Carbohydrate-deficient Transferrin Research Articles

Alcohol consumption and liver phenotype of individuals with alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate-deficient transferrin (CDT). In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a <30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease. Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.

C60 Fullerene Reduces the Level of Liver Damage in Chronic Alcohol Intoxication of Rats.

The liver is the main organ responsible for the metabolism of ethanol, which suffers significantly as a result of tissue damage due to oxidative stress. It is known that C60 fullerenes are able to efficiently capture and inactivate reactive oxygen species in in vivo and in vitro systems. Therefore, the purpose of this study is to determine whether water-soluble C60 fullerene reduces the level of pathological process development in the liver of rats induced by chronic alcohol intoxication for 3, 6, and 9 months, depending on the daily dose (oral administration; 0.5, 1, and 2 mg/kg) of C60 fullerene throughout the experiment. In this context, the morphology of the C60 fullerene nanoparticles in aqueous solution was studied using atomic force microscopy. Such biochemical parameters of experimental animal blood as ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma-glutamyl transferase) and ALP (alkaline phosphatase) enzyme activities, CDT (carbohydrate-deficient transferrin) level, values of pro-antioxidant balance indicators (concentrations of H2O2 (hydrogen peroxide) and GSH (reduced glutathione), activities of CAT (catalase), SOD (superoxide dismutase) and GPx (selenium-dependent glutathione peroxidase)), and pathohistological and morphometric features of liver damage were analyzed. The most significant positive change in the studied biochemical parameters (up to 29 ± 2% relative to the control), as markers of liver damage, was recorded at the combined administration of alcohol (40% ethanol in drinking water) and water-soluble C60 fullerenes in the optimal dose of 1 mg/kg, which was confirmed by small histopathological changes in the liver of rats. The obtained results prove the prospective use of C60 fullerenes as powerful antioxidants for the mitigation of pathological conditions of the liver arising under prolonged alcohol intoxication.

Preclinical Online Sсreening for Stress-Associated Disorders in Combatants

Background: the need to improve standards, organizational methods and practical scientific approaches to the prevention and treatment of mental pathology and the restoration of mental health of military personnel involved in combat operations determines the importance of developing and implementing effective strategies for correcting the mental state of combatants. The aim: to analyze the results of preclinical online screening of stress-associated disorders in combatants to assess its effectiveness in conducting routine psychoprophylactic examinations of military personnel after returning from the combat zone. Subjects and methods: 176 male employees of the Russian Guard who returned after a business trip of up to 90 days in the combat zone were examined. All combatants underwent preclinical online screening for the detection of stress-associated mental disorders, including methods regulated by the Ministry of Health of the Russian Federation. After testing, the obtained data were processed using cluster analysis by the K-means method. Clinical and psychopathological examination and laboratory studies were conducted, including: the content of carbohydrate-deficient transferrin (CDT), testosterone and cortisol levels, processing of the data obtained using statistical methods. Results: the combination of high levels of evening cortisol and CDT in combatants may indicate a complex interaction of physical stress, psychological trauma and possible alcohol abuse, which may be the result of both specific conditions of military service and a way to cope with post-war stress and trauma. Conclusions: it was found that the data of preclinical screening testing are consistent with clinical and laboratory results. Online screening testing for the detection of stress-associated disorders in combatants, combined with the determination of testosterone, evening cortisol and CDT levels, can serve as markers of the presence of stress-associated disorders.

Detection of Fluorescently Labeled Carbohydrate-Deficient Transferrin, a Marker of Alcohol Dependence, in Dried Blood Spots

A fluorescence-based (HPLC-FLD) method was developed for the detection of carbohydrate-deficient transferrin (CDT), a marker of alcohol dependence, in dried blood spots (DBS). Dried blood spots were cut and immersed in hydrochloric acid to leach out proteins, labeled with terbium ions, and then sent to high-performance liquid chromatography coupled with a fluorescence detector for detection. The levels of CDT in the dried blood spot samples of 10 clinically alcohol-dependent individuals were in general agreement with the results of the assayed levels of CDT in serum samples from the same source. The method can effectively amplify the detection signal of micro samples with high sensitivity and specificity, and the sampling method is simple and convenient to ensure the accuracy of the results, which is suitable for the qualitative and quantitative analysis of CDT in clinical micro samples.

