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Olof Beck - One of the best experts on this subject based on the ideXlab platform.
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elimination characteristics of the Alcohol biomarker phosphatidylethanol peth in blood during Alcohol Detoxification
Alcohol and Alcoholism, 2019Co-Authors: Anders Helander, Michael Bottcher, Norbert Dahmen, Olof BeckAbstract:AIMS: The study documented elimination characteristics of three phosphatidylethanol (PEth) homologs in serially collected blood samples from 47 heavy drinkers during ~2 weeks of Alcohol Detoxification at hospital. METHODS: Venous whole blood and urine samples were collected every 1-2 days during treatment. Concentrations of PEth, and of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) to detect relapse drinking, were measured using liquid chromatography-tandem mass spectrometry. RESULTS: When included in the study, negative or decreasing breath ethanol concentrations demonstrated that the patients were in the elimination phase. The EtG and EtS measurements further confirmed Alcohol abstinence during the study, with three exceptions. On admission, all patients tested positive for PEth, the total concentration ranging 0.82-11.7 (mean 6.35, median 5.88) μmol/l. PEth 16:0/18:1, 16:0/18:2 and 16:0/20:4 accounted for on average ~42%, ~26% and ~9%, respectively, of total PEth in these samples. There were good correlations between total PEth and individual homologs (P < 0.0001). There was no significant difference in PEth values between male and female subjects. During abstinence, the elimination half-life values ranged 3.5-9.8 days for total PEth, 3.7-10.4 days for PEth 16:0/18:1, 2.7-8.5 days for PEth 16:0/18:2 and 2.3-8.4 days for PEth 16:0/20:4. CONCLUSIONS: The results demonstrated a very high sensitivity (100%) of PEth as Alcohol biomarker for recent heavy drinking, but considerable differences in the elimination rates between individuals and between different PEth forms. This indicates that it is possible to make only approximate estimates of the quantity and recency of Alcohol intake based on a single PEth value.
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detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during Alcohol Detoxification
Alcohol and Alcoholism, 2008Co-Authors: Anders Helander, Michael Bottcher, Christoph Fehr, Norbert Dahmen, Olof BeckAbstract:AIMS: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugated ethanol metabolites formed in low amounts after Alcohol consumption. Compared with ethanol, EtG and EtS are excreted in urine for a prolonged time, making them useful as sensitive Alcohol biomarkers. This study determined the detection times for EtG and EtS in Alcoholic patients undergoing Alcohol Detoxification. METHODS: Alcohol-dependent patients (n = 32) with an initial Alcohol concentration >or=1 g/L based on breath testing were followed during Detoxification. Urine samples for determination of EtG, EtS, ethanol and creatinine were collected on admission to the hospital and thereafter once daily for several days. EtG and EtS measurements were performed by liquid chromatography-mass spectrometry (LC-MS) and EtG also using an immunochemical assay (DRI-EtG EIA, ThermoFisher/Microgenics). RESULTS: The detection time for urinary EtG was weakly correlated (r = 0.434, P = 0.013) with the initial Alcohol concentration (range 1.0-3.4 g/L). For EtG, the individual time range until return to below the applied cut-off limit (<0.5 mg/L) was approximately 40-130 h (median 78) with a similar time course observed for EtS. After correction for urine dilution, the time until an EtG/creatinine ratio <0.5 mg/g was approximately 40- 90 h (median 65). The detection times after an estimated zero ethanol concentration were approximately 30-110 h (median 66) for EtG and approximately 30- 70 h (median 56) for EtG/creatinine. The EtG results by LC-MS and the immunoassay were in good agreement. CONCLUSIONS: During Alcohol Detoxification, EtG and EtS remained detectable in urine for several days. The detection times showed wide inter-individual variations, also after adjusting values for urine dilution and to the estimated times for a completed ethanol elimination.
