Low-dose ondansetron: A candidate prospective precision medicine to treat alcohol use disorder endophenotypes.

BACKGROUND: Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects. METHODS: This was a phase III, 6-month, 25-site, randomized, placebo-controlled clinical trial using AD04 to treat DSM-V-categorized AUD individuals who were pre-stratified into the endophenotypes of heavy or very heavy drinking individuals and possessed a pre-defined profile of genetic variants related to the serotonin transporter and serotonin-3AB receptor. Participants (N = 303) presented moderate to severe AUD, >80 % were men, mostly in their fifties, and >95 % were of European descent. Low-dose AD04 (approx. 033 mg twice daily) or a matching placebo was administered twice daily for 6 months. Brief Behavioral Compliance Enhancement Treatment (BBCET [53]) was administered every two weeks to enhance medication compliance and clinic attendance. RESULTS: There was a significant reduction in the monthly percentage of heavy drinking days, PHDD (-46·7 % (2·7 %), 95 %CI: -52·1 % to -41·2 % vs. -38·1 % (2·9 %), 95 %CI: -43·8 % to -32·5 %, respectively; LS mean difference=-8·5 %; p = 0.03) among AD04-treated vs. placebo-receiving heavy drinking individuals at month 6. Heavy drinking individuals were also less likely to be diagnosed with AUD [Month 1: -32·0 % (2·8 %), 95 %CI: -37·5 % to -26·5 % vs. -23·2 % (2·9 %), 95 %CI: -28·9 to -17·5 %; LS mean difference= -8·8 %; p = 0·026)], and improved on the WHO quality of life BREF scale with a significant effect for at least a 1-level downward shift (OR = 3.4; 95 % CI: 1·03-11·45, p = 0·044). Importantly, heavy drinking individuals, as distinct from very heavy drinking individuals, were the bio-psychosocial endophenotype more predictive of therapeutic response to AD04. AD04 had an exceptional safety and tolerability profile, like the placebo's. CONCLUSIONS: In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure.

Safety and compliance of long-term low-dose ondansetron in alcohol use disorder treatment.

BACKGROUND: The increasing prevalence of alcohol use disorder (AUD) and the parallel surge in alcohol-associated liver disease (ALD) emphasize the urgent need for comprehensive alcohol management strategies. Low-dose ondansetron (AD04, a 5-HT3 antagonist) was shown recently to be a promising treatment for AUD with a specific genotypic profile (5-marker). The liver safety of AD04 has never been evaluated in subjects with AUD. The aim of the present study was to assess the liver safety profile of AD04 compared with placebo in subjects with AUD. METHODS: Liver biochemical parameters were assessed in subjects with AUD with a 5-marker genetic profile who participated in a Phase 3 randomized controlled trial and received either twice-daily, low-dose AD04 (ondansetron 0.33 mg twice daily) or matching placebo, combined with brief psychosocial counseling. ALT, AST, GGT, Serum Bilirubin, MCV, and Prothrombin were evaluated at weeks 0, 12, and 24. Adverse cardiac events, general well-being, and study completion were also assessed. RESULTS: Low-dose AD04 did not significantly change biochemical markers of liver injury, such as ALT, AST, and Serum Bilirubin. While patients with AUD displayed elevated GGT levels, typically associated with increased alcohol consumption, this parameter remained unaffected by low-dose AD04. Notably, no significant adverse effects were observed due to oral low-dose AD04 treatment. CONCLUSIONS: Low-dose AD04 has the potential to be a safe treatment option for subjects with AUD and ALD, indicating the need for an RCT for this specific cohort. Such a trial would pave the way for the design of a precision treatment for combined AUD with ALD.

Intranasal as needed naloxone in the treatment of gambling disorder: A randomised controlled trial.

