How gender and low mental health literacy are related to unmet need for mental healthcare: a cross-sectional population-based study in Sweden.

BACKGROUND: Men are more likely to have unmet need for mental healthcare than women. However, an under-investigated aspect of the gender difference is the role of mental health literacy. This study investigated how combinations of gender and mental health literacy were related to two indicators of unmet need: not perceiving a need for mental healthcare despite poor mental health, and refraining from seeking mental healthcare. METHODS: This cross-sectional study was based on a questionnaire sent to a general population sample, aged 16-84 years, in Stockholm County, Sweden, in 2019. Of the 1863 respondents (38%), 1563 were included (≥18 years). The sample was stratified into four groups, men and women with low or high mental health literacy, using the third quartile of the Mental Health Knowledge Schedule. The likelihood of not perceiving a need for mental healthcare and refraining from seeking mental healthcare, at any time in life, were investigated by calculating odds ratios with 95% confidence intervals. RESULTS: Men with low mental health literacy were most likely to not perceive a need for mental healthcare, also when adjusting for age, education, and poor mental health (OR 5.3, 95% CI 3.6-7.7), and to refrain from seeking mental healthcare, also when adjusting for age and education (OR 3.3, 95% CI 1.7-6.4), followed by men with high mental health literacy (OR 1.9, 95% CI 1.5-2.4, and OR 1.5, 95% CI 1.0-2.2) and women with low mental health literacy (OR 1.9, 95% CI 1.2-2.9, and OR 2.1, 95% CI 1.1-3.9). Women with high mental health literacy were least likely (reference group). CONCLUSION: The results show differences in the likelihood of unmet need for mental healthcare based on combinations of gender and mental health literacy level, with men having low mental health literacy being most at risk, and women with high mental health literacy being least at risk. This challenges generalisations of a gender difference in unmet need by showing heterogeneity among men and women based on mental health literacy. Men with low mental health literacy may be particularly in need of targeted interventions to reduce potential individual and societal consequences of their unmet need.

Bullying experiences before and after the transition from lower to upper secondary school: associations with subsequent mental health in a Swedish cohort.

BACKGROUND: Previous research has shown that exposure to bullying is linked to long-term adverse mental health consequences. However, prospective studies examining the persistence of bullying, using information from repeated time points, are limited. The aim of this study was to examine, firstly, the extent to which exposure to bullying among adolescents in Sweden changes between grades 9 (age 15-16) and 11 (age 17-18) (i.e., before and after the transition from lower to upper secondary school); secondly, whether being bullied in grade 9 or 11 is associated with depression and anxiety symptoms at age 20-21; and thirdly, if being bullied in both grade 9 and 11 is linked to an even higher likelihood of subsequent depression and anxiety symptoms. Potential differences by gender were investigated throughout. METHODS: Data was derived from the Swedish cohort study Futura01 involving individuals attending grade 9 in the school year 2016/17 (n = 2323). We utilised self-reported information from three survey waves conducted in 2017, 2019, and 2022, and linked registry information on sociodemographic characteristics. Bullying was assessed using a single item in waves 1 and 2. Depression and anxiety symptoms were measured using the Patient Health Questionnaire-4 (PHQ-4) in wave 3. Gender stratified binary logistic regressions were performed. RESULTS: Among those who were bullied in grade 9, 22.6% of males and 35.8% of females continued to experience bullying in grade 11. For females, exposure to bullying in grade 9 or 11 was associated with an increased likelihood of reporting depression and anxiety symptoms at age 20-21, with the highest odds for those bullied at both time points. For males, only one statistically significant association was identified - specifically, between being bullied in grade 9 and subsequent depression symptoms. CONCLUSIONS: For a majority of adolescents who experience bullying in lower secondary school, but not all, the transition to upper secondary school proves to be beneficial as the bullying typically does not persist. However, bullying can have long-term health effects, in particular for females. These findings emphasise the importance of effective measures to address bullying within schools.

Functional Variation in the FAAH Gene Is Directly Associated with Subjective Well-Being and Indirectly Associated with Problematic Alcohol Use.