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detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during Alcohol Detoxification
Alcohol and Alcoholism, 2008Co-Authors: Anders Helander, Michael Bottcher, Christoph Fehr, Norbert Dahmen, Olof BeckAbstract:Aims: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugated ethanol metabolites formed in low amounts after Alcohol consumption. Compared with ethanol, EtG and EtS are excreted in urine for a prolonged time, making them useful as sensitive Alcohol biomarkers. This study determined the detection times for EtG and EtS in Alcoholic patients undergoing Alcohol Detoxification. Methods: Alcohol-dependent patients ( n = 32) with an initial Alcohol concentration ≥1 g/L based on breath testing were followed during Detoxification. Urine samples for determination of EtG, EtS, ethanol and creatinine were collected on admission to the hospital and thereafter once daily for several days. EtG and EtS measurements were performed by liquid chromatography-mass spectrometry (LC-MS) and EtG also using an immunochemical assay (DRI-EtG EIA, ThermoFisher/Microgenics). Results: The detection time for urinary EtG was weakly correlated ( r = 0.434, P = 0.013) with the initial Alcohol concentration (range 1.0–3.4 g/L). For EtG, the individual time range until return to below the applied cut-off limit (<0.5 mg/L) was ∼40–130 h (median 78) with a similar time course observed for EtS. After correction for urine dilution, the time until an EtG/creatinine ratio <0.5 mg/g was ∼40– 90 h (median 65). The detection times after an estimated zero ethanol concentration were ∼30–110 h (median 66) for EtG and ∼30– 70 h (median 56) for EtG/creatinine. The EtG results by LC-MS and the immunoassay were in good agreement. Conclusions: During Alcohol Detoxification, EtG and EtS remained detectable in urine for several days. The detection times showed wide inter-individual variations, also after adjusting values for urine dilution and to the estimated times for a completed ethanol elimination.
Sebastian Mueller - One of the best experts on this subject based on the ideXlab platform.
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non invasive biomarkers of liver inflammation and cell death in response to Alcohol Detoxification
Frontiers in Physiology, 2021Co-Authors: Manuela G Neuman, J Mueller, Sebastian MuellerAbstract:Introduction Alcohol-related liver disease (ALD) represents the most common liver disease worldwide, however, the underlying molecular mechanisms are still poorly understood. Namely centrilobular inflammation and programmed cell death are characteristic to ALD and it remains to be elucidated why they persist despite the absence of Alcohol. Aims To study the effects of Alcohol withdrawal in a cohort of heavy drinkers and the role of cirrhosis by using non-invasive biomarkers such as cytokines, apoptotic and angiogenic markers. Methods Caspase 3-cleaved M30, M65, cytokines (IL-6, IL-8), tumor necrosis factor alpha (TNF-α), transforming growth factor (TGF-β) and vascular endothelial growth factor (VEGF) were measured in 114 heavy drinkers. The role of Alcohol Detoxification was investigated in 45 patients. The liver histology was available in 23 patients. Fibrosis stage and steatosis were assessed by measuring liver stiffness (LS) and controlled attenuation parameter (CAP) in all patients using transient elastography (FibroScan, Echosens, Paris). Mean observation interval between the measurements was 5.7 ± 1.4 days (mean + -SD). Results Patients consumed a mean of 204 ± 148 g/day Alcohol with a heavy drinking duration of 15.3 ± 11.0 years. Mean LS was 20.7 ± 24.4 kPa and mean CAP was 303 ± 51 dB/m. Fibrosis distribution was F0-38.1%, F1-2-31%, F3-7.1 and F4-23.9%. Apoptotic markers M30 and M65 were almost five times above normal. In contrast, TNF- α a, IL-8 and VEGF were only slightly elevated. Patients with manifest liver cirrhosis (F4) had significantly higher levels of M30, M65, IL-6 and IL-8. Histology features such as hepatocyte ballooning, Mallory-Denk bodies, inflammation and fibrosis were all significantly associated with elevated LS, and serum levels of TNF-alpha, M30 and M65 but not with CAP and other cytokines. During Alcohol Detoxification, LS, transaminases, TGF- β, IL-6, IL-8 and VEGF decreased significantly. In contrast, no significant changes were observed for M30, M65 and TNF- α and M30 even increased during Detoxification in non-cirrhotic patients. Profibrogenic cytokine TGF-beta and pro-angiogenic cytokine VEGF showed a delayed decrease in patients with manifest cirrhosis. Conclusion Patients with Alcohol-related cirrhosis have a pronounced apoptotic activity and a distinct inflammatory response that only partly improves after 1 week of Alcohol Detoxification. Alcohol withdrawal may represent an important approach to better dissect the underlying mechanisms in the setting of Alcohol metabolism.