BACKGROUND: Gambling disorder (GD) is a global phenomenon affecting millions of people. GD can result in severe social and financial difficulties and efficacious treatments are warranted. Psychosocial treatments form the basis of treatment. Opioid antagonists (OAs) have however shown promise in previous studies. In a recent imaging study intranasal naloxone was found to rapidly and fully occupy brain µ-opioid receptors. This trial investigates the effect and safety of as needed naloxone in the treatment of gambling disorder. METHODS: This was a 12-week double blind, randomised control trial comparing intranasal naloxone to placebo. The primary endpoint was gambling urge measured by the Gambling symptom Assessment Scale (G-SAS). Secondary outcome measures were gambling severity measures (PGSI) as well as quality of life (WHO:EUROHIS-8), alcohol consumption (AUDIT), depression (MARDS) and internet use (IDS-9SF). In addition, safety of treatment was assessed. Both treatment groups received psychosocial support. RESULTS: 126 participants were randomised to treatment groups in a 1:1 ratio. 106 patients completed the study. Gambling urge (GSAS) and other gambling related measured improved in both groups, but no statistically significant difference could be found. Intranasal naloxone was well tolerated, no subjects discontinued the study due to adverse events. No serious adverse drug reactions were observed. CONCLUSIONS: This study found no difference between the as-needed administration of intranasal naloxone and placebo in reducing gambling urge in persons with GD. Intranasal naloxone was safe and well tolerated.

Consensus and Controversies Between Pain and Addiction Experts on the Prevention, Diagnosis, and Management of Prescription Opioid Use Disorder.

OBJECTIVES: Prescription opioid use disorder (POUD) is an established public health crisis in many countries, and current evidence indicates it is a growing problem in Europe. Many specialists play a role, including pain and addiction medicine specialists, in the diagnosis and management of POUD, but neither group can fully address these patients' needs alone. The purpose of this consensus process was to bring together experts from pain and addiction medicine to examine the positions of both specialties. METHODS: In all, 13 international pain medicine, addiction medicine, and addiction psychiatry experts convened a meeting to formulate a set of consensus statements on the diagnosis and management of POUD. The statements were further refined by a wider group of 22 European expert clinicians. At a second meeting of all 35 participants, a set of controversy statements was also developed to recognize some of the key areas of divergent opinion. RESULTS/CONCLUSIONS: There was a high level of agreement between pain and addiction specialists. Key themes that emerged were the need to strengthen interdisciplinary communication, a desire for greater education and training for clinicians in both specialties, and mutual acknowledgment of the importance of multidisciplinary management of POUD. The blurred line between poorly managed pain and POUD was also a subject of much discussion, reflecting the difficulties in defining and diagnosing this complex condition.

Opioid-related deaths in Europe: Strategies for a comprehensive approach to address a major public health concern.

Use of illicit opioids and misuse of prescription opioids are the main causes of drug-related deaths across the world, and the continuing rise in opioid-related mortality, especially affecting North America, Australia and Europe, is a public health challenge. Strategies that may help to decrease the high levels of opioid-related mortality and morbidity and improve care across Europe include risk assessment and interventions to improve the use of opioid analgesics, e.g. prescription drug-monitoring programmes, education on pain management to reduce opioid prescribing, and the implementation of evidence-based primary prevention programmes to reduce the demand for opioids. For patients who develop opioid use disorder (a chronic and relapsing problematic use of opioids that causes clinical impairment or distress), treatment combining opiate receptor full or partial agonist medications for opioid-use disorder (MOUD) with psychosocial interventions is essential. However, in Europe a substantial proportion of the 1.3 million high-risk opioid users (defined as injecting drug use or regular use of opioids, mainly heroin) remain outside of dedicated treatment programmes. More widespread and easier access to MOUD could reduce mortality levels; via approaches such as primary care-led treatment models, and efforts to improve patient retention and adherence to treatment programmes. Other harm-reduction strategies, such as the use of MOUD at optimal doses, the provision of take-home naloxone, the introduction of supervised drug-consumption facilities, and patient education to reduce the risk of overdose may also be beneficial.

Problem gambling and support preferences among Finnish prisoners: a pilot study in an adult correctional population.

