Prediction of estimated risk for bipolar disorder using machine learning and structural MRI features.

BACKGROUND: Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features. METHODS: Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar). RESULTS: For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11-0.361) and a balanced accuracy of 63.1% (95% CI 55.9-70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI -0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6-67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance. CONCLUSIONS: Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.

Larger putamen in individuals at risk and with manifest bipolar disorder.

BACKGROUND: Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations. METHODS: In 410 male and female participants aged 17-35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites. RESULTS: Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake. CONCLUSIONS: Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.

Effects of Early Clozapine Treatment on Remission Rates in Acute Schizophrenia (The EARLY Trial): Protocol of a Randomized-Controlled Multicentric Trial.

BACKGROUND: Quick symptomatic remission after the onset of psychotic symptoms is critical in schizophrenia treatment, determining the subsequent disease course and recovery. In this context, only every second patient with acute schizophrenia achieves symptomatic remission within three months of initiating antipsychotic treatment. The potential indication extension of clozapine-the most effective antipsychotic-to be introduced at an earlier stage (before treatment-resistance) is supported by several lines of evidence, but respective clinical trials are lacking. METHODS: Two hundred-twenty patients with acute non-treatment-resistant schizophrenia will be randomized in this double-blind, 8-week parallel-group multicentric trial to either clozapine or olanzapine. The primary endpoint is the number of patients in symptomatic remission at the end of week 8 according to international consensus criteria ('Andreasen criteria'). Secondary endpoints and other assessments comprise a comprehensive safety assessment (i. e., myocarditis screening), changes in psychopathology, global functioning, cognition, affective symptoms and quality of life, and patients' and relatives' views on treatment. DISCUSSION: This multicentre trial aims to examine whether clozapine is more effective than a highly effective second-generation antipsychotics (SGAs), olanzapine, in acute schizophrenia patients who do not meet the criteria for treatment-naïve or treatment-resistant schizophrenia. Increasing the likelihood to achieve symptomatic remission in acute schizophrenia can improve the overall outcome, reduce disease-associated burden and potentially prevent mid- and long-term disease chronicity.

Excess costs of mental disorders by level of severity.

INTRODUCTION: Mental disorders are highly prevalent in Germany, and associated with decreased quality of life for those affected as well as high economic burden for the society. The purpose of this study was to determine the excess costs of mental disorders and to examine how these differ with respect to disease severity. METHODS: We analyzed mean 6-month costs using the baseline data from the RECOVER trial in Hamburg, Germany, which evaluates an innovative stepped-care model for mental disorders. Four severity levels were classified based on the current level of mental illness, loss of functioning, and psychiatric diagnosis. In this work, direct costs (outpatient, inpatient, and social/informal care) and indirect costs (sick leave, unemployment, and early retirement) were estimated using interview-based data on health care utilization and productivity losses. Excess costs were determined by matching a comparison group of the German general population without mental disorders. Group differences in sociodemographic covariates and somatic comorbidities were balanced using entropy balancing. Excess costs by severity levels were estimated using generalized linear models (GLM) with gamma distribution and log-link function. RESULTS: Overall, the RECOVER group included n = 816 and the comparison group included n = 3226 individuals. Mean total 6-month excess costs amounted to 19,075€, with higher indirect excess costs (13,331€) than direct excess costs (5744€) in total excess costs. The excess costs increased with increasing disease severity, ranging from 6,123€ with mild disease severity (level 1) to 31,883€ with severe mental illness (level 4). Indirect excess costs ranged from 5612€ in level 1 to 21,399€ in level 4, and were statistically significant for all disease severity levels. In contrast, direct excess costs were only statistically significant for the levels 2 to 4, and ranged from 511€ in level 1 to 10,485€ in level 4. The main cost drivers were hospital stays (level 2-4), sick leave and unemployment (all levels), and early retirement (level 3-4). DISCUSSION: Mental disorders are associated with high costs that increase with the level of disease severity, which was also shown for individual ICD-10 diagnosis groups. Due to their influence on costs, indirect costs and disease severity levels should be considered in future cost-of-illness studies of mental disorders. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, trial registration number NCT03459664.

