HIF-1α targeted deletion in myeloid cells decreases MDSC accumulation and alters microbiome in neonatal mice.

The newborn's immune system is faced with the challenge of having to learn quickly to fight off infectious agents, but tolerating the colonization of the body surfaces with commensals without reacting with an excessive inflammatory response. Myeloid-derived suppressor cells (MDSC) are innate immune cells with suppressive activity on other immune cells that regulate fetal-maternal tolerance during pregnancy and control intestinal inflammation in neonates. Until now, nothing is known about the role of MDSC in microbiome establishment. One of the transcription factors regulating MDSC homeostasis is the hypoxia-inducible factor 1α (HIF-1α). We investigated the impact of HIF-1α on MDSC accumulation and microbiome establishment during the neonatal period in a mouse model with targeted deletion of HIF-1α in myeloid cells (Hif1a loxP/loxP LysMCre+). We show that in contrast to wildtype mice, where an extensive expansion of MDSC was observed, MDSC expansion in neonatal Hif1a loxP/loxP LysMCre+ mice was dramatically reduced both systemically and locally in the intestine. This was accompanied by an altered microbiome composition and intestinal T-cell homeostasis. Our results point toward a role of MDSC in inflammation regulation in the context of microbiome establishment and thus reveal a new aspect of the biological role of MDSC during the neonatal period.

Impact of perinatal administration of probiotics on immune cell composition in neonatal mice.

BACKGROUND: Newborns and especially preterm infants are much more susceptible to infections than adults. The pathogens causing infections in newborns are often detectable in the intestinal flora of affected children even before disease onset. Therefore, it seems reasonable to prevent dysbiosis in newborns and preterm infants. An approach followed in many neonatal intensive care units (NICUs) is to prevent infections in preterm infants with probiotics however their mechanisms of action of probiotics are incompletely understood. Here, we investigated the effect of perinatal probiotic exposure on immune cells in newborn mice. METHODS: Pregnant mice were orally treated with a combination of Lactobacillus acidophilus and Bifidobacterium bifidum (Infloran®) from mid-pregnancy until the offspring were harvested. Immune cell composition in organs of the offspring were analyzed by flow cytometry. RESULTS: Perinatal probiotic exposure had profound effects on immune cell composition in the intestine, liver and lungs of newborn mice with reduction of myeloid and B cells and induction of T cells in the probiotic treated animals' organs at weaning. Furthermore, probiotic exposure had an effect on T cell development in the thymus. CONCLUSION: Our results contribute to a better understanding of the interaction of probiotics with the developing immune system. IMPACT: probiotics have profound effects on immune cell composition in intestines, livers and lungs of newborn mice. probiotics modulate T cell development in thymus of newborn mice. effects of probiotics on neonatal immune cells are particularly relevant in transition phases of the microbiome. our results contribute to a better understanding of the mechanisms of action of probiotics in newborns.

Psychiatrists' perceptions of conditions and consequences associated with the implementation of open notes: qualitative investigation.

OBJECTIVE: In a growing list of countries, patients are granted access to their clinical notes ("open notes") as part of their online record access. Especially in the field of mental health, open notes remain controversial with some clinicians perceiving open notes as a tool for improving therapeutic outcomes by increasing patient involvement, while others fear that patients might experience psychological distress and perceived stigmatization, particularly when reading clinicians' notes. More research is needed to optimize the benefits and mitigate the risks. METHODS: Using a qualitative research design, we conducted semi-structured interviews with psychiatrists practicing in Germany, to explore what conditions they believe need to be in place to ensure successful implementation of open notes in psychiatric practice as well as expected subsequent changes to their workload and treatment outcomes. Data were analyzed using thematic analysis. RESULTS: We interviewed 18 psychiatrists; interviewees believed four key conditions needed to be in place prior to implementation of open notes including careful consideration of (1) diagnoses and symptom severity, (2) the availability of additional time for writing clinical notes and discussing them with patients, (3) available resources and system compatibility, and (4) legal and data protection aspects. As a result of introducing open notes, interviewees expected changes in documentation, treatment processes, and doctor-physician interaction. While open notes were expected to improve transparency and trust, participants anticipated negative unintended consequences including the risk of deteriorating therapeutic relationships due to note access-related misunderstandings and conflicts. CONCLUSION: Psychiatrists practiced in Germany where open notes have not yet been established as part of the healthcare data infrastructure. Interviewees were supportive of open notes but had some reservations. They found open notes to be generally beneficial but anticipated effects to vary depending on patient characteristics. Clear guidelines for managing access, time constraints, usability, and privacy are crucial. Open notes were perceived to increase transparency and patient involvement but were also believed to raise issues of stigmatization and conflicts.