PURPOSE: The purpose of this paper is to explore the prevalence of potential problem gambling among Finnish prisoners; the associations between problem gambling and demographics, substance use and crime-related factors; and problem gamblers' support preferences. DESIGN/METHODOLOGY/APPROACH: Prisoners (n=96) from two Finnish prisons were recruited between December 2017 and January 2018. The estimated response rate was 31 percent. Gambling problems were measured using the Brief Biosocial Gambling Screen. The participants were asked to report their gambling both for one year prior to their incarceration and for the past year. The independent variables were demographics (age, gender and marital status), substance use (alcohol, smoking and narcotics) and crime-related factors (crime type, prison type and previous sentence). Statistical significance (p) was determined using Fischer's exact test. FINDINGS: Past-year pre-conviction problem gambling prevalence was 16.3 percent and past-year prevalence 15 percent. Age, gender, smoking, alcohol or illicit drug use were not associated with past-year problem gambling before sentencing. One-third of the prisoners (33.3 percent) who were sentenced for a property crime, financial crime or robbery were problem gamblers. One-quarter (24 percent) of all participants showed an interest in receiving support by identifying one or more support preferences. The most preferred type of support was group support in its all forms. RESEARCH LIMITATIONS/IMPLICATIONS: It is recommended that correctional institutions undertake systematic screening for potential problem gambling, and implement tailored intervention programs for inmates with gambling problems. ORIGINALITY/VALUE: This study provides a deeper understanding of problem gambling in prisons. Problem gambling is associated with crime and also seems to be linked with serving a previous sentence. Early detection and tailored interventions for problem gambling may help to reduce reoffending rates.

Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice.

Opioid use disorder (OUD) is a major public health issue that has reached epidemic levels in some parts of the world. It is a chronic and complex neurobiological disease associated with frequent relapse to drug taking. Craving, defined as an overwhelmingly strong desire or need to use a drug, is a central component of OUD and other substance use disorders. In this review, we describe the neurobiological and neuroendocrine pathways that underpin craving in OUD and also focus on the importance of assessing and treating craving in clinical practice. Craving is strongly associated with patients returning to opioid misuse and is therefore an important treatment target to reduce the risk of relapse and improve patients' quality of life. Opioid agonist therapies (OAT), such as buprenorphine and methadone, can significantly reduce craving and relapse risk, and it is essential that patients are treated optimally with these therapies. There is also evidence to support the benefits of non-pharmacological approaches, such as cognitive behavioral therapy and mindfulness-based interventions, as supplementary treatments to opioid agonist therapies. However, despite the positive impact of these treatments on craving, many OUD patients continue to suffer with negative affect and dysphoria. There is a clear need for further studies to progress our understanding of the neurobiological basis of craving and addiction and to identify novel therapeutic strategies as well as to optimize the use of existing treatments to improve outcomes for the growing numbers of patients affected by OUD.

Treating gambling disorder with as needed administration of intranasal naloxone: a pilot study to evaluate acceptability, feasibility and outcomes.

BACKGROUND AND AIM: There is growing interest in the use of medication-assisted treatments for gambling disorder (GD). Opioid receptor antagonists are hypothesised to blunt the craving associated with gambling. This study was designed to assess the feasibility of using an intranasal naloxone spray to treat GD. DESIGN: An 8-week, open-label, uncontrolled pilot study. SETTING: A single study site in the capital region of Finland. SUBJECTS: Twenty problem gamblers (nine men) were randomised into two groups. Group A (n=10) took one dose into one nostril (2 mg naloxone), as needed, with a maximum of 4 doses/day (max. 8 mg/day). Group B (n=10) took one dose into each nostril (4 mg naloxone) as needed, with a maximum of 4 doses/day (max. 16 mg/day). INTERVENTION: Naloxone hydrochloride nasal spray. MEASURES: Acceptability and feasibility of the intervention were assessed. Use of study medication, adverse events, gambling frequency and gambling expenditure were recorded in a mobile diary. Problem gambling: South Oaks Gambling Screen (SOGS), depressive symptoms: Beck Depression Inventory (BDI) and alcohol use: Alcohol Use Disorders Identification Test were recorded. RESULTS: Study completion rate was 90%. Acceptability and feasibility scores were high. Group B used intranasal naloxone more frequently than group A, and consequently used more naloxone. No serious adverse events were reported. The postintervention SOGS scores were lower (median=4 (IQR=3.75) versus preintervention scores (median=12 (IQR=4.75)). Depressive symptoms were reduced during the trial (preintervention BDI median=9, IQR=9 vs postintervention BDI median=6, IQR=6). CONCLUSIONS: The acceptability and feasibility of using intranasal naloxone were high, and no serious adverse events were reported. Preliminary results suggest mixed results in terms of gambling behaviour (ie, reduced frequency but not expenditure) and decreased depressive symptoms. TRIAL REGISTRATION NUMBER: EudraCT2016-001828-56.