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caspase cleaved keratin 18 fragments increase during Alcohol withdrawal and predict liver related death in patients with Alcoholic liver disease
Hepatology, 2017Co-Authors: Sebastian Mueller, V Rausch, Carolin Lackner, Eray Yagmur, Helmut K Seitz, Beate K Straub, Pierre Nahon, Tessa Peccerella, I Silva, Pierre RufatAbstract:Noninvasive assessment of disease activity in patients with nonAlcoholic fatty liver disease (NAFLD) and Alcoholic liver disease (ALD) is still unsettled, but essential for the evaluation of disease progression. We here studied the association of total (M65) and caspase-cleaved (M30) serum keratin-18 fragments (n = 204) with histological parameters (n = 106) in heavy drinkers primarily admitted for Alcohol withdrawal before and after Alcohol Detoxification. An age-, sex-, and fibrosis-stage matched NAFLD cohort (n = 30) was used for comparison. The prognostic value of M30 and M65 levels were assessed in an additional prospectively followed-up cohort of 230 patients with Alcoholic cirrhosis (AC) using competing risk analyses. Among the histological parameters, both M30/65 correlated significantly and better than any other serum marker with apoptosis and liver damage, such as ballooning (r = 0.65; P < 0.001), followed by lobular inflammation (0.48; P < 0.001), steatosis (0.46; P < 0.001), but less with fibrosis (0.24; P < 0.001). Area under the receiver operating characteristics curves to detect ballooning, steatosis, or steatohepatitis (SH) were slightly better for M30 (P < 0.005). Optimal M30 cut-off values for mild and severe ballooning were 330 and 420 U/L, and 290 and 330 U/L for SH grades 1 and 2. No significant differences of M30/65 were found between the matched NAFLD and ALD cohort. In contrast to aspartate-amino-transferase and M65, M30 levels increased significantly from 391 to 518 U/L during Alcohol Detoxification. Moreover, levels of M30 and M65 predicted non–hepatocellular carcinoma liver-related mortality in patients with AC during a mean observation interval of 67.2 months. Conclusion: Our data suggest M30 as highly specific marker of liver apoptosis both in ALD and NAFLD. In addition, hepatocellular apoptosis, as determined by M30 levels, occurs during Alcohol withdrawal, and survival data point toward a novel underestimated role of apoptosis in patients with ALD. (Hepatology 2017;66:96–107).
