HAMLET, a human milk protein-lipid complex, modulates amoxicillin induced changes in an ex vivo biofilm model of the oral microbiome.

Challenges from infections caused by biofilms and antimicrobial resistance highlight the need for novel antimicrobials that work in conjunction with antibiotics and minimize resistance risk. In this study we investigated the composite effect of HAMLET (human alpha-lactalbumin made lethal to tumor cells), a human milk protein-lipid complex and amoxicillin on microbial ecology using an ex vivo oral biofilm model with pooled saliva samples. HAMLET was chosen due to its multi-targeted antimicrobial mechanism, together with its synergistic effect with antibiotics on single species pathogens, and low risk of resistance development. The combination of HAMLET and low concentrations of amoxicillin significantly reduced biofilm viability, while each of them alone had little or no impact. Using a whole metagenomics approach, we found that the combination promoted a remarkable shift in overall microbial composition compared to the untreated samples. A large proportion of the bacterial species in the combined treatment were Lactobacillus crispatus, a species with probiotic effects, whereas it was only detected in a minor fraction in untreated samples. Although resistome analysis indicated no major shifts in alpha-diversity, the results showed the presence of TEM beta-lactamase genes in low proportions in all treated samples but absence in untreated samples. Our study illustrates HAMLET's capability to alter the effects of amoxicillin on the oral microbiome and potentially favor the growth of selected probiotic bacteria when in combination. The findings extend previous knowledge on the combined effects of HAMLET and antibiotics against target pathogens to include potential modulatory effects on polymicrobial biofilms of human origin.

Role of the polyamine transporter PotABCD during biofilm formation by Streptococcus pneumoniae.

Streptococcus pneumoniae is a bacterium of great global importance, responsible for more than one million deaths per year. This bacterium is commonly acquired in the first years of life and colonizes the upper respiratory tract asymptomatically by forming biofilms that persist for extended times in the nasopharynx. However, under conditions that alter the bacterial environment, such as viral infections, pneumococci can escape from the biofilm and invade other niches, causing local and systemic disease of varying severity. The polyamine transporter PotABCD is required for optimal survival of the organism in the host. Immunization of mice with recombinant PotD can reduce subsequent bacterial colonization. PotD has also been suggested to be involved in pneumococcal biofilm development. Therefore, in this study we aimed to elucidate the role of PotABCD and polyamines in pneumococcal biofilm formation. First, the formation of biofilms was evaluated in the presence of exogenous polyamines-the substrate transported by PotABCD-added to culture medium. Next, a potABCD-negative strain was used to determine biofilm formation in different model systems using diverse levels of complexity from abiotic surface to cell substrate to in vivo animal models and was compared with its wild-type strain. The results showed that adding more polyamines to the medium stimulated biofilm formation, suggesting a direct correlation between polyamines and biofilm formation. Also, deletion of potABCD operon impaired biofilm formation in all models tested. Interestingly, more differences between wild-type and mutant strains were observed in the more complex model, which emphasizes the significance of employing more physiological models in studying biofilm formation.

Effectiveness and Acceptability of Cognitive Behavioral Therapy and Family Therapy for Gaming Disorder: Protocol for a Nonrandomized Intervention Study of a Novel Psychological Treatment.

BACKGROUND: Gaming disorder (GD) is a new official diagnosis in the International Classification of Diseases, 11th Revision, and with its recognition, the need to offer treatment for the condition has become apparent. More knowledge is needed about the type of treatment needed for this group of patients. OBJECTIVE: This study aims to evaluate the effectiveness and acceptability of a novel module-based psychological treatment for GD based on cognitive behavioral therapy and family therapy. METHODS: This study is a nonrandomized intervention study, with a pretest, posttest, and 3-month follow-up design. It will assess changes in GD symptoms, psychological distress, and gaming time, alongside treatment satisfaction, working alliance, and a qualitative exploration of patients' and relatives' experiences of the treatment. RESULTS: This study started in March 2022 and the recruitment is expected to close in August 2024. CONCLUSIONS: This study evaluates the effectiveness and acceptability of a psychological treatment for patients with problematic gaming behavior and GD. It is an effectiveness trial and will be conducted in routine care. This study will have high external validity and ensure that the results are relevant for a diverse clinical population with psychiatric comorbidity. TRIAL REGISTRATION: ClinicalTrials.gov NCT06018922; https://clinicaltrials.gov/study/NCT06018922. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56315.