Fatty acid amide hydrolase (FAAH) is an enzyme that degrades anandamide, an endocannabinoid that modulates mesolimbic dopamine release and, consequently, influences states of well-being. Despite these known interactions, the specific role of FAAH in subjective well-being remains underexplored. Since well-being is a dynamic trait that can fluctuate over time, we hypothesized that we could provide deeper insights into the link between FAAH and well-being using longitudinal data. To this end, we analyzed well-being data collected three years apart using the WHO (Ten) Well-Being Index and genotyped a functional polymorphism in the FAAH gene (rs324420, Pro129Thr) in a sample of 2822 individuals. We found that the A-allele of rs324420, which results in reduced FAAH activity and elevated anandamide levels, was associated with lower well-being scores at both time points (Wave I, B: -0.52, p = 0.007; Wave II, B: -0.41, p = 0.03, adjusted for age and sex). A subsequent phenome-wide association study (PheWAS) affirmed our well-being findings in the UK Biobank (N = 126,132, alternative C-allele associated with elevated happiness, p = 0.008) and revealed an additional association with alcohol dependence. In our cohort, using lagged longitudinal mediation analyses, we uncovered evidence of an indirect association between rs324420 and problematic alcohol use (AUDIT-P) through the pathway of lower well-being (indirect effect Boot: 0.015, 95% CI [0.003, 0.030], adjusted for AUDIT in Wave I). We propose that chronically elevated anandamide levels might influence disruptions in the endocannabinoid system-a biological contributor to well-being-which could, in turn, contribute to increased alcohol intake, though multiple factors may be at play. Further genetic studies and mediation analyses are needed to validate and extend these findings.

Indications of alcohol or drug use disorders in five different national registers in Sweden: a cross-sectional population-based study.

OBJECTIVE: The purpose of this study is to examine the prevalence of indications of alcohol or drug use disorders in five different national Swedish registers and to investigate the correlation between these registers. Furthermore, the intent is to investigate whether combining data from different registers increases the prevalence of these indications in the population due to the identification of different demographic groups in different registers. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Individuals living in Sweden aged 20-64 years in 2006, n=5 453 616. PRIMARY OUTCOME: National registers included the Registers of Inpatient Care, Outpatient Care, Medications, Social Insurance and Convictions. Demographic variables were sex, age, migrant status, education and civil status. Indications of alcohol or drug use disorders were presented as prevalence in percentage (%), correlation was examined using phi correlation coefficients and differences across demographic factors were studied using logistic regression. RESULTS: The prevalence of an indication of alcohol or drug use disorder varied between registers, meaning that prevalence increased when all registers were considered together. The prevalence of alcohol use disorder increased by 60% and 66% among men and women, respectively, while the prevalence of drug use disorder increased by 45% and 80% among men and women, respectively, when all registers were combined, compared with only using the register with the highest prevalence. Registers contributed different indications of drug and alcohol use disorders. CONCLUSIONS: Accurate estimates of alcohol or drug use disorders are critical for healthcare and rehabilitation. This study shows that using a single register alone underestimates the burden of disease unevenly, while combining a range of registers can provide a more accurate picture.

Early substance use disorders and subsequent NEET-not in education, employment or training-a national cohort study.

BACKGROUND: Substance use problems have been associated with poor labour market outcomes. This study investigated whether substance use disorders (SUD) in emerging adulthood increase the likelihood of later being not in employment, education or training (NEET). METHODS: A national cohort study of 23 5295 males and 227 792 females born between 1981 and 1987. SUD was assessed between ages 17 and 24 years. Logistic regression models were used to estimate the odds ratios (ORs) of NEET, between ages 25-34. Sibling-comparison analysis was performed to account for potential shared genetic and environmental factors. RESULTS: Having been diagnosed with a SUD was associated with the likelihood of being NEET among males [OR = 1.37, 95% confidence interval (CI), 1.25-1.49] and females (1.19, 1.13-1.27) after adjusting for domicile, origin, psychiatric diagnosis and parental psychiatric diagnosis. Early SUD was also associated with a gradual increase in the ORs of accumulation of years being NEET. This was more evident among females. In the sibling-comparison analysis, we found a higher OR of NEET among same-sex sibling males 1.39 (1.06-1.82) and females 1.28 (0.99-1.66) with SUD. These risks were fully attenuated when another psychiatric diagnosis was adjusted for. CONCLUSION: Early SUD was associated with an increased likelihood of being NEET in both males and females. Neither origin, domicile, psychiatric diagnoses nor parental psychiatric diagnoses did fully explain the association. The combination of unmeasured familial factors and having other psychiatric disorders largely explained these associations.