Health-related quality of life in severe psychotic disorders during integrated care: 5-year course, prediction and treatment implications (ACCESS II).

PURPOSE: Studies on outcomes mapping Quality of Life (QoL) as patient-reported outcome over a longer period in severe psychotic disorders are scarce. However, such data would be particularly important for structuring, implementing and operating effective and efficient care models and for promoting satisfaction with care, service engagement and adherence. METHODS: The ACCESS II study is a prospective long-term study of an integrated care model for people with severe psychotic disorders. The model includes Therapeutic Assertive Community Treatment within a cross-sectoral and interdisciplinary network. This publication analyses the course of QoL assessed with the Q-LES-Q-18 using a mixed model for repeated measures. RESULTS: Mapping the course of QoL in N = 329 participants, there is a significant increase in the first 6 weeks of treatment (early course). Comparison to a published norm show significant lower QoL for severe psychotic disorders. The variable having a traumatic event before the age of 18 was significantly negatively associated with QoL. A decrease in the severity of depressive as well as in positive symptomatology in the first six weeks after admission was associated with increase of QoL. CONCLUSION: Results indicate that the overall symptom burden at time of inclusion is not decisive for the perceived QoL in the long-term course while the reduction in the severity of depressive and positive symptoms is important. This means focusing even more on the treatment of depressive symptoms and include traumatherapeutic aspects in the long-term treatment of severe psychotic disorders if needed. TRAIL REGISTRATION: ClinicalTrials.gov (identifier: NCT01888627).

Assessment of risk factors of treatment discontinuation among patients on paliperidone palmitate and risperidone microspheres in France, Germany and Belgium.

BACKGROUND: Long-acting antipsychotics (e.g. 1-monthly (PP1M) / 3-monthly (PP3M) injection forms of paliperidone palmitate) have been developed to improve treatment continuation in schizophrenia patients. We aim to assess risk factors of treatment discontinuation of patients on paliperidone palmitate and risperidone microsphere. Additionally, treatment discontinuation between patients with PP1M and PP3M was compared. METHODS: The IQVIA Longitudinal Prescription databases were used. Risk factors of treatment discontinuation were identified by a multilevel survival regression using Cox proportional hazards model. Kaplan Meier analyses were performed by identified significant risk factors. RESULTS: Twenty-five thousand three hundred sixty-one patients (France: 9,720; Germany: 14,461; Belgium: 1,180) were included. Over a one-year follow-up period, a significant lower treatment discontinuation was observed for patients newly initiated on paliperidone palmitate (53.8%) than those on risperidone microspheres (85.4%). Additionally, a significantly lower treatment discontinuation was found for 'stable' PP3M patients (19.2%) than 'stable' PP1M patients (37.1%). Patients were more likely to discontinue when drugs were prescribed by GP only (HR = 1.68, p < 0.001 vs. psychiatrist only) or if they were female (HR = 1.07, p < 0.001), whereas discontinuation decreased with age (31-50 years: HR = 0.95, p = 0.006 and > 50 years: HR = 0.91, p < 0.001 vs. 18-30 years). CONCLUSIONS: This study demonstrates that patients stay significantly longer on treatment when initiated on paliperidone palmitate as compared to risperidone microspheres. It also indicated a higher treatment continuation of PP3M over PP1M. Treatment continuation is likely to be improved by empowering GPs with mental health knowledge and managing patients by a collaborative primary care-mental health model. Further research is needed to understand why females and younger patients have more treatment discontinuation.

Study protocol of a randomized controlled trial evaluating home treatment with peer support for acute mental health crises (HoPe).