Biofilm-dispersed pneumococci induce elevated leukocyte and platelet activation.

Introduction: Streptococcus pneumoniae (the pneumococcus) effectively colonizes the human nasopharynx, but can migrate to other host sites, causing infections such as pneumonia and sepsis. Previous studies indicate that pneumococci grown as biofilms have phenotypes of bacteria associated with colonization whereas bacteria released from biofilms in response to changes in the local environment (i.e., dispersed bacteria) represent populations with phenotypes associated with disease. How these niche-adapted populations interact with immune cells upon reaching the vascular compartment has not previously been studied. Here, we investigated neutrophil, monocyte, and platelet activation using ex vivo stimulation of whole blood and platelet-rich plasma with pneumococcal populations representing distinct stages of the infectious process (biofilm bacteria and dispersed bacteria) as well as conventional broth-grown culture (planktonic bacteria). Methods: Flow cytometry and ELISA were used to assess surface and soluble activation markers for neutrophil and monocyte activation, platelet-neutrophil complex and platelet-monocyte complex formation, and platelet activation and responsiveness. Results: Overall, we found that biofilm-derived bacteria (biofilm bacteria and dispersed bacteria) induced significant activation of neutrophils, monocytes, and platelets. In contrast, little to no activation was induced by planktonic bacteria. Platelets remained functional after stimulation with bacterial populations and the degree of responsiveness was inversely related to initial activation. Bacterial association with immune cells followed a similar pattern as activation. Discussion: Differences in activation of and association with immune cells by biofilm-derived populations could be an important consideration for other pathogens that have a biofilm state. Gaining insight into how these bacterial populations interact with the host immune response may reveal immunomodulatory targets to interfere with disease development.

Impulse control disorders in Parkinson's disease: a national Swedish registry study on high-risk treatments and vulnerable patient groups.

BACKGROUND: Impulse control disorders (ICDs) are known psychiatric conditions in Parkinson's disease (PD), especially as a side effect of antiparkinsonian therapy. Screening for vulnerable patients and avoiding high-risk treatments can be an effective approach to reduce the ICD burden in patients with PD. Thus, our goal was to identify risk factors for ICDs in PD in the Swedish total population. METHODS: Our longitudinal study was based on records of all patients with PD in the Swedish National Patient Registries and the Prescribed Drug Register (n=55 235). Patients with incident gambling disorder and other ICDs were compared with a control group on demographic factors, psychiatric comorbidity, antiparkinsonian dopaminergic treatment and therapies for advanced disease. Potential risk factors were analysed using logistic regressions and relative frequency comparisons (Fisher's exact test). RESULTS: Main predictors for incident gambling disorder were treatment with dopamine agonists (Frequency ratio 1.4, p=0.058), monoamine oxidase B (MAO-B) inhibitors (Frequency ratio 1.8, p=0.006) and a prescription for drugs used in addictive disorders (OR 5.85, 95% CI 2.00 to 17.10). Main predictors for other ICDs were dopamine agonist treatment (frequency ratio 1.6, p=0.003), anxiety disorders (OR 7.04, 95% CI 2.96 to 16.71) and substance use disorders other than alcohol (OR 5.66, 95% CI 1.75 to 18.23). CONCLUSIONS: Our results support possible risk factors for incident ICDs that had previously been identified, like dopamine agonist treatment and raise additional attention for risk factors like MAO-B inhibitor treatment and specific psychiatric comorbidities. These findings enable tailoring antiparkinsonian therapy to individual patient-specific risk profiles.

Gambling Habits and Attitudes among Athlete and Non-Athlete High School Students in Skåne Region, Sweden.