Selecting an appropriate alcohol pharmacotherapy: review of recent findings.

PURPOSE OF REVIEW: Only a few pharmacological treatments are available for treating alcohol use disorders (AUDs). Disulfiram, naltrexone and acamprosate are Food and Drug Administration (FDA)-approved and nalmefene is EMA-approved in European Union. Off-label medications, such as baclofen, gabapentin, ondansetron and topiramate are medications commonly prescribed for the treatment of AUD. The aim of this review is to give an update on recent randomized controlled trials (RCTs) and reviews evaluating pharmacological treatment for AUD. RECENT FINDINGS: A literature search was conducted for pharmacological treatment for alcohol use disorder, published from January 2017 to January 2019. An additional search from two ongoing-study databases was performed. A total of 13 studies, 11 reviews and 7 on-going clinical trials were identified. Interest in studying baclofen as a treatment for AUD was greater compared with other medications, yet with inconclusive results. Three new RCTs of first-line medication naltrexone showed reduction in drinking. SUMMARY: Three new published RCTs focus on baclofen and naltrexone. These results are consistent with old findings demonstrating that naltrexone reduces heavy drinking. Several RCT on baclofen do not support the use of baclofen for treatment of AUD. Encouraging results have been reported for topiramate, gabapentin and also varenicline, which might be useful in patients with comorbid nicotine dependence.

Intranasal naloxone rapidly occupies brain mu-opioid receptors in human subjects.

Nasal spray formulations of naloxone, a mu-opioid receptor (MOR) antagonist, are currently used for the treatment of opioid overdose. They may have additional therapeutic utility also in the absence of opioid agonist drugs, but the onset and duration of action at brain MORs have been inadequately characterized to allow such projections. This study provides initial characterization of brain MOR availability at high temporal resolution following intranasal (IN) naloxone administration to healthy volunteers in the absence of a competing opioid agonist. Fourteen participants were scanned twice using positron emission tomography (PET) and [11C]carfentanil, a selective MOR agonist radioligand. Concentrations of naloxone in plasma and MOR availability (relative to placebo) were monitored from 0 to 60 min and at 300-360 min post naloxone. Naloxone plasma concentrations peaked at ~20 min post naloxone, associated with slightly delayed development of brain MOR occupancy (half of peak occupancy reached at ~10 min). Estimated peak occupancies were 67 and 85% following 2 and 4 mg IN doses, respectively. The estimated half-life of occupancy disappearance was ~100 min. The rapid onset of brain MOR occupancy by IN naloxone, evidenced by the rapid onset of its action in opioid overdose victims, was directly documented in humans for the first time. The employed high temporal-resolution PET method establishes a model that can be used to predict brain MOR occupancy from plasma naloxone concentrations. IN naloxone may have therapeutic utility in various addictions where brain opioid receptors are implicated, such as gambling disorder and alcohol use disorder.

Gambling involvement, type of gambling and grade point average among 18-29-year-old Finnish men and women.

AIMS: This study explores the associations between gambling involvement, type of gambling, at-risk and problem gambling (ARPG) and register-based grade point average (GPA), among Finnish people aged 18-29 years (N = 676). It is assumed that high gambling involvement and engaging in certain types of gambling are linked to ARPG, and that low school achievement is positively associated with these measures. METHODS: A nationwide cross-sectional random sample was collected in 2015. The data were weighted based on gender, age and region. Analyses were carried out using logistic regression models. RESULTS: Frequent gambling, playing several game types, online gambling and ARPG were more common among men than women. Those with low GPA played fast and low-paced daily lottery games and used online casinos significantly more often than men and women with average/high GPA. Men with a low GPA were also more likely to gamble on a weekly basis and played casino games and online poker more often. For women with a low GPA online gambling and playing slot machines were more common than for women with an average/high GPA. When controlling for sociodemographic variables and gambling involvement, men's participation in daily lottery games and online poker was significantly associated with a low GPA, but among women none of the game types remained statistically significant. Among women, playing several different game types was linked with a low GPA. CONCLUSIONS: It seems that poorer school achievement is associated not only with frequent gambling, a large number of game types played and online gambling, but also, to some extent at least, with game type preferences.

Standards for opioid use disorder care: An assessment of Nordic approaches.

