Bariatric surgery patients in AUD treatment in Norway-an exploratory cross-sectional study.

AIMS: Patients who have undergone some forms of bariatric surgery have increased risk of developing alcohol use disorder (AUD). In the present observational study, we compared patients with AUD who themselves reported to having undergone bariatric surgery with other patients in treatment for AUD. MATERIALS: One-hundred-and-six consecutively enrolled patients in residential treatment for AUD were asked if they had undergone bariatric surgery. Sociodemographics, mental health-related, and alcohol use-related parameters were compared between those who had and those who had not undergone bariatric surgery. RESULTS: Of the 106 patients with AUD, seven (6.6%; 95% confidence interval, 2.7%-13.1%) had undergone bariatric surgery. Six of seven patients had undergone such surgery were women (P < .001). The patients with AUD who had undergone bariatric surgery were similar to other patients with AUD on most other parameters, the exception being a larger number of alcohol units ingested to feel an effect of alcohol (adjusted odds ratio 7.1; 95% confidence interval 2.0-12.2; P = .007). CONCLUSION: The high number of patients with AUD that reported having undergone bariatric surgery emphasizes the risks following such a procedure. The overrepresentation of women may reflect than more women undergo such procedures. The unexpected finding that patients with AUD having undergone bariatric surgery seemed to need more alcohol to feel intoxicated warrants further research.

Cytokines in hepatitis C-infected patients with or without opioid maintenance therapy.

OBJECTIVE: Both chronic hepatitis C virus (HCV) infection and opioids cause altered blood levels of cytokines. Previous studies have investigated levels of selected groups of cytokines in patients on opioid maintenance treatment. Little is known about the levels of multiple cytokines in patients with chronic HCV infection on opioid maintenance treatment. Our aim was to investigate the cytokine profile in patients with active HCV infection with and without opioid maintenance treatment. METHODS: We conducted a cross-sectional study in an out-patients population included upon referral for antiviral hepatitis C infection treatment. The level of 27 cytokines was measured in serum using multiplex technology. Patients were interviewed using a modified version of the European addiction severity index. Data pertaining to weight, height, current medication, smoking habits, allergies, previous medical history and ongoing withdrawal symptoms were collected. Non-parametric testing was used to investigate differences in levels of cytokines between the two groups. A 3-model hierarchical regression analysis was used to analyse associations between cytokines and confounding variables. RESULTS: Out of 120 included patients, 53 were on opioid maintenance treatment. Median duration of opioid treatment was 68.4 months. There were no demographical differences between the two groups other than age. IL-1ß was lower and eotaxin-1 higher in the group on opioid maintenance treatment than in the non-opioid group. No other inter-group differences in the remaining cytokine levels were found. CONCLUSION: In HCV infection patients, the impact of chronic opioid administration on peripheral circulating cytokine level is minimal.

Methadone pharmacokinetics in opioid agonist treatment: Influencing factors and clinical implications.

BACKGROUND: A considerable inter-individual variability has been reported in the relationship between methadone doses applied and serum concentrations achieved in methadone maintenance treatment. However, the underlying causes for this variability are not fully understood. OBJECTIVES: We investigated the influence of genetic, pathophysiological and pharmacological factors on serum methadone concentration-to-dose ratio (CDR) and discussed the clinical implications of the findings. METHODS: We used data from two retrospective laboratory databases and a prospective cohort study to investigate the impact on methadone CDR of hepatic cytochrome P450 enzyme system (CYP) genetic polymorphisms, age, sex, concomitant medication, liver fibrosis and body mass index through linear mixed model analyses. FINDINGS: A positive association was found between CDR and the homozygous CYP2B6*6 genotype, concurrent treatment with CYP3A4 inhibitors and body mass index. CDR was lower among women and during concomitant use of CYP inducers. CDR was not associated with age or the degree of liver fibrosis in our investigations. CONCLUSIONS: This research work supports the need for individually tailored dosage considering the various factors that influence methadone CDR. The gained knowledge can contribute to reducing the risks associated with the treatment and optimizing the desired outcomes.

National health registries - a 'goldmine' for studying non-communicable disease occurrence in Norway - the NCDNOR project.