Previous literature has reported increased rates of gambling problems in athletes compared to non-athletes. More liberal gambling-related attitudes have been suggested as a reason, although this rarely has been researched. The present study aimed to examine gambling experience, gambling problems, and gambling-related attitudes and parental gambling experience in high school students, comparing student-athletes to students at conventional schools. This is a cross-sectional web survey study in high school students (N = 473, 53% at sports high schools, 57% male) at eleven schools in the Skåne region, Sweden, who answered a web survey addressed gambling experiences, parental gambling and gambling-related attitudes, and included validated screening instruments for gambling problems and psychological distress. A history of any gambling was common and increased with age. Problem gambling was detected in 10% (13% of males and 5% of females, p < .001), and was associated with paternal and maternal gambling but not with psychological distress. Sports high school students were not more likely (9%) than other students (10%) to endorse gambling problems and history of each gambling type. However, paternal (but not maternal) gambling was more commonly reported in athletes, who also had more positive attitudes to gambling's effects on society and gambling availability. In contrast to other studies, this study did not demonstrate higher prevalence of gambling or gambling problems among young athletes than among other students, but liberal attitudes towards gambling, and experience of parental gambling on the father's side, were more common among athletes than among non-athletes. Gambling attitudes in adolescents may need to be targeted in future preventive efforts in young athletes and others.

Prolonged Fatigue and Mental Health Challenges in Critical COVID-19 Survivors.

Background: The aim of this study was to investigate the development of fatigue and mental illness between 3 and 12 months after critical COVID-19 and explore risk factors for long-lasting symptoms. Study Design and Methods: A prospective, multicenter COVID-19 study in southern Sweden, including adult patients (≥18 years) with rtPCR-confirmed COVID-19 requiring intensive care. Survivors were invited to a follow-up at 3 and 12 months, where patient-reported symptoms were assessed using the Modified Fatigue Impact Scale (MFIS), the Hospital Anxiety and Depression Scale (HADS) and the Posttraumatic Stress Disorder Checklist version 5 (PCL-5). The development between 3 and 12 months was described by changes in relation to statistical significance and suggested values for a minimally important difference (MID). Potential risk factors for long-lasting symptoms were analyzed by multivariable logistic regression. Results: At the 3-month follow-up, 262 survivors (87%) participated, 215 (72%) returned at 12 months. Fatigue was reported by 50% versus 40%, with a significant improvement at 12 months (MFIS; median 38 vs. 33, P < .001, MID ≥4). There were no significant differences in symptoms of mental illness between 3 and 12 months, with anxiety present in 33% versus 28%, depression in 30% versus 22%, and posttraumatic stress disorder in 17% versus 13%. A worse functional outcome and less sleep compared to before COVID-19 were risk factors for fatigue and mental illness at 12 months. Conclusions: Fatigue improved between 3 and 12 months but was still common. Symptoms of mental illness remained unchanged with anxiety being the most reported. A worse functional outcome and less sleep compared to before COVID-19 were identified as risk factors for reporting long-lasting symptoms.

Concussion history associated with adolescent psychological distress but not hazardous gambling: a cross-sectional study.

BACKGROUND: Sustaining multiple concussions over one's lifetime may be associated with behavioral and mood changes beyond the acute phase of injury. The present cross-sectional study examined the relationship between concussion history, the incidence of current moderate-severe psychological distress, and lifetime adolescent hazardous gambling in high school students. METHODS: Four-hundred fifty-nine high school students from southern Sweden (age: 16.81 ± 0.83, 58.2% male) completed a survey assessing concussion history (0,1,2…>8), psychological distress using the Kessler-6 scale, and lifetime hazardous gambling using the NODS-CLiP scale. RESULTS: Participants who self-reported three or more concussions were more likely to endorse moderate-severe symptoms of psychological distress than those with no concussion history while controlling for covariates, OR = 2.71, 95% CI [1.19, 6.18]. In contrast, concussion history was not associated with hazardous gambling after controlling for confounding variables. CONCLUSIONS: Self-reporting three or more concussions was associated with increased current psychological distress beyond the acute phase of injury among high school students. Adolescents who have sustained multiple concussions should undergo mental health evaluations beyond the acute phase of injury to identify and treat psychological distress, but probing for hazardous gambling may not be clinically relevant in this previously concussed adolescent population.