Does a history of cannabis use influence onset and course of schizophrenia?

INTRODUCTION: While evidence strongly supports a causal effect of cannabis on psychosis, it is less clear whether the symptom pattern, clinical course, and outcomes differ in cases of schizophrenia with and without a background of cannabis use. METHODS: Analysis of medical records from a longitudinal follow-up of Swedish conscripts with data on cannabis use in adolescence and subsequent incidence of schizophrenia. One hundred sixty patients with schizophrenia were assessed using the OPCRIT protocol. Cases were validated for diagnosis schizophrenia according to OPCRIT. RESULTS: Patients with a cannabis history (n = 32), compared to those without (n = 128), had an earlier age at onset, a higher number of hospital admissions and a higher total number of hospital days. There was no significant difference in type of onset and clinical symptom profiles between the groups. CONCLUSION: Our findings indicate that the disease burden of schizophrenia is greater in individuals who use cannabis during adolescence. Strengthening evidence on causality and teasing out long-term effects of pre-illness cannabis use from continued post-illness has clinical implications for improving schizophrenia outcomes.

The Major Depression Inventory for diagnosing according to DSM-5 and ICD-11: Psychometric properties and validity in a Swedish general population.

OBJECTIVES: The Major Depression Inventory (MDI) was constructed to assess DSM-IV and ICD-10 depression symptoms, and does not fully cover the symptoms listed in DSM-5 and ICD-11. This study aimed to augment the MDI to the new diagnostic standards by adding a new item, and to assess and compare the measurement performance of the MDI items and diagnostic algorithms for major depression according to DSM-IV, ICD-10, DSM-5 and ICD-11. METHODS: Surveys collected 2001-2003 and 2021, including self-assessed MDI were used. A new hopelessness item was constructed and analyzed alongside the hopelessness item in the Symptom Checklist. The performance of items was compared using Rasch and Mokken analyses. Criterion validity was examined using equivalent diagnoses from psychiatric interview (Schedules for Clinical Assessments in Neuropsychiatry [SCAN]) as standard. RESULTS: MDI information was provided by 8511 individuals in 2001-2003 (SCAN subsample n = 878), and 8863 in 2021. All items, including hopelessness had good psychometric properties. Sensitivity ranged between 56% and 70%, and specificity between 95% and 96%, indicating similar criterion validity. CONCLUSIONS: Hopelessness and the MDI items had good psychometrics. MDI for DSM-5 and ICD-11 had similar validity as for DSM-IV and ICD-10. We recommend that MDI is updated to DSM-5 and ICD-11 by adding a hopelessness item.

Long-term stability in obsessive thoughts and compulsive behavior in the general population: a longitudinal study in Sweden.

OBJECTIVE: Obsessive thoughts and compulsive behavior and their related disorder Obsessive-Compulsive Disorder (OCD) commonly occur in the general population. Clinical populations indicate a high level of stability, although there are few longitudinal studies in the general population. The recommended drug treatments are SSRIs/TCAs. However, there are few long-term follow up studies. The goal of this study was to 1) examine the occurrence and stability of obsessions, compulsions, and OCD in a longitudinal population-based survey, 2) investigate the use of SSRI and TCA and the potential effect on symptoms. METHODS: A ten-year longitudinal general population in Stockholm was used (2000 and 2010, n = 5650) Obsessional washing, checking, intrusive unpleasant thoughts and the level of suffering due to these symptoms were measured by self-report. Information on use of SSRIs and TCAs by these individuals was obtained from registers. Stability was examined using contingency tables and multinomial logistic regression. RESULTS: At baseline, 2.1, 11.7 and 11.9% reported obsessional washing, checking and intrusive thoughts. A total of 5% reported considerable suffering from these (i.e. OCD). Based on psychiatric interview only 0.4% had OCD. Ten years later a quarter of OCD cases were still classified as having OCD, one quarter reported any obsessive or compulsive symptom and half were classified as symptom-free. Treatment receipt was low and controlling for medication did not change the stability. CONCLUSION: Obsessive thoughts and compulsive behavior are common and stable. While this group is potentially undertreated, there is no indication that those treated display a different pattern of recovery.