A complement C4-derived glycopeptide is a biomarker for PMM2-CDG.

BACKGROUNDDiagnosis of PMM2-CDG, the most common congenital disorder of glycosylation (CDG), relies on measuring carbohydrate-deficient transferrin (CDT) and genetic testing. CDT tests have false negatives and may normalize with age. Site-specific changes in protein N-glycosylation have not been reported in sera in PMM2-CDG.METHODSUsing multistep mass spectrometry-based N-glycoproteomics, we analyzed sera from 72 individuals to discover and validate glycopeptide alterations. We performed comprehensive tandem mass tag-based discovery experiments in well-characterized patients and controls. Next, we developed a method for rapid profiling of additional samples. Finally, targeted mass spectrometry was used for validation in an independent set of samples in a blinded fashion.RESULTSOf the 3,342 N-glycopeptides identified, patients exhibited decrease in complex-type N-glycans and increase in truncated, mannose-rich, and hybrid species. We identified a glycopeptide from complement C4 carrying the glycan Man5GlcNAc2, which was not detected in controls, in 5 patients with normal CDT results, including 1 after liver transplant and 2 with a known genetic variant associated with mild disease, indicating greater sensitivity than CDT. It was detected by targeted analysis in 2 individuals with variants of uncertain significance in PMM2.CONCLUSIONComplement C4-derived Man5GlcNAc2 glycopeptide could be a biomarker for accurate diagnosis and therapeutic monitoring of patients with PMM2-CDG and other CDGs.FUNDINGU54NS115198 (Frontiers in Congenital Disorders of Glycosylation: NINDS; NCATS; Eunice Kennedy Shriver NICHD; Rare Disorders Consortium Disease Network); K08NS118119 (NINDS); Minnesota Partnership for Biotechnology and Medical Genomics; Rocket Fund; R01DK099551 (NIDDK); Mayo Clinic DERIVE Office; Mayo Clinic Center for Biomedical Discovery; IA/CRC/20/1/600002 (Center for Rare Disease Diagnosis, Research and Training; DBT/Wellcome Trust India Alliance).

Recommendations on the measurement and use of the alcohol consumption biomarker CDT. A position paper from the IFCC Working Group on CDT standardisation

BackgroundCarbohydrate deficient transferrin (CDT) is a biomarker for excessive alcohol consumption utilized in clinical and forensic medicine and workplace testing. Previously, many different analytical methods for CDT were used and the measurand varied considerably, making direct comparison of test results difficult. To end this confusion, the IFCC established a working group on CDT standardisation (WG-CDT) which completed its tasks in 2017. MethodsThis IFCC position paper by the WG-CDT summarizes state of the art information about the measurand and the analytical methods and gives concise recommendations for its utilization. ResultsThe results achieved by the CDT standardisation process led to accuracy improvements in national external quality assessment schemes over the years. A brief review of ROC based comparison studies with the traditional biomarkers (GGT, MCV, ALT and AST) discusses the bias resulting from inadequate study populations. In large groups of the general population the superior diagnostic performance of CDT is confirmed. ConclusionThe relationship between alcohol intake versus resulting CDT is discussed as well as the cutoff and measurement uncertainty. Concerning the application in practice, potential pitfalls are considered and recommendations handling both analytical and preanalytical caveats are given. Finally, some examples of serious misunderstandings in publications about CDT are addressed.

Driving under the influence of alcohol and alcohol use disorder: the relevance of early identification from an Italian retrospective outpatient study.

Worldwide, almost 1.2 million people drive under the influence of alcohol. However, early identification of alcohol use disorder (AUD) in subjects driving under the influence (DUI) of alcohol is seldom achieved. The aim of our retrospective study is to investigate the presence of AUD in a population of DUI subjects who had their driving license suspended, and if they were following a specific rehabilitation program. 750 subjects were retrospectively enrolled from 2018 to 2021. DSM-V to assess AUD was used. Forty-eight (6.4%) subjects presented a diagnosis of AUD, after one month they showed a statistically significant reduction of carbohydrate-deficient transferrin (CDT) (p<0.0001); however, none were following a program for the treatment of AUD. This outpatient setting may be considered a place of primary and secondary prevention where DUI subjects with a diagnosis of AUD may be entrusted to a Centre in order to follow rehabilitation treatment.

ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome

ABSTRACT Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (ZSCAN25) and CDT strongly predicted severe AWS with ATS (p < 0.007) and cg07375256 (p < 6 × 10–5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.

Defining trimester-specific reference intervals for carbohydrate deficient transferrin in pregnant women

ObjectivesExtensive consumption of alcohol during pregnancy can lead to severe complications for the unborn child. Carbohydrate-deficient transferrin (CDT) levels in serum have become a common biomarker for excessive alcohol intake. However, during pregnancy CDT levels can rise to levels above commonly used cut-off values, for reasons unrelated to alcohol intake. The aim of this study is to investigate the changes in CDT values during pregnancy and to determine accurate, trimester dependent reference intervals. Methods439 serum samples of 147 healthy pregnant women were obtained for trimester 1, 2, 3, and post-partum and were analysed by high-performance liquid chromatography (HPLC) and an N-Latex immunonephelometric assay. New trimester-specific reference intervals were established. ResultsThis study demonstrates there is a trimester-dependent increase of %CDT, as up to 39.4% of the population exceeded the previously established upper reference limit of 1.7%. In our study the estimated upper reference limit for %DST/%CDT were 1.55%, 1.96%, 2.05% and 1.35% for trimester 1, 2, 3 and post-partum for the HPLC-method and 2.02%, 2.19%, 2.19% and 1.96% for the N-Latex immunoassay. ConclusionsWe demonstrate that CDT levels rise during pregnancy. The magnitude of the increase is method-dependent and needs to be taken into account. We have established method- and trimester-specific reference intervals to prevent false-positive results in alcohol abuse screening tests during pregnancy.

Narrowing the Patient-Physician Gap Based on Self-Reporting and Monthly Hepatologist Feedback for Patients With Alcohol-Related Liver Disease: Interventional Pilot Study Using a Journaling Smartphone App.

Screening and intervention for alcohol use disorders (AUDs) are recommended to improve the prognosis of patients with alcohol-related liver disease (ALD). Most patients' smartphone app diaries record drinking behavior for self-monitoring. A smartphone app can be expected to also be helpful for physicians because it can provide rich patient information to hepatologists, leading to suitable feedback. We conducted this prospective pilot study to assess the use of a smartphone app as a journaling tool and as a self-report-based feedback source for patients with ALD. The aims of this study were assessment of whether journaling (self-report) and self-report-based feedback can help patients maintain abstinence and improve liver function data. This pilot study used a newly developed smartphone journaling app for patients, with input data that physicians can review. After patients with ALD were screened for harmful alcohol use, some were invited to use the smartphone journaling app for 8 weeks. Their self-reported alcohol intake, symptoms, and laboratory data were recorded at entry, week 4, and week 8. Biomarkers for alcohol use included gamma glutamyl transferase (GGT), percentage of carbohydrate-deficient transferrin to transferrin (%CDT), and GGT-CDT (GGT-CDT= 0.8 × ln[GGT] + 1.3 × ln[%CDT]). At each visit, their recorded data were reviewed by a hepatologist to evaluate changes in alcohol consumption and laboratory data. The relation between those outcomes and app usage was also investigated. Of 14 patients agreeing to participate, 10 completed an 8-week follow-up, with diary input rates between 44% and 100% of the expected days. Of the 14 patients, 2 withdrew from clinical follow-up, and 2 additional patients never used the smartphone journaling app. Using the physician's view, a treating hepatologist gave feedback via comments to patients at each visit. Mean self-reported alcohol consumption dropped from baseline (100, SD 70 g) to week 4 (13, SD 25 g; P=.002) and remained lower at week 8 (13, SD 23 g; P=.007). During the study, 5 patients reported complete abstinence. No significant changes were found in mean GGT and mean %CDT alone, but the mean GGT-CDT combination dropped significantly from entry (5.2, SD 1.2) to the week 4 visit (4.8, SD 1.1; P=.02) and at week 8 (4.8, SD 1.0; P=.01). During the study period, decreases in mean total bilirubin (3.0, SD 2.4 mg/dL to 2.4, SD 1.9 mg/dL; P=.01) and increases in mean serum albumin (3.0, SD 0.9 g/dL to 3.3, SD 0.8 g/dL; P=.009) were recorded. These pilot study findings revealed that a short-term intervention with a smartphone journaling app used by both patients and treatment-administering hepatologists was associated with reduced drinking and improved liver function. UMIN CTR UMIN000045285; http://tinyurl.com/yvvk38tj.

