Enhancing a deep learning model for pulmonary nodule malignancy risk estimation in chest CT with uncertainty estimation.

OBJECTIVE: To investigate the effect of uncertainty estimation on the performance of a Deep Learning (DL) algorithm for estimating malignancy risk of pulmonary nodules. METHODS AND MATERIALS: In this retrospective study, we integrated an uncertainty estimation method into a previously developed DL algorithm for nodule malignancy risk estimation. Uncertainty thresholds were developed using CT data from the Danish Lung Cancer Screening Trial (DLCST), containing 883 nodules (65 malignant) collected between 2004 and 2010. We used thresholds on the 90th and 95th percentiles of the uncertainty score distribution to categorize nodules into certain and uncertain groups. External validation was performed on clinical CT data from a tertiary academic center containing 374 nodules (207 malignant) collected between 2004 and 2012. DL performance was measured using area under the ROC curve (AUC) for the full set of nodules, for the certain cases and for the uncertain cases. Additionally, nodule characteristics were compared to identify trends for inducing uncertainty. RESULTS: The DL algorithm performed significantly worse in the uncertain group compared to the certain group of DLCST (AUC 0.62 (95% CI: 0.49, 0.76) vs 0.93 (95% CI: 0.88, 0.97); p < .001) and the clinical dataset (AUC 0.62 (95% CI: 0.50, 0.73) vs 0.90 (95% CI: 0.86, 0.94); p < .001). The uncertain group included larger benign nodules as well as more part-solid and non-solid nodules than the certain group. CONCLUSION: The integrated uncertainty estimation showed excellent performance for identifying uncertain cases in which the DL-based nodule malignancy risk estimation algorithm had significantly worse performance. CLINICAL RELEVANCE STATEMENT: Deep Learning algorithms often lack the ability to gauge and communicate uncertainty. For safe clinical implementation, uncertainty estimation is of pivotal importance to identify cases where the deep learning algorithm harbors doubt in its prediction. KEY POINTS: • Deep learning (DL) algorithms often lack uncertainty estimation, which potentially reduce the risk of errors and improve safety during clinical adoption of the DL algorithm. • Uncertainty estimation identifies pulmonary nodules in which the discriminative performance of the DL algorithm is significantly worse. • Uncertainty estimation can further enhance the benefits of the DL algorithm and improve its safety and trustworthiness.

Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial.

BACKGROUND: There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS: A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS: Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS: In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.).

Prior CT Improves Deep Learning for Malignancy Risk Estimation of Screening-detected Pulmonary Nodules.

Background Prior chest CT provides valuable temporal information (eg, changes in nodule size or appearance) to accurately estimate malignancy risk. Purpose To develop a deep learning (DL) algorithm that uses a current and prior low-dose CT examination to estimate 3-year malignancy risk of pulmonary nodules. Materials and Methods In this retrospective study, the algorithm was trained using National Lung Screening Trial data (collected from 2002 to 2004), wherein patients were imaged at most 2 years apart, and evaluated with two external test sets from the Danish Lung Cancer Screening Trial (DLCST) and the Multicentric Italian Lung Detection Trial (MILD), collected in 2004-2010 and 2005-2014, respectively. Performance was evaluated using area under the receiver operating characteristic curve (AUC) on cancer-enriched subsets with size-matched benign nodules imaged 1 and 2 years apart from DLCST and MILD, respectively. The algorithm was compared with a validated DL algorithm that only processed a single CT examination and the Pan-Canadian Early Lung Cancer Detection Study (PanCan) model. Results The training set included 10 508 nodules (422 malignant) in 4902 trial participants (mean age, 64 years ± 5 [SD]; 2778 men). The size-matched external test sets included 129 nodules (43 malignant) and 126 nodules (42 malignant). The algorithm achieved AUCs of 0.91 (95% CI: 0.85, 0.97) and 0.94 (95% CI: 0.89, 0.98). It significantly outperformed the DL algorithm that only processed a single CT examination (AUC, 0.85 [95% CI: 0.78, 0.92; P = .002]; and AUC, 0.89 [95% CI: 0.84, 0.95; P = .01]) and the PanCan model (AUC, 0.64 [95% CI: 0.53, 0.74; P < .001]; and AUC, 0.63 [95% CI: 0.52, 0.74; P < .001]). Conclusion A DL algorithm using current and prior low-dose CT examinations was more effective at estimating 3-year malignancy risk of pulmonary nodules than established models that only use a single CT examination. Clinical trial registration nos. NCT00047385, NCT00496977, NCT02837809 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Horst and Nishino in this issue.