Agreement between self-reports and statutory health insurance claims data on healthcare utilization in patients with mental disorders.

BACKGROUND: Data on resource use are frequently required for healthcare assessments. Studies on healthcare utilization (HCU) in individuals with mental disorders have analyzed both self-reports and administrative data. Source of data may affect the quality of analysis and compromise the accuracy of results. We sought to ascertain the degree of agreement between self-reports and statutory health insurance (SHI) fund claims data from patients with mental disorders. METHODS: Claims data from six German SHI and self-reports were obtained along with a cost-effectiveness analysis performed as a part of a controlled prospective multicenter cohort study conducted in 18 psychiatric hospitals in Germany (PsychCare), including patients with pre-defined psychiatric disorders. Self-reports were collected using the German adaption of the Client Sociodemographic and Service Receipt Inventory (CSSRI) questionnaire with a 6-month recall period. Data linkage was performed using a unique pseudonymized identifier. Missing responses were coded as non-use for all analyses. HCU was calculated for inpatient and outpatient care, day-care services, home treatment, and pharmaceuticals. Concordance was measured using Cohen's Kappa (κ) and intraclass correlation coefficient (ICC). Regression approaches were used to investigate the effect of independent variables on the agreements. RESULTS: In total 274 participants (mean age 47.8 [SD = 14.2] years; 47.08% women) were included in the analysis. No significant differences were observed between the linked and unlinked patients in terms of baseline characteristics. Total agreements values were 63.9% (κ = 0.03; PABAK = 0.28) for outpatient contacts, 69.3% (κ = 0.25; PABAK = 0.39) for medication use, 81.0% (κ = 0.56; PABAK = 0.62) for inpatient days and 86.1% (κ = 0.67; PABAK = 0.72) for day-care services. There was varied quantitative agreement between data sources, with the poorest agreement for outpatient care (ICC [95% CI] = 0.22 [0.10-0.33]) and the best for psychiatric day-care services (ICC [95% CI] = 0.72 [0.66-0.78]). Marital status and time since first treatment positively affected the chance of agreement on utilization of outpatient services. CONCLUSIONS: Although there were high levels of absolute agreement, the measures of concordance between administrative records and self-reports were generally minimal to moderate. Healthcare investigations should consider using linked or at least different data sources to estimate HCU for specific utilization areas, where unbiased information can be expected. TRIAL REGISTRATION: This study was part of the multi-center controlled PsychCare trial (German Clinical Trials Register No. DRKS00022535; Date of registration: 2020-10-02).

Depletion of Ly6G-Expressing Neutrophilic Cells Leads to Altered Peripheral T-Cell Homeostasis and Thymic Development in Neonatal Mice.

Newborns and especially preterm infants are much more susceptible to infections than adults. Due to immature adaptive immunity, especially innate immune cells play an important role in a newborn's infection defense. Neonatal neutrophils exhibit profound differences in their functionality compared to neutrophils of adults. In particular, neonates possess a relevant population of suppressive neutrophils, which not only inhibit but also specifically modulate the function of T-cells. In this study, we investigated whether neonatal neutrophils are already involved in T-cell development in the thymus. For this purpose, we used a newly developed model of antibody-mediated immune cell depletion in which we administered a depleting antibody to pregnant and then lactating dams. Using this method, we were able to sufficiently deplete Ly6G-positive neutrophils in offspring. We demonstrated that the depletion of neutrophils in newborn mice resulted in altered peripheral T-cell homeostasis with a decreased CD4+/CD8+ T-cell ratio and decreased expression of CD62L. Neutrophil depletion even affected T-cell development in the thymus, with increased double positive thymocytes and a decreased CD4+/CD8+ single positive thymocyte ratio. Altogether, we demonstrated a previously unknown mechanism mediating neutrophils' immunomodulatory effects in newborns.

Group B streptococci infection model shows decreased regulatory capacity of cord blood cells.