AIMS: Outcomes in opioid use disorder (OUD) in Nordic countries have improved with integrated treatment and harm-reduction programmes. Approaches and the standard of care are different across the region. Evidence of treatment needs and current approaches are defined from evidence to inform development of a common standard. METHOD: Evidence of population sizes and treatment approach collected. Common standards for care (harm reduction, pharmacotherapy, psychology/social therapy) defined for each country. RESULTS: Evidence defines number in treatment; potential population needing treatment not defined for all countries. Populations sizes, treatment access (ratio in treatment programme compared to total country population) defined: Sweden 4,000 in OUD care (access ratio 40); Finland 3,000 (55); Norway 8,000 (154); Denmark 7,500 (132). Approach to treatment similar: integrated treatment programmes standard. Care provided by specialists in outpatient clinics/primary care; secondary care/inpatient services are available. Harm reduction is limited in Sweden but available and more accessible elsewhere. Treatment entry criteria: access relatively unlimited in Norway and Denmark, more limited in Finland and Sweden. Standards of care defined: easy access to high-quality services, individual planning, care not limited by time, management of relapse, education for patients, continuous engagement, holistic approach including management of comorbidities, needle equipment programmes without limit, treatment in prisons as community. CONCLUSION: There are opportunities to improve OUD care in the Nordics. Policy makers and clinicians can advance OUD care and share common success factors. Collaborative work across the Nordic countries is valuable. Further research in clinical practice development can yield important results for the benefit of patients with OUD.

Gambling expenditure by game type among weekly gamblers in Finland.

BACKGROUND: Excessive expenditure and financial harms are core features of problem gambling. There are various forms of gambling and their nature varies. The aim was to measure gambling expenditure by game type while controlling for demographics and other gambling participation factors. A further aim was to find out how each game type was associated with gambling expenditure when the number of game types played is adjusted for. METHODS: Using data from the 2015 Finnish Gambling survey on adult gamblers (n = 3555), multiple log-linear regression was used to examine the effects of demographics, gambling participation, and engaging in different game types on weekly gambling expenditure (WGE) and relative gambling expenditure (RGE). RESULTS: Male gender, lower education level, higher gambling frequency and higher number of game types increased both WGE and RGE, while younger age decreased WGE but increased RGE. Furthermore, seven specific game types increased both WGE and RGE. Weekly horse race betting and non-monopoly gambling had the strongest increasing effect on expenditure. Betting games and online poker were associated with higher expenditure even when they were played less often than weekly. Among weekly gamblers the highest mean WGE was recorded for those who played non-monopoly games (146.84 €/week), online poker (59.61 €/week), scratch games (51.77 €/week) and horse race betting (48.67 €/week). Those who played only 1-2 game types a week had the highest mean WGE and RGE on horse race betting and other betting games. CONCLUSIONS: It seems that overall gambling frequency is the strongest indicator of high gambling expenditure. Our results showed that different game types had different effect sizes on gambling expenditure. Weekly gambling on horse races and non-monopoly games had the greatest increasing effect on expenditure. However, different game types also varied based on their popularity. The extent of potential harms caused by high expenditure therefore also varies on the population level. Based on our results, future prevention and harm minimization efforts should be tailored to different game types for greater effectiveness.

Principles for managing OUD related to chronic pain in the Nordic countries based on a structured assessment of current practice.

BACKGROUND: Long-term use of opioid analgesics (OA) for chronic pain may result in opioid use disorder (OUD). This is associated with adverse outcomes for individuals, families and society. Treatment needs of people with OUD related to chronic pain are different compared to dependence related to use, and also injection, of illicit opioids. In Nordic countries, day-to-day practical advice to assist clinical decision-making is insufficient. AIM: To develop principles based on expert clinical insights for treatment of OUD related to the long-term use of OA in the context of chronic pain. METHODS: Current status including an assessment of barriers to effective treatment in Finland, Denmark, Iceland, Norway, Sweden was defined using a patient pathway model. Evidence to describe best practice was identified from published literature, clinical guidelines and expert recommendations from practice experience. RESULTS: Availability of national treatment guidelines for OUD related to chronic pain is limited across the Nordics. Important barriers to effective care identified: patients unlikely to present for help, healthcare system set up limits success, diagnosis tools not used, referral pathways unclear and treatment choices not elucidated. Principles include the development of a specific treatment pathway, awareness/ education programs for teams in primary care, guidance on use of diagnostic tools and a flexible treatment plan to encourage best practice in referral, treatment assessment, choice and ongoing management via an integrated care pathway. Healthcare systems and registries in Nordic countries offer an opportunity to further research and identify population risks and solutions. CONCLUSIONS: There is an opportunity to improve outcomes for patients with OUD related to chronic pain by developing and introducing care pathways tailored to specific needs of the population.