Cannabis use, mental health, and problematic Internet use in Quebec: A study protocol.

BACKGROUND: Problematic Internet use is characterized by excessive use of online platforms that can result in social isolation, family problems, psychological distress, and even suicide. Problematic Internet use has been associated with cannabis use disorder, however knowledge on the adult population remains limited. In Quebec, cannabis use has significatively increased since 2018, and it is associated with various risks in public safety, public health, and mental health. This study aims to identify factors associated with problematic Internet use among adult cannabis users and to better understand their experiences. METHOD: This project is a mixed explanatory sequential study consisting of two phases. Phase 1 (n = 1500) will be a cross-sectional correlational study using probability sampling to examine variables that predispose individuals to problematic Internet use, characteristics associated with cannabis use, Internet use, and the mental health profile of adult cannabis users in Quebec. Descriptive analyses and regression models will be used to determine the relationship between cannabis use and Internet use. Phase 2 (n = 45) will be a descriptive qualitative study in the form of semi-structured interviews aimed at better understanding the experience and background of cannabis users with probable problematic Internet use. DISCUSSION: The results of this study will support the development of public policies and interventions for the targeted population, by formulating courses of action that contribute to the prevention and reduction of harms associated with cannabis use and problematic Internet use. Furthermore, an integrated knowledge mobilization plan will aid in the large-scale dissemination of information that can result useful to decision-makers, practitioners, members of the scientific community, and the general population regarding the use of cannabis and the Internet.

Treatment seeking for gambling disorder in nationwide register data - observations around a major shift in legislation.

Background: Treatment seeking for gambling disorder is known to be low and there has been a lack of longitudinal research regarding treatment opportunities. The present study aimed to assess possible changes in treatment uptake after a formal introduction of gambling disorder in social services and health care legislations, by using register data, including patient characteristics with respect to socio-demographics and comorbidities. Methods: Nationwide register data were collected for the years 2005-2019, describing diagnoses in specialized out-patient health care and in in-patient hospital care. Numbers and characteristics of patients with gambling disorder were followed longitudinally. Also, a new legislation for treatment by public institutions was introduced in 2018, and data were compared for the years before and after the shift in legislation, both nationally, for each of the three major urban regions, and for the rest of the country. Comparisons were made with respect to concurrent mental health comorbidities, age and gender. Results: The number of out-patient gambling disorder diagnoses increased over time, but without any significant step changes around the shift in legislation. Over time, patients were younger, became more likely to have gambling disorder as their primary diagnosis, and less likely to have mental health comorbidities, whereas gender distribution did not change. Among the smaller group of patients diagnosed in in-patient settings, mental health comorbidity increased over time. Despite gradual changes over time, no changes in demographics were seen around the actual shift in legislation, although the psychiatric comorbidity appeared to increase after this change. Conclusion: After the introduction of gambling disorder in the responsibility of social services and health care settings in Sweden, the number of patients diagnosed with gambling disorder increased only modestly. Likely, further implementation of gambling disorder treatment is required in the health care services. Also, longer longitudinal studies are needed in order to understand to what extent patients not seeking health care treatment are received by municipal social services or remain outside the treatment system.

Individual Placement and Support for persons with alcohol and drug addiction in a Swedish context (IPS-ADAS): study protocol for a randomised controlled trial.