BACKGROUND: Sepsis is one of the leading causes of morbidity and mortality in the neonatal period. Compared to adults, neonates are more susceptible to infections, especially to systemic infections with Group B Streptococcus (GBS). Furthermore, neonates show defects in terminating inflammation. The immunological causes for the increased susceptibility to infection and the prolonged inflammatory response are still incompletely understood. METHODS: In the present study, we aimed to investigate the reaction of cord blood mononuclear cells (MNC) to stimulation with GBS in comparison to that of MNC from adult blood with focus on the proliferative response in an in vitro infection model with heat-inactivated GBS. RESULTS: We demonstrate that after stimulation with GBS the proliferation of T cells from adult blood strongly decreased, while the proliferation of cord blood T cells remained unchanged. This effect could be traced back to a transformation of adult monocytes, but not cord blood monocytes, to a suppressive phenotype with increased expression of the co-inhibitory molecule programmed death ligand 1 (PD-L1). CONCLUSIONS: These results point towards an increased inflammatory capacity of neonatal MNC after stimulation with GBS. Targeting the prolonged inflammatory response of neonatal immune cells may be a strategy to prevent complications of neonatal infections. IMPACT: Neonatal sepsis often leads to post-inflammatory complications. Causes for sustained inflammation in neonates are incompletely understood. We show that cord blood T cells exhibited increased proliferative capacity after stimulation with group B streptococci (GBS) in comparison to adult T cells. Adult monocytes but not cord blood monocytes acquired suppressive activity and expressed increased levels of PD-L1 after GBS stimulation. Increased proliferative capacity of neonatal T cells and decreased suppressive activity of neonatal monocytes during GBS infection may contribute to prolonged inflammation and development of post-inflammatory diseases in newborns.

Differential metabolism of choline supplements in adult volunteers.

BACKGROUND: Adequate intake of choline is essential for growth and homeostasis, but its supply does often not meet requirements. Choline deficiency decreases phosphatidylcholine (PC) and betaine synthesis, resulting in organ pathology, especially of liver, lung, and brain. This is of particular clinical importance in preterm infants and cystic fibrosis patients. We compared four different choline supplements for their impact on plasma concentration and kinetics of choline, betaine as a methyl donor and trimethylamine oxide (TMAO) as a marker of bacterial degradation prior to absorption. METHODS: Prospective randomized cross-over study (1/2020-4/2020) in six healthy adult men. Participants received a single dose of 550 mg/d choline equivalent in the form of choline chloride, choline bitartrate, α-glycerophosphocholine (GPC), and egg-PC in randomized sequence at least 1 week apart. Blood was taken from t = - 0.1-6 h after supplement intake. Choline, betaine, TMAO, and total PC concentrations were analyzed by tandem mass spectrometry. Results are shown as medians and interquartile range. RESULTS: There was no difference in the AUC of choline plasma concentrations after intake of the different supplements. Individual plasma kinetics of choline and betaine differed and concentrations peaked latest for PC (at ≈3 h). All supplements similarly increased plasma betaine. All water-soluble supplements rapidly increased TMAO, whereas egg-PC did not. CONCLUSION: All supplements tested rapidly increased choline and betaine levels to a similar extent, with egg-PC showing the latest peak. Assuming that TMAO may have undesirable effects, egg-PC might be best suited for choline supplementation in adults. STUDY REGISTRATION: This study was registered at "Deutsches Register Klinischer Studien" (DRKS) (German Register for Clinical Studies), 17.01.2020, DRKS00020454.

Equal access to outreach mental health care? Exploring how the place of residence influences the use of intensive home treatment in a rural catchment area in Germany.

