Falsely low phosphatidylethanol may be associated with biomarkers of haemolytic disease.

AIMS: Falsely lower or even negative phosphatidylethanol (PEth) levels may theoretically be seen in patients with haemolytic diseases, and the present study aimed to elucidate this hypothesis. METHODS: PEth and carbohydrate-deficient transferrin (CDT) from 9893 serum and whole blood samples were included along with markers of haemolysis (i.e. haptoglobin, HbA1c, reticulocytes, LD and Hb). Cases showing discrepancy between PEth and CDT, that is, a low PEth value and a high CDT value, were considered to be possibly caused by falsely lowered PEth despite high alcohol consumption. These cases (N = 233) were compared to the control group without PEth and CDT mismatch. RESULTS: The levels of haptoglobin were significantly lower in the cases showing low PEth and high CDT (estimate = -0.62, p = 0.002). The levels of HbA1c (estimate = -3.26, p = 0.001) and Hb (estimate = -0.507, p < 0.001) were also significantly lower in this group. These findings indicate haemolytic diseases in the low PEth/high CDT group. There were no significant differences for reticulocytes and LD concentrations between the low PEth/high CDT group and the control group. CONCLUSIONS: These results indicate that falsely low PEth values could be associated with markers of haemolytic diseases, although more research is needed to highlight this further.

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.

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.

[New biomarkers for assesing alcohol consumption]. / Nye markører for påvisning av alkoholbruk.

Alcohol abuse has significant medical, social and socioeconomic consequences. Alcohol biomarkers may serve as a useful tool in identifying individuals with excessive alcohol consumption in medical as well as medico-legal contexts.

Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services.

PURPOSE: More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. METHODS: The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. FINDINGS: All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. IMPLICATIONS: The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries.

Characteristics of methadone-related fatalities in Norway.

There are currently over 7000 patients enrolled in opioid maintenance treatment (OMT) programs in Norway. A rise in methadone-related deaths proportional to increasing methadone sales over the period 2000-2006 has been observed, but the causative factors for these fatalities have been elusive. In the present study, individual characteristics, methadone concentrations and additional toxicological findings were analyzed. Methadone intoxication deaths (n = 264) were divided into 3 groups according to toxicological findings in whole blood: group 1 - methadone detected alone, or together with one additional drug at low or therapeutic levels, or a low concentration of ethanol (<1 g/L) (n = 21); group 2 - multiple additional drugs/substances detected below lethal levels (n = 175); group 3 - one or more additional drugs/substances detected at lethal levels, or ethanol >3 g/L (n = 55). Methadone blood concentrations in decedents who had been enrolled in OMT were higher than for decedents not in treatment, in all groups. Blood methadone concentrations around 1 mg/L were present in fatal multi-drug intoxications in OMT patients. Results suggest that some patients may be at risk of dying when combining therapeutic concentrations of methadone with other psychoactive substances. Somatic disease was a common finding among deceased OMT patients. Concentrations in methadone users not enrolled in OMT were predominantly between 0.3 and 0.4 mg/L and were not related to the presence of other drugs. However, methadone concentrations below 0.1 mg/L may be associated with intoxication following methadone use, both alone and in combination with other drugs. Younger male users (mean age 34 years) seemed to have a higher susceptibility to methadone intoxication.

Vitamin D deficiency in alcohol-use disorders and its relationship to comorbid major depression: a cross-sectional study of inpatients in Nepal.

BACKGROUND: Mounting evidence suggests that deficiency of vitamin D may be associated with major health problems, including alcohol-use disorders (AUD) and major depression (MD). This study aimed to identify the vitamin D status of Nepalese inpatients with an AUD. We explored socio-demographic and alcohol-use related correlates and the relationship between vitamin D deficiency and comorbid MD. METHODS: A cross-sectional study was conducted on AUD inpatients (N=174) at eight alcohol/drug treatment centres around Kathmandu. Structured questionnaires were administered to assess the socio-demographic and alcohol-use parameters and to establish DSM-IV diagnoses of AUD and MD. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25(OH)D) concentration of <50 nmol/L. RESULTS: The prevalence of vitamin D deficiency was 64%. Higher age, having a stable job or business, shorter time since last alcohol intake and winter serum samples were related to having lower 25(OH)D levels. Several features of AUD severity were associated with low vitamin D levels: guilt about drinking, using alcohol as eye-opener, and history of relapse after alcohol treatment (p ≤ 0.03). Patients with a comorbid major depression, in particular secondarily depressed cases, were less likely to have vitamin D deficiency (X(2)=6.8; p=0.01). CONCLUSIONS: This study confirms high rates of vitamin D deficiency in alcohol treatment sample and shows a positive association between vitamin D deficiency and severity of alcohol-use disorders. Competing risk and other confounders may help explain the vitamin D status among patients with alcohol-use disorders and comorbid major depression.