BACKGROUND: Employment is a vital source for experiencing well-being and lowering the risk of long-term social marginalisation and poverty. For persons with alcohol and drug addiction, it may also improve sobriety. However, the unemployment situation for this group reflects the knowledge gap in effective interventions to support employment. While Individual Placement and Support (IPS) is recognised as evidence-based supported employment for those with serious mental health problems, no scientific evidence for the target group of addiction exists to date. The aim of the present IPS for Alcohol and Drug Addiction in Sweden (IPS-ADAS) trial is to study whether IPS has an effect on gaining employment for this group. METHODS: The IPS-ADAS trial is a multisite, pragmatic, parallel, and single-blinded, superiority randomised controlled trial (RCT). Participants (N = 330) will be randomly assigned (1:1) and participate in IPS plus treatment as usual within Addiction Services (IPS + TAU) or Traditional Vocational Rehabilitation (TVR) available plus TAU (TVR + TAU) for 12 months. The principle of intention-to-treat (ITT) will be applied. The hypothesis is that a significantly larger proportion of IPS + TAU participants will be employed for > 1 day (primary outcome), reach employment sooner, work more hours and longer periods of time, and have a higher income as compared to TVR + TAU participants at 18-month follow-up. We further anticipate that those who benefit from IPS + TAU will use less alcohol and drugs, experience better health, and use less care and support, including support from the justice system, in comparison to TVR + TAU participants, at 6, 12, and 18 months. A supplementary process evaluation, using the IPS Fidelity Scale (25 items) and adhered interviews will address delivery and receipt of the IPS as well as contextual hinders and barriers for coproduction and implementation. Working age (18-65), willingness to work, unemployment, participation in an information meeting about the RCT, treatment for addiction diagnosis, and being financially supported by welfare, constitute eligible criteria. DISCUSSION: A primary study on the effectiveness of IPS on employment for the new target group of addictions will add to the international IPS knowledge base and inform national policy to include the underrepresented group in working life. TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform ISRCTN10492363. Registered on 14 August 2023.

Causes and circumstances of death in stimulant and opioid use-A comparative study.

AIMS: To investigate the individual characteristics, causes and circumstances around deaths in stimulant use, and to examine how individuals who died with stimulants in their body differ from individuals who died with opioids in their body. METHODS: This study includes individuals who died during the years 2000-2018 and underwent a forensic autopsy at Forensic Medicine in Lund, Skåne County, Sweden. All individuals over 18 years of age with stimulants (n = 310), opioids (n = 2,039) or both stimulants and opioids (n = 385) in the body at the time of death, were included. The three groups were assessed regarding gender, age, place of death, BMI, other substances detected in forensic toxicological analysis, organ weights and underlying and contributing causes of death. The data were analysed by frequency and proportion calculations, cross-tabulations and comparisons of medians. RESULTS: The median age at death of the study population (n = 2,734) was 45.5 years (interquartile range ☯IQR] 32-60 years) and 73.2% were men. The most common cause of death in the stimulant group was suicide (26.8%), higher proportion compared to the opioid group (20.8%) (p = 0.017) and in the polysubstance group accidental poisoning (38.2%), higher proportion compared to the opioid group (18.0%) (p<0.001). Death by transport accidents was significantly associated with the stimulant group (p<0.001) as well as death by other accidents (p = 0.016). CONCLUSIONS: Individuals who died with stimulants in their body died at a higher rate from suicide, transport accidents and other accidents, compared to individuals who died with opioids in their body. This study indicates the need to identify and prevent psychiatric conditions, elevated suicide risk, and risk-taking behaviors among people who use stimulants.

Motivational telephone intervention to risk gamblers by a state-owned gambling operator in Sweden.

Background and aims: Few studies have tested the effect of a motivational telephone intervention from a gambling operator to clients with high-risk gambling practices. This study aimed to study subsequent limit setting, self-exclusions and gambling post-intervention, compared to controls. Methods: The study assessed a motivational, personalized telephone intervention by the state-owned Swedish gambling operator AB Svenska Spel within its subsection of sports, poker, online casino and bingo gambling. Clients successfully reached with the telephone intervention (n = 1,420) were compared to clients who could not be reached (n = 1,504). Gambling practices during 8 weeks pre-intervention were assessed, and outcome measures limit setting, self-exclusion, and gambling 4 weeks post-intervention. Results: The telephone intervention was associated with increased limit settings (10 vs. 5 percent, p < 0.001), self-exclusions (11 vs. 8 percent, p < 0.01), lowered theoretical losses (p < 0.001), but not significantly associated with gambling abstinence (18 vs. 15 percent, p = 0.07). In unadjusted analyses of sub-groups, significant associations of the intervention with full gambling abstinence were seen in people who gamble on online casino/bingo (19 vs. 14 percent, p < 0.01), but not in sports bettors. In logistic regression, the intervention was not associated with full week 1-4 abstinence. Conclusion: A personalized motivational telephone intervention to people displaying high-risk gambling, delivered by a gambling operator, is promising, and effects were seen on the uptake of responsible gambling tools post-intervention. Effects may be more pronounced in users of chance-based, online games, than in sports bettors.

