Psychoactive substances and previous hospital admissions, triage and length of stay in rural injuries: a prospective observational study.

BACKGROUND: Patients admitted to hospital after an injury are often found to have used psychoactive substances prior to the injury. The aim of this study was to investigate the associations between psychoactive substances (alcohol, psychoactive medicinal drugs and illicit drugs) and previous hospital admissions, triage and length of stay in the arctic Norwegian county of Finnmark. METHODS: Patients ≥ 18 years admitted due to injury to trauma hospitals in Finnmark from January 2015 to August 2016 were approached. Parameters regarding admittance and hospital stay were collected from 684 patients and blood was analysed for psychoactive substances. Using a prospective, observational design, time, triage, length of stay in hospital, use of intensive care unit (ICU), injury severity, Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) and number of previous admittances were investigated by bivariable testing and logistical regression analysis. RESULTS: Of 943 patients approached, 81% consented and 684 were included in the study. During the weekend, 51.5% tested positive for any substance versus 27.1% Monday-Friday. No associations were identified between testing positive and either triage or injury severity for any substance group although triage level was lower in patients with AUDIT-C ≥ 5. Short length of stay was associated with alcohol use prior to injury [odds ratio (OR) 0.48 for staying > 12 h, confidence interval (CI) 0.25-0.90]. The OR for staying > 24 h in the ICU when positive for an illicit substance was 6.33 (CI 1.79-22.32) while negatively associated with an AUDIT-C ≥ 5 (OR 0.30, CI 0.10-0.92). Patients testing positive for a substance had more often previously been admitted with the strongest association for illicit drugs (OR 6.43 (CI 1.47-28.08), compared to patients in whom no substances were detected. CONCLUSIONS: Triage level and injury severity were not associated with psychoactive substance use. Patients using alcohol are more often discharged early, but illicit substances were associated with longer ICU stays. All psychoactive substance groups were associated with having been previously admitted.

Crash-involved THC-positive drivers in Norway have a high frequency of polysubstance use.

BACKGROUND: Tetrahydrocannabinol (THC) is the most frequently detected drug in blood samples from apprehended drug driving suspects in Norway. This investigation aimed to study the extent of polysubstance use among apprehended crash-involved drivers with THC concentrations above the legal limit and explore the importance of THC in polysubstance cases. METHODS: We selected all drug driving cases where blood samples had been submitted for forensic toxicology testing after involvement in road traffic crashes during 2013-2020, except drivers who were fatally injured. RESULTS: Twenty percent (n = 2133) of the 10,520 apprehended crash-involved drivers had concentrations of THC in their blood above the legal limit of 1.3 ng/mL, and 84 % of those also had concentrations of alcohol or other drugs above the legal limits; 61 % for sedatives, 38 % for stimulants, 33 % for alcohol, and 10 % for opioids. The most frequent substance combination was cannabis together with sedatives and stimulants (22.9 %; n = 488). Polysubstance use was least common among drivers under 24 years. The proportion of drivers with THC > 5 ng/mL was highest if the blood sample was collected within 90 min after the crash, and when only THC was detected. There was a statistically significant inverse association between THC > 5 ng/mL and concentrations of alcohol or amphetamines at the highest sanction level. CONCLUSIONS: Most apprehended crash-involved THC-positive drivers also tested positive for other psychoactive substances. Drivers with high blood THC concentrations had less often high concentrations of other substances; cannabis might then have been a more important contributor to impairment.

Comparative Study of Postmortem Concentrations of Benzodiazepines and Z-Hypnotics in Several Different Matrices.

