The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

BACKGROUND: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. METHODS: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. RESULTS: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. CONCLUSIONS: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

Multistep estimators of the between-study covariance matrix under the multivariate random-effects model for meta-analysis.

A wide variety of methods are available to estimate the between-study variance under the univariate random-effects model for meta-analysis. Some, but not all, of these estimators have been extended so that they can be used in the multivariate setting. We begin by extending the univariate generalised method of moments, which immediately provides a wider class of multivariate methods than was previously available. However, our main proposal is to use this new type of estimator to derive multivariate multistep estimators of the between-study covariance matrix. We then use the connection between the univariate multistep and Paule-Mandel estimators to motivate taking the limit, where the number of steps tends toward infinity. We illustrate our methodology using two contrasting examples and investigate its properties in a simulation study. We conclude that the proposed methodology is a fully viable alternative to existing estimation methods, is well suited to sensitivity analyses that explore the use of alternative estimators, and should be used instead of the existing DerSimonian and Laird-type moments based estimator in application areas where data are expected to be heterogeneous. However, multistep estimators do not seem to outperform the existing estimators when the data are more homogeneous. Advantages of the new multivariate multistep estimator include its semi-parametric nature and that it is computationally feasible in high dimensions. Our proposed estimation methods are also applicable for multivariate random-effects meta-regression, where study-level covariates are included in the model.

A robust and readily implementable method for the meta-analysis of response ratios with and without missing standard deviations.

The log response ratio, lnRR, is the most frequently used effect size statistic for meta-analysis in ecology. However, often missing standard deviations (SDs) prevent estimation of the sampling variance of lnRR. We propose new methods to deal with missing SDs via a weighted average coefficient of variation (CV) estimated from studies in the dataset that do report SDs. Across a suite of simulated conditions, we find that using the average CV to estimate sampling variances for all observations, regardless of missingness, performs with minimal bias. Surprisingly, even with missing SDs, this simple method outperforms the conventional approach (basing each effect size on its individual study-specific CV) with complete data. This is because the conventional method ultimately yields less precise estimates of the sampling variances than using the pooled CV from multiple studies. Our approach is broadly applicable and can be implemented in all meta-analyses of lnRR, regardless of 'missingness'.

Efficacy of Acceptance and Commitment Therapy in Daily Life in Early Psychosis: Results from the Multi-Center INTERACT Randomized Controlled Trial.

INTRODUCTION/OBJECTIVE: This study aimed to investigate efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in addition to treatment as usual (TAU) for psychotic distress, in comparison to TAU. METHODS: Individuals aged 15-65 years with clinically established ultra-high risk or first episode of psychosis were randomly assigned to TAU or ACT-DL+TAU. ACT-DL+TAU consisted of 8 ACT-sessions augmented with an EMI-app. The primary outcome was psychotic distress assessed with the Comprehensive Assessment scale of At Risk Mental State (CAARMS) at post-intervention and 6- and 12-month follow-up. Secondary outcomes were functioning, symptom severity, and momentary psychotic distress. We performed multivariate mixed models according to intent-to-treat principles. RESULTS: Between June 1, 2015 and December 31, 2018, 668 participants were referred, of whom 148 were randomized to ACT-DL+TAU (n = 71) or TAU (n = 77). One hundred and fifteen (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of greater reduction in the primary outcome measure CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3) = 2.36; p = 0.50). However, out of the tested secondary outcomes, global functioning (χ2(3) = 9.05; p = 0.033), and negative symptoms (χ2(3) = 19.91; p<0.001) improved in ACT-DL+TAU compared to TAU, as did momentary psychotic distress (χ2(3) = 21.56; p < 0.001). CONCLUSIONS: INTERACT did not support a significant effect of ACT-DL over TAU on the primary outcome measure of psychotic distress as assessed with the CAARMS. Although significant improvements were found for some secondary outcome measures, further replication studies are needed to confirm the strength and specificity of these effects.

Mental Health Symptoms and Associations with Tobacco Smoking, Dependence, Motivation, and Attempts to Quit: Findings from a Population Survey in Germany (DEBRA Study).