BACKGROUND: Internationally, intensive psychiatric home treatment has been increasingly implemented as a community-based alternative to inpatient admission. Since 2018, the so-called Inpatient Equivalent Home Treatment (IEHT; German: "Stationsäquivalente Behandlung", short: "StäB") has been introduced as a particularly intensive form of home treatment that provides at least one daily treatment contact in the service users' (SU) home environment. Prior research shows that this can be challenging in rural catchment areas. Our paper investigates to which extent the location of the SU home location within the catchment area as well as the distance between the home and the clinic influence the utilisation of inpatient treatment compared to IEHT. METHOD: Routine data of one psychiatric hospital in the federal state of Brandenburg in Germany were analysed for the observational period 07/2018-06/2021. Two comparison groups were formed: SU receiving inpatient treatment and SU receiving IEHT. The SU places of residence were respectively anonymised and converted into geo-coordinates. A geographic information system (GIS) was used to visualise the places of residence, and car travel distances as well as travel times to the clinic were determined. Spatial analyses were performed to show the differences between comparison groups. In a more in-depth analysis, the proximity of SU residences to each other was examined as an indicator of possible clustering. RESULTS: During the observational period, the location of 687 inpatient and 140 IEHT unique SU were mapped using the GIS. SU receiving treatment resided predominantly within the catchment area, and this proportion was slightly higher for SU receiving IEHT than for those treated in inpatient setting (95.3% vs. 84.7%). In the catchment area, the geographical distribution of SU place of residence was similar in the two groups. There was a general higher service provision in the more densely populated communities close to Berlin. SU with residence in peripheral communities were mainly treated within the inpatient setting. The mean travel times and distances to the place of residence only differed minimally between the two groups of SU (p > 0.05). The places of residence of SU treated with IEHT were located in greater proximity to each other than those of SU treated in inpatient setting (p < 0.1). CONCLUSION: In especially peripheral parts of the examined catchment area, it may be more difficult to have access to IEHT rather than to inpatient services. The results raise questions regarding health equity and the planning of health care services and have important implications for the further development of intensive home treatment. Telehealth interventions such as blended-care approaches and an increase of flexibility in treatment intensity, e.g. eliminating the daily visit requirement, could ease the implementation of intensive home treatment especially in rural areas.

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.

["iFightDepression" in inpatient treatment : Evaluation of a web-based, therapist-guided self-management program on a specialized ward for affective disorders]. / "iFightDepression" im stationären Setting : Evaluation eines internetbasierten, therapeutenbegleiteten Selbstmanagementprogramms auf einer Spezialstation für affektive Störungen.

BACKGROUND: E­mental health mainly plays a role in the outpatient treatment of patients with depressive disorders. The goal of this study was to implement and evaluate the web-based, therapist-guided self-management tool "iFightDepression" (iFD) to clarify if there is a benefit for inpatient use. MATERIAL AND METHODS: In this study 78 inpatients with affective disorders (ICD-10 F32.0­3, F33.0-3) or dysthymia (F34) were recruited. The intervention duration with the iFD tool went from admission until discharge, therapeutic support was granted by the ward staff. Symptom severity, intervention expectations and experience with therapy were processed in an online questionnaire before the intervention (T0) while intervention satisfaction was captured after the intervention shortly before discharge (T1) in a paper-pencil questionnaire. RESULTS: Out of 78 participating inpatients 42 used the iFD tool at least once. Moderate to high levels of expectation regarding the iFD tool and mildly above-average level of satisfaction after the intervention were observed. Of the active users 67% indicated they would continue to use the iFD tool after discharge. The main reasons for not using the iFD tool were short duration of stay, severity of disease and lack of digital literacy. CONCLUSION: An implementation of the iFD tool is feasible on principle. Active users gave positive feedback concerning the intervention and most participants claimed to continue using the iFD tool after discharge; however, low usage rates among study participants (42/78, 54%) showed barriers of implementation that have to be addressed and underline the importance of adaptations regarding the use of the intervention in a clinical setting.

[Outsourcing of nursing staff costs in psychiatry? : A secondary data analysis of possible effects on the remuneration system in psychiatry]. / Ausgliederung der Pflegekosten in der Psychiatrie? : Eine Sekundärdatenanalyse möglicher Auswirkungen auf das PEPP-System.

BACKGROUND: Nursing staff were excluded from the German DRG system for somatic hospital treatment and will be funded separately in the future. In psychiatry and psychosomatic medicine, binding personnel requirements have been defined but there has been no regulation of how these personnel requirements are adequately financed. OBJECTIVE: The objective of this study was to analyze the costs of inpatient psychiatry and psychosomatic medicine and to evaluate possible effects of funding nursing staff separately. MATERIAL AND METHODS: This analysis is based on aggregated daily treatment costs of selected hospitals (data year 2018), which annually submit their performance and cost data to the Institute for the Hospital Remuneration System (InEK) for the empirical further development of the remuneration system. RESULTS: Nursing staff represent the largest cost factor in inpatient psychiatry and psychosomatic medicine. Excluding nursing staff drastically reduces the variance of psychiatric DRG renumeration and even exceeds its proportion of the total costs. After outsourcing nursing costs, psychiatric DRGs achieve only a very limited cost separation. CONCLUSION: The binding personnel requirements necessitate adequate financing of nursing staff. This raises the debate about the further development of psychiatric remuneration. The question arises as to whether the effort associated with using the psychiatric DRG system justifies its usefulness as an instrument for budgeting when core functions such as cost separation are only given to a limited extent. Alternative approaches to budgeting should also be examined for putting costs and benefits in a better ratio.

