Liver stiffness and associated risk factors among people with a history of injecting drugs: a prospective cohort study.

BACKGROUND: Persons with opioid use disorders (OUD) and persons with substance use disorders (SUD) who inject substances have a reduced life expectancy of up to 25 years compared with the general population. Chronic liver diseases are a substantial cause of this. Screening strategies based on liver stiffness measurements (LSM) may facilitate early detection, timely intervention, and treatment of liver disease. This study aims to investigate the extent of chronic liver disease measured with transient elastography and the association between LSM and various risk factors, including substance use patterns, hepatitis C virus (HCV) infection, alcohol use, body mass index, age, type 2 diabetes mellitus, and high-density lipoprotein (HDL) cholesterol among people with OUD or with SUD who inject substances. METHODS: Data was collected from May 2017 to March 2022 in a cohort of 676 persons from Western Norway. The cohort was recruited from two populations: Persons receiving opioid agonist therapy (OAT) (81% of the sample) or persons with SUD injecting substances but not receiving OAT. All participants were assessed at least once with transient elastography. A linear mixed model was performed to assess the impact of risk factors such as HCV infection, alcohol use, lifestyle-associated factors, and substance use on liver stiffness at baseline and over time. Baseline was defined as the time of the first liver stiffness measurement. The results are presented as coefficients (in kilopascal (kPa)) with 95% confidence intervals (CI). RESULTS: At baseline, 12% (n = 83) of the study sample had LSM suggestive of advanced chronic liver disease (LSM ≥ 10 kPa). Advanced age (1.0 kPa per 10 years increments, 95% CI: 0.68;1.3), at least weekly alcohol use (1.3, 0.47;2.1), HCV infection (1.2, 0.55;1.9), low HDL cholesterol level (1.4, 0.64;2.2), and higher body mass index (0.25 per increasing unit, 0.17;0.32) were all significantly associated with higher LSM at baseline. Compared with persistent chronic HCV infection, a resolved HCV infection predicted a yearly reduction of LSM (-0.73, -1.3;-0.21) from baseline to the following liver stiffness measurement. CONCLUSIONS: More than one-tenth of the participants in this study had LSM suggestive of advanced chronic liver disease. It underscores the need for addressing HCV infection and reducing lifestyle-related liver risk factors, such as metabolic health factors and alcohol consumption, to prevent the advancement of liver fibrosis or cirrhosis in this particular population.

Integrated exercise program in opioid agonist therapy clinics and effect on psychological distress: study protocol for a randomized controlled trial (BAReAktiv).

BACKGROUND: Substance use disorder is associated with unhealthy lifestyle choices, resulting in adverse social and health consequences. People with opioid use disorder receiving opioid agonist therapy, in particular, have high morbidity and reduced quality of life. Physical activity is recommended as an adjunctive treatment for people with substance use disorder, but there is minimal evidence from randomized controlled trials on the effects of this among people with substance use disorder receiving opioid agonist therapy. METHODS: BAReAktiv is a multicentre randomized controlled trial. The study aims to recruit 324 patients receiving opioid agonist therapy (parallel groups randomized 1:1 to integrated exercise intervention or control, superiority trial). A 16-week group-based integrated exercise intervention with workouts twice a week. The exercise program consists of endurance and resistance training. The target group will be patients 18 years and older receiving opioid agonist therapy in outpatient clinics in several centers in Western Norway. The primary outcome of the study is the effect on psychological distress measured by Hopkins' symptom checklist with ten items. Secondary outcome measures include physical functioning assessed with a 4-min step test, activity level, fatigue symptoms, quality of life, and changes in inflammation markers. This study will provide improved knowledge on the effects of an integrated exercise program in opioid agonist therapy. DISCUSSION: Systematically integrating exercise programs for people receiving opioid agonist therapy could lead to a shift towards a stronger focus on health behaviors in outpatient care. Integrating exercise could benefit patient recovery and reduce disease burden. Further scale-up will be considered if the provided exercise program is safe and effective. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05242848. Registered on February 16, 2022.

The association of psychological distress and economic and health worries with tobacco smoking behavior during the COVID-19 pandemic: a two-year longitudinal cohort study.