A multicomponent positive psychology intervention for euthymic patients with bipolar disorder to improve mental well-being and personal recovery: A pragmatic randomized controlled trial.

OBJECTIVE: Mental well-being and personal recovery are important treatment targets for patients with bipolar disorder (BD). The goal of this study was to evaluate the effectiveness of an 8-week group multicomponent positive psychology intervention (PPI) for euthymic patients with BD as an adjunct to treatment as usual (TAU) compared to TAU alone. METHODS: Patients with BD were randomized to receive TAU (n = 43) or the PPI in addition to TAU (n = 54). The primary outcome was well being measured with the Mental Health Continuum-Short Form. Personal recovery was measured with the Questionnaire about the Process of Recovery. Data were collected at baseline, mid-treatment, post-treatment and 6- and 12-month follow-up. Life chart interviews were conducted at 12 months to retrospectively assess recurrence of depression and mania. RESULTS: Significant group-by-time interaction effects for well-being and personal recovery were found favouring the PPI. At post-treatment, between-group differences were significant for well-being (d = 0.77) and personal recovery (d = 0.76). Between-group effects for well-being were still significant at 6-month follow-up (d = 0.72). Effects on well-being and personal recovery within the intervention group were sustained until 12-month follow-up. Survival analyses showed no significant differences in time to recurrence. CONCLUSIONS: The multicomponent PPI evaluated in this study is effective in improving mental well-being and personal recovery in euthymic patients with BD and would therefore be a valuable addition to the current treatment of euthymic BD patients. The fact that the study was carried out in a pragmatic RCT demonstrates that this intervention can be applied in a real-world clinical setting.

Trends in the incidence of pulmonary nodules in chest computed tomography: 10-year results from two Dutch hospitals.

OBJECTIVE: To study trends in the incidence of reported pulmonary nodules and stage I lung cancer in chest CT. METHODS: We analyzed the trends in the incidence of detected pulmonary nodules and stage I lung cancer in chest CT scans in the period between 2008 and 2019. Imaging metadata and radiology reports from all chest CT studies were collected from two large Dutch hospitals. A natural language processing algorithm was developed to identify studies with any reported pulmonary nodule. RESULTS: Between 2008 and 2019, a total of 74,803 patients underwent 166,688 chest CT examinations at both hospitals combined. During this period, the annual number of chest CT scans increased from 9955 scans in 6845 patients in 2008 to 20,476 scans in 13,286 patients in 2019. The proportion of patients in whom nodules (old or new) were reported increased from 38% (2595/6845) in 2008 to 50% (6654/13,286) in 2019. The proportion of patients in whom significant new nodules (≥ 5 mm) were reported increased from 9% (608/6954) in 2010 to 17% (1660/9883) in 2017. The number of patients with new nodules and corresponding stage I lung cancer diagnosis tripled and their proportion doubled, from 0.4% (26/6954) in 2010 to 0.8% (78/9883) in 2017. CONCLUSION: The identification of incidental pulmonary nodules in chest CT has steadily increased over the past decade and has been accompanied by more stage I lung cancer diagnoses. CLINICAL RELEVANCE STATEMENT: These findings stress the importance of identifying and efficiently managing incidental pulmonary nodules in routine clinical practice. KEY POINTS: • The number of patients who underwent chest CT examinations substantially increased over the past decade, as did the number of patients in whom pulmonary nodules were identified. • The increased use of chest CT and more frequently identified pulmonary nodules were associated with more stage I lung cancer diagnoses.