Veno-arterial CO2 difference and lactate for prediction of early mortality after cardiac arrest.

Patients admitted to intensive care after cardiac arrest are at risk of circulatory shock and early mortality due to cardiovascular failure. The aim of this study was to evaluate the ability of the veno-arterial pCO2 difference (∆pCO2 ; central venous CO2 - arterial CO2 ) and lactate to predict early mortality in postcardiac arrest patients. This was a pre-planned prospective observational sub-study of the target temperature management 2 trial. The sub-study patients were included at five Swedish sites. Repeated measurements of ∆pCO2 and lactate were conducted at 4, 8, 12, 16, 24, 48, and 72 h after randomization. We assessed the association between each marker and 96-h mortality and their prognostic value for 96-h mortality. One hundred sixty-three patients were included in the analysis. Mortality at 96 h was 17%. During the initial 24 h, there was no difference in ∆pCO2 levels between 96-h survivors and non-survivors. ∆pCO2 measured at 4 h was associated with an increased risk of death within 96 h (adjusted odds ratio: 1.15; 95% confidence interval [CI]: 1.02-1.29; p = .018). Lactate levels were associated with poor outcome over multiple measurements. The area under the receiving operating curve to predict death within 96 h was 0.59 (95% CI: 0.48-0.74) and 0.82 (95% CI: 0.72-0.92) for ∆pCO2 and lactate, respectively. Our results do not support the use of ∆pCO2 to identify patients with early mortality in the postresuscitation phase. In contrast, non-survivors demonstrated higher lactate levels in the initial phase and lactate identified patients with early mortality with moderate accuracy.

Educational level and the risk of mental disorders, substance use disorders and self-harm in different age-groups: A cohort study covering 1,6 million subjects in the Stockholm region.

OBJECTIVE: To investigate the associations between low education and risk of mental disorders, substance use disorders and self-harm in different age-groups. METHODS: All subjects in Stockholm born between 1931 and 1990 were linked to their own or their parent's highest education in 2000 and followed-up for these disorders in health care registers 2001-2016. Subjects were stratified into four age-groups: 10-18, 19-27, 28-50, and 51-70 years. Hazard Ratios with 95% Confidence Intervals (CIs) were estimated with Cox proportional hazard models. RESULTS: Low education increased the risk of substance use disorders and self-harm in all age-groups. Males aged 10-18 with low education had increased risks of ADHD and conduct disorders, and females a decreased risk of anorexia, bulimia and autism. Those aged 19-27 years had increased risks of anxiety and depression, and those aged 28-50 had increased risks of all mental disorders except anorexia and bulimia in males with Hazard Ratios ranging from 1.2 (95% CIs 1.0-1.3) for bipolar disorder to 5.4 (95% CIs 5.1-5.7) for drug use disorder. Females aged 51-70 years had increased risks of schizophrenia and autism. CONCLUSION: Low education is associated with risk of most mental disorders, substance use disorders and self-harm in all age-groups, but especially among those aged 28-50 years.

Risk of readmission among individuals with cannabis use disorder during a 15-year cohort study: the impact of socio-economic factors and psychiatric comorbidity.

BACKGROUND AND AIM: Cannabis use disorder (CUD) is one of the main reasons for seeking substance treatment in the Nordic countries, but there are few studies on readmission to care. We aimed to characterize CUD readmission and estimate the magnitude of how socio-economic factors and psychiatric comorbidity influence the risk of CUD readmission. DESIGN, SETTING AND PARTICIPANTS: This was a nation-wide cohort study carried out between 2001 and 2016 in Sweden. The participants were individuals with CUD, aged 17 years and above (n = 12 143). MEASUREMENTS: Information on predictors was obtained from registers and included education, income and psychiatric comorbidity assessed by six disease groups. The outcome measure was readmission, defined as a CUD visit to health-care at least 6 months after initial CUD diagnosis. Hazard ratios (HR) were estimated using Cox survival analyses and flexible parametric survival analyses to assess risk of readmission and how the risk varied with age. FINDINGS: The vast majority of CUD visits took place in outpatient care (~80%). Approximately 23% of the included individuals were readmitted to care during follow-up. The fully adjusted model showed an increased risk of readmission among those with schizophrenia and other psychotic disorders [HR = 1.54, 95% confidence interval (CI) = 1.29-1.84], low education (HR = 1.40, 95% CI = 1.24-1.57), personality disorders (HR = 1.27, 95% CI = 1.05-1.54) or mood disorders (HR = 1.27, 95% CI = 1.12-1.45). Flexible parametric modeling revealed increased risk of readmission mainly in individuals aged 18-35 years. CONCLUSIONS: The risk of readmission was highest among those with low education, schizophrenia and other psychotic disorders, mood-related disorders or personality disorders. Individuals aged 18-35 years showed the highest risk of readmission. Our findings highlight individuals with complex health-care needs.