To estimate occurrence of non-communicable diseases (NCDs) over the life-course in the Norwegian population, national health registries are a vital source of information since they fully represent the entire non-institutionalised population. However, as they are mainly established for administrative purposes, more knowledge about how NCDs are recorded in the registries is needed. To establish this, we begin by counting the number of individuals registered annually with one or more NCDs in any of the registries. The study population includes all inhabitants who lived in Norway from 2004 to 2020 (N~6.4m). The NCD outcomes are diabetes, cardiovascular diseases, chronic obstructive lung diseases, cancer and mental disorders/substance use disorders. Further, we included hip fractures in our NCD concept. The data sources used to identify individuals with NCDs, including detailed information on diagnoses in primary and secondary health care and dispensings of prescription drugs, are the Cancer Registry of Norway, The Norwegian Patient Registry, The Norwegian Control and Payment of Health Reimbursement database, and The Norwegian Prescription Database. The number of individuals registered annually with an NCD diagnosis and/or a dispensed NCD drug increased over the study period. Changes over time may reflect changes in disease incidence and prevalence, but also changes in disease-specific guidelines, reimbursement schemes and access to and use of health services. Data from more than one health registry to identify individuals with NCDs are needed since the registries reflect different levels of health care services and therefore may reflect disease severity.

Incidence of SARS-CoV-2 and all-cause mortality in persons with co-occurring substance use disorder and mental illness during the pandemic: a Norwegian cohort study.

PURPOSE: Most people were affected by the COVID-19 pandemic. Persons with co-occurring substance use disorder (SUD) and mental illness (MI) are already a marginalized group, with above average mortality. Thus, the study aim was to investigate SARS-CoV-2 incidence and mortality among persons with SUD/MI during the first two years of the pandemic. METHODS: This historical cohort study merged data from the Norwegian Patient Register, the Norwegian Surveillance System for Communicable Diseases and census data from Statistics Norway. We calculated crude mortality rates for persons with SUD and mild/moderate vs. severe MI and compared them to persons with physical illnesses or healthy controls. The incidence rate ratios for SARS-CoV-2 infection and mortality were estimated using Poisson regression models. RESULTS: Compared to healthy controls, the SARS-Cov-2-infection rate was marginally lower in persons with SUD and mild/moderate MI (IRR,1.19 [95%CI,1.09-1.30]) as in persons with physical illness (IRR,1.35 [95%CI, 1.23-1.47]), whereas persons with SUD and severe MI showed a lower rate compared to healthy controls. Crude mortality rates for persons with SUD/MI were substantially higher and increased much more during the pandemic than for persons with physical illnesses or healthy controls. The IRR for mortality in persons with SUD and mild/moderate MI was 10.61 (95%CI,7.19-15.67) and 11.44 (95%CI,7.50-17.45) for SUD and severe MI, compared to 5.03 (3.34-7.57]) for persons with physical illnesses only. CONCLUSION: The analysis showed excess mortality during COVID-19-pandemic for SUD/MI, but without higher SARS-CoV-2 infection rates in this group. Consequently, excess mortality among persons with SUD/MI was not due to SARS-CoV-2 infection.

Levels of IL-6 are Associated with Lifetime Attempted Suicide in Alcohol Use Disorder Patients.

Background: Patients with alcohol use disorder (AUD) have an increased risk of suicide. Neuroimmunological measures, such as cytokines, are shown to deviate in people with attempted suicide. Few studies have investigated this among AUD patients. Patients and Methods: One-hundred and fourteen patients undergoing residential treatment for AUD were interviewed on lifetime suicide attempts (SA) along with several other background variables and clinical characteristics. Serum blood samples were drawn for analysis of cytokines. Results: Thirty-one patients (27%) reported at least one SA. These patients had more symptoms of current affective disorders and more severe dependence. In bivariate analysis only IL-6 and IL-10 appeared to be associated with lifetime SA but without reaching statistical significance. In multivariate linear regression, adjusting for sex, nicotine use, somatic illness, and the use of anti-inflammatory drugs, IL-6 was associated to SA (p = 0.033). Conclusion: The cytokine IL-6 has repeatedly been found to be associated with suicidality. The present study concurs with this role of IL-6 in a naturalistic observational study of AUD patients.

The temporal association between suicide and comorbid mental disorders in people treated for substance use disorders: a National registry study.