BACKGROUND: Home treatment (HT) is a treatment modality for patients with severe mental illness (SMI) in acute mental crises. It is frequently considered equivalent to psychiatric inpatient treatment in terms of treatment outcome. Peer Support (PS) means that people with lived experience of a mental illness are trained to support others on their way towards recovery. While PS is growing in international importance and despite a growing number of studies supporting its benefits, it is still not comprehensively implemented into routine care. The HoPe (Home Treatment with Peer Support) study investigates a combination of both - HT and PS - to provide further evidence for a recovery-oriented treatment of psychiatric patients. METHODS: In our randomized controlled trial (RCT), HT with PS is compared with HT without PS within a network of eight psychiatric clinical centers from the North, South and East of Germany. We investigate the effects of a combination of both approaches with respect to the prevention of relapse/recurrence defined as first hospitalization after randomization (primary outcome), disease severity, general functioning, self-efficacy, psychosocial health, stigma resistance, recovery support, and service satisfaction (secondary outcomes). A sample of 286 patients will be assessed at baseline after admission to HT care (data point t0) and randomized into the intervention (HT + PS) and control arm (HT). Follow-Up assessments will be conducted 2, 6 and 12 months after admission (resulting in three further data points, t1 to t3) and will be analyzed via intention-to-treat approach. DISCUSSION: This study may determine the positive effects of PS added to HT, prove additional evidence for the efficacy of PS and thereby facilitate its further implementation into psychiatric settings. The aim is to improve quality of mental health care and patients' recovery as well as to reduce the risk of relapses and hospitalizations for patients with SMI. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov: NCT04336527 , April 7, 2020.

[Characteristics of psychoses in adolescence-Longitudinal data of integrated care]. / Charakteristika von Psychosen in der Adoleszenz ­ longitudinale Daten der Integrierten Versorgung.

BACKGROUND: Integrated care according to the Hamburg model combines therapeutic assertive community treatment (TACT) with initiatives for early detection and early treatment of schizophrenia and affective psychoses. The aim of this study was to identify the clinical characteristics of adolescents in comparison to adult patients and to derive knowledge for transition-specific treatment approaches. METHODOLOGY: Sociodemographic and clinical variables as well as treatment performance and clinical outcome were investigated over a period of 12 months in 167 patients with psychoses (16-25 years, n = 88; and >25 years, n = 79). RESULTS: Patients with psychosis in adolescence had significantly more outpatient treatment contacts (3.5/week vs. 1.6/week; p < 0.001), while adults were hospitalized for twice as long (10 days vs. 21 days; p = 0.003). The duration of untreated psychoses was significantly shorter in the adolescent group than in adults (122 weeks vs. 208 weeks; p = 0.002). The proportion of comorbid mental disorders was significantly higher in the adolescent group (87% vs. 63%; p < 0.001). In addition, the adolescence patients already showed greater impairment of daily functions and a higher severity of illness at the start of treatment. DISCUSSION: The treatment of psychoses in adolescence was characterized by a particularly high need for flexibility across all sectors and support systems, taking comorbid problem areas into account. Care models for adolescents and young adults with psychoses should therefore combine treatment approaches for severely ill patients with transition psychiatric interventions to avoid breaks in care and to meet the complex requirements of young patients with severe mental illnesses.

[Mental Diseases in Adolescence - Approaches of Treatment and Clinical Insights]. / Psychische Erkrankungen in der Adoleszenz ­ Behandlungsansätze und klinische Erfahrungen.

Adolescents and young adults with mental illness have an increased risk of long-term unfavourable development and show high clinical severity and multiple psychosocial needs at an early age. In this context, several specific transitional psychiatric treatment services have been developed during the last years. The experience gained so far in adolescent psychiatry shows that a close interdisciplinary cooperation of child and adolescent psychiatry and adult psychiatry is necessary to address interface problems with the aim of a successful transition, as well as to prevent the development of severe and chronicmental illnesses. At the same time, there are many structural and content-related challenges that need to be integrated and addressed. In this review, different treatment models are presented and the requirements for successful transition psychiatry are discussed in the context of the existing evidence.