BACKGROUND: The COVID-19 pandemic and other life events may trigger worries and psychological distress. These impacts may lead to unhealthy behaviors, such as tobacco smoking, but the degree of such associations is unclear. The current three-wave longitudinal study examines changes in tobacco smoking in Norway between 2020 and 2022 and their associations with psychological distress as well as health- and economy-related worries. METHODS: Data were collected in April 2020 (baseline), January 2021, and January 2022 in Bergen, Norway, from an online longitudinal population-based survey. Smoking tobacco (the outcome variable) was dichotomized based on the responses to the question of whether participants smoked cigarettes or not. Tobacco smoking and its associations with psychological distress were assessed among 24,914 participants (response rate 36%) in a mixed model regression presented with coefficients and 95% confidence intervals (CI), adjusting for COVID-19-related worries, home office/study, occupational situation, age, gender, education, having children below 18 years living at home, living alone, and alcohol consumption. RESULTS: A total of 10% of the study sample were current smokers at baseline. At baseline, smoking tobacco was associated with high levels of psychological distress (absolute difference 13%, 95% CI 10%; 15%), advanced age (50-59 years: 11%, CI 10%; 13%), and hazardous alcohol use (4%, CI 3%; 5%) compared to their counterparts. Higher education (-5%, CI -6%; -4%), working from home (-4%, CI -5%; -4%), and higher physical activity levels (-4%, CI -5%; -3%) were associated with non-smoking. The prevalence of smoking among individuals experiencing severe psychological distress decreased slightly over time (-2% per year, CI -3%; -1%). CONCLUSIONS: Smoking was associated with severe psychological distress, advanced age, and hazardous alcohol use at baseline; non-smoking was associated with high education, working from home, and high physical activity. Nevertheless, the smoking rate among individuals experiencing severe psychological distress slightly decreased over the course of the COVID-19 pandemic.

Update of statistical analysis plan for: Integration of smoking cessation into standard treatment for patients receiving opioid agonist therapy who are smoking tobacco: protocol for a randomised controlled trial (ATLAS4LAR).

This protocol paper presents an updated statistical analysis plan of the protocol of a randomised controlled trial. The randomised controlled trial investigates the effect of integrating smoking cessation interventions at outpatient opioid agonist therapy (OAT) clinics for persons with opioid dependency receiving OAT medication. The intervention group receives weekly follow-up including a short behavioural intervention and provision of nicotine replacement products. The control group receives standard treatment. The duration of the intervention is 16 weeks and the follow-up was completed by the end of October 2023. The primary outcome is defined as the proportion of participants reducing the number of cigarettes smoked by at least a 50% at week 16 of the intervention period. The primary outcome will be analysed according to intention-to-treat principles. Missing outcome data will be set equal to the baseline values. Development and reporting of the statistical analysis plan follow the Guidelines for the Content of Statistical Analysis Plans in Clinical Trials.Trial registration ClinicalTrials.gov NCT05290025. Registered on 22 March 2022.

Effect of integrated hepatitis C virus treatment on psychological distress in people with substance use disorders.

People with substance use disorders (SUD) have a high prevalence of chronic hepatitis C virus (HCV) infection and mental health disorders. We aimed to assess the impact of integrated HCV treatment on psychological distress measured by Hopkins-symptom-checklist-10 (SCL-10). This multi-center randomized controlled trial evaluated psychological distress as a secondary outcome of integrated HCV treatment (INTRO-HCV trial). From 2017 to 2019, 289 participants were randomly assigned to receive either integrated or standard HCV treatment with direct-acting antiviral therapy. Integrated HCV treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in internal medicine outpatient clinics at centralized hospitals. Participants in the integrated treatment arm had a sustained virologic response of 93% compared to 73% for those in standard treatment arm. Psychological distress was assessed using SCL-10 prior to initiation of HCV treatment and 12 weeks after treatment completion. The mean SCL-10 score prior to HCV treatment was 2.2 (standard deviation [SD]: 0.7) for patients receiving integrated HCV treatment and 2.2 (SD: 0.8) for those receiving standard HCV treatment. Twelve weeks after the end of treatment, the mean SCL-10 score change was - 0.1 (- 0.3;0.0) in the integrated compared to the standard arm. Psychological distress did not substantially change during the treatment period and was not significantly different between the treatment arms.

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.

Changes in Body Mass Index and Their Associations with Psychological Distress, Worries, and Emotional Eating during the COVID-19 Pandemic: A Norwegian Cohort Study.