INTRODUCTION: This study aimed to estimate prevalence rates of mental health symptoms (anxiety, depression, and overall psychological distress) by tobacco smoking status, and associations between such symptoms and the level of dependence, motivation, and attempts to quit smoking in the German population. METHODS: Cross-sectional analysis of data from six waves of a nationally representative household survey collected in 2018/19 (N = 11,937 respondents aged ≥18). Mental health symptoms were assessed with the Patient Health Questionnaire-4. Associations with smoking status, dependence, motivation to quit, and ≥1 past-year quit attempt (yes/no) were analysed with adjusted regression models among the total group, and among subgroups of current (n = 3,248) and past-year smokers (quit ≤12 months ago, n = 3,357). RESULTS: Weighted prevalence rates of mental health symptoms among current, former, and never smokers were: 4.1%, 2.4%, 2.5% (anxiety), 5.4%, 4.7%, 4.0% (depression), and 3.1%, 2.5%, 2.4% (psychological distress). Current versus never smokers were more likely to report symptoms of anxiety and depression. Smokers with higher versus lower levels of dependence were more likely to report higher levels of all three mental health symptoms. Higher versus lower levels of overall psychological distress were associated with a higher motivation to quit smoking and, among past-year smokers, with higher odds of reporting a past-year quit attempt. CONCLUSIONS: We found various relevant associations between mental health symptoms and smoking behaviour. Healthcare professionals need to be informed about these associations and trained to effectively support this vulnerable group in translating their motivation into abstinence.

Intervention mechanisms of an experience sampling intervention for spousal carers of people with dementia: a secondary analysis using momentary data.

Objectives: A psychosocial intervention for spousal carers of people with dementia promoted emotional well-being through self-monitoring and personalized feedback, as demonstrated in a previous randomized controlled trial. The mechanism behind the intervention effects is thought to lie in increased awareness of, and thus, engagement in behaviours that elicit positive emotions (PA). This secondary analysis tests the assumption by investigating momentary data on activities, affect, and stress and explores the relevance of personalized feedback compared to self-monitoring only.Methods: The intervention was based on the experience sampling method (ESM), meaning that carers self-monitored own affect and behaviours 10 times/day over 6 weeks. The experimental group received personalized feedback on behaviours that elicit PA, while the pseudo-experimental group performed self-monitoring only. A control group was also included. ESM-data of 72 carers was analysed using multilevel mixed-effects models.Results: The experimental group reported significant increases in passive relaxation activities over the 6 weeks (B = 0.28, SE = 0.12, Z = 2.43, p < .05). Passive relaxation in this group was negatively associated with negative affect (r = -0.50, p = .01) and positively associated with activity-related stress (r = 0.52, p = .007) from baseline to post-intervention. Other activities in this or the other groups did not change significantly.Conclusion: Carer's daily behaviours were only affected when self-monitoring was combined with personalized feedback. Changing one's daily behaviour while caring for a person with dementia is challenging and aligned with mixed emotions. Acknowledging simultaneously positive and negative emotions, and feelings of stress is suggested to embrace the complexity of carer's life and provide sustainable support.

Introducing our series: research synthesis and meta-research in biology.

Research synthesis is the process of bringing together findings and attributes from different publications, for example, to give a more complete description of phenomena than is usually possible in a single work. We bring the Research Synthesis Series to BMC Biology to promote meta-analyses, other research syntheses including meta-research studies, and research synthesis methodologies in biology, facilitating their dissemination to broader communities.

Dimensions over categories: a meta-analysis of taxometric research.

Taxometric procedures have been used extensively to investigate whether individual differences in personality and psychopathology are latently dimensional or categorical ('taxonic'). We report the first meta-analysis of taxometric research, examining 317 findings drawn from 183 articles that employed an index of the comparative fit of observed data to dimensional and taxonic data simulations. Findings supporting dimensional models outnumbered those supporting taxonic models five to one. There were systematic differences among 17 construct domains in support for the two models, but psychopathology was no more likely to generate taxonic findings than normal variation (i.e. individual differences in personality, response styles, gender, and sexuality). No content domain showed aggregate support for the taxonic model. Six variables - alcohol use disorder, intermittent explosive disorder, problem gambling, autism, suicide risk, and pedophilia - emerged as the most plausible taxon candidates based on a preponderance of independently replicated findings. We also compared the 317 meta-analyzed findings to 185 additional taxometric findings from 96 articles that did not employ the comparative fit index. Studies that used the index were 4.88 times more likely to generate dimensional findings than those that did not after controlling for construct domain, implying that many taxonic findings obtained before the popularization of simulation-based techniques are spurious. The meta-analytic findings support the conclusion that the great majority of psychological differences between people are latently continuous, and that psychopathology is no exception.

Childhood trauma- and cannabis-associated microstructural white matter changes in patients with psychotic disorder: a longitudinal family-based diffusion imaging study.