Benzodiazepines and z-hypnotics are detected in the majority of fatal overdose cases in Norway, often in combination with other drugs of abuse, and their concentrations in peripheral blood (PB) might be important to elucidate the cause of death. In some forensic autopsies, PB is however not available. The aim of the present study was to compare concentrations of benzodiazepines and z-hypnotics in five alternative matrices to assess whether these concentrations are comparable to concentrations in PB. A total of 109 forensic autopsy cases were included. PB, cardiac blood (CB), pericardial fluid (PF), psoas muscle (PM), lateral vastus muscle (LVM) and vitreous humor (VH) from each case were analyzed using ultra high performance liquid chromatography--tandem mass spectrometry. We were able to detect clonazepam, 7-aminoclonazepam, flunitrazepam, 7-aminoflunitrazepam, nitrazepam, 7-aminonitrazepam, diazepam, nordiazepam, oxazepam, alprazolam, midazolam, zopiclone and zolpidem in all the analyzed matrices. Concentrations measured in VH were generally much lower than those of PB for all compounds except zopiclone. 7-Amino metabolite concentrations were high compared to the parent compounds, although less so for the muscle samples. Concentrations of the parent nitrobenzodiazepines in muscles were higher than those in PB, but for the other compounds, concentrations in muscle showed good correspondence with PB. Both CB and PF were viable alternative matrices for PB, although a larger variation and a tendency for higher concentrations in PF were observed. This study shows that CB, PM, LVM and PF can give comparable concentrations to PB for benzodiazepines and z-hypnotics, while VH was less suitable. The concentrations in alternative matrices must, however, be interpreted carefully.

Which illicit drugs are injected in Oslo? A study based on analysis of drug residues in used injection equipment and self-reported information.

BACKGROUND: People who inject drugs (PWID) have a high risk of premature death due to fatal overdoses. Newly emerged fentanyls, much more potent than heroin and other opioids, may increase this risk further. Therefore, precise information on injected drugs is critical to improving prevention strategies. AIMS: This study aimed to analyse drug residues in used injection equipment in order to determine drug and drug combinations and compare and complement findings with self-reported information. METHODS: Used syringes and needles (n=766) were collected at the supervised drug consumption facilities, the needle exchange service and two low-threshold health services for problem drug users in Oslo, Norway. The material was collected every third month from June 2019 to June 2020 and analysed for 64 substances using highly specific analytical methods (ultra-high performance liquid chromatography tandem mass spectrometry). Additionally, a street-recruited sample of PWID was interviewed from 2017 to 2019 regarding their drug injection habits (n=572). RESULTS: Heroin (65.5%) or amphetamines (59.8%), often in combination (30.5%), were commonly detected in drug residues. Other opioids, stimulants or benzodiazepines were rarely detected (6.1%). Fentanyl was detected in only one syringe. Heroin was the most reported drug (77.6% during the past four weeks, 48.3% daily/almost daily), followed by amphetamines (57.5% during the past four weeks, 23.1% daily or almost daily). Injection of methadone, buprenorphine and dissolved tablets was self-reported more frequently than determined in drug residue findings. CONCLUSIONS: Analysis of the injection equipment proved useful as a non-invasive, rapid and accurate means to obtain detailed information on injected drugs in Oslo and supplement traditional PWID survey information.

Systematic screening of substance use upon hospitalisation. / Systematisk kartlegging av rusbruk ved innleggelse.

Many people can improve their health by reducing their consumption of alcohol and habit-forming medications. By screening for this in connection with emergency hospital admissions, we can help to reduce use.

Deaths associated with MDMA in the period 2000-2019. / Dødsfall assosiert med MDMA i perioden 2000­19.

BACKGROUND: The use of MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, has increased in Norway in recent years. Since MDMA has the potential to be toxic and cause death, we studied whether increased availability and use correlates with the increase in MDMA-associated deaths. MATERIAL AND METHOD: The study includes post-mortems with findings of MDMA in blood, linked to information about cause of death from the Norwegian Cause of Death Registry. These data were compared with the number of arrested drug drivers with MDMA detected in their blood as well as annual seizure statistics from Kripos (The National Criminal Investigation Service) in the period 2000-2019. RESULTS: In the period 2000-2019, MDMA was detected in 142 fatalities, and the cause of death was known for 132 of these. The number of annual MDMA-associated deaths varied from 1 to 18. The median MDMA concentration among the fatalities increased from 1.9 µmol/L (interquartile range (IQR) 0.9 to 5.0) in 2000-2004 to 3.8 µmol/L (1.4 to 12.0) in 2015-2019. In 47/132 (36 %) of cases, MDMA and other central nervous system (CNS) stimulant drugs contributed to the death. Among arrested drug drivers with detected MDMA, the annual number of detected cases was 7-262 in this period, but the median concentration remained stable. INTERPRETATION: MDMA may have contributed to numerous deaths in Norway. Increased availability, increased use and increased strength of contents seem to be significant.