Measurement of Mental Health Among Adolescents at the Population Level: A Multicountry Protocol for Adaptation and Validation of Mental Health Measures.

PURPOSE: Mental disorders are among the leading causes of disability among adolescents aged 10-19 years. However, data on prevalence of mental health conditions are extremely sparse across low- and middle-income countries, even though most adolescents live in these settings. This data gap is further exacerbated because few brief instruments for adolescent mental health are validated in these settings, making population-level measurement of adolescent mental health especially cumbersome to carry out. In response, the UNICEF has undertaken the Measurement of Mental Health Among Adolescents at the Population Level (MMAP) initiative, validating open-access brief measures and encouraging data collection in this area. METHODS: This protocol presents the MMAP mixed-methods approach for cultural adaptation and clinical validation of adolescent mental health data collection tools across settings. Qualitative activities include an initial translation and adaptation, review by mental health experts, focus-group discussions with adolescents, cognitive interviews, synthesis of findings, and back-translation. An enriched sample of adolescents with mental health problems is then interviewed with the adapted tool, followed by gold-standard semistructured diagnostic interviews. RESULTS: The study protocol is being implemented in Belize, Kenya, Nepal, and South Africa and includes measures for anxiety, depression, functional limitations, suicidality, care-seeking, and connectedness. Analyses, including psychometrics, will be conducted individually by country and combined across settings to assess the MMAP methodological process. DISCUSSION: This protocol contributes to closing the data gap on adolescent mental health conditions by providing a rigorous process of cross-cultural adaptation and validation of data collection approaches.

Validation of the Kriol and Belizean English Adaptation of the Revised Children's Anxiety and Depression Scale for Use With Adolescents in Belize.

PURPOSE: To validate a culturally-adapted Kriol and Belizean English version of the Revised Children's Anxiety and Depression Scale (RCADS) through comparison with clinical diagnoses made using the Kiddie Schedule of Affective Disorders and Schizophrenia. METHODS: Participants comprised of 256 adolescents aged 10-14 years and 15-19 years, who completed the adapted RCADS (10 depression items, 12 anxiety items) in one-on-one interviews, followed by a diagnostic assessment using Kiddie Schedule of Affective Disorders and Schizophrenia administered by trained clinicians. Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic odds ratios, area under the curve (AUC), and Youden's Index were calculated for RCADS cutoffs and scores on the total scale and anxiety and depression subscales. RESULTS: For adolescents aged 10-14 years (n = 161), the AUC was 0.72 for the full scale, 0.67 for anxiety subscale, and 0.76 for depression subscale. For adolescents aged 15-19 years (n = 95), the AUCs were 0.82, 0.77, and 0.83. Most depression items performed well in discriminating those with and without diagnoses. Separation anxiety items performed poorly. "Thoughts of death" were common even among adolescents not meeting diagnostic criteria. The RCADS depression subscale presented the strongest psychometric properties with adolescents aged 15-19 years (at cutoff of 13, sensitivity = 0.83, specificity = 0.77, positive predictive value = 0.47, negative predictive value = 0.95, odds ratio = 15.96). CONCLUSION: The adapted RCADS-22 had acceptable categorization for adolescents aged 10-14 years and excellent categorization for adolescents aged 15-19 years; therefore, the tool is recommended for use among the latter age group. Based on sensitivity and specificity values at different cutoffs, guidance is provided to select different thresholds to suit clinical, public health, or other uses to detect and quantify adolescent depression and anxiety in Belize.

Cannabis use disorder in relation to socioeconomic factors and psychiatric comorbidity: A cluster analysis of three million individuals born in 1970-2000.