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primary liver injury and delayed resolution of liver stiffness after Alcohol Detoxification in heavy drinkers with the pnpla3 variant i148m
World Journal of Hepatology, 2016Co-Authors: V Rausch, T Peccerella, Carolin Lackner, Eray Yagmur, Helmut K Seitz, Thomas Longerich, Sebastian MuellerAbstract:Primary liver injury and delayed resolution of liver stiffness after Alcohol Detoxification in heavy drinkers with the PNPLA3 variant I148M
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Alcohol Dependence and Alcoholic Liver Disease
European Medical Journal, 2015Co-Authors: Karl Mann, Sebastian MuellerAbstract:Alcohol dependence is a disabling condition that has a high prevalence, but in Europe only a small fraction of the people diagnosed with Alcohol abuse and dependence are treated, representing the widest treatment gap, as compared with other mental disorders. Early diagnosis and monitoring of Alcoholic liver disease (ALD) is still insufficiently solved. Although ALD is the most common cause for liver disease in the Western world, it largely remains underestimated and underdiagnosed for many reasons. The recent introduction of non-invasive elastographic techniques such as transient elastography (TE) has significantly improved the early diagnosis of Alcoholic liver cirrhosis (ALC). As demonstrated in the literature, inflammation-associated liver stiffness (LS) rapidly decreases during Alcohol Detoxification, and is also directly correlated to change in LS in both abstinent and relapsing patients. Newly published data show that LS could be used to monitor and validate hepatoprotective effects during nalmefene usage. Nalmefene is an opioid system modulator that diminishes the reinforcing effects of Alcohol, helping the patient to reduce drinking. Three randomised, multicentre, double-blind, placebo-controlled, parallelgroup Phase III studies were designed to assess the efficacy and safety of nalmefene in reducing Alcohol consumption. Patients with a high or very high drinking risk level (DRL) at baseline and randomisation show a clinically significant effect from nalmefene treatment, which is generally well tolerated. Moreover, reduced Alcohol consumption supported by nalmefene in combination with psychosocial support may indeed help to reduce the Alcohol-related burden and the large treatment gap
Spero M Manson - One of the best experts on this subject based on the ideXlab platform.
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Alcohol Detoxification completion acceptance of referral to substance abuse treatment and entry into substance abuse treatment among alaska native people
Addictive Behaviors, 2017Co-Authors: Ursula Running Bear, Douglas K Novins, Janette Beals, Spero M MansonAbstract:Abstract Background Little is known about factors associated with Detoxification treatment completion and the transition to substance abuse treatment following Detoxification among Alaska Native people. This study examined 3 critical points on the substance abuse continuum of care (Alcohol Detoxification completion, acceptance of referral to substance abuse treatment, entry into substance abuse treatment following Detoxification). Methods The retrospective cohort included 383 adult Alaska Native patients admitted to a tribally owned and managed inpatient Detoxification unit. Three multiple logistic regression models estimated the adjusted associations of each outcome separately with demographic/psychosocial characteristics, clinical characteristics, use related behaviors, and health care utilization. Results Seventy-five percent completed Detoxification treatment. Higher global assessment functioning scores, longer lengths of stay, and older ages of first Alcohol use were associated with completing Detoxification. A secondary drug diagnosis was associated with not completing Detoxification. Thirty-six percent accepted a referral to substance abuse treatment following Detoxification. Men, those with legal problems, and those with a longer length of stay were more likely to accept a referral to substance abuse treatment. Fifty-eight percent had a confirmed entry into a substance abuse treatment program at discharge. Length of stay was the only variable associated with substance abuse treatment entry. Conclusions Services like motivational interviewing, counseling, development of therapeutic alliance, monetary incentives, and contingency management are effective in linking patients to services after Detoxification. These should be considered, along with the factors associated with each point on the continuum of care when linking patients to follow-up services.
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impact of adaptive functioning on readmission to Alcohol Detoxification among alaska native people
Drug and Alcohol Dependence, 2014Co-Authors: Ursula Running Bear, Heather D Anderson, Spero M Manson, Jay H Shore, Allan V Prochazka, Douglas K NovinsAbstract:Background This study examined predictors associated with readmission to Detoxification in a sample of adult Alaska Native patients admitted to inpatient Alcohol Detoxification. Even though Alaska Native people diagnosed with Alcoholism have been identified as frequent utilizers of the health care system and at elevated risk of death, little is known about factors associated with readmission to Detoxification for this group.
Anders Helander - One of the best experts on this subject based on the ideXlab platform.
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elimination characteristics of the Alcohol biomarker phosphatidylethanol peth in blood during Alcohol Detoxification
Alcohol and Alcoholism, 2019Co-Authors: Anders Helander, Michael Bottcher, Norbert Dahmen, Olof BeckAbstract:AIMS: The study documented elimination characteristics of three phosphatidylethanol (PEth) homologs in serially collected blood samples from 47 heavy drinkers during ~2 weeks of Alcohol Detoxification at hospital. METHODS: Venous whole blood and urine samples were collected every 1-2 days during treatment. Concentrations of PEth, and of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) to detect relapse drinking, were measured using liquid chromatography-tandem mass spectrometry. RESULTS: When included in the study, negative or decreasing breath ethanol concentrations demonstrated that the patients were in the elimination phase. The EtG and EtS measurements further confirmed Alcohol abstinence during the study, with three exceptions. On admission, all patients tested positive for PEth, the total concentration ranging 0.82-11.7 (mean 6.35, median 5.88) μmol/l. PEth 16:0/18:1, 16:0/18:2 and 16:0/20:4 accounted for on average ~42%, ~26% and ~9%, respectively, of total PEth in these samples. There were good correlations between total PEth and individual homologs (P < 0.0001). There was no significant difference in PEth values between male and female subjects. During abstinence, the elimination half-life values ranged 3.5-9.8 days for total PEth, 3.7-10.4 days for PEth 16:0/18:1, 2.7-8.5 days for PEth 16:0/18:2 and 2.3-8.4 days for PEth 16:0/20:4. CONCLUSIONS: The results demonstrated a very high sensitivity (100%) of PEth as Alcohol biomarker for recent heavy drinking, but considerable differences in the elimination rates between individuals and between different PEth forms. This indicates that it is possible to make only approximate estimates of the quantity and recency of Alcohol intake based on a single PEth value.
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detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during Alcohol Detoxification
Alcohol and Alcoholism, 2008Co-Authors: Anders Helander, Michael Bottcher, Christoph Fehr, Norbert Dahmen, Olof BeckAbstract:AIMS: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugated ethanol metabolites formed in low amounts after Alcohol consumption. Compared with ethanol, EtG and EtS are excreted in urine for a prolonged time, making them useful as sensitive Alcohol biomarkers. This study determined the detection times for EtG and EtS in Alcoholic patients undergoing Alcohol Detoxification. METHODS: Alcohol-dependent patients (n = 32) with an initial Alcohol concentration >or=1 g/L based on breath testing were followed during Detoxification. Urine samples for determination of EtG, EtS, ethanol and creatinine were collected on admission to the hospital and thereafter once daily for several days. EtG and EtS measurements were performed by liquid chromatography-mass spectrometry (LC-MS) and EtG also using an immunochemical assay (DRI-EtG EIA, ThermoFisher/Microgenics). RESULTS: The detection time for urinary EtG was weakly correlated (r = 0.434, P = 0.013) with the initial Alcohol concentration (range 1.0-3.4 g/L). For EtG, the individual time range until return to below the applied cut-off limit (<0.5 mg/L) was approximately 40-130 h (median 78) with a similar time course observed for EtS. After correction for urine dilution, the time until an EtG/creatinine ratio <0.5 mg/g was approximately 40- 90 h (median 65). The detection times after an estimated zero ethanol concentration were approximately 30-110 h (median 66) for EtG and approximately 30- 70 h (median 56) for EtG/creatinine. The EtG results by LC-MS and the immunoassay were in good agreement. CONCLUSIONS: During Alcohol Detoxification, EtG and EtS remained detectable in urine for several days. The detection times showed wide inter-individual variations, also after adjusting values for urine dilution and to the estimated times for a completed ethanol elimination.