In 2020, the COVID-19 pandemic highlighted obesity's long-term rise. Some of the impacts of the pandemic were increased psychological distress, emotional eating, higher consumption of high-sugar foods and drinks, and a more sedentary lifestyle. This study examined BMI changes over time and their associations with psychological distress and lifestyle changes. This population-based cohort study had 24,968 baseline participants and 15,904 and 9442 one- and two-year follow-ups, respectively. Weight, height, psychological distress, high-sugar foods and drinks, physical activity, and emotional eating were assessed. These factors and BMI were examined at baseline and over time. We used mediation analyses and structural equation modeling to determine how psychological distress affects BMI. The mean BMI was 25.7 kg/m2 at baseline and 26.2 kg/m2 at two years. High psychological distress, daily emotional eating, and low physical activity were associated with higher BMI at baseline and higher yearly increases in BMI compared to reference levels. Emotional eating mediated 33% of the psychological distress BMI effect. Overall, BMI increased during the pandemic. Psychological distress during the pandemic was linked to weight gain partly through emotional eating. This association remained strong over time during different stages of the pandemic.

Cost-effectiveness of integrated treatment for hepatitis C virus (HCV) among people who inject drugs in Norway: An economic evaluation of the INTRO-HCV trial.

BACKGROUND AND AIMS: The INTRO-HCV randomized controlled trial conducted in Norway over 2017-2019 found that integrated treatment, compared with standard-of-care hospital treatment, for hepatitis C virus (HCV) with direct-acting antivirals (DAAs) improved treatment outcomes among people who inject drugs (PWID). We evaluated cost-effectiveness of the INTRO-HCV intervention. DESIGN: A Markov health state transition model of HCV disease progression and treatment with cost-effectiveness analysis from the health-provider perspective. Primary cost, utility, and health outcome data were derived from the trial. Costs and health benefits (quality-adjusted life-years, QALYs) were tracked over 50 years. Probabilistic and univariate sensitivity analyses investigated DAA price reductions and variations in HCV treatment and disease care cost assumptions, using costs from different countries (Norway, United Kingdom, United States, France, Australia). SETTING AND PARTICIPANTS: PWID attending community-based drug treatment centers for people with opioid dependence in Norway. MEASUREMENTS: Incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained, compared against a conventional (€70 000/QALY) willingness-to-pay threshold for Norway and lower (€20 000/QALY) threshold common among high-income countries. FINDINGS: Integrated treatment resulted in an ICER of €13 300/QALY gained, with 99% and 71% probability of being cost-effective against conventional and lower willingness-to-pay thresholds, respectively. A 30% lower DAA price reduced the ICER to €6 900/QALY gained, with 91% probability of being cost-effective at the lower willingness-to-pay threshold. A 60% and 90% lower DAA price had 36% and >99% probability of being cost-saving, respectively. Sensitivity analyses suggest integrated treatment was cost-effective at the lower willingness-to-pay threshold (>60% probability) across different assumptions on HCV treatment and disease care costs with 30% DAA price reduction, and became cost-saving with 60%-90% price reductions. CONCLUSIONS: Integrated hepatitis C virus treatment for people who inject drugs in community settings is likely cost-effective compared with standard-of-care referral pathways in Norway and may be cost-saving in settings with particular characteristics.

The association between psychological distress and alcohol consumption and physical activity: a population-based cohort study.