BACKGROUND: Cannabis use disorder (CUD) is one of the main reasons for seeking substance use treatment. It is thus important to monitor and increase knowledge of individuals with CUD utilizing healthcare. We aimed to examine the number of CUD diagnoses over time, compare individuals with CUD with those without and identify subgroups based on CUD diagnosis, sex, birth year, socioeconomic factors and psychiatric comorbidity. METHODS: A Swedish, population-based study with 3,307,759 individuals, born in 1970-2000, with register data extending to 2016. K-mode cluster analysis was used to identify potential subgroups. RESULTS: The number of individuals with a CUD diagnosis was 14,046 (0.42%). CUD diagnoses increased over time (born 1990-1994: 61 per 100,000, born 1995-2000: 107 per 100,000, by 2016). A majority of those with a CUD had another psychiatric diagnosis (80%, compared with 19% for those without CUD). Four clusters were identified. Cluster 1 comprised mainly men with low income and substance use disorders, clusters 2, 3 and 4 comprised mainly women with higher proportions of mood-related, neurotic and stress-related and behavioural disorders. CONCLUSIONS: There was an increase in CUD diagnoses in Sweden over time, especially among younger birth cohorts. Individuals with CUD were more often male, from younger birth cohorts, with lower education and income than those without CUD. Men and women with CUD exhibited differences in education, income and psychiatric comorbidity. Our results demonstrate the importance of monitoring the impact of socioeconomic factors and psychiatric comorbidity in relation to CUD.

Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial.

BACKGROUND: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients' outcome. METHODS: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. RESULTS: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93-1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95-1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). CONCLUSIONS: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. TRIAL REGISTRATION: clinicaltrials.gov NCT02908308 , Registered September 20, 2016.

Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients: a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial.

PURPOSE: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. METHODS: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. RESULTS: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2-8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5-9) cmH20, plateau pressure was 20 cmH20 (IQR = 17-23), driving pressure was 12 cmH20 (IQR = 10-15), mechanical power 16.2 J/min (IQR = 12.1-21.8), ventilatory ratio was 1.27 (IQR = 1.04-1.6), and respiratory rate was 17 breaths/minute (IQR = 14-20). Median partial pressure of oxygen was 87 mmHg (IQR = 75-105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36-45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003-1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001-1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. CONCLUSIONS: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.

The cannabinoid receptor-1 gene interacts with stressful life events to increase the risk for problematic alcohol use.

Problematic alcohol use is a major contributor to the global burden of death and disabilities, and it represents a public health concern that has grown substantially following the COVID-19 pandemic. The available treatment options remain limited and to develop better pharmacotherapies for alcohol misuse we need to identify suitable biological targets. Previous research has implicated the brain's endocannabinoid system (ECS) in psychiatric and stress-related outcomes, including substance use and habituation to repeated stress. Moreover, genetic variants in the cannabinoid-1 receptor gene (CNR1; CB1R) have been associated with personality traits, which are in turn predictors of substance use disorders. To date, however, no human genome-wide association study has provided evidence for an involvement of the ECS in substance use outcomes. One reason for this ECS-related "missing heritability" may be unexamined gene-environment interactions. To explore this possibility, we conducted cross-sectional analyses using DNA samples and stress-exposure data from a longitudinal Swedish population-based study (N = 2,915). Specifically, we genotyped rs2023239, a functional C/T single nucleotide polymorphism in CNR1, previously reported to be associated with CNR1 binding in the brain, subjective reward following alcohol intake, and alcohol cue-elicited brain activation. Our two outcomes of interest were (i) problematic alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), and (ii) personality trait scores based on the Five Factor Model. We found no baseline association between rs2023239 and problematic alcohol use or personality traits. However, there was a clear trend for interaction between rs2023239's risk allele (C) and stressful life events (SLEs) in both childhood and adulthood, which predicted problematic alcohol use. Although not significant, there was also some indication that the risk allele interacted with child SLEs to increase scores on neuroticism. Our study supports the notion that the ECS can affect alcohol intake behaviors by interacting with life adversities and is-to the best of our knowledge-the first to focus on the interaction between CNR1 and stressors in both childhood and adulthood in humans. Further studies are warranted to confirm these findings.

Poverty in adolescence and later drug use disorders: understanding the mediation and interaction effects of other psychiatric disorders.

BACKGROUND: Poverty in adolescence is associated with later drug use. Few studies have evaluated the role of adolescent psychiatric disorders in this association. AIMS: This study aimed to investigate mediation and interaction simultaneously, enabling the disentanglement of the role of adolescent psychiatric disorders in the association between poverty in adolescent and later drug use disorders. METHOD: A national cohort study of 634 223 individuals born in 1985-1990, residing in Sweden between the ages of 13 and 18 years, was followed from age 19 years until the first in-patient or out-patient care visit with a diagnosis of drug use disorder. A four-way decomposition method was used to determine the total effect of the association with poverty and possible mediation by and/or interaction with diagnosis of adolescent psychiatric disorders. RESULTS: The hazard ratios for drug use disorders among those experiencing poverty compared with those 'never in poverty' were 1.40 (95% CI, 1.32-1.63) in females and 1.43 (95% CI, 1.37-1.49) in males, after adjusting for domicile, origin and parental psychiatric disorders. Twenty-four per cent of this association in females, and 13% in males, was explained by interaction with and/or mediation by adolescent psychiatric disorders. CONCLUSIONS: Part of the association between poverty in adolescence and later drug use disorders was due to mediation by and/or interaction with psychiatric disorders. Narrowing socioeconomic inequalities in adolescence might help to reduce the risks of later drug use disorders. Interventions aimed at adolescents with psychiatric disorders might be especially important.

Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial.

INTRODUCTION: Mechanical ventilation is a fundamental component in the management of patients post cardiac arrest. However, the ventilator settings and the gas-exchange targets used after cardiac arrest may not be optimal to minimise post-anoxic secondary brain injury. Therefore, questions remain regarding the best ventilator management in such patients. METHODS AND ANALYSIS: This is a preplanned analysis of the international randomised controlled trial, targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (OHCA)-target temperature management 2 (TTM2). The primary objective is to describe ventilatory settings and gas exchange in patients who required invasive mechanical ventilation and included in the TTM2 trial. Secondary objectives include evaluating the association of ventilator settings and gas-exchange values with 6 months mortality and neurological outcome. Adult patients after an OHCA who were included in the TTM2 trial and who received invasive mechanical ventilation will be eligible for this analysis. Data collected in the TTM2 trial that will be analysed include patients' prehospital characteristics, clinical examination, ventilator settings and arterial blood gases recorded at hospital and intensive care unit (ICU) admission and daily during ICU stay. ETHICS AND DISSEMINATION: The TTM2 study has been approved by the regional ethics committee at Lund University and by all relevant ethics boards in participating countries. No further ethical committee approval is required for this secondary analysis. Data will be disseminated to the scientific community by abstracts and by original articles submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02908308.

Trajectories of NEET (Not in Education, Employment, and Training) in emerging adulthood, and later drug use disorder - a national cohort study.

BACKGROUND: Being not in education, employment, or training (NEET) has been associated with poor health outcomes. This study aimed to investigate the association between NEET during emerging adulthood and later drug use disorder (DUD) among males and females. METHOD: A national cohort comprising 383,116 Swedish males and 362,002 females born between 1984 and 1990. NEET exposure was assessed annually between the ages 17 and 24 years, and follow-up for DUD between ages 25-33. Trajectories of NEET were estimated using group-based trajectory analysis. Cox regression analysis was used to estimate hazard ratios (HR) of DUD. Sibling-comparison model was performed to account for potential shared genetic and environmental factors. RESULTS: Four trajectories of NEET were identified: "constant low", "transient peak", "late increase", and "constant high". Compared with the "constant low", all other trajectories were associated with increased HRs of DUD. HR was highest among males and females in the "late increase trajectory"; HR = 4.10 (3.79-4.44, 95% CI) and HR = 3.73 (3.29-4.24, 95% CI), after adjusting for domicile, origin, birth year, psychiatric diagnoses, and parental psychiatric diagnoses. This association was reduced to about a twofold increased risk in the sibling comparison analysis. CONCLUSION: Being NEET during emerging adulthood was associated with later DUD for both males and females. Neither origin, psychiatric diagnoses, parental psychiatric diagnoses, nor shared familial factors did fully explain the association. Males and females belonging to the late increase NEET trajectory had about a twofold increased risk of DUD.