Concentrations of psychoactive substances in blood samples from non-fatal and fatal opioid overdoses.

AIM: The primary aim was to compare concentrations of psychoactive substances in blood in non-fatal and fatal opioid overdoses. The secondary aim was to assess the concentration levels of naloxone in blood in non-fatal overdoses and the association between naloxone findings and concomitantly detected drugs. METHOD DESIGN: Case-control study. SETTING: Norway. Fatal overdoses from 2017 and non-fatal overdoses from February 2018 to September 2019. CASES: Thirty-one non-fatal and 160 fatal opioid overdose cases. Data from the non-fatal overdoses were collected from hospital records and blood samples, and data from the fatal overdoses were collected from autopsy reports. Concentrations of psychoactive substances (including ethanol) in blood samples were collected at the time of hospital admission for the non-fatal overdoses and during autopsy for the fatal overdoses. RESULTS: The median number of different substances detected was four for fatal and five for non-fatal overdoses. The fatal overdoses had higher pooled concentrations of opioids (188 vs 57.2 ng/mL, P < .001), benzodiazepines (5467 vs 2051 ng/mL, P = .005) and amphetamines (581 vs 121 ng/mL, P < .001) than the non-fatal overdoses. A linear relationship between naloxone and concomitant pooled opioid concentrations was found (95% confidence interval = 0.002-0.135, P < .05). CONCLUSION: The total load of drug concentrations was associated with the fatal outcome of an overdose, while the number of drugs used, to a lesser extent, differentiated between those who survived and those who died from an overdose. Higher opioid concentrations were associated with treatment with higher naloxone doses.

Methadone, Buprenorphine, Oxycodone, Fentanyl and Tramadol in Multiple Postmortem Matrices.

Peripheral blood (PB) concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas, etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid (PF), muscle and vitreous humor (VH) have been suggested as alternatives to blood, but only a few studies have investigated the detection of opioids in these matrices. In this study, we aimed to investigate the detection of methadone, buprenorphine, oxycodone, fentanyl and tramadol in postmortem samples of PF, skeletal muscle and VH, in addition to PB and cardiac blood and if drug concentrations in these alternative matrices were comparable to those in PB and thereby useful for interpretation. In most of the 54 included cases, only one opioid was detected. Methadone, oxycodone, fentanyl and tramadol were detected in all of the alternative matrices in almost all cases, while buprenorphine was detected less often. For methadone, the concentrations in the alternative matrices, except in VH, were relatively similar to those in PB. Larger variations in concentrations were found for buprenorphine, oxycodone and tramadol. Quantitative analyses appeared useful for fentanyl, in all of the alternative matrices, but only four cases were included. Toxicological analyses of opioids in these alternative postmortem matrices can be useful for detection, but quantitative results must be interpreted with caution.

The alcohol marker phosphatidylethanol is closely related to AST, GGT, ferritin and HDL-C.