Carbohydrate-Deficient Transferrin (CDT) as a Biomarker of Alcohol Abuse: A Retrospective Study of the Italian Drinking Trend among Drivers from 2016 to 2022.

Alcohol abuse is still one of the leading causes of death worldwide. Early diagnosis of alcohol abuse enables preventive intervention on the effects and risks associated with its consumption. Carbohydrate-deficient transferrin (CDT) is one of the most reliable biomarkers of chronic alcohol misuse. We retrospectively studied a population of 12,624 subjects who had their driving license suspended for driving under the influence of alcohol or drugs from 2016 to 2022. The analytical determination of CDT was performed following a certified high-performance liquid chromatography (HPLC) method. Data were split by year, age and gender. The majority of subjects with positive %CDT were male, although the trend of positivity was similar between males and females. A steady increase in both the number of tests performed and the number of positives was observed over the years. Patients aged 41-50 years had the highest prevalence, followed by 51-60, 31-40 and 18-30 years. CDT continues to be a steady marker for diagnosis of alcohol abuse in the majority of cases. Data emerging from our study are in line with the increasing national trends on traffic accidents, injuries and deaths related to alcohol and drug DUI (driving under the influence), requiring the implementation of preventive measures to limit this ever-growing phenomenon.

Brief history of the alcohol biomarkers CDT, EtG, EtS, 5-HTOL, and PEth.

This article traces the historical development of various biomarkers of acute and/or chronic alcohol consumption. Much of the research in this domain of clinical and laboratory medicine arose from clinics and laboratories in Sweden, as exemplified by carbohydrate deficient transferrin (CDT) and phosphatidylethanol (PEth). Extensive studies of other alcohol biomarkers, such as ethyl glucuronide (EtG), ethyl sulfate (EtS), and 5-hydroxytryptophol (5-HTOL), also derive from Sweden. The most obvious test of recent drinking is identification of ethanol in a sample of the person's blood, breath, or urine. However, because of continuous metabolism in the liver, ethanol is eliminated from the blood at a rate of 0.15 g/L/h (range 0.1-0.3g/L/h), so obtaining positive results is not always possible. The widow of detection is increased by analysis of ethanol's non-oxidative metabolites (EtG and EtS), which are more slowly eliminated from the bloodstream. Likewise, an elevated ratio of serotonin metabolites in urine (5-HTOL/5-HIAA) can help to disclose recent drinking after ethanol is no longer measurable in body fluids. A highly specific biomarker of hazardous drinking is CDT, a serum glycoprotein (transferrin), with a deficiency in its N-linked glycosylation. Another widely acclaimed biomarker is PEth, an abnormal phospholipid synthesized in cell membranes when people drink excessively, having a long elimination half-life (median ~6days) during abstinence. Research on the subject of alcohol biomarkers has increased appreciably and is now an important area of drug testing and analysis.