Policy responses to hepatitis C in the Nordic countries: Gaps and discrepant reporting in the Hep-Nordic study.

BACKGROUND AND AIMS: In the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden), the prevalence of chronic hepatitis C virus (HCV) infection is relatively low in the general population, but is much higher among people who inject drugs (PWID). We conducted an exploratory study to investigate the extent to which these countries have policies supporting key elements of the public health response that is necessary to achieve the global goal of eliminating HCV as a public health threat. METHODS: Fourteen stakeholders representing government agencies, medical societies, and civil society organisations (CSOs) in the Nordic countries completed a cross-sectional online survey that included 21 policy questions related to national coordination, prevention, testing, linkage to care, and treatment. We summarised the findings in a descriptive analysis, and noted discrepant responses from stakeholders within the same country. RESULTS: Stakeholders reported that three of the five study countries have national viral hepatitis strategies, while only Iceland has a national HCV elimination goal. The availability of harm reduction services varies, with opioid substitution therapy provided for the general population throughout all countries, but not needle and syringe programmes. No country has access to anonymous HCV testing in all parts of the country. National HCV treatment guidelines are available in all countries except Finland, and all countries provide publicly funded direct-acting antiviral treatment. Disagreement regarding policies was observed across countries, and CSOs were the stakeholder group that most frequently answered survey questions incorrectly. CONCLUSION: The Nordic region as a whole has not consistently expressed its commitment to tackling HCV, despite the existence of large HCV epidemics among PWID in these countries. Stakeholder alignment and an established elimination goal with an accompanying strategy and implementation plan should be recognised as the basis for coordinated national public health efforts to achieve HCV elimination in the Nordic region and elsewhere.

Compulsory school achievement and gambling among men and women aged 18-29 in Finland.

AIMS: This study aims to explore the associations between final compulsory school grades and gambling and their relation to substance use and perceived mental health among people aged 18-29 in Finland (N = 831). METHODS: Cross-sectional random sample data, weighted on the basis of age, gender and region of residence, were collected in 2015. The data were analysed using logistic regression models adjusted for sociodemographic variables, risky alcohol use, daily smoking, and perceived mental health. RESULTS: Weekly gambling and at-risk and problem gambling (ARPG) were more common among men. Weekly gambling was linked to smoking and risky alcohol use among men and smoking among women. Additionally, ARPG was linked to risky alcohol use among men. ARPG was associated with moderate/poor mental health among men and women, but this was not the case with weekly gambling. Among men, low and average final school grades at age 16 were associated with weekly gambling later in life, even when adjusting for other variables. Among women, low and average final school grades were not associated with weekly gambling when adjusting for substance use. Lower final school grades were associated with ARPG among women but not among men when all potential confounders were adjusted for. CONCLUSIONS: Adolescents with lower final school grades are more likely to gamble weekly later in life. Lower final school grades are also linked with ARPG among women. It is important therefore for schools to have clear policies on gambling and to implement early prevention programmes.

The relationship between gambling expenditure, socio-demographics, health-related correlates and gambling behaviour-a cross-sectional population-based survey in Finland.