Distribution of intranasal naloxone to potential opioid overdose bystanders in Sweden: effects on overdose mortality in a full region-wide study.

OBJECTIVES: Distribution of take-home naloxone is suggested to reduce opioid-related fatalities, but few studies have examined the effects on overdose deaths in the general population of an entire community. This study aimed to assess the effects on overdose deaths of a large-scale take-home naloxone programme starting in June 2018, using an observational design with a historic control period. DESIGN: From the national causes of death register, deaths diagnosed as X42 or Y12 (International Classification of Diseases, 10th revision, ICD-10) were registered as overdoses. Numbers of overdoses were calculated per 100 000 inhabitants in the general population, and controlled for data including only individuals with a prior substance use disorder in national patient registers, to focus on effects within the primary target population of the programme. The full intervention period (2019-2021) was compared with a historic control period (2013-2017). SETTING: Skåne county, Sweden. PARTICIPANTS: General population. INTERVENTIONS: Large-scale take-home naloxone distribution to individuals at risk of overdose. PRIMARY AND SECONDARY OUTCOME MEASURES: Decrease in overdose deaths per 100 000 inhabitants, in total and within the population with substance use disorder diagnosis. RESULTS: Annual average number of overdose deaths decreased significantly from 3.9 to 2.8 per 100 000 inhabitants from the control period to the intervention period (a significant decrease in men, from 6.7 to 4.3, but not in women, from 1.2 to 1.3). Significant changes remained when examining only prior substance use disorder patients, and decreases in overdose deaths could not be attributed to a change in treatment needs for opioid use disorders in healthcare and social services. CONCLUSIONS: The present study, involving 3 years of take-home naloxone distribution, demonstrated a decreased overdose mortality in the population, however, only in men. The findings call for further implementation of naloxone programmes, and for further studies of potential effects and barriers in women. TRIAL REGISTRATION NUMBER: NCT03570099.

Can the presence of specialized addiction staff in primary health care increase the number of alcohol-related medical consultations - A controlled intervention study.

Background: Few individuals with alcohol use disorders receive treatment. Primary care has been suggested as an arena for early treatment for these disorders. Aim: To evaluate whether the presence of a specialized addiction nurse can increase alcohol-related physician consultations in a primary care setting. Method: This controlled intervention study included one intervention and one control primary care unit in Malmö, Sweden. At the intervention unit, an addiction nurse experienced in alcohol use disorder treatment was present 20 h weekly for 12 months. At both units, an educational lecture on alcohol use disorders was given at study start. The outcome was physicians' monthly number of alcohol-related diagnostic codes. Data were compared between intervention and control units using Poisson Regression. Eight statistical models were analyzed and Akaike information criterion was used to select the final model. Results: The intervention was significantly associated with an increased number of registered alcohol-related diagnostic codes (risk ratio 1.33, 95 confidence interval 1.08-1.62). However, in sensitivity analyses, such a slope effect was more uncertain and no step effect was seen. A significant association was seen between the educational lecture and an increase in the number of registered alcohol-related codes at the sites (risk ratio 2.47, 1.37-4.46). Conclusion: The presence of specialized addiction staff in a primary healthcare setting might increase the number of alcohol-related physician consultations in primary care, although more research is needed. An educational lecture about alcohol use disorders could be a simple but effective intervention to increase alcohol-related physician consultations in primary care.

Societal costs of illegal drug use in Sweden.