BACKGROUND: Decreased white matter (WM) integrity in patients with psychotic disorder has been a consistent finding in diffusion tensor imaging (DTI) studies. However, the contribution of environmental risk factors to these WM alterations is rarely investigated. The current study examines whether individuals with (increased risk for) psychotic disorder will show increased WM integrity change over time with increasing levels of childhood trauma and cannabis exposure. METHODS: DTI scans were obtained from 85 patients with a psychotic disorder, 93 non-psychotic siblings and 80 healthy controls, of which 60% were rescanned 3 years later. In a whole-brain voxel-based analysis, associations between change in fractional anisotropy (ΔFA) and environmental exposures as well as interactions between group and environmental exposure in the model of FA and ΔFA were investigated. Analyses were adjusted for a priori hypothesized confounding variables: age, sex, and level of education. RESULTS: At baseline, no significant associations were found between FA and both environmental risk factors. At follow-up as well as over a 3-year interval, significant interactions between group and, respectively, cannabis exposure and childhood trauma exposure in the model of FA and ΔFA were found. Patients showed more FA decrease over time compared with both controls and siblings when exposed to higher levels of cannabis or childhood trauma. CONCLUSIONS: Higher levels of cannabis or childhood trauma may compromise connectivity over the course of the illness in patients, but not in individuals at low or higher than average genetic risk for psychotic disorder, suggesting interactions between the environment and illness-related factors.

Enhancing Behavior Change Technique Coding Methods: Identifying Behavioral Targets and Delivery Styles in Smoking Cessation Trials.

BACKGROUND: The behavior change technique (BCT) taxonomy v1 is often used in systematic reviews for identifying active components of interventions. Its utility could be enhanced by linking BCTs to specific target behaviors and qualifying BCT delivery style. PURPOSE: To determine whether behavioral targets and delivery styles of BCTs can be coded reliably and to determine the utility of coding these characteristics. METHODS: As part of a large systematic review of 142 smoking cessation trials, two researchers independently coded publicly and privately held intervention and comparator group materials, specifying the behavioral target (quitting, abstinence, medication adherence, or treatment engagement) and delivery style (tailored vs. not tailored; active participation vs. passive receipt) of each BCT. RESULTS: Researchers coded 3,843 BCTs, which were reliably attributed to behavioral targets (AC1 = 0.92, PABAK = 0.91). Tailoring (AC1 = 0.80, PABAK = 0.74) and participation (AC1 = 0.71, PABAK = 0.64) were also coded reliably. There was considerable variability between groups in quitting and abstinence BCTs (ranges: 0-41; 0-18) and in tailoring and participation (ranges: 0-20; 0-32), but less variability for medication adherence and treatment engagement (ranges: 0-6; 0-7). CONCLUSIONS: Behavioral targets and delivery styles of BCTs can be reliably identified and occur with sufficient frequency in smoking cessation trials for inclusion in quantitative syntheses (e.g., meta-regression analyses). Systematic reviewers could consider adopting these methods to evaluate the impact of intervention components targeting different behaviors, as well as the benefits of different BCT delivery styles.

Effectiveness of training general practitioners to improve the implementation of brief stop-smoking advice in German primary care: study protocol of a pragmatic, 2-arm cluster randomised controlled trial (the ABCII trial).

BACKGROUND: The German clinical guideline on tobacco addiction recommends that general practitioners (GPs) provide brief stop-smoking advice to their patients according to the "5A" or the much briefer "ABC" method, but its implementation is insufficient. A lack of training is one barrier for GPs to provide such advice. Moreover, the respective effectiveness of a 5A or ABC training regarding subsequent delivery of stop-smoking advice has not been investigated. We developed a training for GPs according to both methods, and conducted a pilot study with process evaluation to optimize the trainings according to the needs of GPs. This study aims at evaluating the effectiveness of both trainings. METHODS: A pragmatic 2-arm cluster randomised controlled trial with a pre-post data collection will be conducted in 48 GP practices in North Rhine-Westphalia (Germany). GPs will be randomised to receive a 3.5-h-training in delivering either 5A or ABC, including peer coaching and intensive role plays with professional actors. The patient-reported primary outcome (receipt of GP advice to quit: yes/no) and secondary outcomes (recommendation rates of smoking cessation treatments, group comparison (5A versus ABC): receipt of GP advice to quit) will be collected in smoking patients routinely consulting their GP within 4 weeks prior, and 4 weeks following the training. Additional secondary outcomes will be collected at 4, 12 and 26 weeks following the consultation: use of cessation treatments during the last quit attempt (if so) since the GP consultation, and point-prevalence abstinence rates. The primary data analysis will be conducted using a mixed-effects logistic regression model with random effects for the cluster variable. DISCUSSION: If the training increases the rates of delivery of stop-smoking advice, it would offer a low-threshold strategy for the guideline implementation in German primary care. Should one method prove superior, a more specific guideline recommendation can be proposed. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00012786); registered on 22th August 2017, prior to the first patient in.