Efficacy of cognitive-behavioral group therapy in patients at risk for serious mental illness presenting with subthreshold bipolar symptoms: Results from a prespecified interim analysis of a multicenter, randomized, controlled study.

OBJECTIVE: Most patients with bipolar disorders (BD) exhibit prodromal symptoms before a first (hypo)manic episode. Patients with clinically significant symptoms fulfilling at-risk criteria for serious mental illness (SMI) require effective and safe treatment. Cognitive-behavioral psychotherapy (CBT) has shown promising results in early stages of BD and in patients at high risk for psychosis. We aimed to investigate whether group CBT can improve symptoms and functional deficits in young patients at risk for SMI presenting with subthreshold bipolar symptoms. METHOD: In a multicenter, randomized, controlled trial, patients at clinical risk for SMI presenting with subthreshold bipolar symptoms aged 15-30 years were randomized to 14 weeks of at-risk for BD-specific group CBT or unstructured group meetings. Primary efficacy endpoints were differences in affective symptomatology and psychosocial functioning at 14 weeks. At-risk status was defined as a combination of subthreshold bipolar symptomatology, reduction of psychosocial functioning and a family history for (schizo)affective disorders. A prespecified interim analysis was conducted at 75% of the targeted sample. RESULTS: Of 128 screened participants, 75 were randomized to group CBT (n = 38, completers = 65.8%) vs unstructured group meetings (n = 37, completers = 78.4%). Affective symptomatology and psychosocial functioning improved significantly at week 14 (P < .001) and during 6 months (P < .001) in both groups, without significant between-group differences. Findings are limited by the interim character of the analysis, the use of not fully validated early detection interviews, a newly adapted intervention manual, and the substantial drop-outs. CONCLUSIONS: Results suggest that young patients at-risk for SMI presenting with subthreshold bipolar symptoms benefit from early group sessions. The degree of specificity and psychotherapeutic interaction needed requires clarification.

[Early Intervention in Schizophrenia - an Update]. / Frühintervention bei Schizophrenie ­ ein Update.

In Germany, psychoses are still diagnosed too late. The average duration of untreated psychosis is (DUP) one year. Early intervention should, therefore, be given higher priority. The shorter the duration of the DUP, the higher the probability of permanent recovery and a better long-term prognosis. Public education work and specialised early detection centres with low-threshold access can improve care and thus the prospects of patients, mostly young, and already in the early phase of the disease. In addition to anti-psychotic therapy, evidence-based psychotherapeutic procedures, family and peer work, as well as accompanying offers are necessary to support patients individually in being or remaining reintegrated into the labour market ("Individual Placement and Support", IPS). While in some countries, such as Denmark and Australia, the possibility of early intervention is already part of standard care, Germany has not yet gone beyond model projects. Changing this must be one of the main objectives for the coming years. With this review, the authors would therefore like to encourage further thinking and action.

[Healthcare research in the living environment]. / Versorgungsforschung in der Lebenswelt.

BACKGROUND: Healthcare research in the living environment is focused on the scientific investigation of care, which is delivered in the personal environment of those affected by diseases. OBJECTIVE: Presentation of the healthcare policy starting position, content and evidence of forms of care by which treatment focuses on the living environment of affected persons. Presentation of the RECOVER model, by which these forms of care are integrated and coordinated in a care model. MATERIAL AND METHODS: Literature search on "care or treatment models" and "psychiatric disease" over the last 10 years. RESULTS: Many experts are calling for the introduction of integrated and coordinated care as well as the digitalization of the healthcare system as essential future solutions. Evidence-based forms of care, which have a main focus on the living environment of those concerned, play an important role here. These include, for example early diagnosis and treatment of psychoses (early psychosis services, EPS), crisis resolution team (CRT), assertive community treatment (ACT), supported employment (SE) and e­mental health. With the exception of CRT, which can be financed as a hospital ward equivalent treatment according to §§ 39 and 115d (German Social Code V, SGB V), many of these treatment models are not yet part of standard care in Germany. In an integrated and coordinated care system these components work together in a meaningful and coordinated manner in defined care processes. This approach is currently being tested using the so-called RECOVER model, a severity level, evidence-based and cross-sectoral coordinated care model, where implementation, testing and transfer from 2017-2020 will be promoted by the Innovation Fund of the Joint Federal Committee (G-BA).