[Flexible and integrative treatment in psychiatry: implementation of specific care components at model and standard care clinics in Germany (PsychCare study)]. / Settingübergreifende Behandlung in der Psychiatrie: Umsetzung spezifischer Versorgungsmerkmale an Kliniken der Modell- und Regelversorgung (PsychCare-Studie).

BACKGROUND: Since 2003 a new remuneration and care model has been implemented in currently 22 psychiatric clinics in Germany, which provides flexible and integrative treatment (FIT) across different settings of treatment, including assertive outreach care. The FIT is based on a global treatment budget covering costs for all psychiatric hospital services and is related to the number of patients treated per year. Previous research identified 11 program components that describe treatment structures and processes of FIT. The present analysis quantitatively compared FIT with standard care, aiming to validate these components. METHODS: As part of the PsychCare study, grading according to FIT-specific components was carried out and comparatively analyzed in nine hospitals that used FIT and seven hospitals of standard care. The FIT models were examined in depth in subgroups, which were divided according to the share of the FIT model in the total hospital budget. RESULTS: Of the 11 FIT program components 7 (flexible care management across settings, therapeutic group sessions across all settings, outreach home care, involvement of informal caregivers, accessibility of services, cooperation across sectors and expansion of professional expertise) showed a high statistical differentiation. These differences were even stronger in the subgroup of those hospitals that had a model contract with all health insurers. CONCLUSION: Specific components of FIT are suitable for evaluating the quality of implementation of intersectoral, flexible and outreach psychiatric care.

Extracellular vesicles released by myeloid-derived suppressor cells from pregnant women modulate adaptive immune responses.

Immunological pregnancy complications are a main challenge in reproductive medicine. Mechanisms regulating the adaptation of the maternal immune system to pregnancy are incompletely understood and therapeutic options limited. Myeloid derived suppressor cells (MDSC) are immune-modulatory cells expanding during healthy pregnancy and seem to play a crucial role for maternal-fetal tolerance. Recent studies showed that exosomes produced by MDSC have immune-modulatory effects corresponding to their parental cells under different pathological conditions. Here, we investigated immunological effects of exosomes of GR-MDSC during pregnancy. Isolated GR-MDSC exosomes from peripheral blood of pregnant women were tested for functionality in different in vitro assays. We show that GR-MDSC exosomes exhibited profound immune-modulatory effects such as suppression of T-cell proliferation, T helper 2 (Th2)-cell polarization, induction of regulatory T-cells and inhibition of lymphocyte cytotoxicity. Our results confirm that MDSC-derived exosomes functionally correspond to their parental cells and identify them as an interesting therapeutic target for immunological pregnancy complications.

Implementation, efficacy, costs and processes of inpatient equivalent home-treatment in German mental health care (AKtiV): protocol of a mixed-method, participatory, quasi-experimental trial.