Compliance and Retention With the Experience Sampling Method Over the Continuum of Severe Mental Disorders: Meta-Analysis and Recommendations.

BACKGROUND: Despite the growing interest in the experience sampling method (ESM) as a data collection tool for mental health research, the absence of methodological guidelines related to its use has resulted in a large heterogeneity of designs. Concomitantly, the potential effects of the design on the response behavior of the participants remain largely unknown. OBJECTIVE: The objective of this meta-analysis was to investigate the associations between various sample and design characteristics and the compliance and retention rates of studies using ESM in mental health research. METHODS: ESM studies investigating major depressive disorder, bipolar disorder, and psychotic disorder were considered for inclusion. Besides the compliance and retention rates, a number of sample and design characteristics of the selected studies were collected to assess their potential relationships with the compliance and retention rates. Multilevel random/mixed effects models were used for the analyses. RESULTS: Compliance and retention rates were lower for studies with a higher proportion of male participants (P<.001) and individuals with a psychotic disorder (P<.001). Compliance was positively associated with the use of a fixed sampling scheme (P=.02), higher incentives (P=.03), higher time intervals between successive evaluations (P=.02), and fewer evaluations per day (P=.008), while no significant associations were observed with regard to the mean age of the sample, the study duration, or other design characteristics. CONCLUSIONS: The findings demonstrate that ESM studies can be carried out in mental health research, but the quality of the data collection depends upon a number of factors related to the design of ESM studies and the samples under study that need to be considered when designing such protocols.

A comparison of seven random-effects models for meta-analyses that estimate the summary odds ratio.

Comparative trials that report binary outcome data are commonly pooled in systematic reviews and meta-analyses. This type of data can be presented as a series of 2-by-2 tables. The pooled odds ratio is often presented as the outcome of primary interest in the resulting meta-analysis. We examine the use of 7 models for random-effects meta-analyses that have been proposed for this purpose. The first of these models is the conventional one that uses normal within-study approximations and a 2-stage approach. The other models are generalised linear mixed models that perform the analysis in 1 stage and have the potential to provide more accurate inference. We explore the implications of using these 7 models in the context of a Cochrane Review, and we also perform a simulation study. We conclude that generalised linear mixed models can result in better statistical inference than the conventional 2-stage approach but also that this type of model presents issues and difficulties. These challenges include more demanding numerical methods and determining the best way to model study specific baseline risks. One possible approach for analysts is to specify a primary model prior to performing the systematic review but also to present the results using other models in a sensitivity analysis. Only one of the models that we investigate is found to perform poorly so that any of the other models could be considered for either the primary or the sensitivity analysis.

Sensitivity to Peer Evaluation and Its Genetic and Environmental Determinants: Findings from a Population-Based Twin Study.

Adolescents and young adults are highly focused on peer evaluation, but little is known about sources of their differential sensitivity. We examined to what extent sensitivity to peer evaluation is influenced by interacting environmental and genetic factors. A sample of 354 healthy adolescent twin pairs (n = 708) took part in a structured, laboratory task in which they were exposed to peer evaluation. The proportion of the variance in sensitivity to peer evaluation due to genetic and environmental factors was estimated, as was the association with specific a priori environmental risk factors. Differences in sensitivity to peer evaluation between adolescents were explained mainly by non-shared environmental influences. The results on shared environmental influences were not conclusive. No impact of latent genetic factors or gene-environment interactions was found. Adolescents with lower self-rated positions on the social ladder or who reported to have been bullied more severely showed significantly stronger responses to peer evaluation. Not genes, but subjective social status and past experience of being bullied seem to impact sensitivity to peer evaluation. This suggests that altered response to peer evaluation is the outcome of cumulative sensitization to social interactions.

Cardiovascular and neuropsychiatric risks of varenicline and bupropion in smokers with chronic obstructive pulmonary disease.