BACKGROUND: The time after contact with specialized health services for mental health and substance use is associated with an increased risk of suicide, where temporal aspects of suicide and comorbid mental disorders in patients with substance use disorders could be associated. This study aimed to examine the temporal association between time from last treatment contact to suicide and comorbid mental disorders in patients with substance use disorders. METHODS: This study is a historical prospective case series using nationwide registry data. It included 946 individuals registered the year before suicide with a substance use disorder (F10-F19) in Norway's specialized health services for treating substance use and mental health disorders between 2010 and 2020. The outcome was the number of weeks from the last contact with services to suicide. The exposure was comorbid mental disorders divided into 'no comorbid mental disorder'; 'psychosis or bipolar disorders' (F20-F31), 'depressive or anxiety disorders' (F32-F49); and 'personality disorders' (F60-F69). Covariates included gender, age, last diagnosed substance use disorder, registered deliberate self-harm last year, and the number of in- and outpatient contacts the previous year. RESULTS: The number of weeks from last service contact to suicide differed (p = < 0.001) between patients with no comorbid mental disorders (Median = 7; IQR 2-23), psychosis or bipolar disorders (Median = 2; IQR = 1-7), depressive or anxiety disorders (Median = 3; IQR = 1-11) and personality disorders (Median = 1; IQR = 1-5.5). Significantly decreased adjusted incidence rate ratios (aIRR) were found for psychosis or bipolar disorders [aIRR = 0.67 (95% CI 0.53-0.85)] and personality disorders [aIRR = 0.56 (0.42-0.77)] compared to no comorbid mental disorder when adjusted for individual characteristics and service contact. For depressive and anxiety disorders compared to no comorbid mental disorder, the association was significant when adjusted for individual characteristics [aIRR = 0.55 (0.46-0.66)]. CONCLUSIONS: While patients with substance use disorders generally died by suicide a short time after contact with services, patients with comorbid mental disorders died an even shorter time after such contact and significantly shorter than patients without such comorbidities.

Exploring dog ownership in the lives of people with substance use disorder: a qualitative study.

BACKGROUND: Recovery from substance use is commonly seen as a process of integrating social relationships and creating a sense of meaning in one's life. Dog owners describe a close relationship with their dog that impacts many aspects of their everyday life. Yet for individuals with substance use disorder (SUD), little is known about how dog ownership could affect their lives. The aim of this study was to explore how people living with SUD experience and describe their everyday life when owning a dog. METHOD: Eight semi-structured in-depth individual interviews were conducted with people having personal experience of living with SUD and owning a dog. Data were gathered and analysed using qualitative content analysis. RESULTS: The analysis yielded four categories, reflecting different aspects of dog ownership. Living with SUD and owning a dog was primarily something positive in their life. People increased their social connections personally and within society. They felt a belonging which gave a sense of agency and purpose, and they developed structure in their day and boundaries to their environment. Dog ownership, however, could hinder access to services which was found to be challenging for some participants. CONCLUSIONS: The owning of a dog can lead to changes that parallel those of a recovery process. This finding adds to the research on the connection that dogs can provide and shows how pertinent this can be particularly for vulnerable persons such as those with SUD.

Education and Training in Addiction Medicine and Psychology across Europe: A EUFAS Survey.

INTRODUCTION: Training in addiction medicine and addiction psychology is essential to ensure the quality of treatment for patients with substance use disorders. Some earlier research has shown varying training between countries, but no comprehensive study of addiction training across Europe has been performed. The present study by the European Federation for Addiction Societies (EUFAS) aimed to fill this gap. METHODS: A Delphi process was used to develop a questionnaire on specialist training in addiction treatment in 24 European countries. The final questionnaire consisted of 14 questions on either addiction medicine or addiction psychology, covering the nature and content of the training and institutional approval, the number of academic professorial positions, and the estimated number of specialists in each country. RESULTS: Information was not received from all countries, but six (Belgium, Denmark, Ireland, Italy, Poland, and Romania) reported no specialized addiction medicine training, while 17 countries did. Seven countries (Belgium, France, Ireland, Italy, Russia, Switzerland, and the Netherlands) reported no specialized addiction psychology training, while 14 countries did. Training content and evaluation methods varied. Approval was given either by governments, universities, or professional societies. Eighteen countries reported having professorships in addiction medicine and 12 in addiction psychology. The number of specialists in addiction medicine or psychology varied considerably across the countries. DISCUSSION: The survey revealed a large heterogeneity in training in addiction medicine and addiction psychology across Europe. Several countries lacked formal training, and where formal training was present, there was a large variation in the length of the training. Harmonization of training, as is currently the case for other medical and psychology specializations, is warranted to ensure optimal treatment for this under-served patient group.