BACKGROUND: Over the last decades, many high-income countries have successfully implemented assertive outreach mental health services for acute care. Despite evidence that these services entail several benefits for service users, Germany has lagged behind and has been slow in implementing outreach services. In 2018, a new law enabled national mental health care providers to implement team-based crisis intervention services on a regular basis, allowing for different forms of Inpatient Equivalent Home Treatment (IEHT). IEHT is similar to the internationally known Home Treatment or Crisis Resolution Teams. It provides acute psychiatric treatment at the user's home, similar to inpatient hospital treatment in terms of content, flexibility, and complexity. METHODS/DESIGN: The presented naturalistic, quasi-experimental cohort study will evaluate IEHT in ten hospitals running IEHT services in different German regions. Within a multi-method research approach, it will evaluate stakeholders' experiences of care, service use, efficacy, costs, treatment processes and implementation processes of IEHT from different perspectives. Quantitative surveys will be used to recruit 360 service users. Subsequently, 180 service users receiving IEHT will be compared with 180 matched statistical 'twins' receiving standard inpatient treatment. Assessments will take place at baseline as well as after 6 and 12 months. The primary outcome is the hospital re-admission rate within 12 months. Secondary outcomes include the combined readmission rate, total number of inpatient hospital days, treatment discontinuation rate, quality of life, psycho-social functioning, job integration, recovery, satisfaction with care, shared decision-making, and treatment costs. Additionally, the study will assess the burden of care and satisfaction with care among relatives or informal caregivers. A collaborative research team made up of researchers with and without lived experience of mental distress will conduct qualitative investigations with service users, caregivers and IEHT staff teams to explore critical ingredients and interactions between implementation processes, treatment processes, and outcomes from a stakeholder perspective. DISCUSSION: By integrating outcome, process and implementation research as well as different stakeholder perspectives and experiences in one study, this trial captures the various facets of IEHT as a special form of home treatment. Therefore, it allows for an adequate, comprehensive evaluation on different levels of this complex intervention. TRIAL REGISTRATION: Trial registrations: 1) German Clinical Trials Register (DRKS), DRKS000224769. Registered December 3rd 2020, https://www.drks.de/drks_web/setLocale_EN.do ; 2) ClinicalTrials.gov, Identifier: NCT0474550 . Registered February 9th 2021.

[Implementation of New Flexible and Integrative Psychiatric Care Models (According to §64b SGB V) in Rural Northern Germany in Comparison to Federal Territory]. / Analyse von Implementierungsmerkmalen psychiatrischer Modellvorhaben (nach §64b SGB V) in Schleswig-Holstein im Vergleich zum Bundesgebiet.

AIM: New treatment models (according to §64b German Social Code) have been introduced in Germany to improve flexible and integrated forms of psychiatric care. The aim of this study was to analyse the specific conditions under which many of these models have been implemented in the federal state of Schleswig-Holstein (SH) in comparison to other federal regions. METHODS: A standardized survey reached 383 patients in seven psychiatric departments, among them three departments in SH. In addition, routine data and data evaluating the grade of implementation in these departments were analysed. RESULTS: Departments in SH showed more developed implementation processes, compared with departments in other regions. Implemented changes were perceived and evaluated as being better by patients in SH. CONCLUSIONS: Implementation processes of flexible and integrated forms of care according to §64b were particularly successful in SH. Extensive political support is discussed as a major reason, among others, for this development.

[DNVF-Discussion paper - Specificities, Challenges and Aims of Mental Health Service Research in Germany]. / DNVF-Diskussionspapier ­ Besonderheiten, Herausforderungen und Ziele der Versorgungsforschung im Feld der seelischen Gesundheit.

Research in mental health services in Germany is of increasing relevance. To this end, the recently founded "Mental Health Working Group" as part of the German Network of Health Services Research (DNVF) has written a discussion paper presenting key specifics, challenges, and goals of health service research in the field of mental health. Some research-relevant specifics in the area of mental health care, pragmatic challenges of research organization, ethical problems, and particular research topics in this field are presented and discussed critically.

[Implementation and Stakeholders' Experiences with Home Treatment in Germany's Integrative and Flexible Psychiatric Care Models - A Mixed-Methods Study]. / Implementierungsstand und Erfahrungen der Stakeholder mit der Zuhause-Behandlung in psychiatrischen Modellvorhaben (nach §64b SGB V) ­ Eine Mixed-Methods Untersuchung.

OBJECTIVE: This paper seeks to illustrate current implementation of and the stakeholders' experiences with Home Treatment (=HT) according to §64b of the German Social Code Book V (=SGB V). METHODS: 381 Patients from 8 hospitals were questioned about their experiences and evaluation of HT using a standardized questionnaire (SEPICC-Scale). Further interviews and focus groups with 37 participants (including users, carers and employees) were thematically analysed. In addition, structural and performance data were collected from participating hospitals and HT teams. RESULTS: HT according to §64b SGB V is implemented quite heterogeneously, especially between rural and urban catchment areas. It provides a long-term, cross-sectoral care, which seems to strengthen the integration of patients' everyday life, treatment flexibility and continuity of care. After having experienced HT once, it is generally rated better. CONCLUSION: An important strength of HT (§64b SGB V) is its adaption to the users' needs and to regional distinctions. Implications for the implementation of outreach services on a larger scale in Germany can be drawn.