BACKGROUND: Varenicline and bupropion are effective smoking cessation treatments, but there are concerns about their safety in smokers with COPD. OBJECTIVE: To investigate whether varenicline and bupropion are associated with serious adverse cardiovascular and neuropsychiatric events in smokers with COPD. METHODS: In a retrospective cohort study, we used data from 14 350 patients with COPD included in the QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients with COPD who received a prescription of nicotine replacement therapy (NRT; N=10 426; reference group), bupropion (N=350) or varenicline (N=3574) in the period between January 2007 and June 2012. Patients were followed up for 6 months to compare incident cardiovascular (ie, ischaemic heart disease, stroke, heart failure, peripheral vascular disease and cardiac arrhythmias) and neuropsychiatric (ie, depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders. Propensity score analysis was used as an additional approach to account for potential confounding by indication. We also modelled the effects of possible unmeasured confounders. RESULTS: Neither bupropion nor varenicline showed an increased risk of adverse events compared with NRT. Varenicline was associated with a significantly reduced risk of heart failure (HR=0.56, 95% CI 0.34 to 0.92) and depression (HR=0.73, 95% CI 0.61 to 0.86). Similar results were obtained from the propensity score analysis. Modelling of unmeasured confounding provided additional evidence that an increased risk of these adverse events was very unlikely. CONCLUSION: In smokers with COPD, varenicline and bupropion do not appear to be associated with an increased risk of cardiovascular events, depression or self-harm in comparison with NRT.

High Incidence and Prevalence of Drug-Related Movement Disorders in Young Patients With Psychotic Disorders.

BACKGROUND: Drug-related movement disorders (DRMDs) reduce quality of life and contribute to medication noncompliance of patients with psychotic disorders. Little is known about the epidemiology of DRMDs in relatively young patients a few years after onset of psychosis. This is an important period to study, as the impact of the antipsychotic treatment on the long-term potentiation of the neural pathways associated with psychotic disorders and DRMDs is still minimal. This study investigated the prevalence, incidence, persistence, and clinical correlates of DRMDs in patients during their first years after disease onset. METHODS: The Genetic Risk and Outcome of Psychosis study is a longitudinal study of 1120 relatively young patients with nonaffective psychosis and a mean age and illness duration of 27 and 4 years, respectively. The following drug-related movement disorders were assessed at baseline and at the 3-year follow-up: parkinsonism, akathisia, tardive dyskinesia, and tardive dystonia. We determined prevalence, incidence, and persistence and investigated clinical correlates at and over the baseline and follow-up assessment. RESULTS: Patients' mean age and illness duration at baseline were 27.1 and 4.3 years, respectively. In 4 patients, 1 developed a DRMD over the 3-year study period. Prevalence, incidence, and persistence rates were highest for parkinsonism (32%, 21%, and 53%) followed by akathisia (9%, 5%, and 17%) and tardive dyskinesia (4%, 3%, and 20%). Significant associations were found between DRMDs and the patients' age, IQ, and psychopathology. CONCLUSIONS: The prevalence, persistence, and incidence of DRMDs in this sample were high despite the relatively young age, recent onset of the disorder, and treatment primarily with second-generation antipsychotics. These findings emphasize that screening, diagnosis, and treatment of DRMDs are still important.

Gene-based interaction analysis shows GABAergic genes interacting with parenting in adolescent depressive symptoms.

BACKGROUND: Most gene-environment interaction studies (G × E) have focused on single candidate genes. This approach is criticized for its expectations of large effect sizes and occurrence of spurious results. We describe an approach that accounts for the polygenic nature of most psychiatric phenotypes and reduces the risk of false-positive findings. We apply this method focusing on the role of perceived parental support, psychological control, and harsh punishment in depressive symptoms in adolescence. METHODS: Analyses were conducted on 982 adolescents of Caucasian origin (Mage (SD) = 13.78 (.94) years) genotyped for 4,947 SNPs in 263 genes, selected based on a literature survey. The Leuven Adolescent Perceived Parenting Scale (LAPPS) and the Parental Behavior Scale (PBS) were used to assess perceived parental psychological control, harsh punishment, and support. The Center for Epidemiologic Studies Depression Scale (CES-D) was the outcome. We used gene-based testing taking into account linkage disequilibrium to identify genes containing SNPs exhibiting an interaction with environmental factors yielding a p-value per single gene. Significant results at the corrected p-value of p < 1.90 × 10-4 were examined in an independent replication sample of Dutch adolescents (N = 1354). RESULTS: Two genes showed evidence for interaction with perceived support: GABRR1 (p = 4.62 × 10-5 ) and GABRR2 (p = 9.05 × 10-6 ). No genes interacted significantly with psychological control or harsh punishment. Gene-based analysis was unable to confirm the interaction of GABRR1 or GABRR2 with support in the replication sample. However, for GABRR2, but not GABRR1, the correlation of the estimates between the two datasets was significant (r (46) = .32; p = .027) and a gene-based analysis of the combined datasets supported GABRR2 × support interaction (p = 1.63 × 10-4 ). CONCLUSIONS: We present a gene-based method for gene-environment interactions in a polygenic context and show that genes interact differently with particular aspects of parenting. This accentuates the importance of polygenic approaches and the need to accurately assess environmental exposure in G × E.