Modelling trajectories of change in psychopathology and well-being during eating disorder outpatient treatment.

Objective: There are considerable differences in how eating disorder (ED) patients respond to treatment. This study aimed to identify change trajectories of mental health during treatment. Method: Longitudinal data of 442 patients was used with five time points during a year of outpatient treatment. ED psychopathology and well-being were used as primary measures. A series of latent growth mixture models were applied to model trajectories of change. Results: Three latent classes were found for ED psychopathology and well-being. For ED psychopathology, a high baseline severity and slow recovery class (55.9% of the patients), a high baseline severity followed by a substantial recovery class (19.9%) and a moderate baseline severity and no significant recovery class (24.2%) were found. For well-being, a low baseline followed by a slow growth class (44.6%), a low baseline and substantial growth class (9.5%) and a moderate and stable well-being class (45.9%) was found. General psychopathology, early symptom change, hope for recovery, intrinsic motivation and the ED type were predictive of class membership in either ED psychopathology or well-being. Conclusions: This study shows variability in ED psychopathology and well-being change trajectories, modelled in meaningful latent recovery classes. These results may have clinical implications, such as adjusting patients' treatment based on change trajectories.

Exploring mental health dynamics during eating disorder treatment: A psychometric network study with panel data.

To explore mental health associations during eating disorder (ED) treatment. Based on the dual-continua model of mental health, general and ED-specific psychopathology, as well as emotional, psychological, and social well-being were considered as mental health domains.Network analyses with panel data were applied to explore within- (temporal and contemporaneous networks) and between-person effects in a sample of 1250 female ED patients during 12 months of outpatient treatment. The associations between the domains and their centrality were examined. Autoregressive and cross-lagged effects were also estimated.ED psychopathology was the most central domain in the temporal network. ED psychopathology changes predicted further ED psychopathology changes and small changes in the other domains. Weak bi-directional associations were found between changes in the well-being domains and general psychopathology. In contrast to the temporal network, ED psychopathology was the least central and psychological well-being the most central domain in the contemporaneous and between-subjects networks. This suggests a central role of psychological well-being for experiencing mental health within time points.ED psychopathology may change relatively independent from other mental health domains. Well-being domains may be considered as more stable aspects of mental health.

Examining well-being in posttraumatic stress disorder treatment: An explorative study.

Although the importance of well-being in mental health is widely acknowledged, well-being as a predictor of and outcome in the treatment for posttraumatic stress disorder (PTSD) has received little attention. This naturalistic study aimed to investigate well-being in the context of care-as-usual treatment for PTSD. Patients with PTSD attending a community mental health center (N = 318) completed measures of well-being and PTSD symptoms before and after symptom-focused treatment. Following treatment, well-being increased among patients with PTSD, with emotional, d = -0.25, and psychological well-being, d = -0.24, showing the largest improvements relative to social well-being, d = -0.15. Although levels of well-being improved overall within the sample, participant scores on measures of well-being remained low compared with the general population. Well-being predicted treatment efficiency such that participants with more severe PTSD symptoms benefitted more from care-as-usual treatment when they reported relatively high levels of well-being at the start of treatment. The findings suggest a benefit to including well-being as a pretreatment and outcome variable when evaluating PTSD treatments.

Exploring associations between personality trait facets and emotional, psychological and social well-being in eating disorder patients.

