Effectiveness of integrated care including therapeutic assertive community treatment in severe schizophrenia spectrum and bipolar I disorders: the 24-month follow-up ACCESS II study

OBJECTIVE The ACCESS treatment model offers assertive community treatment embedded in an integrated care program to patients with psychoses. Compared to standard care and within a controlled study, it proved to be more effective in terms of service disengagement and illness outcomes in patients with schizophrenia spectrum disorders over 12 months. ACCESS was implemented into clinical routine and its effectiveness assessed over 24 months in severe schizophrenia spectrum disorders and bipolar I disorder with psychotic features (DSM-IV) in a cohort study. METHOD All 115 patients treated in ACCESS (from May 2007 to October 2009) were included in the ACCESS II study. The primary outcome was rate of service disengagement. Secondary outcomes were change of psychopathology, severity of illness, psychosocial functioning, quality of life, satisfaction with care, medication nonadherence, length of hospital stay, and rates of involuntary hospitalization. RESULTS Only 4 patients (3.4%) disengaged with the service. Another 11 (9.6%) left because they moved outside the catchment area. Patients received a mean of 1.6 outpatient contacts per week. Involuntary admissions decreased from 34.8% in the 2 previous years to 7.8% during ACCESS (P < .001). Mixed models repeated-measures analyses revealed significant improvements among all patients in psychopathology (effect size d = 0.64, P < .001), illness severity (d = 0.84, P = .03), functioning level (d = 0.65, P < .001), quality of life (d = 0.50, P < .001), and client satisfaction (d = 0.11, P < .001). At 24 months, 78.3% were fully adherent to medication, compared to 25.2% at baseline (P = .002). CONCLUSIONS ACCESS was successfully implemented in clinical routine and maintained excellent rates of service engagement and other outcomes in patients with schizophrenia spectrum disorders or bipolar I disorder with psychotic features over 24 months. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01888627.

Toward stratified treatments for bipolar disorders

In bipolar disorders, there are unclear diagnostic boundaries with unipolar depression and schizophrenia, inconsistency of treatment guidelines, relatively long trial-and-error phases of treatment optimization, and increasing use of complex combination therapies lacking empirical evidence. These suggest that the current definition of bipolar disorders based on clinical symptoms reflects a clinically and etiologically heterogeneous entity. Stratification of treatments for bipolar disorders based on biomarkers and improved clinical markers are greatly needed to increase the efficacy of currently available treatments and improve the chances of developing novel therapeutic approaches. This review provides a theoretical framework to identify biomarkers and summarizes the most promising markers for stratification regarding beneficial and adverse treatment effects. State and stage specifiers, neuropsychological tests, neuroimaging, and genetic and epigenetic biomarkers will be discussed with respect to their ability to predict the response to specific pharmacological and psychosocial psychotherapies for bipolar disorders. To date, the most reliable markers are derived from psychopathology and history-taking, while no biomarker has been found that reliably predicts individual treatment responses. This review underlines both the importance of clinical diagnostic skills and the need for biological research to identify markers that will allow the targeting of treatment specifically to sub-populations of bipolar patients who are more likely to benefit from a specific treatment and less likely to develop adverse reactions.

Polar Nature of Biomimetic Fluorapatite/Gelatin Composites: A Comparison of Bipolar Objects and the Polar State of Natural Tissue

The correspondence of the state of alignment of macromolecules in biomimetic materials and natural tissues is demonstrated by investigating a mechanism of electrical polarity formation: An in vitro grown biomimetic FAp/gelatin composite is investigated for its polar properties by second harmonic (SHGM) and scanning pyroelectric microscopy (SPEM). Hexagonal prismatic seed crystals formed in gelatin gels represent a monodomain polar state, due to aligned mineralized gelatin molecules. Later growth stages, showing dumbbell morphologies, develop into a bipolar state because of surface recognition by gelatin functionality: A reversal of the polar alignment of macromolecules, thus, takes place close to that basal plane of the seed. In natural hard tissues (teeth and bone investigated by SPEM) and the biomimetic FAp/gelatin composite, we find a surprising analogy in view of growth-induced states of polarity: The development of polarity in vivo and in vitro can be explained by a Markov-type mechanism of molecular recognition during the attachment of macromolecules.

Using the contribution matrix to evaluate complex study limitations in a network meta-analysis: a case study of bipolar maintenance pharmacotherapy review.

BACKGROUND Limitations in the primary studies constitute one important factor to be considered in the grading of recommendations assessment, development, and evaluation (GRADE) system of rating quality of evidence. However, in the network meta-analysis (NMA), such evaluation poses a special challenge because each network estimate receives different amounts of contributions from various studies via direct as well as indirect routes and because some biases have directions whose repercussion in the network can be complicated. FINDINGS In this report we use the NMA of maintenance pharmacotherapy of bipolar disorder (17 interventions, 33 studies) and demonstrate how to quantitatively evaluate the impact of study limitations using netweight, a STATA command for NMA. For each network estimate, the percentage of contributions from direct comparisons at high, moderate or low risk of bias were quantified, respectively. This method has proven flexible enough to accommodate complex biases with direction, such as the one due to the enrichment design seen in some trials of bipolar maintenance pharmacotherapy. CONCLUSIONS Using netweight, therefore, we can evaluate in a transparent and quantitative manner how study limitations of individual studies in the NMA impact on the quality of evidence of each network estimate, even when such limitations have clear directions.