Introduction: The COVID-19 pandemic and infection control measures caused changes to daily life for most people. Heavy alcohol consumption and physical inactivity are two important behavioral risk factors for noncommunicable diseases worldwide. The COVID-19 pandemic, with its social distancing measures, home office policies, isolation, and quarantine requirements may have an impact on these factors. This three-wave longitudinal study aims to investigate if psychological distress and worries related to health and economy were associated with levels and changes in alcohol consumption and physical activity during the two first years of the COVID-19 pandemic in Norway. Methods: We used data collected in April 2020, January 2021, and January 2022 from an online longitudinal population-based survey. Alcohol consumption and physical activity status were assessed at all three measuring points via the Alcohol Use Disorder Identification Test (AUDIT-C) and the International Physical Activity Questionnaire (IPAQ-SF). COVID-19-related worries, home office/study, occupational situation, age, gender, children below 18 years living at home, and psychological distress (measured with the Symptom Checklist (SCL-10)) were included as independent variables in the model. A mixed model regression was used and presented with coefficients with 95% confidence intervals (CI). Results: Analysis of data from 25,708 participants demonstrates that participants with substantial symptoms of psychological distress more often reported higher alcohol consumption (1.86 units/week, CI 1.48-2.24) and lower levels of physical activity [-1,043 Metabolic Equivalents of Task (METs) per week, CI -1,257;-828] at baseline. Working/studying from home (0.37 units/week, CI 0.24-0.50) and being male (1.57 units/week, CI 1.45-1.69) were associated with higher alcohol consumption. Working/studying from home (-536 METs/week, CI -609;-463), and being older than 70 years (-503 METs/week, CI -650;-355) were related to lower levels of physical activity. The differences in activity levels between those with the highest and lowest levels of psychological distress reduced over time (239 METs/week, CI 67;412), and similarly the differences in alcohol intake reduced over time among those having and not having children < 18 years (0.10 units/week, CI 0.01-0.19). Conclusion: These findings highlight the substantial increases in risks related to inactivity and alcohol consumption among those with high levels of psychological distress symptoms, and particularly during the COVID-19 pandemic, and increase the understanding of factors associated with worries and health behavior.

Attention-deficit/hyperactivity disorder (ADHD) symptoms and their relation to diagnosed ADHD, sociodemographic characteristics, and substance use among patients receiving opioid agonist therapy: a Norwegian cohort study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms may challenge sufficient treatment of substance use and mental disorders. The literature on the extent of such symptoms among patients receiving opioid agonist therapy (OAT) is scarce. This study examined ADHD symptoms using the ADHD self-report scale (ASRS) and the association between the 'ASRS-memory' and 'ASRS-attention' scores and substance use and sociodemographic characteristics among patients receiving OAT. METHODS: We used data from assessment visits of a cohort of patients in Norway. In total, 701 patients were included from May 2017 to March 2022. All patients responded at least once to two ASRS questions assessing memory and attention, respectively. Ordinal regression analyses were performed to investigate whether the two obtained scores were associated with age, sex, frequent substance use, injecting use, housing status, and educational attainment at baseline, i.e., the first assessment, and over time. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Additionally, a subsample of 225 patients completed an extended interview, including the ASRS-screener and collection of registered mental disorder diagnoses from the medical records. Standard cutoffs were used to define the presence of each ASRS symptom or a positive ASRS-screener ('ASRS-positive'). RESULTS: At baseline, 428 (61%) and 307 (53%) patients scored over the cutoffs on the 'ASRS-memory' and 'ASRS-attention,' respectively. Frequent cannabis use was associated with higher 'ASRS-memory' (OR: 1.7, 95% CI: 1.1-2.6) and 'ASRS-attention' (1.7, 1.1-2.5) scores compared with less or no use at baseline, though reduced score on the 'ASRS-memory' over time (0.7, 0.6-1.0). At baseline, frequent stimulant use (1.8, 1.0-3.2) and low educational attainment (0.1, 0.0-0.8) were associated with higher 'ASRS-memory' scores. In the subsample fulfilling the ASRS-screener, 45% of the patients were 'ASRS-positive,' of whom 13% with a registered ADHD diagnosis. CONCLUSIONS: Our findings illustrate a relationship between the ASRS-memory and -attention scores and frequent cannabis and stimulant use. Furthermore, nearly half of the subsample was 'ASRS-positive.' Patients receiving OAT might benefit from being further assessed for ADHD, but improved diagnostic methods are required.

The efficacy of integrated hepatitis C virus treatment in relieving fatigue in people who inject drugs: a randomized controlled trial.