PURPOSE: Personality functioning is strongly linked to well-being in the general population. Yet, there is a lack of scientific knowledge about the pathways between personality trait facets and emotional, psychological and social well-being in ED patients. The general aim was to examine potential associations between maladaptive personality trait facets and the three main dimensions of well-being. METHODS: Participants were 1187 female eating disorder patients who were referred for specialized treatment. Patients were diagnosed with anorexia nervosa (31.7%), bulimia nervosa (21.7%), binge eating disorder (11%) and other specified eating disorders (35.5%). The Personality Inventory for the DSM 5 (PID-5) was used to measure 25 trait facets, and well-being was measured with the Mental Health Continuum Short Form (MHC-SF). Multiple hierarchical regression analyses were applied to examine potential associations between personality and well-being while controlling for background and illness characteristics. RESULTS: Personality trait facets led to a statistically significant increase of the explained variance in emotional (38%), psychological (39%), and social well-being (26%) in addition to the background and illness characteristics. The personality trait facets anhedonia and depression were strongly associated with all three well-being dimensions. CONCLUSION: Personality traits may play an essential role in the experience of well-being among patients with EDs. To promote overall mental health, it may be critical for clinicians to address relevant personality trait facets, such as anhedonia and depression, associated with well-being in treatment. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Deep Learning for Malignancy Risk Estimation of Pulmonary Nodules Detected at Low-Dose Screening CT.

Background Accurate estimation of the malignancy risk of pulmonary nodules at chest CT is crucial for optimizing management in lung cancer screening. Purpose To develop and validate a deep learning (DL) algorithm for malignancy risk estimation of pulmonary nodules detected at screening CT. Materials and Methods In this retrospective study, the DL algorithm was developed with 16 077 nodules (1249 malignant) collected -between 2002 and 2004 from the National Lung Screening Trial. External validation was performed in the following three -cohorts -collected between 2004 and 2010 from the Danish Lung Cancer Screening Trial: a full cohort containing all 883 nodules (65 -malignant) and two cancer-enriched cohorts with size matching (175 nodules, 59 malignant) and without size matching (177 -nodules, 59 malignant) of benign nodules selected at random. Algorithm performance was measured by using the area under the receiver operating characteristic curve (AUC) and compared with that of the Pan-Canadian Early Detection of Lung Cancer (PanCan) model in the full cohort and a group of 11 clinicians composed of four thoracic radiologists, five radiology residents, and two pulmonologists in the cancer-enriched cohorts. Results The DL algorithm significantly outperformed the PanCan model in the full cohort (AUC, 0.93 [95% CI: 0.89, 0.96] vs 0.90 [95% CI: 0.86, 0.93]; P = .046). The algorithm performed comparably to thoracic radiologists in cancer-enriched cohorts with both random benign nodules (AUC, 0.96 [95% CI: 0.93, 0.99] vs 0.90 [95% CI: 0.81, 0.98]; P = .11) and size-matched benign nodules (AUC, 0.86 [95% CI: 0.80, 0.91] vs 0.82 [95% CI: 0.74, 0.89]; P = .26). Conclusion The deep learning algorithm showed excellent performance, comparable to thoracic radiologists, for malignancy risk estimation of pulmonary nodules detected at screening CT. This algorithm has the potential to provide reliable and reproducible malignancy risk scores for clinicians, which may help optimize management in lung cancer screening. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Tammemägi in this issue.

Web-based self-help intervention for partners of cancer patients based on acceptance and commitment therapy and self-compassion training: a randomized controlled trial with automated versus personal feedback.