BACKGROUND: The aim of this study was to evaluate the quantitative relation between common clinical chemical analyses and ethanol use, measured by a combination of the two alcohol markers phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT). METHODS: Results of PEth and CDT in whole blood and serum, respectively, were included, together with information on 10 different commonly measured clinical chemical analytes, as well as age and sex. PEth was analysed by UPC2 -MS/MS and CDT was measured by capillary electrophoresis. RESULTS: Samples from 4873 patients were included. The strongest relation to alcohol consumption as measured by PEth, when correcting for age and sex, was found for HDL-C (standardized ß = 0.472, p < 0.001), AST (standardized ß = 0.372, p < 0.001), ferritin (standardized ß = 0.332, p < 0.001) and GGT (standardized ß = 0.325, p < 0.001). The relation to PEth was weak for total cholesterol, TG and ALP. No relation was found for Hb and LDL-C. CONCLUSIONS: When using PEth as a marker for alcohol consumption, this study demonstrated the quantitative relation to commonly used test as AST or GGT, but also an important relation to ferritin or HDL-C. In clinical practice, elevated levels of these clinical chemical analytes should initiate further work-up on possibly harmful alcohol use.

Multimorbidity, psychoactive substance use and psychological distress among acute medically ill patients: a cross-sectional study.

BACKGROUND: In order to target the complex health needs of patients with multimorbidity using psychoactive substances, knowledge regarding the association between substance use and multimorbidity in an acute setting is needed. AIMS: Examine psychoactive substance use patterns among acute medically ill patients, and determine the association between multimorbidity and substance use, and psychological distress. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 2874 acute medically ill patients admitted to a medical emergency department in Oslo, Norway. MEASUREMENTS: Primary outcome: multimorbidity recorded by the presence of ≥2 International Classification of Diseases 10th revision-physical and/or mental health conditions per patient, extracted from medical records. Predictor variables: self-reported data on age, sex, occupational status, psychological distress (Hopkins Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4) and results from blood samples on psychoactive medicinal and illicit drugs. FINDINGS: Of all patients, 57.2% had multimorbidity. Of these, 62.6% reported psychological distress, 85.5% consumed either alcohol, medicinal and/or illicit drugs and 64.4% combined alcohol with psychoactive medicinal drugs. Patients with risky alcohol use were more likely to have multimorbidity compared with patients with low-risk alcohol use (OR 1.53; 95% CI 1.05 to 2.24). Patients using psychoactive medicinal drugs were more likely to have multimorbidity compared with non-users (OR 1.34; 95% CI 1.07 to 1.67). CONCLUSION: Multimorbidity was associated with psychoactive medicinal drug and risky alcohol use, and psychological distress. Substance use was widespread, with alcohol and psychoactive medicinal drugs most frequently combined. Monitoring substance use among multimorbid patients is necessary to develop tailored treatments, and reduce burden on the healthcare system.

Distribution of tetrahydrocannabinol and cannabidiol in several different postmortem matrices.

Cannabis is the most widely used illicit substance worldwide. A limited number of studies have investigated whether tetrahydrocannabinol (THC) and cannabidiol (CBD) can be detected in other postmortem matrices than blood and urine. The aim of this study was to investigate the distribution of THC and CBD in several different postmortem matrices. Concentrations in peripheral blood were compared to those in cardiac blood, pericardial fluid, psoas muscle, vastus lateralis muscle, and vitreous humor. A total of 39 postmortem forensic autopsy cases were included. THC and CBD were analyzed using gas chromatography-mass spectrometry. We were able to detect both THC and CBD in most of the analyzed matrices. For vitreous humor, however, only approximately 50% of the cases were available for analysis, and only two were found to be positive. Median concentrations in peripheral blood were 0.0040 (0.00042-0.056) mg/L for THC and 0.0013 (0-0.023) mg/L for CBD. The concentration ratios between pericardial fluid and cardiac blood compared to peripheral blood were< 1 for both THC and CBD for the majority of the cases. For THC, a median ratio of 0.60 (0.063-7.2) and 0.65 (0.068-4.8) were found for pericardial fluid and cardiac blood, respectively, compared to peripheral blood, whereas for CBD the corresponding median ratios were 0.40 (0.010-1.9) and 0.80 (0.017-2.4). The THC concentrations in psoas muscle and vastus lateralis muscle were high compared to those in peripheral blood in several cases, and large variations in the muscles to peripheral blood concentration ratios were seen. This was also the case for CBD. Our study shows that THC and CBD can be detected in postmortem matrices other than peripheral blood, and results from other matrices might provide important information in forensic cases where peripheral blood is not available. However, vitreous humor was not suitable for detecting neither THC nor CBD.

Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents.

Methiopropamine is a novel psychoactive substance (NPS) that is associated with several cases of clinical toxicity, yet little information is available regarding its neuropharmacological properties. Here, we employed in vitro and in vivo methods to compare the pharmacokinetics and neurobiological effects of methiopropamine and its structural analog methamphetamine. Methiopropamine was rapidly distributed to the blood and brain after injection in C57BL/6 mice, with a pharmacokinetic profile similar to that of methamphetamine. Methiopropamine induced psychomotor activity, but higher doses were needed (Emax 12.5 mg/kg; i.p.) compared to methamphetamine (Emax 3.75 mg/kg; i.p.). A steep increase in locomotor activity was seen after a modest increase in the methiopropamine dose from 10 to 12.5 mg/kg, suggesting that a small increase in dosage may engender unexpectedly strong effects and heighten the risk of unintended overdose in NPS users. In vitro studies revealed that methiopropamine mediates its effects through inhibition of norepinephrine and dopamine uptake into presynaptic nerve terminals (IC50 = 0.47 and 0.74 µM, respectively), while the plasmalemmal serotonin uptake and vesicular uptake are affected only at high concentrations (IC50 > 25 µM). In summary, methiopropamine closely resembles methamphetamine with regard to its pharmacokinetics, pharmacodynamic effects and mechanism of action, with a potency that is approximately five times lower than that of methamphetamine.

Does the preparation for intravenous administration affect the composition of heroin injections? A controlled laboratory study.

AIMS: To study whether the preparation procedure, and its acidic and heating conditions, used by heroin users to prepare heroin for intravenous administration affects the final composition of the fluid to be injected. METHODS: Samples from different seizures of illegal heroin provided by the Norwegian police were prepared by adding water and ascorbic acid before heating under controlled conditions in the laboratory. Further, three seizures were prepared with different amounts of ascorbic or citric acid relative to their diacetylmorphine content. Pure diacetylmorphine base or salt was also submitted to the procedure applying two different heating intensities. The seizures and the final product after preparation were analysed for diacetylmorphine, 6-acetylmorphine and morphine using liquid chromatography with tandem mass spectrometry (LC-MS-MS). RESULTS: After preparation, a decrease of 19.8% (25th and 75th percentiles = -29.2 and -15.3) in the initial diacetylmorphine content was observed. Both the 6-acetylmorphine and morphine content increased but, due to their low content in the initial product, diacetylmorphine still represented 83.9% (25th and 75th percentiles = 77.3 and 88.0) of the sum of these three opioids in the final solution. The loss of water during preparation caused an increase in the concentration of diacetylmorphine, 6-acetylmorphine and morphine, depending on the heating intensity applied. The content of these opioids was affected by the quantity and type of acid added in relation to the heroin purity and the level of diacetylmorphine dissolved being proportional to the amount of ascorbic acid, but not citric acid, in the sample with high heroin purity. CONCLUSIONS: Preparation of heroin for intravenous injection appears to change the amount or concentration of diacetylmorphine and its active metabolites, 6-acetylmorphine and morphine in the final product, depending on heroin purity, amount and type of acid used or heating conditions. These circumstances can contribute to unintentional variations in the potency of the final injected solution, and therefore affect the outcome after injection.

The Association between the Alcohol Biomarker Phosphatidylethanol (PEth) and Self-Reported Alcohol Consumption among Russian and Norwegian Medical Patients.

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.

Psychoactive substances have major impact on injuries in rural arctic Norway - A prospective observational study.