BACKGROUND: Most people who inject drugs (PWIDs) suffer from severe fatigue, and chronic hepatitis C virus (HCV) infection may play a role in this. However, there is scarce evidence about interventions that alleviate fatigue among PWIDs. The present study investigated the effect of integrated HCV treatment on fatigue in this population compared to the effect of standard HCV treatment, adjusted for sustained virological response of the HCV treatment. METHODS: This multi-center, randomized controlled trial evaluated fatigue as a secondary outcome of integrated HCV treatment (the INTRO-HCV trial). From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in specialized infectious disease outpatient clinics at referral hospitals. Fatigue was assessed prior to treatment and 12 weeks after treatment using the nine-item Fatigue Severity Scale (FSS-9). We applied a linear mixed model to evaluate the impact of integrated HCV treatment on changes in FSS-9 (ΔFSS-9) sum scores. RESULTS: At baseline, the mean FSS-9 sum score was 46 (standard deviation (SD): 15) for participants on integrated HCV treatment and 41 (SD: 16) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean FSS-9 sum score for participants receiving integrated HCV treatment was 42 (SD: 15) and 40 (SD: 14) for those receiving standard HCV treatment. Integrated HCV treatment did not reduce the FSS-9 scores compared to standard HCV treatment (ΔFSS-9: -3.0, 95% confidence interval (CI): -6.4;0.4). CONCLUSIONS: Fatigue is a common symptom among PWIDs. Integrated HCV treatment is at least equal to standard HCV treatment in improving fatigue. TRIAL REGISTRATION: ClinicalTrials.gov.no NCT03155906, 16/05/2017.

Emotional Eating and Changes in High-Sugar Food and Drink Consumption Linked to Psychological Distress and Worries: A Cohort Study from Norway.

Psychological distress is linked to unhealthy eating behaviors such as emotional eating and consumption of high-sugar food and drinks. Cross-sectional studies from early in the COVID-19 pandemic showed a high occurrence of worries and psychological distress, and this was associated with emotional eating. Few larger studies have examined how this coping pattern develops over time. This cohort study with 24,968 participants assessed changes over time in emotional eating, consumption of sugary foods as an example of unhealthy food choices, and consumption of fruits and vegetables as an example of healthy food choices. Further, associations between these and psychological distress, worries, and socio-demographic factors were assessed. Data were collected at three time points (April 2020, initially in the COVID-19 pandemic, then one and two years later). Emotional eating and intake of sugary foods and drinks were high at the start of the pandemic, followed by a reduction over time. High psychological distress was strongly associated with higher levels of emotional eating and high-sugar food intake, and lower levels of healthy eating habits. The strength of this association reduced over time. Our findings indicate the high frequency in unhealthy food choices seen early in the COVID-19 pandemic improved over time.

Association between oral and general health related quality of life among Norwegian patients with substance use disorders in opioid agonist therapy.

OBJECTIVE: Assess the association between oral and general health related quality of life using oral impacts on daily performances (OIDP) and the quality of life tool EQ-5D-5L from EuroQoL among patients with substance use disorder (SUD) who receive opioid agonist therapy. METHOD: 609 patients with SUD completed the EQ-5D-5L. A dental sub-study of 167 patients completed OIDP and an oral examination when attending outpatient clinics in Western Norway for their opioid agonist therapy. The merged analytical sample consisted of 165 patients. The association between OIDP and EQ-5D-5L was assessed by Spearman's rho and a linear multiple variable regression analysis. A line graph and a Pen's parade displayed the distributions of OIDP sum scores and EQ-5D-5L index values. RESULTS: Overall mean summary- and index EQ-5D-5L scores were 9.97 (sd 3.25) and 0.69 (sd 0.22). Mean score for OIDP was 9.75 (sd 9.59). Spearman's rho was 0.34 (p < .01) between OIDP and EQ-5D-5L summary scores. Linear regression revealed an association adjusted for sex and age of 0.12 (95% CI 0.07-0.17) and a coefficient of determination of 0.1460. CONCLUSION: This study reveals a strong association between OIDP and EQ-5D-5L reflecting the importance of oral health to general health for patients with SUD. Health care professionals should pay attention to oral health. Effective interventions might improve patients' oral and health related quality of life.

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.

[A woman in her twenties with paranoid delusions] / En kvinne i 20-årene med paranoide vrangforestillinger.