[Stakeholders' experiences with flexible and integrative treatment models in German child and adolescent psychiatry according to § 64b SGB V - A qualitative study]. / Erfahrungen der Stakeholder mit den Modellvorhaben nach § 64b SGB V in der Kinder- und Jugendpsychiatrie und -psychotherapie ­ eine qualitative Studie.

Stakeholders' experiences with flexible and integrative treatment models in German child and adolescent psychiatry according to § 64b SGB V - A qualitative study Abstract. Background and Aims: Since 2013, new possibilities for flexible and integrative forms of treatment (FIT) exist within the German mental healthcare system. These FIT models, created according to § 64b of the Social Security Code V, have been implemented in adult as well as child and adolescent psychiatry over the past years. This paper investigates stakeholders' experiences with these innovative FIT models. Methods: Focus groups were conducted in two hospital departments that had implemented a FIT model according to § 64b. In total, 36 participants were included, comprising employees, patients, and their caretakers. We also conducted a thematic analysis. Results: According to all stakeholders, these forms of acute outpatient treatment form a core component of FIT models that may serve to prepare, replace, or follow-up on inpatient treatment. In addition, the flexibility of treatment and increased continuity of care were mentioned as benefits of FIT models according to § 64b. Third, these FIT models allow for a better integration of caretakers in the treatment of their kin, which also produces various challenges for this stakeholder group. Conclusions: The introduction of FIT models in German child and adolescent psychiatry has complex implications for the treatment process and the experiences of all stakeholders. They perceive it as a needs-adapted extension of current forms of psychiatric support.

Cord blood granulocytic myeloid-derived suppressor cells impair monocyte T cell stimulatory capacity and response to bacterial stimulation.

BACKGROUND: Neonatal sepsis is a leading cause of perinatal morbidity and mortality. In comparison to adults, neonates exhibit a higher susceptibility to infections. Myeloid-derived suppressor cells (MDSCs) are myeloid cells with suppressive activity on other immune cells accumulating during foetal life and controlling inflammation in neonates. Most studies investigating the mechanisms for MDSC-mediated immune suppression have been focused on T-cells. Thus far, little is known about the role of MDSC for monocyte function. METHODS: The impact of human cord blood MDSCs (CB-MDSCs) on monocytes was investigated in an in vitro model. CB-MDSCs were co-cultured with peripheral blood mononuclear cells and monocytes were analysed for expression of surface markers, T cell stimulatory and phagocytic capacity, as well as the production of intracellular cytokines by flow cytometry. RESULTS: CB-MDSCs increased the expression of co-inhibitory molecules and decreased the expression of major histocompatibility complex class II molecules on monocytes, leading to an impaired T-cell stimulatory capacity. Upon bacterial stimulation, expression of phagocytosis receptors, phagocytosis rates and production of tumor necrosis factor-α by monocytes was diminished by CB-MDSCs. CONCLUSION: We show that CB-MDSCs profoundly modulate monocyte functions, thereby indirectly impairing T-cell activation. Further research is needed to figure out if MDSCs could be a therapeutic target for inflammatory diseases in neonates like neonatal sepsis.

[Users' Experiences with Psychosocial Counselling Services in a Community Mental Health Centre]. / Psychosoziale Beratung in einem gemeindepsychiatrischen Zentrum ­ eine qualitative Studie über die Erfahrungen der Nutzer.

OBJECTIVE: Analysis of users experiences with a low-threshold psychosocial counselling and case management service across separate sectors (e. g., outpatient, inpatient) and legal provisions (e. g., V and XII Books of Social Code). METHODS: Nine semi-structured interviews were conducted and analysed using content analysis. RESULTS: Several aspects of the users' experiences with counselling services have contributed towards their satisfaction with the service. The importance of short waiting times and the on-call telephone service as well as sufficient time taken for consultations, the availability of outreach counselling and the quality of the relationship with the counsellor were all highlighted. Potential for improvement was seen in the visibility of the service in the community. CONCLUSION: The investigated counselling and case management service can help to provide a low-threshold crisis intervention and could place users in more custom-fit community integration services.