Mortality and alcohol-related morbidity in patients with delirium tremens, alcohol withdrawal state or alcohol dependence in Norway: A register-based prospective cohort study.

BACKGROUND AND AIMS: Little is known about long-term consequences of delirium tremens (DT). This study aimed to compare all-cause and cause-specific mortality and alcohol-related morbidity between patients with: (i) DT, (ii) alcohol withdrawal state (AWS) and (iii) alcohol dependence (AD). DESIGN: A national longitudinal health registry study with linked data from the Norwegian Patient Registry and the Norwegian Cause of Death Registry. SETTING: Norway. PARTICIPANTS: All patients registered in the Norwegian Patient Registry between 2009 and 2015 with a diagnosis of AD (ICD-10 code F10.2), AWS (F10.3) or DT (F10.4) and aged 20-79 years were included (n = 36 287). MEASUREMENTS: Patients were categorized into three mutually exclusive groups; those with DT diagnosis were categorized as DT patients regardless of whether or not they had received another alcohol use disorder diagnosis during the observation period or not. Outcome measures were: annual mortality rate, standardized mortality ratios (SMR) for all-cause and cause-specific mortality and proportion of alcohol-related morbidities which were registered in the period from 2 years before to 1 year after the index diagnosis. FINDINGS: DT patients had higher annual mortality rate (8.0%) than AWS (5.0%) and AD (3.6%) patients, respectively. DT patients had higher mortality [SMR = 9.8, 95% confidence interval (CI) = 8.9-10.7] than AD patients (SMR = 7.0, 95% CI = 6.8-7.2) and AWS patients (SMR = 7.8, 95% CI = 7.2-8.4). SMR was particularly elevated for unnatural causes of death, and more so for DT patients (SMR = 26.9, 95% CI = 21.7-33.4) than for AD patients (SMR = 15.2, 95% CI = 14.2-16.3) or AWS patients (SMR = 20.1, 95% CI = 16.9-23.9). For all comorbidities, we observed a higher proportion among DT patients than among AWS or AD patients (P < 0.001). CONCLUSIONS: People treated for delirium tremens appear to have higher rates of mortality and comorbidity than people with other alcohol use disorders.

Transition From Substance-Induced Psychosis to Schizophrenia Spectrum Disorder or Bipolar Disorder.

Objective: The authors investigated transitions to schizophrenia spectrum or bipolar disorder following different types of substance-induced psychosis and the impact of gender, age, number of emergency admissions related to substance-induced psychosis, and type of substance-induced psychosis on such transitions. Methods: All patients in the Norwegian Patient Registry with a diagnosis of substance-induced psychosis from 2010 to 2015 were included (N=3,187). The Kaplan-Meier method was used to estimate cumulative transition rates from substance-induced psychosis to either schizophrenia spectrum disorder or bipolar disorder. Cox proportional hazard regression was used to estimate hazard ratios for transitions to schizophrenia spectrum or bipolar disorders associated with gender, age, number of emergency admissions, and type of substance-induced psychosis. Results: The 6-year cumulative transition rate from substance-induced psychosis to schizophrenia spectrum disorder was 27.6% (95% CI=25.6­29.7). For men, the risk of transition was higher among younger individuals and those with either cannabis-induced psychosis or psychosis induced by multiple substances; for both genders, the risk of transition was higher among those with repeated emergency admissions related to substance-induced psychosis. The cumulative transition rate from substance-induced psychosis to bipolar disorder was 4.5% (95% CI=3.6­5.5), and the risk of this transition was higher for women than for men. Conclusions: Transition rates from substance-induced psychosis to schizophrenia spectrum disorder were six times higher than transition rates to bipolar disorder. Gender, age, number of emergency admissions, and type of substance-induced psychosis affected the risk of transition.

The Association Between Regular Physical Activity and Depressive Symptoms Among Patients in Treatment of Alcohol and Substance Use Disorders.