AIMS: To investigate gambling expenditure and its relationship with socio-demographics, health-related correlates and past-year gambling behaviour. DESIGN: Cross-sectional population survey. SETTING: Population-based survey in Finland. PARTICIPANTS: Finnish people aged 15-74 years drawn randomly from the Population Information System. The participants in this study were past-year gamblers with gambling expenditure data available (n = 3251, 1418 women and 1833 men). MEASUREMENTS: Expenditure shares, means of weekly gambling expenditure (WGE, €) and monthly gambling expenditure as a percentage of net income (MGE/NI, %) were calculated. The correlates used were perceived health, smoking, mental health [Mental Health Inventory (MHI)-5], alcohol use [Alcohol Use Disorders Identification Test (AUDIT)-C], game types, gambling frequency, gambling mode and gambling severity [South Oaks Gambling Screen (SOGS)]. FINDINGS: Gender (men versus women) was found to be associated significantly with gambling expenditure, with exp(ß) = 1.40, 95% confidence interval (CI) = 1.29, 1.52 and P < 0.005 for WGE, and exp(ß) = 1.39, 95% CI = 1.27, 1.51 and P < 0.005 for MGE/NI. All gambling behaviour correlates were associated significantly with WGE and MGE/NI: gambling frequency (several times a week versus once a month/less than monthly, exp(ß) = 30.75, 95% CI = 26.89, 35.17 and P < 0.005 for WGE, and exp(ß) = 31.43, 95% CI = 27.41, 36.03 and P < 0.005 for MGE/NI), gambling severity (probable pathological gamblers versus non-problem gamblers, exp(ß) = 2.83, 95% CI = 2.12, 3.77 and P < 0.005 for WGE, and exp(ß) = 2.67, 95% CI = 2.00, 3.57 and P < 0.005 for MGE/NI) and on-line gambling (on-line and land-based versus land-based only, exp(ß) = 1.35, 95% CI = 1.24, 1.47 and P < 0.005 for WGE, and exp(ß) = 1.35, 95% CI = 1.24, 1.47 and P < 0.005 for MGE/NI). CONCLUSIONS: In Finland, male gender is associated significantly with both weekly gambling expenditure and monthly gambling expenditure related to net income. People in Finland with lower incomes contribute proportionally more of their income to gambling compared with middle- and high-income groups.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Recommendations for buprenorphine and methadone therapy in opioid use disorder: a European consensus.

INTRODUCTION: Management of patients with opioid use disorder (OUD) commonly includes opioid agonist therapy (OAT) as a part of an integrated treatment plan. These interventions are associated with proven benefits to the individual and society. Areas covered: The use of methadone and buprenorphine within an integrated treatment plan in the management of patients with OUD: this work provides consensus recommendation on pharmacotherapy in OUD to assist clinicians with practical decision making in this field. Expert opinion: Pharmacotherapy is recommended as part of an integrated OUD treatment approach with psychosocial interventions, with the goal of reducing risks of illicit opioid use, overdose mortality, infection with HIV or HCV, improving health, psychological and social outcomes. Access to OAT should be prioritised in the treatment of OUD. Treatment choices in OUD pharmacotherapy should be based on the needs of the individual and characteristics of medications. Recommendations for choices of OAT are based on clinical efficacy, safety, patient preference, side effects, pharmacological interactions, quality of life, dose titration potential and outcomes (control craving, ongoing opioids consumption or other drugs, and potentially psychiatric comorbidities). Special groups, pregnant women, prisoners, patients with mental health problems have specific needs which must be addressed with expert input.

Serotonin transporter density in binge eating disorder and pathological gambling: A PET study with [11C]MADAM.

Behavioral addictions, such as pathological gambling (PG) and binge eating disorder (BED), appear to be associated with specific changes in brain dopamine and opioid function, but the role of other neurotransmitter systems is less clear. Given the crucial role of serotonin in a number of psychiatric disorders, we aimed to compare brain serotonergic function among individuals with BED, PG and healthy controls. Seven BED patients, 13 PG patients and 16 healthy controls were scanned with high-resolution positron emission tomography (PET) using the serotonin transporter (SERT) tracer [11C]MADAM. Both region-of-interest and voxel-wise whole brain analyses were performed. Patients with BED showed increased SERT binding in the parieto-occipital cortical regions compared to both PG and healthy controls, with parallel decreases in binding in the nucleus accumbens, inferior temporal gyrus and lateral orbitofrontal cortex. No differences between PG patients and controls were observed. None of the subjects were on SSRI medications at the time of imaging, and there were no differences in the level of depression between PG and BED patients. The results highlight differences in brain SERT binding between individuals with BED and PG and provide further evidence of different neurobiological underpinnings in behavioral addictions that are unrelated to the co-existing mood disorder. The results aid in the conceptualization of behavioral addictions by characterizing the underlying serotonin changes and provide a framework for additional studies to examine syndrome-specific pharmaceutical treatments.