PURPOSE: To evaluate the effectiveness of two versions (personal or automated feedback) of a psychological Web-based self-help intervention targeting partners of cancer patients. The intervention was based on acceptance and commitment therapy (ACT) and self-compassion training. Participants' adherence and their satisfaction were also studied. METHODS: Two hundred three partners of patients with heterogeneous entities of cancer were randomized into three conditions: personal feedback (PF) (n = 67), automated feedback (AF) (n = 70), or waiting list (WL) control (n = 66). Participants completed measures at baseline (T0) and post-intervention (T1; 3 months after baseline) to assess psychological distress (HADS; primary outcome), positive mental health, caregiver strain, general health (secondary outcomes), posttraumatic growth, resilience, self-compassion, psychological flexibility, sense of mastery, and relational communication style (process measures). Participants in the two experimental conditions also completed these measures at follow-up (T2; 6 months after baseline). RESULTS: There was no significant difference in change in psychological distress, positive mental health, caregiver strain and general health from T0 to T1 for either of the experimental conditions compared with the WL-condition. However, when compared to a WL-condition, the PF-condition was effective in increasing psychological flexibility (effect size d = 0.49) and resilience (d = 0.12) and decreasing overprotection (d = 0.25), and the AF-condition was effective in reducing overprotection (d = 0.36) and improving protective buffering (d = 0.36). At follow-up, the PF-condition was more effective than the AF-condition for improving mental health (d = 0.36), psychological flexibility (d = 0.60), mastery (d = 0.48), and protective buffering (d = 0.24). Participants positively appreciated the intervention and 69% participants were adherent. CONCLUSION: This study demonstrates that a Web-based intervention based on ACT and self-compassion training with automated or personal feedback does not seem to improve psychological distress; however, it may have the potential to support partners of cancer patients to cope with the difficult situation they are facing. The condition with personal feedback seemed to be more beneficial.

A randomized controlled trial on the efficacy of life review therapy targeting incurably ill cancer patients: do their informal caregivers benefit?

PURPOSE: Investigate whether Life Review Therapy and Memory Specificity Training (LRT-MST) targeting incurably ill cancer patients may also have a beneficial effect on caregiving burden, symptoms of anxiety and depression, and posttraumatic growth of the informal caregivers. METHODS: Data was collected in the context of a randomized controlled trial (RCT) (secondary analyses) on the effect of LRT-MST among incurably cancer patients. Informal caregivers of participating patients were asked to complete outcome measures at baseline (T0), post-intervention (T1), and 1-month follow-up (T2): caregiver burden (caregivers reaction assessment scale (CRA)), symptoms of anxiety and depression (hospital anxiety and depression scale), and posttraumatic growth (posttraumatic growth inventory). Linear mixed models (intention to treat) were used to assess group differences in changes over time. Effect size and independent samples t tests were used to assess group differences at T1 and T2. RESULTS: In total, 64 caregivers participated. At baseline, 56% of the caregivers experienced anxiety and 30% depression. No significant effect was found on these symptoms nor on posttraumatic growth or most aspects of caregiver burden. There was a significant effect of LRT-MST on the course of self-esteem (subscale CRA) (p = 0.013). Effect size was moderate post-intervention (ES = - 0.38, p = 0.23) and at 3-month follow-up (ES = 0.53, p = 0.083). CONCLUSIONS: Many caregivers of incurably ill cancer patients experience symptoms of anxiety and depression. LRT-MST does not improve symptoms of depression and anxiety, negative aspects of caregiver burden, or posttraumatic growth. LRT-MST may have a protective effect on self-esteem of informal caregivers (positive aspect of caregiver burden). TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR 2256), registered on 23-3-2010.

Integration of Well-Being Therapy and Positive Psychotherapy: A Response to Fava and Guidi's (2021) Commentary on Radstaak et al. (2020).

The results of our study on the effects of well-being therapy (WBT) compared with a treatment-as-usual (TAU) control condition among individuals with residual symptoms of posttraumatic stress disorder (PTSD) were recently published in the Journal of Traumatic Stress (Radstaak et al., 2020). In a subsequent commentary, Fava and Guidi (2020) raised several conceptual and methodological issues that they asserted potentially limited the interpretation of the results. In this response, we aim to clarify these issues, thus contributing to the optimal interpretation of the findings.

The psychometric network structure of mental health in eating disorder patients.