Background: Alcohol and other substance use disorders and major depression often co-occur. A sedentary lifestyle is related to major depression and even moderate exercise may prevent and contribute to the treatment of depression. Studies have found an effect of physical activity on depression in alcohol and other substance use disorder patients even in clinical settings. Aim: To investigate the relationship between level of physical activity and depressive symptoms over time in alcohol and substance use disorder inpatients. Methods: Eighty-nine substance use disorder inpatients were followed for 6 months during treatment. The International Physical Activity Questionnaire was used to categorize 3 groups of low, moderate, or high level of physical activity. In addition to background variables and alcohol and drug use measures, data on biometric measures and on sleep were gathered. Becks Depression Inventory version II (BDI-II) measured depressive symptoms. A multilevel logistic regression was used to analyze the longitudinal relationship between physical activity and depressive symptoms. Results: Most patients (57%) reported low activity, while 24% reported moderate and 19% high activity. Few changed their activity level during treatment. Moderate physical activity was related to lower score on BDI-II (P = .029). Level of physical activity was closely related to insomnia (P = .024). In the multivariate analysis the relationship between depressive symptoms and physical activity did not withstand the adjustment for insomnia. However, in the multilevel logistic regression higher physical activity was related to lower BDI-II score in a dose dependent manner. Conclusions: Among these alcohol and other substance use disorders patients in treatment, there was a relationship between depressive symptoms and physical activity. The low level of physical activity identified among these patients was related to a high level of depressive symptoms. The level of depressive symptoms declined over time; but this change was not related to an increase in physical activity.

Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco.

BACKGROUND: Smoking and alcohol use often co-occur, and the use of nicotine-containing products is particularly common among persons with alcohol use disorder (AUD). Recent evidence shows that chronic alcohol use leads to inflammation through increased gut permeability and dysregulated cytokine levels. While cigarette smoking also has detrimental health effects, nicotine has immune dampening effects in some settings. Preclinical evidence demonstrates that nicotine can dampen alcohol-induced inflammation, but inflammatory responses after nicotine use has not been studied in persons with AUD. This study compared the level of circulating cytokines in abstinent AUD inpatients who were non-tobacco users, smokers, users of Swedish snus, or dual tobacco users. METHODS: We collected blood samples and information about somatic and mental health and tobacco habits from 111 patients in residential treatment for AUD and 69 healthy controls. Levels of interferon (IFN)-γ, interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-17a, IL-1ß, IL-6, IL-8, IL-1 receptor antagonist (ra), and monocyte chemoattractant protein (MCP)-1 were examined using a multiplex assay. RESULTS: Patients with AUD had higher levels of seven cytokines than healthy controls. Among the AUD patients, nicotine users had lower levels of IL-10, TNF-α, IL-17a, IL-1ß, IL-8, and MCP-1 (all p < 0.05). CONCLUSIONS: Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD. Nonetheless, nicotine use cannot be recommended as a viable therapeutic option to reduce alcohol-induced inflammation because of its other adverse effects. Additional studies of the effects of tobacco or nicotine products on cytokine patterns in relation to mental or somatic health conditions are warranted.

Associations of Adolescent Alcohol Use and Self-Reported Alcohol Tolerance With Risk of Self-Harm and Suicide in Early Adulthood: A Birth-Cohort Study.

OBJECTIVE: We aimed to assess the predictive associations of age at first drink (AFD), age at first intoxication (AFI), frequency of intoxication, and self-reported alcohol tolerance at ages 15-16 with self-harm requiring medical attention or suicide death by age 33. METHOD: In an ongoing follow-up study, the Northern Finland Birth Cohort 1986, a total of 7,735 individuals were included at ages 15-16. Information on alcohol and other substance use was assessed via questionnaires. Information on self-harm or suicide was collected from national registers until the participants were 33 years of age. Baseline psychiatric symptomatology measured with the Youth Self-Report questionnaire and sociodemographic background variables were controlled for in multivariable analyses using Cox regression analyses. RESULTS: Male gender and psychiatric symptoms at ages 15-16 were consistently associated with greater risk of self-harm and suicide death. When baseline psychiatric symptomatology and other background variables were adjusted for, younger AFI (hazard ratio [HR] = 2.28, 95% CI [1.16, 4.47]) and high inherent alcohol tolerance (HR = 3.76, 95% CI [1.55, 9.08]) were associated with self-harm. Furthermore, frequent alcohol intoxication (HR = 5.39, 95% CI [1.44, 20.23]) and high inherent alcohol tolerance (HR = 6.20, 95% CI [1.18, 32.45]) were associated with suicide death by age 33. CONCLUSIONS: High alcohol tolerance, age at onset of intoxication, and frequency of alcohol intoxication in adolescence appear to be significant predictors of self-harm and suicide in early adulthood. Self-reported alcohol tolerance in adolescence is a novel empirical approach to assess adolescent alcohol use associating with subsequent harms.