Biomarkers of alcohol abuse potentially predict delirium, delirium duration and mortality in critically ill patients

Carbohydrate-deficient transferrin (CDT) and the γ-glutamyltransferase-CDT derived Anttila-Index are established biomarkers for sustained heavy alcohol consumption and their potential role to predict delirium and mortality in critically ill patients is not clear. In our prospective observational study, we included 343 consecutive patients admitted to our ICU, assessed the occurrence of delirium and investigated its association with biomarkers of alcohol abuse measured on the day of ICU admission. 35% of patients developed delirium during ICU stay. We found significantly higher CDT levels (p= 0.011) and Anttila-Index (p= 0.001) in patients with delirium. CDT above 1.7% (OR 2.06), CDT per percent increase (OR 1.26, AUROC 0.75), and Anttila-Index per unit increase (OR 1.28, AUROC 0.74) were associated with delirium development in adjusted regression models. Anttila-Index and CDT also correlated with delirium duration exceeding 5days. Additionally, Anttila-Index above 4, Anttila-Index per unit increase, and CDT per percent increase were independently associated with hospital mortality.

FRI-461 - Carbohydrate-deficient transferrin is a suitable drinking marker for patients with metabolic dysfunction-associated fatty liver disease

FRI-461 - Carbohydrate-deficient transferrin is a suitable drinking marker for patients with metabolic dysfunction-associated fatty liver disease

Alcohol consumption in healthcare workers and risk of workplace injury: a case-control study

Medical surveillance for alcohol abuse and dependency at work is mandatory for a list of high-risk occupations. The occupational physician is the only figure entitled to perform alcohol and laboratory tests on employees. This study aims to investigate alcohol-induced injuries in healthcare workers, by using Carbohydrate-Deficient Transferrin (CDT) as a marker during medical surveillance visits. A retrospective study was carried out in an Italian healthcare unit. The sample consisted in 75 healthcare workers who sustained an occupational injury. To assess alcohol consumption, CDT levels were tested as well as serum alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), mean corpuscular volume (MCV). No worker had positive CDT levels (cut-off 2%); 12% of cases (5 male and 4 female workers) had γ-GT level higher than normal range (cut-off: 36 U/L). Most injuries (53.33%) occurred during morning shifts, 33.33% during afternoon shifts and 13.33% during night shifts. Female workers had a higher injury rate (73%); biological injuries were the most frequent (36%), followed by slipping and falling 33%. This study seems to indicate that alcohol does not represent an important cause of occupational injuries, as no cases of workplace injury were found positive for CDT. CDT as a biomarker in health surveillance programs could be used to assess alcohol consumption when used alongside other biochemical parameters, and its routine use during medical surveillance could act as a deterrent.

An Unexpected Diagnosis of MAGT1 Deficiency in a Patient with CVID-like Features, Molluscum Contagiosum and Atopy

Case DescriptionA 6-year-old boy presented to the immunology clinic with recurrent infections. He started to have recurrent otitis media at the age of 18 months. He also had multiple sinus infections and 3–4 episodes of pneumonia. Immunologic evaluation revealed an IgG of 498 (ref 608–1229 mg/dL), an IgA of 20.8 (ref 33–200 mg/dL) and an impaired response to the Streptococcus pneumoniae vaccine. T and B lymphocyte counts were normal. He was started on subcutaneous immunoglobulin replacement therapy after which his IgG level normalized and his frequency of sinopulmonary infections improved. He also has a history of eczema, chronic cough and environmental allergies for which he receives allergen-specific subcutaneous immunotherapy in addition to treatment with an inhaled corticosteroid and omalizumab. The patient also had persistent skin warts on his hands and extensive molluscum contagiosum lesions. He underwent targeted genetic testing for a primary immunodeficiency which revealed a hemizygous pathogenic variant in the magnesium transporter 1 (MAGT1) gene (c.580dup; p.Ser194Phefs*3). This variant is a duplication at nucleotide position 580 that creates a premature stop codon 3 amino acids downstream from this location. The patient subsequently underwent a carbohydrate deficient transferrin test (CDT) for congenital disorders of glycosylation (CDG) that revealed moderately elevated transferrin mono-oligosaccharide to di-oligosaccharide and Apo CIII-1/Apo CIII-2 ratios, consistent with the diagnosis of MAGT1-CDG (XMEN; X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia). Additionally, NKG2D surface expression was reduced by ~90% on the CD8T cells, and by ~85% on the NK cells in the patient sample compared to the control sample assessed in parallel. The patient continues to test negative for EBV infection by PCR. ConclusionXMEN disease (OMIM number 300853) is a rare, combined immunodeficiency resulting from a mutation in the magnesium transporter 1 gene (MAGT1) located on the X chromosome. Only 36 patients have been reported to have this disease thus far. While the clinical phenotype is variable, the disease is often associated with EBV infection. This case is unique in that the patient was diagnosed due to a history of severe warts, atopy, and hypogammaglobulinemia in the absence of EBV infection.