BACKGROUND: Rural areas have increased injury mortality with a high pre-hospital death rate. Knowledge concerning the impact of psychoactive substances on injury occurrence is lacking for rural arctic Norway. These substances are also known to increase pre-, per- and postoperative risk. The aim was by prospective observational design to investigate the prevalence and characteristics of psychoactive substance use among injured patients in Finnmark county. METHODS: From January 2015 to August 2016, patients ≥18 years admitted to hospitals in Finnmark due to injury were approached when competent. Blood was analysed for ethanol, sedatives, opioids, hypnotics and illicit substances in consenting patients, who completed a questionnaire gathering demographic factors, self-reported use/behaviour and incident circumstances. RESULTS: In 684 injured patients who consented to participation (81% consented), psychoactive substances were detected in 35.7%, alcohol being the most prevalent (23%). Patients in whom substances were detected were more often involved in violent incidents (odds ratio 8.92 95% confidence interval 3.24-24.61), indicated harmful use of alcohol (odds ratio 3.56, 95% confidence interval 2.34-5.43), reported the incident being a fall (odds ratio 2.21, 95% confidence interval 1.47-3.33) and presented with a reduced level of consciousness (odds ratio 3.91, 95% confidence interval 1.58-9.67). Subgroup analysis revealed significant associations between testing positive for a psychoactive substance and being diagnosed with a head injury or traumatic brain injury. CONCLUSION: A significant proportion of injured patients had used psychoactive substances prior to admission. Use was associated with violence, falls, at-risk alcohol consumption, decreased level of consciousness on admittance and head injury.

Comparison of the Diagnostic Value of Phosphatidylethanol and Carbohydrate-Deficient Transferrin as Biomarkers of Alcohol Consumption.

BACKGROUND: The aim of this study was to compare the results of Phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT) in blood as biomarkers of alcohol consumption in a large clinical cohort and to evaluate concentrations in relation to age and sex. METHODS: Results of PEth 16:0/18:1 in blood and CDT in serum were included, together with information of age and sex, which were extracted from a clinical chemistry database containing samples mostly from patients of primary care physicians and social care institutions. PEth concentrations were determined using Ultra Performance Convergence chromatography mass spectrometer. CDT was quantified by electrophoretic Capillary System. CDT values ≥ 1.7 %-units and PEth values ≥ 0.31 µmol/L were considered to indicate heavy alcohol consumption. RESULTS: Samples from 6705 patients were included. The median age was 54.5 years, and 34 % were females. Only 47 % of the patients with PEth ≥ 0.31 µmol/L had increased CDT ≥ 1.7 %-units examined in the same specimen (Cohen's kappa was 0.43, p < 0.001). Patients above 50 years had significantly higher concentrations for both CDT (1.0 %-units vs. 0.9 %-units, p < 0.001) and PEth (0.340 µmol/L vs. 0.200 µmol/L, p < 0.001) compared with younger patients. Concentrations of CDT were significantly higher in males compared with females (p = 0.002), while no significant sex differences were seen for PEth (p = 0.465). CONCLUSIONS: A high fraction of the patients had PEth values above the suggested cutoff for heavy drinking and normal CDT values, verifying the superior sensitivity of PEth compared with CDT. The effect of age seems to be minor for both markers. Higher concentrations of CDT, but not PEth, were seen in males, indicating that PEth, as opposed to CDT, might be formed equally in men and women. Therefore, the bias due to sex is possibly present only for CDT, not for PEth.

Prevalence of psychoactive substance use among acutely hospitalised patients in Oslo and Moscow: a cross-sectional, observational study.

OBJECTIVES: The 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. SETTING: Two emergency departments (EDs), one in Oslo and one in Moscow, admitting patients to Departments of Internal Medicine. PARTICIPANTS: 5583 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 OUTCOMES: The 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. RESULTS: 32.3% 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. CONCLUSION: A 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.

Post-mortem toxicological analyses of blood samples from 107 patients receiving opioid agonist treatment: substances detected and pooled opioid and benzodiazepine concentrations.