[Innovative care models for people with schizophrenia]. / Innovative Versorgungsmodelle für Menschen mit schizophrenen Erkrankungen.

Schizophrenia is a complex mental disorder. Hence, the mental health system faces enormous structural, therapeutic, and health-economic challenges. Innovative models of healthcare can facilitate making treatment more efficient and effective.This paper aims to give an overview of evidence-based and innovative models of care and treatment for schizophrenia and severe mental illnesses. For this purpose, we performed a literature search covering the last 10 years of publications regarding "care or treatment models" and "schizophrenia," "psychosis," or "severe mental illness."Many publications do not provide details about the tested care model. Innovative care models for schizophrenia comprise early psychosis services (EPSs) or models for severe mental illnesses (SMI) integrating, combining and/or developing the treatment models crisis resolution team (CRT), assertive community treatment (ACT), and/or (intensive) case management (ICM). For illustration, the innovative models Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia, the Flexible Assertive Community Treatment model in the Netherlands, and the Therapeutic Assertive Community Treatment model in Hamburg are explained. All three models regularly offer integrated, specialized, and assertive care.In Germany, innovative models of care have not been implemented sufficiently: neither EPS nor ACT are part of standard care; CRT can now be funded by health insurances via "ward-equivalent treatment" as defined by a new German law (§§ 39 und 115d SGB V). Regarding the implementation of CRT and ACT in Germany, a clinical study evaluating the RECOVER model is underway. This is a stepped-care, trans-sectorally coordinated and evidence-based treatment model, the evaluation of which is supported by the innovation fund of the Joint Federal Committee (Gemeinsamen Bundesausschuss, G­BA) from 2017 to 2020.

Negative symptoms, anxiety, and depression as mechanisms of change of a 12-month trial of assertive community treatment as part of integrated care in patients with first- and multi-episode schizophrenia spectrum disorders (ACCESS I trial).

Assertive community treatment (ACT) has shown to be effective in improving both functional deficits and quality of life (QoL) in patients with severe mental illness. However, the mechanisms of this beneficial effect remained unclear. We examined mechanisms of change by testing potential mediators including two subdomains of negative symptoms, i.e. social amotivation as well as expressive negative symptoms, anxiety, and depression within a therapeutic ACT model (ACCESS I trial) in a sample of 120 first- and multi-episode patients with a schizophrenia spectrum disorder (DSM-IV). Path modelling served to test the postulated relationship between the respective treatment condition, i.e. 12-month ACT as part of integrated care versus standard care, and changes in functioning and QoL. The final path model resulted in 3 differential pathways that were all significant. Treatment-induced changes in social amotivation served as a starting point for all pathways, and had a direct beneficial effect on functioning and an additional indirect effect on it through changes in anxiety. Expressive negative symptoms were not related to functioning but served as a mediator between changes in social amotivation and depressive symptoms, which subsequently resulted in improvements in QoL. Our results suggest that social amotivation, expressive negative symptoms, depression, and anxiety functioned as mechanisms of change of ACCESS. An integrated and sequential treatment focusing on these mediators may optimise the generalisation effects on functioning as well as on QoL by targeting the most powerful mechanism of change that fits best to the individual patient.

The association of psychopathology with concurrent level of functioning and subjective well-being in persons with schizophrenia spectrum disorders.