BACKGROUND: Illegal drug use is a public health concern with far-reaching consequences for people who use them and for society. In Sweden, the reported use of illegal drugs has been growing and the number of drug-induced deaths is among the highest in Europe. The aim of this study was to provide a comprehensive and up-to-date estimation of the societal costs of illegal drug use in Sweden, relying as much as possible on registry and administrative data. METHODS: A prevalence-based cost-of-illness study of illegal drug use in Sweden in 2020 was conducted. A societal approach was chosen and included direct costs (such as costs of health care, social services, and the criminal justice system), indirect costs (such as lost productivity due to unemployment and drug-induced death), and intangible costs (such as reduced quality of life among people who use drugs and their family members). Costs were estimated by combining registry, administrative, and survey data with unit cost data. RESULTS: The estimated societal costs of illegal drug use were 3.7 billion euros in 2020. This corresponded to 355 euros per capita and 0.78 % of the gross domestic product. The direct and intangible costs were of similar sizes, each contributing to approximately 40 % of total costs, whereas indirect costs contributed to approximately 20 %. The largest individual cost components were reduced quality of life among people who use drugs and costs of the criminal justice system. CONCLUSION: Illegal drug use has a negative impact on the societal aim to create good and equitable health in Sweden. The findings call for evidence-based prevention of drug use and treatment for those addicted. It is important to address the co-morbidity of mental ill-health and drug dependence, to develop low-threshold services and measures for early prevention among children and young adults, as well as to evaluate laws and regulations connected to illegal drug use.

Relapse prevention therapy for internet gaming disorder in Swedish child and adolescent psychiatric clinics: a randomized controlled trial.

Objectives: To evaluate the effectiveness of relapse prevention (RP) as a treatment for internet gaming disorder (IGD). Design: Randomized controlled trial. Setting: Three child and adolescent psychiatry (CAP) units in Region Skåne, Sweden. Participants: Children aged 13-18 years, coming for their first visit to CAP during 2022, were screened for gaming behavior. Those who met the proposed DSM-5 criteria for IGD were offered participation in the trial, if they had the capacity to provide written informed consent and if they spoke Swedish. A total of 111 CAP patients agreed to participate. Out of those, 11 patients were excluded due to incorrect inclusion such as young age (n = 1), or due to the absence of responses to follow-up measures (n = 9). After exclusion, 102 participants remained (intervention = 47, control = 55). Interventions: The intervention, RP, is based on cognitive behavioral treatment (CBT) and was provided individually, comprising of five to seven 45-min sessions over a period of 5 to 7 weeks versus treatment as usual. Outcome measures: Participants were assessed with Game Addiction Scale for Adolescents pre-treatment (GASA) (baseline), post-treatment (treatment group only), and 3 months after baseline (follow-up). Results: The repeated measures ANOVA showed a significant interaction effect between treatment and time. Both the control group and treatment group lowered their mean GASA score from baseline to follow-up significantly, but the improvement was greater in the treatment group (mean difference in control group -5.1, p < 0.001, 95% CI = - 3.390 to -6.755, mean difference in treatment group -9.9, p < 0.001, 95% CI = -11.746 to -8.105). Conclusion: RP was found to be superior to treatment as usual in terms of reduction of IGD symptoms. Future research should address which aspects within a given treatment are effective, who benefits from treatment, in what aspects, and why. Trial registration number: ClinicalTrials.gov, NCT05506384 https://clinicaltrials.gov/ct2/show/NCT05506384.

No obvious effect on mortality from a patient choice reform expanding access to opioid disorder treatment - results from a natural experiment of policy change in Sweden.

BACKGROUND: Opioid-related overdose deaths remain a common cause of death in many settings, and opioid maintenance treatment is evidence-based for the treatment of opioid use disorders. However, access to such treatment varies and is limited in many settings. METHODS: The present study examines the longitudinal effects of a regional patient choice reform which substantially increased availability to opioid maintenance treatment in one Swedish county, starting from 2014. A previous follow-up, limited in time, indicated a possible effect on mortality from this intervention, demonstrating a lower increase in overdose deaths than in counties without this reform. The present study follows overdose deaths through 2021, and compares the intervention county to the remaining parts in the country, using death certificate statistics from the national causes of death register. RESULTS: The present study does not demonstrate any significant difference in the development of overdose mortality in the county where this reform substantially expanded treatment access, compared to other counties in the country. CONCLUSIONS: The study underlines the importance to maintain extensive efforts against overdose deaths over and above the treatment of opioid use disorders, such as low-threshold provision of opioid antidotes or other interventions specifically addressing overdose risk behaviors.