AIMS: To present the substances and their concentrations detected post-mortem in patients receiving opioid agonist treatment (OAT) stratified by cause of death, estimate the pooled opioid and benzodiazepine concentrations using established conversion factors for blood concentrations from the Norwegian Road Traffic Act, and explore the association between drug-induced cause of death and the pooled opioid and benzodiazepine concentrations. DESIGN: Cross-sectional nationwide study. SETTING: Norway. PARTICIPANTS: One hundred and seven patients who died during OAT (i.e. within 5 days after the last intake of OAT medication) between 1 January 2014 and 31 December 2015, with post-mortem femoral blood available for toxicology. Data were collected from hospital records, the Norwegian Cause of Death Registry and autopsy reports. MEASUREMENTS: Presence of alcohol and non-alcohol substances in the bloodstream at time of death, determined through records of toxicology of post-mortem femoral blood. FINDINGS: A median of four substances was detected across the causes of death. At least one benzodiazepine was detected in 81 (76%) patients. The median pooled opioid concentration was significantly higher in drug-induced deaths compared with other causes of death (362 ng/mL versus 182 ng/mL, P < 0.001), in contrast to the pooled benzodiazepine concentration (5466 versus 5701 ng/mL, P = 0.353). The multivariate regression analysis showed that only increasing pooled opioid concentration (ng/ML) was associated with increased odds of a drug-induced cause of death (odds ratio, 1.003; 95% confidence interval: 1.001-1.006). CONCLUSIONS: In Norway, overall opioid concentration seems to play an important role in drug-induced deaths during opioid agonist treatment in patients prescribed methadone or buprenorphine. Patients prescribed buprenorphine tend to replace their agonist with full agonists, while patients prescribed methadone tend to have high opioid concentrations from methadone as the only opioid.

Determination of anticoagulant rodenticides in faeces of exposed dogs and in a healthy dog population.

BACKGROUND: Exposure to anticoagulant rodenticides (ARs) in dogs is among the most common causes of poisoning in small animal practice, but information about toxicokinetic of these rodenticides in dogs is lacking. We analysed blood and faeces from five accidentally exposed dogs and 110 healthy dogs by reversed phase ultra-high performance liquid chromatography-tandem mass spectrometry. The aim of the study was to estimate elimination of brodifacoum, bromadiolone and difenacoum after acute exposure, calculate the half-lives of these rodenticides in dogs, estimate faecal elimination in a litter of puppies born, and further to identify the extent of AR exposure in a healthy dog population. RESULTS: Three dogs were included after single ingestions of brodifacoum; two dogs ingested bromadiolone and one dog ingested difenacoum. Maximum concentrations in faeces were found after day 2-3 for all ARs. The distribution half-lives were 1-10 days for brodifacoum, 1-2 days for bromadiolone and 10 days for difenacoum. Brodifacoum and difenacoum had estimated terminal half-lives of 200-330 days and 190 days, respectively. In contrast, bromadiolone had an estimated terminal half-life of 30 days. No clinical signs of poisoning or coagulopathy were observed in terminal elimination period. In blood, the terminal half-life of brodifacoum was estimated to 8 days. Faeces from a litter of puppies born from one of the poisoned dogs were examined, and measurable concentrations of brodifacoum were detected in all samples for at least 28 days after parturition. A cross-sectional study of 110 healthy domestic dogs was performed to estimate ARs exposure in a dog population. Difenacoum was detected in faeces of one dog. Blood and faecal samples from the remaining dogs were negative for all ARs. CONCLUSIONS: Based on the limited pharmacokinetic data from these dogs, our results suggest that ARs have a biphasic elimination in faeces using a two-compartment elimination kinetics model. We have shown that faecal analysis is suitable and reliable for the assessment of ARs exposure in dogs and a tool for estimating the AR half-lives. Half-lives of ARs could be a valuable indicator in the exposed dogs and provides important information for veterinarians monitoring AR exposure and assessment of treatment length in dogs.