The objective is to investigate the relationship between psychopathology measured by the positive and negative syndrome scale (PANSS) and concurrent global assessment of functioning (GAF) and subjective well-being under neuroleptics (SWN) in patients with schizophrenia spectrum disorder (SSD) regarding severity of illness and disease phase. We analyzed a sample of 202 SSD patients consisting of first episode psychosis (FEP) and multiple episode psychosis (MEP) patients followed up to 12 months using linear mixed models. All PANSS syndromes except excitement were associated with GAF scores (positive syndrome: p < 0.001, d = 1.21; negative syndrome: p = 0.029, d = 0.015; disorganized syndrome: p < 0.001, d = 0.37; anxiety/depression syndrome: p < 0.001, d = 0.49), and positive symptoms had an increasing impact on global functioning with higher severity of illness (mildly ill: p = 0.039, d = 0.22; moderately ill: p < 0.001, d = 0.28; severely ill: p < 0.001, d = 0.69). SWN was associated with positive (p = 0.002, d = 0.22) and anxiety/depression (p < 0.001, d = 0.38) syndromes. Subgroup analyses showed differing patterns depending on illness severity and phase. Over all our results show different patterns of associations of psychopathology and concurrent functioning and subjective well-being. These findings contribute knowledge on the possible role of specific psychopathological syndromes for the functioning and well-being of our patients and may enable tailored treatments depending on severity and phase of illness.

Rates and predictors of 18-months remission in an epidemiological cohort of 661 patients with first-episode psychosis.

OBJECTIVES: Most first episode psychosis (FEP) outcome studies are based on patient samples enrolled through an informed consent procedure, which may induce important biases. Our aim was to study the 18-month outcome of FEP in an epidemiological sample of patients treated at the Early Psychosis Prevention and Intervention Centre (EPPIC). METHODS: The files of 661 FEP patients treated for up to 18 months between 1998 and 2000 were assessed. Symptomatic remission was defined as receiving a score ≤3 on the Clinical Global Impressions (CGI) scales, and functional remission as concurrent fulfillment of occupation/employment and independent living. Predictors were analyzed using stepwise logistic regression models. RESULTS: At endpoint, 63% of FEP patients had reached symptomatic remission and 44% functional remission. Duration of untreated psychosis, baseline symptom intensity, time in service and decrease or remission of substance use, predicted both symptomatic and functional outcome. A history of suicide attempt or non-adherence to medication was linked to lower likelihood to reach symptomatic remission while pre-morbid GAF and employment at baseline were linked to functional outcome. CONCLUSIONS: The development of early intervention strategies should be pursued, in order both to provide treatment before symptoms reach a high intensity and to maintain social integration. Specific strategies need to promote engagement, facilitate adherence to medication and to create a framework where key issues such as substance abuse co-morbidity can be addressed.

Naturally Derived Iron Oxide Nanowires from Bacteria for Magnetically Triggered Drug Release and Cancer Hyperthermia in 2D and 3D Culture Environments: Bacteria Biofilm to Potent Cancer Therapeutic.

Iron oxide nanowires produced by bacteria (Mariprofundus ferrooxydans) are demonstrated as new multifunctional drug carriers for triggered therapeutics release and cancer hyperthmia applications. Iron oxide nanowires are obtained from biofilm waste in the bore system used to pump saline groundwater into the River Murray, South Australia (Australia) and processed into individual nanowires with extensive magnetic properties. The drug carrier capabilities of these iron oxide nanowires (Bac-FeOxNWs) are assessed by loading anticancer drug (doxorubicin, Dox) followed by measuring its elution under sustained and triggered release conditions using alternating magnetic field (AMF). The cytotoxicity of Bac-FeOxNWs assessed in 2D (96 well plate) and 3D (Matrigel) cell cultures using MDA-MB231-TXSA human breast cancer cells and mouse RAW 264.7 macrophage cells shows that these Bac-FeOxNWs are biocompatible even at concentrations as high as 250 µg/mL after 24 h of incubation. Finally, we demonstrate the capabilities of Bac-FeOxNWs as potential hyperthermia agent in 3D culture setup. Application of AMF increased the local temperature by 14 °C resulting in approximately 34% decrease in cell viability. Our results demonstrate that these naturally produced nanowires in the form of biofilm can efficiently act as drug carriers with triggered payload release and magnetothermal heating features for potential anticancer therapeutics applications.