OBJECTIVE: Psychometric network analysis has led to new possibilities to assess the structure and dynamics of psychiatric disorders. The current study focuses on mental health networks in patients with anorexia nervosa, bulimia nervosa, binge eating disorder and other specified eating disorders (EDs). METHOD: Network analyses were applied with five mental health domains (emotional, psychological and social well-being, and general and specific psychopathology) among 905 ED patients. Also, networks of 36 underlying symptoms related to the domains were estimated. The network stability, structure and (bridge) centrality of the nodes were assessed for the total group and each ED type. Network differences between the ED types were also examined. RESULTS: ED psychopathology was only weakly connected with the well-being domains. Psychological well-being was the most central node in the domain network. The most central nodes in the symptom network were feeling depressed, feeling worthless, purpose in life and self-acceptance. Bridge symptoms between well-being and psychopathology were self-acceptance, environmental mastery, interested in life and feeling depressed. There were no network differences between the ED types in both the domain and symptom networks. CONCLUSIONS: This study shows novel associations between well-being and psychopathology in ED patients. Central domains and their underlying symptoms may be especially important to consider in treatment for promoting mental health in ED patients.

COVID-19 on Chest Radiographs: A Multireader Evaluation of an Artificial Intelligence System.

Background Chest radiography may play an important role in triage for coronavirus disease 2019 (COVID-19), particularly in low-resource settings. Purpose To evaluate the performance of an artificial intelligence (AI) system for detection of COVID-19 pneumonia on chest radiographs. Materials and Methods An AI system (CAD4COVID-XRay) was trained on 24 678 chest radiographs, including 1540 used only for validation while training. The test set consisted of a set of continuously acquired chest radiographs (n = 454) obtained in patients suspected of having COVID-19 pneumonia between March 4 and April 6, 2020, at one center (223 patients with positive reverse transcription polymerase chain reaction [RT-PCR] results, 231 with negative RT-PCR results). Radiographs were independently analyzed by six readers and by the AI system. Diagnostic performance was analyzed with the receiver operating characteristic curve. Results For the test set, the mean age of patients was 67 years ± 14.4 (standard deviation) (56% male). With RT-PCR test results as the reference standard, the AI system correctly classified chest radiographs as COVID-19 pneumonia with an area under the receiver operating characteristic curve of 0.81. The system significantly outperformed each reader (P < .001 using the McNemar test) at their highest possible sensitivities. At their lowest sensitivities, only one reader significantly outperformed the AI system (P = .04). Conclusion The performance of an artificial intelligence system in the detection of coronavirus disease 2019 on chest radiographs was comparable with that of six independent readers. © RSNA, 2020.

Prefrontal but not cerebellar tDCS attenuates renewal of extinguished conditioned eyeblink responses.

An extended neural network is known to underlie extinction learning. As yet, comparatively little is known about the possible contribution of the cerebellum and the dorsolateral prefrontal cortex (dlPFC). In the present study, transcranial direct current stimulation (tDCS) was used to provide further evidence that the dlPFC and the cerebellum are involved in extinction-related processes. A total of 100 young and healthy human participants were randomly assigned to one of five stimulation groups: (1) anodal tDCS of the cerebellum, (2) cathodal tDCS of the cerebellum, (3) anodal tDCS of the dlPFC, (4) cathodal tDCS of the dlPFC, and (5) sham stimulation. Participants underwent delay eyeblink conditioning using an A-B-A/B renewal paradigm. Two different colors of background light (orange and blue) were used as contexts. On day 1, acquisition of conditioned eyeblink responses was performed in context A, followed by extinction in context B. tDCS was applied during extinction. On day 2, extinction recall was tested in contexts A and B with higher incidence of conditioned responses in acquisition context A compared to extinction context B indicating renewal effects. All groups showed significant effects of acquisition of conditioned eyeblink responses and significant effects of extinction. There was no significant difference in extinction between stimulation groups. During extinction recall, renewal effects were present in all groups, except the group which had received anodal tDCS of the dlPFC during extinction. In the present study, no direct effects of dlPFC or cerebellar tDCS were demonstrated on extinction. Anodal tDCS of the dlPFC, but not the cerebellum, resulted in delayed effects on context-related processes of extinction, possibly explained by shifting attention away from the context and towards the conditioned stimulus during extinction learning. Anodal tDCS of the dlPFC attenuated context-related recall of learned aversive responses. Effects of tDCS, however, were weak and need to be confirmed in future studies. Lack of cerebellar tDCS effects do not exclude a possible role of the cerebellum in extinction-related processes, and are likely explained by methodological limitations of cerebellar tDCS.

The long and winding road to happiness: A randomized controlled trial and cost-effectiveness analysis of a positive psychology intervention for lonely people with health problems and a low socio-economic status.

BACKGROUND: Our objective was to evaluate the effectiveness and cost-effectiveness of the positive psychology intervention 'Happiness Route' compared to an active control condition in a vulnerable population with an accumulation of health and psychosocial problems. METHODS: We conducted a randomized, single-blind, actively-controlled, parallel group study in seven municipalities in the Netherlands. To be eligible, participants had to experience loneliness, health problems and low socio-economic status. Each group received several home visits by a counsellor (two in the control condition, two to six in the experimental condition). In the Happiness Route, a happiness-based approach was used, whereas the control condition used a traditional problem-based approach. The primary outcome was well-being, measured with the Mental Health Continuum-Short Form (MHC-SF). RESULTS: Fifty-eight participants were randomized to the Happiness Route, 50 to the control condition. Participants were severely lonely, had on average three health problems and less than 5% had paid work. The total MHC-SF score, emotional and social well-being, depression and loneliness improved significantly over the nine-month period in both conditions (p < .05), but there were no significant changes between the conditions across time. Languishing decreased significantly from 33% at baseline to 16% at follow-up among the Happiness Route participants but did not change significantly in the control condition. No significant improvement over time was found in psychological well-being, resilience, purpose in life, health-related quality of life and social participation. Cost-effectiveness analysis showed that expected saved costs per QALY lost was €219,948 for the Happiness Route, relative to the control condition. The probability was 83% that the Happiness Route was cost saving and 54% that the Happiness Route was cost-effective at a willingness to accept a threshold of €100,000. CONCLUSIONS: Mental health status of both groups improved considerably. However, we could not demonstrate that the Happiness Route yielded better health outcomes compared to the control condition. Nevertheless, the results of the cost-effectiveness analysis suggested that the Happiness Route is an acceptable intervention from a health-economic point of view. Our results should be viewed in light of the fact that we could not include the planned number of participants. TRIAL REGISTRATION: Netherlands Trial Register: NTR3377. Registered 2 Apr 2012.

The relationship between emotion regulation and well-being in patients with mental disorders: A meta-analysis.

BACKGROUND: The importance of both specific emotion regulation strategies and overall deficits in emotion regulation in the context of psychopathology is widely recognized. Besides alleviating psychological symptoms, improving mental well-being is increasingly considered important in treatment of people with mental disorders. However, no comprehensive meta-analysis on the relationship between emotion regulation and well-being in people with mental disorders has been conducted yet. OBJECTIVE: The aim of the current study was to synthesize and meta-analyze evidence regarding the relationship between emotion regulation and well-being in clinical samples across studies. METHOD: A systematic literature search was conducted in PsycINFO, PubMed and Scopus and 94 cross-sectional effect sizes from 35 studies were meta-analyzed to explore this relationship. To be eligible for the meta-analysis, studies had to include a clinical sample, assess at least one specific emotion regulation strategy or overall deficits in emotion regulation and include well-being as outcome. RESULTS: The findings showed significant small to moderate negative relationships with well-being for the strategies avoidance (r = -0.31) and rumination (r = -0.19) and positive relationships with reappraisal (r = 0.19) and acceptance (r = 0.42). Grouping together putative adaptive and maladaptive strategies revealed similar sized relationships with well-being in the expected direction. Overall deficits in emotion regulation showed a negative moderate correlation with well-being (r = -0.47). No substantial difference in relationships was found when clustering studies into hedonic and eudaimonic well-being. CONCLUSION: Our findings suggest that emotion regulation is not merely related with psychopathology, but also with well-being in general as well as hedonic and eudaimonic well-being. Therefore, it might also be important to improve emotion regulation when aiming to improve well-being in people with mental disorders.

Effectiveness of a guided ACT-based self-help resilience training for depressive symptoms during pregnancy: Study protocol of a randomized controlled trial embedded in a prospective cohort.

BACKGROUND: During pregnancy, about 10 to 20% of women experience depressive symptoms. Subclinical depression increases the risk of peripartum depression, maternal neuro-endocrine dysregulations, and adverse birth and infant outcomes. Current treatments often comprise face-to-face psychological or pharmacological treatments that may be too intensive for women with subclinical depression leading to drop-out and moderate effectiveness. Therefore, easily accessible, resilience enhancing and less stigmatizing interventions are needed to prevent the development of clinical depression. This paper describes the protocol of a prospective cohort study with an embedded randomized controlled trial (RCT) that aims to improve mental resilience in a sample of pregnant women through a self-help program based on the principles of Acceptance and Commitment Therapy (ACT). Maternal and offspring correlates of the trajectories of peripartum depressive symptoms will also be studied. METHODS: Pregnant women (≥ 18 years) receiving care in Dutch midwifery practices will participate in a prospective cohort study (n ~ 3500). Between 12 and 18 weeks of pregnancy, all women will be screened for depression with the Edinburgh Postnatal Depression Scale (EPDS). Women with an EPDS score ≥ 11 will be evaluated with a structured clinical interview. Participants with subclinical depression (n = 290) will be randomized to a 9-week guided self-help ACT-training or to care as usual (CAU). Primary outcomes (depressive symptoms and resilience) and secondary outcomes (e.g. anxiety and PTSD, bonding, infant development) will be collected via online questionnaires at four prospective assessments around 20 weeks and 30 weeks gestation and at 6 weeks and 4 months postpartum. Maternal hair cortisol concentrations will be assessed in a subsample of women with a range of depressive symptoms (n = 300). The intervention's feasibility will be assessed through qualitative interviews in a subsample of participants (n = 20). DISCUSSION: This is the first study to assess the effectiveness of an easy to administer intervention strategy to prevent adverse mental health effects through enhancing resilience in pregnant women with antepartum depressive symptomatology. This longitudinal study will provide insights into trajectories of peripartum depressive symptoms in relation to resilience, maternal cortisol, psychological outcomes, and infant developmental milestones. TRIAL REGISTRATION: Netherlands Trial Register (NTR), NL7499 . Registered 5 February 2019.

Well-Being Therapy as Rehabilitation Therapy for Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial.

Many individuals with posttraumatic stress disorder (PTSD) continue to have substantial residual symptoms after completing psychological treatment. Well-being therapy (WBT) has been developed to treat the residual phase of mental disorders, prevent relapse, and promote a full recovery. The present study aimed to compare treatment as usual (TAU) with the long-term effects of WBT as a rehabilitation therapy in adults who successfully completed psychological treatment for PTSD. Participants who did not meet PTSD diagnostic criteria after completing treatment were randomized to WBT (n = 29) or TAU (n = 35) groups. Assessments of well-being, residual PTSD symptoms, and posttraumatic growth were conducted at baseline (T0) and again after 3 months (T1), 6 months (T2), and 1 year (T3). The results of the multilevel analysis revealed that WBT was not more effective than TAU in increasing levels of well-being, γ = 0.02 (SE = 0.11) or posttraumatic growth, γ = 0.10 (SE = 0.13) nor in decreasing PTSD symptoms, γ = -0.04 (SE = 0.05). However, for participants with low levels of well-being at baseline (Mental Health Continuum-Short Form score < 2.6), WBT was more effective than TAU in increasing ratings of well-being, γ = -0.41 (SE = 0.19) and posttraumatic growth, γ = -0.55 (SE = 0.24); this effect was most evident at T3 for posttraumatic growth, d = 1.23. Future research should assess clinically relevant individual characteristics that to optimize the effectiveness and utility of WBT.