Serum Carbohydrate Deficient Transferrin: A Sensitive Marker in Diagnosing Alcohol Abuse

Introduction: Alcohol is a psychoactive substance with dependence producing properties and the burden of disease and death related to alcohol consumption remains significant in most countries. Early detection and proper medication with counselling can restore the alcoholics to normalcy. There is a need for a specific assay procedure to detect alcoholics early, so that proper therapy can be instituted. The traditional biomarkers in liver function test (LFT) are more frequently used for diagnosing alcohol abuse but they have variable and limited sensitivity and specificity. Carbohydrate Deficient Transferrin (CDT) can be considered as a more sensitive and specific marker for diagnosing alcohol abuse. The aim of this study is to determine % CDT in alcoholics and compare it with other alcohol markers in respect with sensitivity and specificity. The results of the study will be helpful in assessment of the alcohol dependence patients and therefore in their early detection and management. Materials and Methods: This is a hospital based comparative cross-sectional study carried out in Dharan. A total of 40 cases of alcohol abuse with ≥2 score in CAGE questionnaire and matched 40 subjects with no history of alcohol intake were enrolled in the study. Informed written consent and ethical approval were taken. Result: Serum %CDT has the highest diagnostic efficacy followed by serum gamma glutamyl transferase (GGT), Aspartate Transaminase (AST), Alanine Transaminase (ALT), AST/AL, and ALP as a biomarker for diagnosing alcohol abuse. Serum %CDT has the highest sensitivity with 97.5% and specificity of 73% at a cut off value of 3.5% compared to serum GGT with the sensitivity and specificity of 87% and 73%, respectively at a cut off value of 33.5 U/L. Conclusion: Serum %CDT is a better marker both in terms of sensitivity and specificity compared to other conventional markers and thus can be used as a tool to early diagnose the alcoholic cases and monitor the therapy and for early identification of the relapses in alcoholics during treatment.

Risk Analysis for Quality Control Part 3: Practical Application of the Precision Quality Control Model.

We developed a theoretical framework (Precision Quality Control [PQC]) to minimize the cost of quality, but it is not known whether the method can be applied in practice. We used data for 2 analytes, cadmium and carbohydrate-deficient transferrin (CDT), and applied the PQC framework to find the optimal control limits. These analytes were selected because they differed with respect to sigma values that are major determinants of control limits. We explored different ways to visualize the results: (a) risk trade-off (false-positive risk vs false-negative risk), (b) cost-risk trade-off (false-positive cost vs false-negative risk), and (c) cost minimization. We were able to use the PQC limit to produce 3 different visualizations to suggest control limits. The risk-based analysis was the simplest to apply, but the most difficult to interpret. The cost vs risk method was easy to apply but was still difficult to interpret. The cost minimization method was easy to interpret but required users to declare a willingness to pay that may be difficult to estimate. The PQC method can be used to find control limits that minimize the cost of quality.

A BRIEF HISTORY OF THE ALCOHOL BIOMARKER CDT AND ITS APPLICATION IN FORENSIC MEDICAL EXPERTISE IN ROAD ACCIDENT INVESTIGATIONS"

It is well known that large-scale binge drinking is one of the leading risk factors for poor public health around the world. This is why an objective assessment of the current state of alcohol abuse is critical to protecting public health and safety, especially in clinical, professional context and in the context of road traffic. The article is devoted to the current problem of the history of the formation of the process of one of the most commonly used biostandards of consumed alcohol, namely carbohydrate-deficient transferrin. Taking into account the observed increase in road accidents while intoxicated, the article substantiates the importance of the CDT biomarker when conducting medical expertise. Keywords: CDT biomarker, road accident, forensic medical expertise, alcohol intoxication, public health protection.

Predictive risk markers in alcoholism.

The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment.