A 12-month prospective study on the time to hospitalization and clinical management of a cohort of bipolar type I and schizoaffective bipolar patients

Background: Schizoaffective disorder, bipolar type (SAD) and bipolar disorder I (BD) present a large clinical overlap. In a 1-year follow-up, we aimed to evaluate days to hospitalization (DTH) and predictors of relapse in a SAD-BD cohort of patients. Methods: A 1-year, prospective, naturalistic cohort study considering DTH as primary outcome and incidence of direct and indirect measures of psychopathological compensation as secondary outcomes. Kaplan-Meyer survival analysis with Log-rank Mantel-Cox test compared BD/SAD subgroups as to DTH. After bivariate analyses, Cox regression was performed to assess covariates possibly associated with DTH in diagnostic subgroups. Results: Of 836 screened patients, 437 were finally included (SAD = 105; BD = 332). Relapse rates in the SAD sample was n = 26 (24.8%) vs. n = 41 (12.3%) in the BD sample (p = 0.002). Mean ± SD DTH were 312.16 ± 10.6 (SAD) vs. 337.62 ± 4.4 (BD) days (p = 0.002). Patients with relapses showed more frequent suicide acts, violent behaviors, and changes in pharmacological treatments (all p 0.0005). Conclusions: SAD patients relapse earlier with higher hospitalization rates and violent behavior during psychotic episodes whereas bipolar patients have more suicide attempts. Psychiatric/psychological follow-up visits may delay hospitalizations by closely monitoring symptoms of self- and hetero-aggression

OpenSIMPLe:A real-world implementation feasibility study of a smartphone-based psychoeducation programme for bipolar disorder

BACKGROUND: Few evidence-based mental health apps are widely available to patients and, conversely, many of the available apps have not been appropriately evaluated. Given that the ultimate goal is to scale-up and open internet-based platforms (IBP), it is crucial to appropriately evaluate their real-world feasibility beforehand. We aimed to evaluate the implementation feasibility of a smartphone-based psychoeducational programme for bipolar disorder, exploring its long-term retention, usability, perceived helpfulness and satisfaction, alongside its impact on secondary health outcomes.METHODS: Participants were recruited via the project website after completing an online screening questionnaire. They were requested to complete web-based questionnaires before using the app and after 6 months of use which included sociodemographic, illness and treatment variables, the world health organisation-five well-being index (WHO-5) and the short form health survey (SF-36). The follow-up questionnaires also contained satisfaction and usefulness questions.RESULTS: 201 participants took part in the study. According to their retention, 66.2% of the participants were classified as noncompleters and 33.8% as completers. The only predictor significantly associated with higher odds of retention was older age (OR = 1.021, p &lt; 0.001). 62% of the users reported they were satisfied with the programme with a higher percentage among completers. Who-5 baseline and follow-up scores showed a significant improvement as well as 6 out of 8 domains of the SF-36.LIMITATIONS: Screening and outcome measures were administered using exclusively self-reported online methods.CONCLUSION: The 6-month attrition rate of the programme was high. Positive outcomes regarding satisfaction were found predominantly among completers. The optimal dosage and retention of IBP mental health programmes remain challenging issues that need further research.</p

Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: a cross-diagnostic cluster analysis on a large, international, observational study

A cross-diagnostic, post-hoc analysis of the BRIDGE-II-MIX study was performed to investigate how unipolar and bipolar patients suffering from an acute major depressive episode (MDE) cluster according to severity and duration. Duration of index episode, Clinical Global Impression-Bipolar Version-Depression (CGI-BP-D) and Global Assessment of Functioning (GAF) were used as clustering variables. MANOVA and post-hoc ANOVAs examined between-group differences in clustering variables. A stepwise backward regression model explored the relationship with the 56 clinical-demographic variables available. Agglomerative hierarchical clustering with two clusters was shown as the best fit and separated the study population (n = 2314) into 65.73% (Cluster 1 (C1)) and 34.26% (Cluster 2 (C2)). MANOVA showed a significant main effect for cluster group (p < 0.001) but ANOVA revealed that significant between-group differences were restricted to CGI-BP-D (p < 0.001) and GAF (p < 0.001), showing greater severity in C2. Psychotic features and a minimum of three DSM-5 criteria for mixed features (DSM-5-3C) had the strongest association with C2, that with greater disease burden, while non-mixed depression in bipolar disorder (BD) type II had negative association. Mixed affect defined as DSM-5-3C associates with greater acute severity and overall impairment, independently of the diagnosis of bipolar or unipolar depression. In this study a pure, non-mixed depression in BD type II significantly associates with lesser burden of clinical and functional severity. The lack of association for less restrictive, researched-based definitions of mixed features underlines DSM-5-3C specificity. If confirmed in further prospective studies, these findings would warrant major revisions of treatment algorithms for both unipolar and bipolar depression

OpenSIMPLe: A real-world implementation feasibility study of a smartphone-based psychoeducation programme for bipolar disorder

Background: Few evidence-based mental health apps are widely available to patients and, conversely, many of the available apps have not been appropriately evaluated. Given that the ultimate goal is to scale-up and open internet-based platforms (IBP), it is crucial to appropriately evaluate their real-world feasibility beforehand. We aimed to evaluate the implementation feasibility of a smartphone-based psychoeducational programme for bipolar disorder, exploring its long-term retention, usability, perceived helpfulness and satisfaction, alongside its impact on secondary health outcomes. Methods: Participants were recruited via the project website after completing an online screening questionnaire. They were requested to complete web-based questionnaires before using the app and after 6 months of use which included sociodemographic, illness and treatment variables, the world health organisation-five well-being index (WHO-5) and the short form health survey (SF-36). The follow-up questionnaires also contained satisfaction and usefulness questions. Results: 201 participants took part in the study. According to their retention, 66.2% of the participants were classified as noncompleters and 33.8% as completers. The only predictor significantly associated with higher odds of retention was older age (OR = 1.021, p < 0.001). 62% of the users reported they were satisfied with the programme with a higher percentage among completers. Who-5 baseline and follow-up scores showed a significant improvement as well as 6 out of 8 domains of the SF-36. Limitations: Screening and outcome measures were administered using exclusively self-reported online methods. Conclusion: The 6-month attrition rate of the programme was high. Positive outcomes regarding satisfaction were found predominantly among completers. The optimal dosage and retention of IBP mental health programmes remain challenging issues that need further research

Psychometric properties of two implementation measures:Normalization MeAsure Development questionnaire (NoMAD) and organizational readiness for implementing change (ORIC)

Background: Effective interventions need to be implemented successfully to achieve impact. Two theory-based measures exist for measuring the effectiveness of implementation strategies and monitor implementation progress. The Normalization MeAsure Development questionnaire (NoMAD) explores the four core concepts (Coherence, Cognitive Participation, Collective Action, Reflexive Monitoring) of the Normalization Process Theory. The Organizational Readiness for Implementing Change (ORIC) is based on the theory of Organizational Readiness for Change, measuring organization members’ psychological and behavioral preparedness for implementing a change. We examined the measurement properties of the NoMAD and ORIC in a multi-national implementation effectiveness study. Method: Twelve mental health organizations in nine countries implemented Internet-based cognitive behavioral therapy (iCBT) for common mental disorders. Staff involved in iCBT service delivery (n = 318) participated in the study. Both measures were translated into eight languages using a standardized forward–backward translation procedure. Correlations between measures and subscales were estimated to examine convergent validity. The theoretical factor structures of the scales were tested using confirmatory factor analysis (CFA). Test–retest reliability was based on the correlation between scores at two time points 3 months apart. Internal consistency was assessed using Cronbach's alpha. Floor and ceiling effects were quantified using the proportion of zero and maximum scores.Results: NoMAD and ORIC measure related but distinct latent constructs. The CFA showed that the use of a total score for each measure is appropriate. The theoretical subscales of the NoMAD had adequate internal consistency. The total scale had high internal consistency. The total ORIC scale and subscales demonstrated high internal consistency. Test–retest reliability was suboptimal for both measures and floor and ceiling effects were absent.Conclusions: This study confirmed the psychometric properties of the NoMAD and ORIC in multi-national mental health care settings. While measuring on different but related aspects of implementation processes, the NoMAD and ORIC prove to be valid and reliable across different language settings.</p

Aggressiveness in depression: a neglected symptom possibly associated with bipolarity and mixed features

OBJECTIVE: To evaluate aggressiveness during a major depressive episode (MDE) and its relationship with bipolar disorder (BD) in a post hoc analysis of the BRIDGE-II-MIX study. METHOD: A total of 2811 individuals were enrolled in this multicenter cross-sectional study. MDE patients with (MDE-A, n = 399) and without aggressiveness (MDE-N, n = 2412) were compared through chi-square test or Student's t-test. A stepwise backward logistic regression model was performed. RESULTS: MDE-A group was more frequently associated with BD (P < 0.001), while aggressiveness was negatively correlated with unipolar depression (P < 0.001). At the logistic regression, aggressiveness was associated with the age at first depressive episode (P < 0.001); the severity of mania (P = 0.03); the diagnosis of BD (P = 0.001); comorbid borderline personality disorder (BPD) (P < 0.001) but not substance abuse (P = 0.63); no current psychiatric treatment (P < 0.001); psychotic symptoms (P = 0.007); the marked social/occupational impairment (P = 0.002). The variable most significantly associated with aggressiveness was the presence of DSM-5 mixed features (P < 0.001, OR = 3.815). After the exclusion of BPD, the variable of lifetime suicide attempts became significant (P = 0.013, OR = 1.405). CONCLUSION: Aggressiveness seems to be significantly associated with bipolar spectrum disorders, independently from BPD and substance abuse. Aggressiveness should be considered as a diagnostic criterion for the mixed features specifier and a target of tailored treatment strategy

The implications of hypersomnia in the context of major depression: Results from a large, international, observational study

According to the DSM-5, 'reduction in the need for sleep' is the only sleep-related criteria for mixed features in depressive episodes. We aimed at studying the prevalence, clinical correlates and the role of hypersomnia in a sample of acutely depressed patients. Secondarily, we factors significantly increasing the odds of hypersomnia were studied. We conducted a post-hoc analysis of the BRIDGE-II-Mix study. Variables were compared between patients with hypersomnia (SLEEP+) and with insomnia (SLEEP-) with standard bivariate tests. A stepwise backward logistic regression model was performed with SLEEP+ as dependent variable. A total of 2514 subjects were dichotomized into SLEEP+ (n = 423, 16.8%) and SLEEP- (n = 2091, 83.2%). SLEEP+ had significant higher rates of obese BMI (p < 0.001), BD diagnosis (p = 0.027), severe BD (p < 0.001), lifetime suicide attempts (p < 0.001), lower age at first depression (p = 0.004) than SLEEP-. Also, SLEEP+ had significantly poorer response to antidepressants (AD) such as (hypo)manic switches, AD resistance, affective lability, or irritability (all 0<0.005). Moreover, SLEEP+ had significantly higher rates of mixed-state specifiers than SLEEP- (all 0 < 0.006). A significant contribution to hypersomnia in our regression model was driven by metabolic-related features, such as 'current bulimia' (OR = 4.21) and 'overweight/obese BMI (OR = 1.42)'. Globally, hypersomnia is associated with poor outcome in acute depression. Hypersomnia is strongly associated with mixed features and bipolarity. Metabolic aspects could influence the expression of hypersomnia, worsening the overall clinical outcome. Along with commonly used screening tools, detection of hypersomnia has potential, costless discriminative validity in the differential diagnosis unipolar and bipolar depression

Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study

<p>Abstract</p> <p>Background</p> <p>The anti-VEGF antibody bevacizumab associated with an irinotecan or oxaliplatin-based chemotherapy was proved to be superior to the chemotherapy alone in first or second line treatment of metastatic colorectal cancer (mCRC). However, it was reported to have no efficacy in 3^rdor later-line, alone or with 5FU. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI or FOLFOX in mCRC who have failed prior chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin.</p> <p>Methods</p> <p>Thirty one consecutive patients treated between May 2005 and October 2006 were included in this retrospective study. All of them have progressed under a chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin and received bevacizumab (5 mg/kg) in combination with FOLFIRI or simplified FOLFOX4 every 14 days.</p> <p>Results</p> <p>Ten patients (32.2%) had an objective response (1 CR, 9 PR) and 12 (38.8%) were stabilized. The response and disease control rates were 45.4% and 100% when bevacizumab was administered in 2^ndor 3^rdline and 25% and 55% in 4^thor later line respectively (p = 0.024 and p = 0.008). Among the patients who had previously received the same chemotherapy than that associated with bevacizumab (n = 28) the overall response rate was 35.7% and 39.3% were stabilized. Median progression free survival (PFS) and overall survival (OS) were of 9.7 and 18.4 months respectively. Except a patient who presented a hypertension associated reversible posterior leukoencephalopathy syndrome, tolerance of bevacizumab was acceptable. A rectal bleeding occurred in one patient, an epistaxis in five. Grade 1/2 hypertension occurred in five patients.</p> <p>Conclusion</p> <p>This study suggests that bevacizumab combined with FOLFOX or FOLFIRI may have the possibility to be active in chemorefractory and selected mCRC patients who did not receive it previously.</p