicine.Participants5583 patients aged ≥18 years participated, distributed evenly between genders and study locations. Patients unable to give informed consent were excluded. The study sites did not admit patients with surgical conditions and/or injuries.Primary and secondary outcomesThe presence of psychoactive substances was determined through blood analysis using liquid chromatography-mass spectrometry. Secondary outcomes comprised demographic data (including age, gender, employment and marital status), degree of psychological distress, concurrent alcohol use, and self-reported alcohol, psychoactive drug and illicit substance use.Results32.3% in Oslo and 12% in Moscow were positive for one or more psychoactive medicinal drugs (benzodiazepines, z-hypnotics, opioids or barbiturates). In Oslo, medicinal drug use was associated with being aged 61 to 70 years (OR 2.40, 95% CI 1.61 to 3.58) compared with 18 to 40 years, and psychological distress (OR 2.61, 95% CI 2.06 to 3.30). In Moscow, psychoactive medicinal drug use was also associated with psychological distress (OR 1.68, 95% CI 1.18 to 2.39), and was less common among patients aged 41 to 60 years (OR 0.62, 95% CI 0.43 to 0.88) than among patients aged 18 to 40 years.ConclusionA significant proportion of admitted patients used one or more psychoactive medicinal drugs, in particular benzodiazepines (Oslo and Moscow) and opiates (Oslo). We suggest formalised screening for inappropriate prescription drug use and increased adherence to clinical prescription guidelines.

Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid.

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