BACKGROUND: A woman in her twenties was admitted to the psychiatric ward with suspected psychosis. Routine tests revealed a rare and potentially dangerous cause of her symptoms. CASE PRESENTATION: The patient had a history of bipolar II disorder, recurrent depressive disorder and hypothyroidism, and presented to the psychiatric emergency department with a one-week history of delusions of persecutory character and increasing insomnia. She had given birth four months prior to admission. Clinical examination was otherwise unremarkable. Bipolar psychosis was considered the most likely diagnosis, and she was started on antipsychotic medication with quetiapine 100 mg × 2. Routine blood tests revealed severe hypothyroidism with thyroid stimulating hormone (TSH) of 151,00 mIU/L and free T4 (fT4) of <3,0 pmol/L (9,5-22,0), and the patient was treated with a high dose of oral levothyroxine. After a few days the patient's psychiatric symptoms resolved completely, and her fT4 increased to 10,8 pmol/L. Upon further questioning, the patient admitted to increasing fatigue and constantly feeling cold over the previous few months, which she attributed to being a parent. She was discharged after a week without any psychiatric symptoms. INTERPRETATION: This case report highlights the importance of a broad somatic differential diagnostic approach to patients with psychosis.

Effect of fruit smoothie supplementation on psychological distress among people with substance use disorders receiving opioid agonist therapy: protocol for a randomised controlled trial (FruktBAR).

BACKGROUND: People with substance use disorders generally have unhealthy diets, including limited intake of fruit and vegetables. Evidence shows substantial health benefits from increasing fruit and vegetable consumption on various indicators and possibly also psychological distress. A pilot study has indicated that supplementation with fruit smoothie could be promising also among people receiving opioid agonist therapy for opioid dependence. FruktBAR will compare the efficacy of added fruit smoothie supplementation to people receiving opioid agonist therapy compared to standard treatment without added supplementation. METHODS: FruktBAR is a multicentre, randomised controlled trial. The trial will aim to recruit 302 patients receiving opioid agonist therapy. The intervention involves daily supplementation with 250 ml fruit smoothie including a variety of fruits such as apple, pineapple, mango, bananas, orange, blueberries, passion fruit, coconut, lime, and blackcurrant. The main endpoints are 16 weeks after intervention initiation. Participants will be included and followed up during and after the intervention. The target group will be patients with opioid dependence receiving opioid agonist therapy from involved outpatient clinics in Bergen and Stavanger, two of the largest cities in Norway. The main outcome is psychological distress assessed with Hopkins Symptom Checklist (SCL-10) at the end of the intervention period 16 weeks after initiation, and will be compared between the intervention and control arms. Secondary outcome measures are changes in fatigue, physical functioning assessed with a 4-minute step-test, health-related quality of life, biochemical indicators of inflammation, and biochemical indicators of fruit intake. DISCUSSION: This study will inform on the relative advantages or disadvantages of fruit supplementation in addition to the current medically and psychologically oriented treatment of people receiving opioid agonist therapy. If the supplementation is efficacious, it can be considered for further scale-up. TRIAL REGISTRATION: Registered 2022-02-08 in ClinicalTrials.gov , identifier NCT05229770.

Vitamin D status and associations with substance use patterns among people with severe substance use disorders in Western Norway.

Chronic and harmful substance use is associated with a cluster of harms to health, including micronutrient deficiencies. Maintaining adequate levels of vitamin D is important for musculoskeletal and other aspects of health. In this prospective longitudinal cohort study, 666 participants drawn from outpatient opioid agonist therapy (OAT) clinics and community care clinics for substance use disorder in Western Norway were assessed annually for determination of serum 25-hydroxyvitamin D [s-25(OH)D] levels. Fifty-seven percent were deficient at baseline (s-25(OH)D < 50 nmol/l), and 19% were severely deficient (s-25(OH)D < 25 nmol/l). Among those deficient/severely deficient at baseline, 70% remained deficient/severely deficient at the last measurement (mean duration 714 days). Substance use patterns and dosage of opioids for OAT were not associated with vitamin D levels. One exception was found for cannabis, where consumption on a minimum weekly basis was associated with lower levels at baseline (mean difference: -5.2 nmol/l, 95% confidence interval [CI]: -9.1, - 1.3), but without clear time trends (mean change per year: 1.4 nmol/l, CI: - 0.86, 3.7). The high prevalence of sustained vitamin D deficiency in this cohort highlights the need for targeted monitoring and supplementation for this and similar at-risk populations.

Integration of smoking cessation into standard treatment for patients receiving opioid agonist therapy who are smoking tobacco: protocol for a randomised controlled trial (ATLAS4LAR).