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detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during Alcohol Detoxification
Alcohol and Alcoholism, 2008Co-Authors: Anders Helander, Michael Bottcher, Christoph Fehr, Norbert Dahmen, Olof BeckAbstract:Aims: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugated ethanol metabolites formed in low amounts after Alcohol consumption. Compared with ethanol, EtG and EtS are excreted in urine for a prolonged time, making them useful as sensitive Alcohol biomarkers. This study determined the detection times for EtG and EtS in Alcoholic patients undergoing Alcohol Detoxification. Methods: Alcohol-dependent patients ( n = 32) with an initial Alcohol concentration ≥1 g/L based on breath testing were followed during Detoxification. Urine samples for determination of EtG, EtS, ethanol and creatinine were collected on admission to the hospital and thereafter once daily for several days. EtG and EtS measurements were performed by liquid chromatography-mass spectrometry (LC-MS) and EtG also using an immunochemical assay (DRI-EtG EIA, ThermoFisher/Microgenics). Results: The detection time for urinary EtG was weakly correlated ( r = 0.434, P = 0.013) with the initial Alcohol concentration (range 1.0–3.4 g/L). For EtG, the individual time range until return to below the applied cut-off limit (<0.5 mg/L) was ∼40–130 h (median 78) with a similar time course observed for EtS. After correction for urine dilution, the time until an EtG/creatinine ratio <0.5 mg/g was ∼40– 90 h (median 65). The detection times after an estimated zero ethanol concentration were ∼30–110 h (median 66) for EtG and ∼30– 70 h (median 56) for EtG/creatinine. The EtG results by LC-MS and the immunoassay were in good agreement. Conclusions: During Alcohol Detoxification, EtG and EtS remained detectable in urine for several days. The detection times showed wide inter-individual variations, also after adjusting values for urine dilution and to the estimated times for a completed ethanol elimination.
Ursula Running Bear - One of the best experts on this subject based on the ideXlab platform.
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Alcohol Detoxification completion acceptance of referral to substance abuse treatment and entry into substance abuse treatment among alaska native people
Addictive Behaviors, 2017Co-Authors: Ursula Running Bear, Douglas K Novins, Janette Beals, Spero M MansonAbstract:Abstract Background Little is known about factors associated with Detoxification treatment completion and the transition to substance abuse treatment following Detoxification among Alaska Native people. This study examined 3 critical points on the substance abuse continuum of care (Alcohol Detoxification completion, acceptance of referral to substance abuse treatment, entry into substance abuse treatment following Detoxification). Methods The retrospective cohort included 383 adult Alaska Native patients admitted to a tribally owned and managed inpatient Detoxification unit. Three multiple logistic regression models estimated the adjusted associations of each outcome separately with demographic/psychosocial characteristics, clinical characteristics, use related behaviors, and health care utilization. Results Seventy-five percent completed Detoxification treatment. Higher global assessment functioning scores, longer lengths of stay, and older ages of first Alcohol use were associated with completing Detoxification. A secondary drug diagnosis was associated with not completing Detoxification. Thirty-six percent accepted a referral to substance abuse treatment following Detoxification. Men, those with legal problems, and those with a longer length of stay were more likely to accept a referral to substance abuse treatment. Fifty-eight percent had a confirmed entry into a substance abuse treatment program at discharge. Length of stay was the only variable associated with substance abuse treatment entry. Conclusions Services like motivational interviewing, counseling, development of therapeutic alliance, monetary incentives, and contingency management are effective in linking patients to services after Detoxification. These should be considered, along with the factors associated with each point on the continuum of care when linking patients to follow-up services.
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impact of adaptive functioning on readmission to Alcohol Detoxification among alaska native people
Drug and Alcohol Dependence, 2014Co-Authors: Ursula Running Bear, Heather D Anderson, Spero M Manson, Jay H Shore, Allan V Prochazka, Douglas K NovinsAbstract:Background This study examined predictors associated with readmission to Detoxification in a sample of adult Alaska Native patients admitted to inpatient Alcohol Detoxification. Even though Alaska Native people diagnosed with Alcoholism have been identified as frequent utilizers of the health care system and at elevated risk of death, little is known about factors associated with readmission to Detoxification for this group.