The effects of exceeding low-risk drinking thresholds on self-rated health and all-cause mortality in older adults: the Tromsø study 1994-2020.

BACKGROUND: Based on findings of increasing alcohol consumption in older adults, it is important to clarify the health consequences. Using data from the Tromsø study, we aimed to investigate the relationship between different levels of alcohol consumption in old adulthood and self-rated health trajectories and all-cause mortality. METHODS: This is an epidemiological study utilizing repeated measures from the Tromsø study cohort. It allows follow-up of participants from 1994 to 2020. A total of 24,590 observations of alcohol consumption were made in older adults aged 60-99 (53% women). PRIMARY OUTCOME MEASURES: Self-rated health (SRH) and all-cause mortality. SRH was reported when attending the Tromsø study. Time of death was retrieved from the Norwegian Cause of Death Registry. The follow-up time extended from the age of study entry to the age of death or end of follow-up on November 25, 2020. PREDICTOR: Average weekly alcohol consumption (non-drinker, < 100 g/week, ≥100 g/week). We fitted two-level logistic random effects models to examine how alcohol consumption was related to SRH, and Cox proportional hazards models to examine its relation to all-cause mortality. Both models were stratified by sex and adjusted for sociodemographic factors, pathology, biometrics, smoking and physical activity. In addition, all the confounders were examined for whether they moderate the relationship between alcohol and the health-related outcomes through interaction analyses. RESULTS: We found that women who consumed ≥100 g/week had better SRH than those who consumed < 100 g/week; OR 1.85 (1.46-2.34). This pattern was not found in men OR 1.18 (0.99-1.42). We identified an equal mortality risk in both women and men who exceeded 100 g/week compared with those who consumed less than 100 g/week; HR 0.95 (0.73-1.22) and HR 0.89 (0.77-1.03), respectively. CONCLUSIONS: There was no clear evidence of an independent negative effect on either self-rated health trajectories or all-cause mortality for exceeding an average of 100 g/week compared to lower drinking levels in this study with up to 25 years follow-up. However, some sex-specific risk factors in combination with the highest level of alcohol consumption led to adverse effects on self-rated health. In men it was the use of sleeping pills or tranquilisers and ≥ 20 years of smoking, in women it was physical illness and older age.

The Self-Rated Effects of Alcohol Are Related to Presystemic Metabolism of Alcohol.

AIMS: A high number of alcohol units required to feel a subjective effect of alcohol predicts future alcohol use disorders (AUDs). The subjective response to alcohol can be measured using the validated retrospective self-rated effects of alcohol (SRE) questionnaire. Few studies have investigated the specific relationship between SRE and blood alcohol concentration (BAC) in an experimental setting. METHODS: Twenty healthy young adult male volunteers who had experience with binge drinking, but did not have AUD, filled out the SRE-questionnaire and were served with a fixed amount of alcohol per body weight. BACs were measured throughout a 12-hour period, reaching a maximum BAC of ~0.13%. Median split of SRE-scores was utilized to compare BACs among participants with relatively high effects (low SRE) and relatively low effects (high SRE) of alcohol. RESULTS: Participants reporting a relatively low SRE-score had a statistically significant higher measured BAC at all time points until alcohol was eliminated. This was especially pronounced during the first 2 hours after alcohol (P = 0.015) without a significant difference in the alcohol elimination rate being detected. CONCLUSION: The study indicates that a self-ated SRE-score is related to BACs after the ingestion of a standardized amount of alcohol per body weight. Reporting a higher number of alcohol units before feeling an effect was related to a lower BAC. As the differences in BAC between relatively high and low self-rated effects appeared rapidly after intake, this could be interpreted as an effect of presystemic metabolism of alcohol.

Impact of liver fibrosis and clinical characteristics on dose-adjusted serum methadone concentrations.

BACKGROUND: There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements. OBJECTIVES: We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations. METHODS: We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016-2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis. RESULTS: When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: -2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (-0.50; -4.59, 3.59; 0.810). CONCLUSIONS: Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations.