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BACKGROUND Individuals with HIV and hepatitis C virus (HCV) who remain untreated with direct-acting antivirals can contribute to HCV transmission and HCV-related mortality. We aimed to compare rates of uptake of direct-acting antivirals following unrestricted access to this treatment in high-income countries and examine factors associated with remaining untreated. METHODS This multinational, prospective cohort study used data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). We analysed data from nine observational cohorts participating in the InCHEHC, including data from six high-income countries (Australia, Canada, France, the Netherlands, Spain, and Switzerland). We included individuals aged 18 years and older, with HIV and HCV (ie, HCV-RNA positive without evidence of spontaneous clearance) during unrestricted access to interferon-free direct-acting antiviral treatment in each country. We calculated the cumulative proportion of participants who remained untreated with direct-acting antivirals, with follow-up starting after the date of unrestricted access or cohort inclusion, whichever occurred most recently. Factors associated with the commencement rate of direct-acting antiviral treatment were assessed using competing-risks regression with the Fine-Gray method. FINDINGS The date of unrestricted access to direct-acting antiviral treatment for people with HIV ranged from Nov 1, 2014, in France to Nov 1, 2017, in Switzerland. We included 4552 individuals with HIV-HCV, mainly men who have sex with men (MSM; n=2156 [47%]) and people who inject or have injected drugs (n=1453 [32%]). 1365 (30%) of 4552 participants remained untreated with direct-acting antivirals. For individuals treated with direct-acting antivirals, median time from start of follow-up to treatment was 5 months (IQR 2-12). For individuals who were not treated with direct-acting antivirals, median follow-up was 22 months (8-30). Being linked to care in Australia, France, or the Netherlands, on antiretroviral therapy, having undetectable HIV RNA, and shorter duration since first positive HCV test were independently associated with higher commencement rate of direct-acting antiviral treatment. Compared with MSM, male heterosexuals and females with unknown or other routes of HIV transmission (ie, neither injection drug use nor heterosexual transmission) had lower rates of commencement. INTERPRETATION Despite unrestricted access, almost a third of individuals with HIV-HCV remained untreated with direct-acting antivirals during follow-up, with variation in commencement rate of HCV treatment between countries and key populations. Increased efforts are required to reach the remaining individuals with HIV who are HCV-viraemic to achieve HIV-HCV micro-elimination. FUNDING None.

Alcohol use disorder is argued to be a highly complex disorder influenced by a multitude of factors on different levels. Common research approaches fail to capture this breadth of interconnecting symptoms. To address this gap in theoretical assumptions and methodological approaches, we used a network analysis to assess the interplay of alcohol use disorder symptoms. We applied the exploratory analysis to two US-datasets, a population sample with 23,591 individuals and a clinical sample with 483 individuals seeking treatment for alcohol use disorder. Using a Bayesian framework, we first investigated differences between the clinical and population sample looking at the symptom interactions and underlying structure space. In the population sample the time spent drinking alcohol was most strongly connected, whereas in the clinical sample loss of control showed most connections. Furthermore, the clinical sample demonstrated less connections, however, estimates were too unstable to conclude the sparsity of the network. Second, for the population sample we assessed whether the network was measurement invariant across external factors like age, gender, ethnicity and income. The network differed across all factors, especially for age subgroups, indicating that subgroup specific networks should be considered when deriving implications for theory building or intervention planning. Our findings corroborate known theories of alcohol use disorder stating loss of control as a central symptom in alcohol dependent individuals.

Background: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective disorders over a nine-year period, comparing a categorical approach using diagnoses to a dimensional approach using symptom severity.Method: Patients with a current depressive and/or anxiety disorder at baseline (N = 1701) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Using psychiatric diagnoses, we described 'consistently recovered,' 'intermittently recovered,' 'intermittently recurrent', and 'consistently chronic' at two-, four-, six-, and nine-year follow-up. Additionally, latent class growth analysis (LCGA) using depressive, anxiety, fear, and worry symptom severity scores was used to identify distinct classes.Results: Considering the categorical approach, 8.5% were chronic, 32.9% were intermittently recurrent, 37.6% were intermittently recovered, and 21.0% remained consistently recovered from any affective disorder at nine-year follow-up. In the dimensional approach, 66.6% were chronic, 25.9% showed partial recovery, and 7.6% had recovered.Limitations: 30.6% of patients were lost to follow-up. Diagnoses were rated by the interviewer and questionnaires were completed by the participant.Conclusions: Using diagnoses alone as discrete categories to describe clinical course fails to fully capture the persistence of affective symptoms that were observed when using a dimensional approach. The enduring, fluctuating presence of sub-threshold affective symptoms likely predisposes patients to frequent relapse. The commonness of subthreshold symptoms and their adverse impact on long-term prognoses deserve continuous clinical attention in mental health care as well further research.

Background & Aims Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking. Methods REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. Results The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4–89.0) in the short arm and 86/95, 90.5% (95% CI 82.7–95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8–95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0–99.7; difference -8.3%, p = 0.025). Conclusions In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. Lay summary In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. ClinicalTrials.gov Identifier NCT02625909 .

IntroductionCurrent treatments for cocaine use disorder (CUD) are not very effective and better treatments are needed. This study investigates the effectiveness of a combined intervention that targets the assumed underlying glutamate pathology in cocaine users. To this end, the combined effects of N-acetylcysteine (NAC) and working memory (WM) training on glutamate concentrations in the dorsal and rostral ACC were investigated in a randomized, double-blind placebo-controlled design.MethodsIn this study, 38 regular cocaine-using men were randomized to either 25-days with 2400 mg/day NAC and WM-training or 25 days with placebo with WM-training. Cocaine use, impulsivity, and glutamate concentrations in the dACC and rACC using proton Magnetic Resonance Spectroscopy were assessed at baseline and after treatment.ResultsTwenty-four participants completed the study, of which 9 received NAC and 15 received placebo. There were no baseline correlations of glutamate concentrations in the dACC or rACC with cocaine use measures or impulsivity. Additionally, there were no effects of NAC, WM-training, or the combination thereof on (changes in) glutamate concentrations in the dACC or rACC.DiscussionThis randomized proof of concept study could not confirm our hypotheses. Possible explanations are insufficient power and the possible absence of deviant baseline glutamate concentrations in the included participants. Future studies should consider larger samples and a non-using control group to confirm baseline deviations in glutamate in cocaine users.

OBJECTIVES:After hospitalization, many older adults need post-acute care, including rehabilitation or home care. However, post-acute care expenses can be as high as the costs for the initial hospitalization. Detailed information on monthly post-acute health care expenditures and the characteristics of patients that make up for a large share of these expenditures is scarce. We aimed to calculate costs in acutely hospitalized older patients and identify patient characteristics that are associated with high post-acute care costs.DESIGN:Prospective multicenter cohort study (between October 2015 and June 2017).SETTING AND PARTICIPANTS:401 acutely hospitalized older persons from internal medicine, cardiology, and geriatric wards.MEASUREMENTS:Our primary outcome was mean post-acute care costs within 90 days postdischarge. Post-acute care costs included costs for unplanned readmissions, home care, nursing home care, general practice, and rehabilitation care. Three costs categories were defined: low [0-50th percentile (p0-50)], moderate (p50-75), and high (p75-100). Multinomial logistic regression analyses were conducted to assess the associations between costs and frailty, functional impairment, health-related quality of life, cognitive impairment, and depressive symptoms.RESULTS:Costs were distributed unevenly in the population, with the top 10.0% (n = 40) accounting for 52.1% of total post-acute care costs. Mean post-acute care costs were €4035 [standard deviation (SD) 4346] or $4560 (SD 4911). Frailty [odds ratio (OR) 3.44, 95% confidence interval (CI) 1.78-6.63], functional impairment (OR 1.80, 95% CI 1.03-3.16), and poor health-related quality of life (OR 1.89, 95% CI 1.09-3.28) at admission were associated with classification in the high-cost group, compared with the low-cost group.CONCLUSIONS/IMPLICATIONS:Post-acute care costs are substantial in a small portion of hospitalized older adults. Frailty, functional impairment, and poor health-related quality of life are associated with higher post-acute care costs and may be used as an indicator of such costs in practice.

Background: Major depression disorder (MDD)11 Abbreviations: BMI: Body mass index; MDD: Major depressive disorder; WHR: wait-to-hip-ratio and obesity are among the most common public health problems. The majority of epidemiological studies demonstrated a strong relationship between sociodemographic factors like age and socioeconomic status and depression. Also, a bidirectional link between depression and obesity is discussed. However, differences regarding sociodemographic factors and obesity between participants with and without lifetime MDD might occur, but potentially not in all individuals. This study intends to contribute to this discussion by investigating whether or not sociodemographic factors, chronic illness status, and overweight differ between individuals with and without lifetime MDD. Methods: In the MooDFOOD depression prevention trial, 1025 overweight or obese participants with subsyndromal symptoms of depression were recruited. Lifetime history of MDD, number of lifetime MDD episodes, sociodemographic data, and chronic illness were assessed via clinical interview, also standardized anthropometric measures (body mass index [BMI], waist-to-hip ratio [WHR]). Results: A lifetime MDD diagnosis was present in 33.5% of the sample. Individuals with lifetime MDD and individuals who never suffered from MDD did not differ regarding sex, age, marital status, educational level, employment status, and income. Further, there were no significant differences in BMI, WHR, and number of chronic illnesses between participants with and without lifetime MDD. Limitations: The cross-sectional nature of the data prohibited causal inferences. Conclusion: Sociodemographic variables, chronic illness status and anthropometric measures seem not to be related to the status of having suffered from MDD in the past vs. not having suffered from MDD in people who are currently overweight or obese.

Introduction Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that is estimated to be carried by one-third of the world population. Latent T. gondii infection has been linked to several neuropsychiatric mood disorders and behaviors. The aim of the present study was to examine whether T. gondii seropositivity is associated with affective disorders, as well as with aggression reactivity and suicidal thoughts. Methods In the Netherlands Study of Depression and Anxiety (NESDA), T. gondii antibodies were assessed in patients with current depressive (n ​= ​133), anxiety (n ​= ​188), comorbid depressive and anxiety (n ​= ​148), and remitted disorders (n ​= ​889), as well as in healthy controls (n ​= ​373) based on DSM-IV criteria. Seropositivity was analyzed in relation to disorder status, aggression reactivity and suicidal thoughts using multivariate analyses of covariance and regression analyses. Results Participants were on average 51.2 years (SD ​= ​13.2), and 64.4% were female. Seropositivity was found in 673 participants (38.9%). A strong positive association between T. gondii seropositivity and age was observed. No significant associations were found between T. gondii seropositivity and disorder status, aggression reactivity and suicidal thoughts. The adjusted odds ratio (OR) for any remitted disorder versus controls was 1.13 (95% CI: 0.87-1.49), and for any current disorder versus controls was 0.94 (95% CI: 0.69-1.28). Conclusions No evidence was found for a relationship between affective disorders and T. gondii infection in the current sample., Highlights • Increasing age is strongly associated with a higher seroprevalence of T. gondii. • No relationship was found between affective disorders and T. gondii infection. • Affective symptom severity measures were not associated with T. gondii infection. • Aggressive and suicidal thoughts were not associated with T. gondii infection.

Background Repetitive negative thinking (RNT) is a common feature of different mental disorders in the affective spectrum. Most measures of RNT are disorder-specific and measure e.g. rumination in depression or worry in anxiety. Methods In the Netherlands Study of Depression and Anxiety (NESDA), 1820 adults completed the Perseverative Thinking Questionnaire to assess content-independent RNT over a 3-year follow-up period. We investigated the relative stability of content-independent RNT (Perseverative Thinking Questionnaire), over time as well as the association between changes in RNT and changes in affective disorder status (Composite International Diagnostic Interview) and depressive and anxiety severity (Inventory of Depressive Symptomatology, Beck Anxiety Inventory, Fear Questionnaire). Results In the total group, baseline RNT was strongly related to RNT three years later, while the difference between the scores at baseline and three years later was negligible. Increases and decreases in RNT were associated with the occurrence and recovery of affective disorders, respectively. Furthermore, changes in RNT between baseline and three years later were associated with corresponding changes in depression, anxiety, and avoidance symptom severity. These associations were small or negligible. Limitations Our findings may not be representative of all affective disorders as individuals with an obsessive-compulsive disorder or bipolar disorder were excluded from our sample. Conclusions The findings suggest that RNT is not primarily an index of disorder status or epiphenomenon of symptom severity and may constitute a relatively stable transdiagnostic person characteristic.

Background The heterogeneity of late-life depression hampers diagnosis and treatment. Data-driven methods have identified several subtypes of depression in older persons, but the longitudinal stability of these subtypes remains unknown. Methods In total 111 older persons with a major depressive disorder both at baseline and 2-year follow-up from the Netherlands Study of Depression in Older persons (NESDO) were included. Latent class analysis was performed to identify subtypes of depression at baseline and at 2-year follow-up, and latent transition analysis was used to examine the stability of these subtypes over time. Transition rates between subtypes and characteristics of groups were examined. Results Two subtypes were identified in both baseline (T0) and follow-up data (T1), including a ‘melancholic’ subtype (prevalence 80.2% (T0) and 62.2% (T1)), and an ‘atypical’ subtype (prevalence 19.8% (T0) and 37.8% (T1)). The melancholic subtype was characterized by decreased appetite and weight and had a stability of 0.86. The atypical subtype was characterized by increased appetite and weight and had a stability of 0.93, although the discriminating power of different symptoms had decreased at T1. Mean age and education differed significantly between stable and transitioning subgroups, other characteristics did not differ between subgroups. Limitations Limited sample size might have hampered the analyses. Conclusions Subtypes of late-life depression are relatively stable, but symptoms of depression (like weight loss) seem to blur with symptoms of (patho)physiological aging. This underlines the clinical relevance of depression subtyping, but also the importance of further research into subtypes and the influence of aging.

This chapter presents factors predating the development of addictive behaviors such as problematic gambling and gaming disorder. Both neurocognitive and personality factors indicated by behavioral and neurocognitive measures of impulsivity and low self-restraint are associated with problem gambling in prospective studies that focus on the prediction of problem gambling from childhood behavior and temperament. For problem gambling as well as problematic gaming and Internet involvement, substantial genetic influence is present, with higher genetic load for more severe gambling problems. For problem gaming and other behavioral addictions, more genetic research is needed, although initial studies show that (shared) environmental factors have a larger effect in females compared with males. In problem gambling and gaming, cognitive misperceptions for gambling and gaming-related cognitions such as perfectionism regarding gaming and perceived control are associated with perceived skill in chance games. For problematic gaming and other behavioral addictive disorders, more research is needed into predictive factors, although the first studies do indicate a larger role for social factors such as higher social integration, school achievement, and higher parental monitoring being related to problematic gaming, compared with the factors involved in problematic gambling, which seem to align to a higher degree with shared risk factors for substance use disorders.

Background In Indonesia, internet-based interventions may represent a promising strategy to reduce the mental health gap given that the level of internet usage in the country continues to increase. To check the acceptability of internet-based interventions, this study investigates factors that contribute to the use of internet-based interventions for depression in Indonesia. Method The survey was conducted online and had 904 participants recruited from specific social networks on mental health and general social media (Mean age = 27.07, 50.22% females). The three dependent variables were (1) behavioral intention to start using internet-based interventions for depression, (2) preference to use it as a substitute for regular treatments and (3) preference to use it to complement regular treatments. The predictor variables included sociodemographic characteristics, perceived mental health conditions, personal situational characteristics, personal innovativeness toward online services, and depression level. Results A large majority reported to be open to using internet-based interventions for depression (73.7%), as well as to use it as a substitution (73.3%) or as a complementary (73%) to regular treatments. Personal innovativeness toward online services was the strongest significant predictor for all types of use, even when corrected for current depression level. When added to the analyses separately, depression level was the second strongest predictive factor for all dependent variables. Conclusion The majority of Indonesians showed openness to use internet-based interventions for depression. To increase the adoption of internet-based interventions for depression, it is important to first promote internet usage to more people across the country, especially for those who are currently depressed., Highlights • Indonesians seem to be open to use internet-based interventions for depression. • Personal innovativeness toward online services is the strongest usage predictor. • Depression level is the second strongest usage predictor.

Background: Psychiatric disorders are highly heterogeneous, defined based on symptoms with little connection to potential underlying biological mechanisms. A possible approach to dissect biological heterogeneity is to look for biologically meaningful subtypes. A recent study Drysdale et al. (2017) showed promising results along this line by simultaneously using resting state fMRI and clinical data and identified four distinct subtypes of depression with different clinical profiles and abnormal resting state fMRI connectivity. These subtypes were predictive of treatment response to transcranial magnetic stimulation therapy. Objective: Here, we attempted to replicate the procedure followed in the Drysdale et al. study and their findings in a different clinical population and a more heterogeneous sample of 187 participants with depression and anxiety. We aimed to answer the following questions: 1) Using the same procedure, can we find a statistically significant and reliable relationship between brain connectivity and clinical symptoms? 2) Is the observed relationship similar to the one found in the original study? 3) Can we identify distinct and reliable subtypes? 4) Do they have similar clinical profiles as the subtypes identified in the original study? Methods: We followed the original procedure as closely as possible, including a canonical correlation analysis to find a low dimensional representation of clinically relevant resting state fMRI features, followed by hierarchical clustering to identify subtypes. We extended the original procedure using additional statistical tests, to test the statistical significance of the relationship between resting state fMRI and clinical data, and the existence of distinct subtypes. Furthermore, we examined the stability of the whole procedure using resampling. Results and conclusion: As in the original study, we found extremely high canonical correlations between functional connectivity and clinical symptoms, and an optimal three-cluster solution. However, neither canonical correlations nor clusters were statistically significant. On the basis of our extensive evaluations of the analysis methodology used and within the limits of comparison of our sample relative to the sample used in Drysdale et al., we argue that the evidence for the existence of the distinct resting state connectivity-based subtypes of depression should be interpreted with caution. Keywords: Clustering, Anxiety, Major depressive disorder, Machine learning, Replication

The link between inflammation and major depressive disorder (MDD) has been widely established. But as MDD is a highly heterogeneous disorder, the association with inflammation may not be present in all persons with MDD. In this chapter, we discuss the relevance of studying depression subtypes in association to inflammation, in particular atypical and melancholic depressive subtypes. We then summarize the available literature on inflammation in atypical and melancholic depression and discuss the (methodological) limitations of the literature. Furthermore, clinical implications and relevance to treatment are discussed, including newer treatment options such as adjuvant anti-inflammatory medication or exercise therapy. Lastly, we link the subtype-inflammation literature on to other known biological disturbances in depression, in particular metabolic dysregulation such as obesity and metabolic syndrome.