The experience sampling method as an mHealth tool to support self-monitoring, self-insight, and personalized health care in clinical practice.

BACKGROUND: The experience sampling method (ESM) builds an intensive time series of experiences and contexts in the flow of daily life, typically consisting of around 70 reports, collected at 8-10 random time points per day over a period of up to 10 days. METHODS: With the advent of widespread smartphone use, ESM can be used in routine clinical practice. Multiple examples of ESM data collections across different patient groups and settings are shown and discussed, varying from an ESM evaluation of a 6-week randomized trial of mindfulness, to a twin study on emotion dynamics in daily life. RESULTS: Research shows that ESM-based self-monitoring and feedback can enhance resilience by strengthening the capacity to use natural rewards. Personalized trajectories of starting or stopping medication can be more easily initiated and predicted if sensitive feedback data are available in real time. In addition, personalized trajectories of symptoms, cognitive abilities, symptoms impacting on other symptoms, the capacity of the dynamic system of mental health to "bounce back" from disturbance, and patterns of environmental reactivity yield uniquely personal data to support shared decision making and prediction in clinical practice. Finally, ESM makes it possible to develop insight into previous implicit patterns of thought, experience, and behavior, particularly if rapid personalized feedback is available. CONCLUSIONS: ESM enhances clinical practice and research. It is empowering, providing co-ownership of the process of diagnosis, treatment evaluation, and routine outcome measurement. Blended care, based on a mix of face-to-face and ESM-based outside-the-office treatment, may reduce costs and improve outcomes.

Critical slowing down as early warning for the onset and termination of depression.

About 17% of humanity goes through an episode of major depression at some point in their lifetime. Despite the enormous societal costs of this incapacitating disorder, it is largely unknown how the likelihood of falling into a depressive episode can be assessed. Here, we show for a large group of healthy individuals and patients that the probability of an upcoming shift between a depressed and a normal state is related to elevated temporal autocorrelation, variance, and correlation between emotions in fluctuations of autorecorded emotions. These are indicators of the general phenomenon of critical slowing down, which is expected to occur when a system approaches a tipping point. Our results support the hypothesis that mood may have alternative stable states separated by tipping points, and suggest an approach for assessing the likelihood of transitions into and out of depression.

Cycling empirical antibiotic therapy in hospitals: meta-analysis and models.

The rise of resistance together with the shortage of new broad-spectrum antibiotics underlines the urgency of optimizing the use of available drugs to minimize disease burden. Theoretical studies suggest that coordinating empirical usage of antibiotics in a hospital ward can contain the spread of resistance. However, theoretical and clinical studies came to different conclusions regarding the usefulness of rotating first-line therapy (cycling). Here, we performed a quantitative pathogen-specific meta-analysis of clinical studies comparing cycling to standard practice. We searched PubMed and Google Scholar and identified 46 clinical studies addressing the effect of cycling on nosocomial infections, of which 11 met our selection criteria. We employed a method for multivariate meta-analysis using incidence rates as endpoints and find that cycling reduced the incidence rate/1000 patient days of both total infections by 4.95 [9.43-0.48] and resistant infections by 7.2 [14.00-0.44]. This positive effect was observed in most pathogens despite a large variance between individual species. Our findings remain robust in uni- and multivariate metaregressions. We used theoretical models that reflect various infections and hospital settings to compare cycling to random assignment to different drugs (mixing). We make the realistic assumption that therapy is changed when first line treatment is ineffective, which we call "adjustable cycling/mixing". In concordance with earlier theoretical studies, we find that in strict regimens, cycling is detrimental. However, in adjustable regimens single resistance is suppressed and cycling is successful in most settings. Both a meta-regression and our theoretical model indicate that "adjustable cycling" is especially useful to suppress emergence of multiple resistance. While our model predicts that cycling periods of one month perform well, we expect that too long cycling periods are detrimental. Our results suggest that "adjustable cycling" suppresses multiple resistance and warrants further investigations that allow comparing various diseases and hospital settings.