[Home treatment--a treatment model of integrated care in Hamburg]. / Home Treatment--aufsuchende Behandlung im Hamburger Modell der Integrierten Versorgung.

Treatment models like "Crisis Resolution and Hometreatment (CRHT)" or "Assertive Community Treatment" (ACT), were found to be effective, enhancing the qualitative level of treatment for patients with severe mental disorders. In Germany, these are implemented only sporadically until today, often as part of a cross-sectoral Integrated Care (IC) treatment system. We will present the implementation of an "Assertive Community Treatment" embedded into an IC-treatment model in Hamburg and discuss the 3-year-outcomes. The IC-treatment model has been designed for severe mentally ill patients with psychotic disorders. Since May 2007 the model is financed by different health insurances as a managed-care "capitation-model" and its effectiveness gets continuously evaluated. The model proved to be effective in earlier studies were compared with standard care low rates of service disengagement were found as well as significantly improved psychopathology, psychosocial functioning, quality of life, satisfaction with care and adherence, while being cost effective. The rates of involuntary admissions declined to 10% in comparison to the years before. In 2011 the model was specified to the indication "first-episode adolescents and young adults in the age of 12-29" in a government-funded study "Integrated Care in Early Psychosis, ICEP Study". In this study an interdisciplinary team of child, adolescent and adult psychiatrists was implemented and since 2012 it is financed by the involved health insurances throughout an expansion of the §140 SGB V agreement.

[Integrated care for patients with first and multiple episodes of severe psychotic illnesses: 3-year results of the Hamburg model]. / Integrierte Versorgung für erst- und mehrfacherkrankte Patienten mit schweren psychotischen Erkrankungen : 3-Jahres-Ergebnisse des Hamburger Modells.

BACKGROUND: The so-called "Hamburg model" is a designated integrated care model according to § 140 of the Social Code Book (SGB) V for psychosis patients fulfilling the definition of severe mental illness (SMI). OBJECTIVES: Description of the model and evaluation of efficacy of all patients being treated for ≥ 3 years. MATERIALS AND METHODS: Service entry illness status, course of illness, and interventions were assessed within a continuous quality assurance study. One hundred and fifty-eight patients who fulfilled the criterion of being treated for ≥ 3 years were analyzed. RESULTS: At service entry, SMI were among others mirrored by a high level of psychopathology (Brief Psychiatric Rating Scale [BPRS]: 80.3) and severity of illness (Clinical Global Impression Severity [CGI-S]/Clinical Global Impression Bipolar scales [CGI-BP]: 5.8), low functioning level (Global Assessment of Functioning scale [GAF]: 35.9), and high rates of comorbid psychiatric (94.3 %) and somatic (81.6 %) disorders. Only 8 patients (5.1 %) disengaged from the service within the 3-year treatment period. The course of the illness over 3 years showed significant and stable improvements in psychopathology (BPRS: p < 0.001), the severity of illness (CGI-S/CGI-BP: p < 0.001), functioning (GAF: p < 0.001), quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q-18]: p < 0.001), and satisfaction with care (Client Satisfaction Questionnaire [CSQ-8]: 2.0 to 3.3; p = 0.164; nonsignificant because of early improvements). Further, compulsory admissions were reduced and medication adherence in addition to working ability improved (all p < 0.001). Data on interventions showed a continuously high frequency of outpatient interventions over time (on average 112.0 per year), a high percentage of patients in psychotherapy (67 %), and a nearly 90 % reduction in inpatient treatment days from year 1 to year 3. CONCLUSION: Integrated care in severely ill patients with psychotic disorders leads to multidimensional illness improvement and stabilization by offering intensive outpatient care.