Effects and Limitations of a Unique, Nationwide, Self-Exclusion Service for Gambling Disorder and Its Self-Perceived Effects and Harms in Gamblers: Protocol for a Qualitative Interview Study.

BACKGROUND: Voluntary self-exclusion from gambling is a common but underdeveloped harm reduction tool in the management of gambling problems or gambling disorders. Large-scale, multi-operator, and operator-independent self-exclusion services are needed. A recent nationwide multi-operator self-exclusion service in Sweden (Spelpaus), involving both land- and web-based gambling sites, is promising, but recent data have revealed limitations to this system and possibilities to breach one's self-exclusion through overseas web-based gambling. More knowledge is needed about the benefits and challenges of such an extensive self-exclusion service, and its effects as perceived by gamblers. OBJECTIVE: This study protocol describes the rationale and design of a qualitative interview study addressing the effects and limitations perceived by individuals with gambling problems and their concerned significant others. The study aims to provide an in-depth experience of this novel self-exclusion service and to inform stakeholders and policymakers in order to further improve harm reduction tools against gambling problems. METHODS: Individuals with gambling problems will be recruited primarily through social media and also from a treatment unit, if needed, for a qualitative interview study. Recorded interview material will be analyzed through content analysis, and recruitment will continue until saturation in the material is reached. This study will provide in-depth information about a harm reduction tool that is promising and commonly used, but which has proven to be breached by a significant number of users, potentially limiting its efficiency. The aim is to interview a sufficient number of gamblers until saturation has been obtained in the interview material. Saturation will be considered through a continuous analysis, comparing recently collected data to previously collected data. RESULTS: Results will be reported as the themes and subthemes identified after the thorough analysis and coding of the transcribed text material and will be accompanied by citations representing relevant themes and subthemes. Results are planned to be provided before the end of 2023. CONCLUSIONS: This study will likely provide new insights into user perspectives on a multi-operator self-exclusion service that involves both web- and land-based gambling operators, and which according to previous literature attracts many gamblers but also appears to have limitations and challenges in the target group of individuals with gambling problems. Policy and legislation implications, as well as clinical implications for treatment providers, will be discussed. Results and conclusions will be disseminated to policy makers in Sweden and internationally, as well as to peer organizations, treatment providers, and the research community. TRIAL REGISTRATION: ClinicalTrials.gov NCT05693155; https://clinicaltrials.gov/study/NCT05693155. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/47528.

Gender and maladaptive personality correlates in problem gambling and over-indebtedness: Novel findings from a cross-sectional study in Sweden.

Although most individuals consider gambling to be an innocent and fun activity, when it develops into problem gambling, it can have detrimental outcomes to one's life, such as over-indebtedness. This cross-sectional study explores the role of maladaptive personality traits and gender in both problem gambling and over-indebtedness, in an online sample of 1479 adult gamblers (65% males) in Sweden. Participants were administered the Problem Gambling Severity Index (PGSI), the Personality Inventory for DSM-5-Brief Form (PID-5-BF), and questions addressing subjective over-indebtedness and other risk factors. Quasi-Poisson loglinear models and logistic regression analyses demonstrated that Disinhibition (OR = 1.38, 95% CI [1.24, 1.53]), and Antagonism (OR = 1.23, 95% CI [1.14, 1.34]) showed the strongest associations to problem gambling, and that only Disinhibition (OR = 1.72, 95% CI [1.22, 1.43]) and Antagonism (OR = 2.00, 95% CI [1.52, 2.66]) were significantly related to over-indebtedness. The prevalence of problem gambling and over-indebtedness was more common among women, and gender moderated the univariate relationships of Negative Affectivity, Disinhibition and Psychoticism to problem gambling. These findings call for future research addressing maladaptive personality traits, problem gambling and over-indebtedness, and highlight the need for tailored interventions and prevention strategies, particularly for women who may be at higher risk.