BACKGROUND: About 85% of patients receiving opioid agonist therapy (OAT) for opioid dependence are smoking tobacco. Although smoke-related pulmonary diseases are significant contributors to morbidity and mortality, few smoking cessation interventions are evaluated within this group, and few OAT patients are offered smoking cessation as an integrated part of their addiction treatment. This study protocol describes an integrated smoking cessation intervention aimed at patients receiving OAT and smoking tobacco. METHODS: This is a multicentre, randomised controlled clinical trial that will recruit 266 daily tobacco smoking patients receiving OAT in OAT outpatient clinics in Bergen and Stavanger, Norway. The patients randomised for the intervention arm will be offered smoking cessation therapy consisting of weekly brief behavioural interventions and prescription-free nicotine replacement products. In the control arm, patients will receive standard care without any added interventions related to smoking cessation. The smoking cessation intervention includes psychoeducational techniques with components from motivational interviewing, and nicotine replacement products such as nicotine lozenges, patches, and chewing gum. The duration of the intervention is 16 weeks, with the option of extending it by a further 8 weeks. The main outcomes are measured at 16 weeks after initiation of the intervention, and sustained effects are evaluated 1 year after intervention initiation. The primary outcome is smoking cessation verified by carbon monoxide (CO) levels or at least a 50% reduction in the number of cigarettes smoked. Secondary outcomes are changes in psychological well-being, biochemical inflammation markers, changes in physical health, quality of life, and fatigue. DISCUSSION: Integration of other treatments to standard OAT care improves adherence and completion rates providing another rationale for integrated smoking cessation treatment. Thus, if integrated smoking cessation treatment is superior to standard care, this trial provides important information on further scale-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT05290025. Registered on 22 March 2022.

Folate Status as a Nutritional Indicator among People with Substance Use Disorder; A Prospective Cohort Study in Norway.

Substance use disorder (SUD) is associated with poor nutrition. Vitamin B9, or folate, is an important micronutrient for health. The aim of this prospective longitudinal cohort study was to assess serum folate levels among people with SUD and to investigate the impact of factors related to substance use severity on folate status. Participants were recruited from outpatient clinics for opioid agonist therapy (OAT) and municipal health-care clinics for SUD in Western Norway. They were assessed annually, including blood sampling for determination of micronutrient status. Overall, 663 participants with a total of 2236 serum folate measurements were included. A linear mixed model was applied, and measures are presented as ß-coefficients with 95% confidence interval (CI). Forty-eight percent (CI: 44−51) of the population had low serum folate levels (s-folate < 10 nmol/L), and 23% (CI: 20−26) were deficient (s-folate < 6.8 nmol/L) at baseline. Sixty percent (CI: 53−65) sustained their poor folate status in at least one subsequent assessment. Except for weekly use of cannabis (mean difference in serum folate [nmol/L]: −1.8, CI: −3.3, −0.25) and alcohol (1.9, CI: 0.15, 3.6), weekly use of no other substance class was associated with baseline differences in serum folate when compared to less frequent or no use. Injecting substances was associated with a reduction in serum folate over time (−1.2, CI: −2.3, −0.14), as was higher dosages of OAT medication (−1.1, CI: −2.2, −0.024). Our findings emphasize the need of addressing nutrition among people with severe SUD.

Vitamin B12 Levels, Substance Use Patterns and Clinical Characteristics among People with Severe Substance Use Disorders: A Cohort Study from Western Norway.

People with severe substance use disorder (SUD) have a higher burden of micronutrient deficiency compared with the general population. The aim of this study was to investigate vitamin B12 status and risk factors of deficiency related to substance use, opioid agonist therapy (OAT), as well as hepatitis C infection and liver fibrosis. In this prospective cohort study, participants were recruited from outpatient OAT and SUD clinics in western Norway, and assessed annually with a clinical interview and exam, including venous blood sampling. Data were collected between March 2016 and June 2020, and a total of 2451 serum vitamin B12 measurements from 672 participants were included. The median serum vitamin B12 concentration was 396 (standard deviation 198) pmol/L at baseline, 22% of the population had suboptimal levels (<300 pmol/L) and 1.2% were deficient at baseline (<175 pmol/L). No clear associations were seen with substance use patterns, but liver disease and younger age were associated with higher vitamin B12 levels. Although the majority of participants had satisfactory vitamin B12 levels, about a fifth had suboptimal levels that might or might not be adequate for metabolic needs. Future studies could investigate potential gains in interventions among patients with suboptimal but non-deficient levels.